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  1. BAFF mediates splenic B cell response and antibody production in experimental Chagas disease.

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    Daniela A Bermejo

    Full Text Available BACKGROUND: B cells and antibodies are involved not only in controlling the spread of blood circulating Trypanosoma cruzi, but also in the autoreactive manifestations observed in Chagas disease. Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies. Since TNF superfamily B lymphocyte Stimulator (BAFF mediates polyclonal B cell response in vitro triggered by T. cruzi antigens, and BAFF-Tg mice show similar signs to T. cruzi infected mice, we hypothesized that BAFF can mediate polyclonal B cell response in experimental Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: BAFF is produced early and persists throughout the infection. To analyze BAFF role in experimental Chagas disease, Balb/c infected mice were injected with BR3:Fc, a soluble receptor of BAFF, to block BAFF activity. By BAFF blockade we observed that this cytokine mediates the mature B cell response and the production of non-parasite specific IgM and IgG. BAFF also influences the development of antinuclear IgG and parasite-specific IgM response, not affecting T. cruzi-specific IgG and parasitemia. Interestingly, BAFF inhibition favors the parasitism in heart. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.

  2. Specific forms of BAFF favor BAFF receptor-mediated epithelial cell survival.

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    Lahiri, Ayan; Varin, Marie-Michèle; Le Pottier, Laëtitia; Pochard, Pierre; Bendaoud, Boutahar; Youinou, Pierre; Pers, Jacques-Olivier

    2014-06-01

    Although B cell activating factor (BAFF) and its receptor BR3 are produced and expressed by many cells, their role has been restricted to the lymphocyte lineage. Using various techniques (RT-PCR, indirect immunofluorescence, flow cytometry analysis), we observed the expression of BR3 and the production of BAFF by the human salivary gland cell line, by epithelial cells from biopsies of Sjögren's syndrome patients and their controls, but also by salivary gland epithelial cells in culture. To decipher the role of BAFF and BR3 on epithelial cells, BAFF and BR3 were neutralized by blocking antibodies or RNA specific inhibitor (siBR3) and epithelial cell survival was analyzed. Blocking BR3 promotes epithelial cell apoptosis in vitro. This apoptosis resulted in the nuclear translocation of PKCδ. BAFF neutralization by various anti-BAFF antibodies leads to different effects depending on the antibody used suggesting that only some forms of BAFF are required for epithelial cell survival. Our study demonstrates that BR3 is involved in the survival of cultured epithelial cells due to an autocrine effect of BAFF. It also suggests that epithelial cells produce different forms of BAFF and that only some of them are responsible for this effect. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Soluble BAFF Cytokine Levels and Antibody-Mediated Rejection of the Kidney Allograft.

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    Slavcev, Antonij; Brozova, Jitka; Slatinska, Janka; Sekerkova, Zuzana; Honsova, Eva; Skibova, Jelena; Striz, Ilja; Viklicky, Ondrej

    2016-12-01

    The B-cell activating factor (BAFF) cytokine has important functions for the survival and maturation of B lymphocytes, which implies that this cytokine might play a role in the development of antibody-mediated rejection (AMR) after kidney transplantation. In our study, we compared the concentrations of the soluble BAFF cytokine in kidney graft recipients with AMR and patients without rejection with the goal of testing the hypothesis whether BAFF level measurement might be useful as a diagnostic marker of AMR. The study included a cohort of 19 high-risk patients with diagnosed AMR and 17 control patients free of rejection. BAFF was measured in all patients before transplantation, during the rejection episodes, and three months after transplantation in patients free of rejection using the Luminex technique. Before transplantation, the serum concentrations of BAFF in patients with AMR and kidney recipients without rejection did not significantly differ. After transplantation, however, BAFF levels were significantly lower in patients with AMR and also in patients with concurrent humoral and cellular rejection compared with patients without rejection (p BAFF and the production of donor-specific antibodies (DSA) before and after transplantation. Patients experiencing AMR and simultaneous cellular and AMR had significantly lower concentrations of BAFF in comparison with patients free of rejection.

  4. Roles of TRAFs in NF-κB signaling pathways mediated by BAFF.

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    Tang, Xiaoyu; Zhang, Lingling; Wei, Wei

    2018-04-01

    B cell activating factor (BAFF) is an important cytokine for the maintenance of B cell development, survival and homeostasis. BAFF/BAFF-R could directly activate nuclear factor kappa B (NF-κB) pathway. Tumour necrosis factor receptor-associated factors (TRAFs) are key regulatory proteins in NF-κB signaling pathways. TRAF1 enhances the activation of tumor necrosis factor receptor 2 (TNF-R2) induced by NF-κB. TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals mediated by BAFF receptor. TRAF5 is most homologous to TRAF3, as well as most functionally similar to TRAF2. TRAF6 is also required for the BAFF-mediated activation of NF-κB signal pathway. TRAF7 is involved in signal transduction pathways that lead either to activation or repression of NF-κB transcription factor. In this article, we reviewed the roles of TRAFs in NF-κB signaling pathway mediated by BAFF. Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  5. Accelerated Central Nervous System Autoimmunity in BAFF-Receptor-Deficient Mice

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    Kim, Susan S.; Richman, David P.; Zamvil, Scott S.; Agius, Mark A.

    2011-01-01

    B cell activating factor (BAFF) is critical for B cell survival, a function that is mediated by BAFF receptor, (BAFF-R). The role of BAFF (or BAFF-R) in the multiple sclerosis model, experimental autoimmune encephalomyelitis (EAE), was examined using BAFF-R-deficient mice. BAFF-R deficiency resulted in paradoxically increased severity of EAE induced by myelin-oligodendrocyte glycoprotein (MOG) peptide 35-55. Inflammatory foci in BAFF-R-deficient mice comprised increased numbers of activated m...

  6. BAFF promotes proliferation of human mesangial cells through interaction with BAFF-R.

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    Zheng, Nuoyan; Wang, Donxian; Ming, Hongyan; Zhang, Haiqing; Yu, Xueqing

    2015-05-15

    B cell activating factor belonging to the TNF family (BAFF) is vital for B cell survival, proliferation and activation. Evidence indicates that BAFF is systemically or locally increased in glomerulonephritis (e.g. lupus nephritis, IgA nephropathy). However, the effect of BAFF on human mesangial cells is not known. The impact of BAFF on the proliferation of a human mesangial cell line in vitro was investigated. The expression of BAFF receptor (BAFF-R) and downstream signal transduction were explored. The influence of BAFF on the expression of related genes was also studied. Our data indicated that BAFF had a proliferative effect on human mesangial cells, as supported by the results of cell proliferation assays and the inhibited expression of the pro-apoptotic gene Bim. BAFF-R was expressed on the cell membrane of human mesangial cells and blockade of BAFF/BAFF-R binding abrogated the proliferative effect of BAFF on human mesangial cells. BAFF stimulation led to rapid phosphorylation of NF-κBp65, Akt and MAPK p38 kinase in human mesangial cells, whereas it had no effect on the expression of NF-κB p100 and phosphorylation of Erk. The phosphorylation of Akt was very sensitive to blockade of BAFF/BAFF-R ligation, although activation of MAPK p38 and NF-κBp65 was not. BAFF treatment resulted in decreased expression of BAFF-R, which implied negative feedback regulation after its binding. BAFF promoted proliferation of human mesangial cells, which was mediated via BAFF-R. The BAFF/BAFF-R interaction triggered Akt, p65 and p38 activation, with Akt phosphorylation being tightly dependent on BAFF/BAFF-R interaction.

  7. BAFF controls neural cell survival through BAFF receptor.

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    Satoru Tada

    Full Text Available Various neuroprotective factors have been shown to help prevention of neuronal cell death, which is responsible for the progression of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS. However, most of these therapeutic potentials have been tested by administration of recombinant proteins, transgenic expression or virus vector-mediated gene transfer. Therefore, it remains to be clarified whether any endogenous factors has advantage for neuroprotection in a pathological nervous system. Here we show the role of BAFF-R signaling pathway in the control of neural cell survival. Both B cell-activating factor (BAFF and its receptor (BAFF-R are expressed in mouse neurons and BAFF-R deficiency reduces the survival of primary cultured neurons. Although many studies have so far addressed the functional role of BAFF-R on the differentiation of B cells, impaired BAFF-R signaling resulted in accelerated disease progression in an animal model of inherited ALS. We further demonstrate that BAFF-R deficient bone marrow cells or genetic depletion of B cells does not affect the disease progression, indicating that BAFF-mediated signals on neurons, not on B cells, support neural cell survival. These findings suggest opportunities to improve therapeutic outcome for patients with neurodegenerative diseases by synthesized BAFF treatment.

  8. Microglia-mediated BAFF-BAFFR ligation promotes neuronal survival in brain ischemia injury.

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    Li, Kai; Yu, Wei; Cao, Rangjuan; Zhu, Zhihua; Zhao, Guoqing

    2017-11-05

    The innate immune responses of brain to vascular occlusion are primarily orchestrated by activated microglia. However, the roles of microglia in inflammatory responses to brain ischemic injuries are controversial. Here, we report a new mechanism by which microglia confer protective effects on ischemic neuronal cells. We found that under ischemic condition, the B-cell-activating factor (BAFF) was vastly upregulated in microglia and this upregulation could at least be attributed to JAK-STAT signaling pathway activated by IFN-γ and IL-10, which were spatio-temporally enriched in I/R-injured brain as well. Meanwhile, the expression of BAFFR, one member of BAFF receptors, was also upregulated on neurons after I/R injury. More importantly, recombinant BAFF treatment not only promoted neuronal survival under ischemic stresses in vitro but also attenuated infarct volume and neural deficit caused by middle cerebral artery occlusion (MCAO) in vivo. Furthermore, blocking BAFF-BAFFR ligation with TACI-Ig abrogated these therapeutic benefits. Taken together, these results indicate that the BAFF-BAFFR ligation bridged between microglia and neurons could play a critical neuroprotective role in I/R injury. Thus, augmenting BAFF-BAFFR signaling might represent a potential target for clinical stroke therapy. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) mediate CD40-independent help by memory CD4 T cells.

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    Gorbacheva, V; Ayasoufi, K; Fan, R; Baldwin, W M; Valujskikh, A

    2015-02-01

    Donor-reactive memory T cells undermine organ transplant survival and are poorly controlled by immunosuppression or costimulatory blockade. Memory CD4 T cells provide CD40-independent help for the generation of donor-reactive effector CD8 T cells and alloantibodies (alloAbs) that rapidly mediate allograft rejection. The goal of this study was to investigate the role of B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in alloresponses driven by memory CD4 T cells. The short-term neutralization of BAFF alone or BAFF plus APRIL synergized with anti-CD154 mAb to prolong heart allograft survival in recipients containing donor-reactive memory CD4 T cells. The prolongation was associated with reduction in antidonor alloAb responses and with inhibited reactivation and helper functions of memory CD4 T cells. Additional depletion of CD8 T cells did not enhance the prolonged allograft survival suggesting that donor-reactive alloAbs mediate late graft rejection in these recipients. This is the first report that targeting the BAFF cytokine network inhibits both humoral and cellular immune responses induced by memory CD4 T cells. Our results suggest that reagents neutralizing BAFF and APRIL may be used to enhance the efficacy of CD40/CD154 costimulatory blockade and improve allograft survival in T cell-sensitized recipients. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. HIV-1 adenoviral vector vaccines expressing multi-trimeric BAFF and 4-1BBL enhance T cell mediated anti-viral immunity.

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    Saravana Kanagavelu

    Full Text Available Adenoviral vectored vaccines have shown considerable promise but could be improved by molecular adjuvants. Ligands in the TNF superfamily (TNFSF are potential adjuvants for adenoviral vector (Ad5 vaccines based on their central role in adaptive immunity. Many TNFSF ligands require aggregation beyond the trimeric state (multi-trimerization for optimal biological function. Here we describe Ad5 vaccines for HIV-1 Gag antigen (Ad5-Gag adjuvanted with the TNFSF ligands 4-1BBL, BAFF, GITRL and CD27L constructed as soluble multi-trimeric proteins via fusion to Surfactant Protein D (SP-D as a multimerization scaffold. Mice were vaccinated with Ad5-Gag combined with Ad5 expressing one of the SP-D-TNFSF constructs or single-chain IL-12p70 as adjuvant. To evaluate vaccine-induced protection, mice were challenged with vaccinia virus expressing Gag (vaccinia-Gag which is known to target the female genital tract, a major route of sexually acquired HIV-1 infection. In this system, SP-D-4-1BBL or SP-D-BAFF led to significantly reduced vaccinia-Gag replication when compared to Ad5-Gag alone. In contrast, IL-12p70, SP-D-CD27L and SP-D-GITRL were not protective. Histological examination following vaccinia-Gag challenge showed a dramatic lymphocytic infiltration into the uterus and ovaries of SP-D-4-1BBL and SP-D-BAFF-treated animals. By day 5 post challenge, proinflammatory cytokines in the tissue were reduced, consistent with the enhanced control over viral replication. Splenocytes had no specific immune markers that correlated with protection induced by SP-D-4-1BBL and SP-D-BAFF versus other groups. IL-12p70, despite lack of anti-viral efficacy, increased the total numbers of splenic dextramer positive CD8+ T cells, effector memory T cells, and effector Gag-specific CD8+ T cells, suggesting that these markers are poor predictors of anti-viral immunity in this model. In conclusion, soluble multi-trimeric 4-1BBL and BAFF adjuvants led to strong protection from

  11. Molecular structure, distribution, and immunology function of TNFSF13B (BAFF) in Nile tilapia (Oreochromis niloticus).

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    Liu, Hongzhen; Zhang, Jiaxin; Li, Jianfeng; Song, Jinyun; Zhang, Shuangquan

    2016-04-01

    B cell-activating factor (BAFF)is a member of the tumor necrosis factor (TNF) family and plays roles in B cell survival and maturation. In this study, the full-length cDNA of Nile tilapia (Oreochromis niloticus) BAFF (tBAFF) was amplified from the spleen by reverse transcription PCR (RT-PCR). The open reading frame of this cDNA encodes a protein of 261 amino acids containing a predicted transmembrane domain and a furin protease cleavage site, similar to mammalian, avian, and reptile BAFF. Real-time quantitative PCR (qPCR) analysis revealed that tBAFF is present in various tissues and is predominantly expressed in the spleen. The predicted three-dimensional (3D) structure of the Nile tilapia (Oreochromis niloticus) soluble BAFF (tsBAFF) monomer was determined by (3D) structure modeling monomeranalyzed by (3D) structure mouse counterpart. Both tsBAFF and EGFP/tsBAFF were efficiently expressed in Escherichia coli BL21 (DE3), as confirmed by SDS-PAGE and Western blot analysis. After purification, the EGFP/tsBAFF fusion protein showed a fluorescence spectrum similar to that of EGFP. Laser scanning confocal microscopy showed that EGFP/tsBAFF bound to its receptor. In vitro, tsBAFF promoted the proliferation of Nile tilapia and mouse splenic B cells together with/without a priming agent (Staphylococcus aureus Cowan 1, SAC) or anti-mouse IgM. Furthermore, tsBAFF showed a similar proliferation-stimulating effect on mouse B cells compared to msBAFF. These findings indicate that tsBAFF plays an important role in the proliferation of Nile tilapia B cells and has functional cross-reactivity among Nile tilapia and mammals. Therefore, BAFF may represent a useful factor for enhancing immunological efficacy in animals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. The role of BAFF in the progression of rheumatoid arthritis.

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    Wei, Fang; Chang, Yan; Wei, Wei

    2015-12-01

    Rheumatoid arthritis (RA) is a common autoimmune disease that is marked by a systemic inflammatory reaction and joint erosions. Elevated levels of B cell activating factor (BAFF) have been detected in the serum and synovial fluid of RA patients. Moreover, the levels of BAFF increase in cases of autoimmune disease and are correlated with the level of disease activity. As an innate cytokine mediator, BAFF affects the immune response of the synovial microenvironment. In this review, we consider recent observations of BAFF and its receptors in RA progression, as well as the effects of BAFF on the cell-cell interactions network. We also summarize the clinical development of BAFF antagonists for the treatment of RA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. BAFF-R Specific Activation of TRAF6 and the PI3K-Pathway in Lymphoma B Cells

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    Secreto, Frank; Manske, Michelle; Price-Troska, Tammy; Ziesmer, Steven; Hodge, Lucy S.; Ansell, Stephen M.; Cerhan, James R.; Novak, Anne J.

    2014-01-01

    BAFF-R is the primary BAFF receptor that is responsible for promoting B-cell development and survival. Malignant B-cells exploit the BAFF/BAFF receptor system and high serum BAFF levels or genetic alterations in BAFF receptors have been found in B-cell cancers. BAFF signaling impacts pro-survival pathways, however, other than NF-κB2, little is known about the specific pathways activated by individual BAFF receptors. Using a novel BAFF-R expression model we now demonstrate that activation of BAFF-R, independent of TACI and BCMA, can induce phosphorylation of Akt and GSK3β. Expression of an activated form of BAFF-R also enhanced a pro-survival gene expression pattern, including the novel BAFF-regulated gene Pin1, whose expression was PI3K-dependent. Additionally, we show that TRAF6 is essential for mediating BAFF-R-dependent activation of Akt. Together these data describe a novel role for TRAF6 in BAFF-R-specific activation of the PI3K pathway and provide evidence suggesting a new role for Pin1 in BAFF-R signaling. PMID:24206092

  14. Unexpected Potency Differences between B-Cell-Activating Factor (BAFF) Antagonist Antibodies against Various Forms of BAFF: Trimer, 60-Mer, and Membrane-Bound.

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    Nicoletti, Amy M; Kenny, Cynthia Hess; Khalil, Ashraf M; Pan, Qi; Ralph, Kerry L M; Ritchie, Julie; Venkataramani, Sathyadevi; Presky, David H; DeWire, Scott M; Brodeur, Scott R

    2016-10-01

    Therapeutic agents antagonizing B-cell-activating factor/B-lymphocyte stimulator (BAFF/BLyS) are currently in clinical development for autoimmune diseases; belimumab is the first Food and Drug Administration-approved drug in more than 50 years for the treatment of lupus. As a member of the tumor necrosis factor superfamily, BAFF promotes B-cell survival and homeostasis and is overexpressed in patients with systemic lupus erythematosus and other autoimmune diseases. BAFF exists in three recognized forms: membrane-bound and two secreted, soluble forms of either trimeric or 60-mer oligomeric states. To date, most in vitro pharmacology studies of BAFF neglect one or more of these forms. Here, we report a comprehensive in vitro cell-based analysis of BAFF in assay systems that measure all forms of BAFF-mediated activation. We demonstrate the effects of these BAFF forms in both a primary human B-cell proliferation assay and in nuclear factor κB reporter assay systems in Chinese hamster ovary cells expressing BAFF receptors and transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI). In contrast to the mouse system, we find that BAFF trimer activates the human TACI receptor. Further, we profiled the activities of two clinically advanced BAFF antagonist antibodies, belimumab and tabalumab. Unexpectedly, we revealed differences in inhibitory potencies against the various BAFF forms, in particular that belimumab does not potently inhibit BAFF 60-mer. Through this increased understanding of the activity of BAFF antagonists against different forms of BAFF, we hope to influence the discovery of BAFF antagonist antibodies with distinct therapeutic mechanisms for improvement in the treatment of lupus or other related autoimmune pathologies. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  15. IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.

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    Catherine Q Nie

    2009-04-01

    Full Text Available Plasmodium falciparum malaria causes 660 million clinical cases with over 2 million deaths each year. Acquired host immunity limits the clinical impact of malaria infection and provides protection against parasite replication. Experimental evidence indicates that cell-mediated immune responses also result in detrimental inflammation and contribute to severe disease induction. In both humans and mice, the spleen is a crucial organ involved in blood stage malaria clearance, while organ-specific disease appears to be associated with sequestration of parasitized erythrocytes in vascular beds and subsequent recruitment of inflammatory leukocytes. Using a rodent model of cerebral malaria, we have previously found that the majority of T lymphocytes in intravascular infiltrates of cerebral malaria-affected mice express the chemokine receptor CXCR3. Here we investigated the effect of IP-10 blockade in the development of experimental cerebral malaria and the induction of splenic anti-parasite immunity. We found that specific neutralization of IP-10 over the course of infection and genetic deletion of this chemokine in knockout mice reduces cerebral intravascular inflammation and is sufficient to protect P. berghei ANKA-infected mice from fatality. Furthermore, our results demonstrate that lack of IP-10 during infection significantly reduces peripheral parasitemia. The increased resistance to infection observed in the absence of IP-10-mediated cell trafficking was associated with retention and subsequent expansion of parasite-specific T cells in spleens of infected animals, which appears to be advantageous for the control of parasite burden. Thus, our results demonstrate that modulating homing of cellular immune responses to malaria is critical for reaching a balance between protective immunity and immunopathogenesis.

  16. IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.

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    Nie, Catherine Q; Bernard, Nicholas J; Norman, M Ursula; Amante, Fiona H; Lundie, Rachel J; Crabb, Brendan S; Heath, William R; Engwerda, Christian R; Hickey, Michael J; Schofield, Louis; Hansen, Diana S

    2009-04-01

    Plasmodium falciparum malaria causes 660 million clinical cases with over 2 million deaths each year. Acquired host immunity limits the clinical impact of malaria infection and provides protection against parasite replication. Experimental evidence indicates that cell-mediated immune responses also result in detrimental inflammation and contribute to severe disease induction. In both humans and mice, the spleen is a crucial organ involved in blood stage malaria clearance, while organ-specific disease appears to be associated with sequestration of parasitized erythrocytes in vascular beds and subsequent recruitment of inflammatory leukocytes. Using a rodent model of cerebral malaria, we have previously found that the majority of T lymphocytes in intravascular infiltrates of cerebral malaria-affected mice express the chemokine receptor CXCR3. Here we investigated the effect of IP-10 blockade in the development of experimental cerebral malaria and the induction of splenic anti-parasite immunity. We found that specific neutralization of IP-10 over the course of infection and genetic deletion of this chemokine in knockout mice reduces cerebral intravascular inflammation and is sufficient to protect P. berghei ANKA-infected mice from fatality. Furthermore, our results demonstrate that lack of IP-10 during infection significantly reduces peripheral parasitemia. The increased resistance to infection observed in the absence of IP-10-mediated cell trafficking was associated with retention and subsequent expansion of parasite-specific T cells in spleens of infected animals, which appears to be advantageous for the control of parasite burden. Thus, our results demonstrate that modulating homing of cellular immune responses to malaria is critical for reaching a balance between protective immunity and immunopathogenesis.

  17. Renal tubular epithelial cell-derived BAFF expression mediates kidney damage and correlates with activity of proliferative lupus nephritis in mouse and men.

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    Schwarting, A; Relle, M; Meineck, M; Föhr, B; Triantafyllias, K; Weinmann, A; Roth, W; Weinmann-Menke, J

    2018-02-01

    B-cell activating factor of the tumour necrosis factor family (BAFF) is a cytokine, mainly produced by hematopoietic cells (e.g. monocytes/macrophages, dendritic cells), indispensable for B-cell maturation. The BLISS studies have demonstrated that blocking BAFF by the human monoclonal antibody belimumab is a valuable therapeutic approach in patients with clinically and serologically active systemic lupus erythematosus (SLE). However, the defined sources of BAFF, which contributes to SLE, are still unclear. Recent findings show that BAFF expression is not restricted to myeloid cells. Since lupus nephritis is the main cause of morbidity and mortality for SLE patients, the aim of this study was to investigate whether renal tubular epithelial cells (TEC) are an important source of BAFF and thus may contribute to the pathogenesis and progression of SLE. We found BAFF expression both in cultured murine and human TEC. These results could be verified with in situ data from the kidney. Moreover, BAFF expression in the kidneys of lupus-prone MRL- Fas lpr mice correlated with disease activity, and BAFF expression on TEC in biopsies of patients with diffuse proliferative lupus nephritis showed a correlation with the histopathological activity index. In vitro functional assays revealed an autocrine loop of BAFF with its binding receptors on TEC, resulting in a strong induction of colony stimulating factor-1. Finally, we identified divergent effects of BAFF on TEC depending on the surrounding milieu ('inflammatory versus non-inflammatory'). Taken together, our findings indicate that renal-derived BAFF may play an important role in the pathophysiology of the systemic autoimmune disease SLE.

  18. BAFF regulates activation of self-reactive T cells through B-cell dependent mechanisms and mediates protection in NOD mice.

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    Mariño, Eliana; Walters, Stacey N; Villanueva, Jeanette E; Richards, James L; Mackay, Charles R; Grey, Shane T

    2014-04-01

    Targeting the BAFF/APRIL system has shown to be effective in preventing T-cell dependent autoimmune disease in the NOD mouse, a spontaneous model of type 1 diabetes. In this study we generated BAFF-deficient NOD mice to examine how BAFF availability would influence T-cell responses in vivo and the development of spontaneous diabetes. BAFF-deficient NOD mice which lack mature B cells, were protected from diabetes and showed delayed rejection of an allogeneic islet graft. Diabetes protection correlated with a failure to expand pathogenic IGRP-reactive CD8(+) T cells, which were maintained in the periphery at correspondingly low levels. Adoptive transfer of IGRP-reactive CD8(+) T cells with B cells into BAFF-deficient NOD mice enhanced IGRP-reactive CD8(+) T-cell expansion. Furthermore, when provoked with cyclophosphamide, or transferred to a secondary lymphopenic host, the latent pool of self-reactive T cells resident in BAFF-deficient NOD mice could elicit beta cell destruction. We conclude that lack of BAFF prevents the procurement of B-cell-dependent help necessary for the emergence of destructive diabetes. Indeed, treatment of NOD mice with the BAFF-blocking compound, BR3-Fc, resulted in a delayed onset and reduced incidence of diabetes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. HIV-1-Mediated BAFF Secretion in Macrophages Does Not Require Endosomal TLRs, Type-I IFN, and Nef, but Depends on the Cellular Phenotype Status.

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    Gomez, Alejandro M; Ouellet, Michel; Deshiere, Alexandre; Breton, Yann; Tremblay, Michel J

    2016-05-01

    HIV-1 infection is characterized by persistent viral replication, chronic immune activation, and CD4(+) T cell depletion. Moreover, several immune dysfunctions are observed in cells that are not targeted by the virus, such as B cells. Some B cell abnormalities include hypergammaglobulinemia, nonspecific B cell activation, class switching, increased cell turnover, breakage of tolerance, and a loss of the capacity to generate and maintain memory. Several cytokines and growth factors that are increased in the serum of HIV-1-infected individuals have been suggested to directly or indirectly trigger B cell activation, and one of these is BAFF. In this study, we investigate the ability of fully competent (R5-tropic) HIV-1 to induce BAFF production by monocyte-derived macrophages (MDMs). We demonstrate here that HIV-1 drives BAFF production in MDMs in a type-I IFN- and TLR-independent manner. Moreover, we determine that HIV-1 Nef accessory protein is dispensable in BAFF upregulation as a nef-deleted HIV-1 strain is still able to increase BAFF at levels similar to the wild type strain. Finally, we show that the macrophage phenotype status affects HIV-1 replication and BAFF induction, as both were abrogated in MDMs displaying a M1 phenotype. This study provides new useful information about the increased levels of BAFF observed during HIV-1 infection and highlights the importance of macrophages as a source of BAFF, a phenomenon that might contribute to B cell dysfunctions at inflammatory tissue sites in infected individuals. Copyright © 2016 by The American Association of Immunologists, Inc.

  20. BAFF and its receptors involved in the inflammation progress in adjuvant induced arthritis rats.

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    Wei, Fang; Xu, Shu; Jia, Xiaoyi; Sun, Xiaojing; Yang, Xuezhi; Wei, Wei; Chang, Yan

    2016-02-01

    This study is in order to clear the roles of BAFF and its receptors in the inflammation course of autoimmune arthritis. We used a T cell-mediated experimental autoimmune model adjuvant-induced arthritis (AA) rat to study the profiles of BAFF and its receptors in spleen during the inflammation arthritis induction and the effects of BAFF on DCs functions. In vivo, the levels of BAFF and the expression of BAFF-R, TACI were increased in spleen from very early stage of AA. The lesions of spleen were definite correlated with increased levels of BAFF in homogenization. The mature of DCs and increased number in spleen were mainly at early stage of arthritis. In addition, the levels of Interleukin (IL)-12 were found highest and IL-10 were found lowest at this time too. In vitro recombinant BAFF promoted maturation of DCs and inhibited the phagocytosis of DCs. Under stimulation of BAFF on DCs, the levels of tumor necrosis factor (TNF)-α, IL-6, IL-12 were increased, IL-10 and transforming growth factor (TGF)-β1 were decreased. Moreover, BAFF-treated DCs induced proliferation of CD4(+) T cell. These findings support the crucial pathogenic role of DCs, BAFF, and its receptors in the development of experimental arthritis. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Clinical Significance of Pre- and Post-Transplant BAFF Levels in Kidney Transplant Recipients.

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    Ji Won Min

    Full Text Available It is well known that pre-transplant B cell activating factor (BAFF levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine. With the same serum specimen, we measured BAFF levels, and in 78 of these patients, pre-transplant BAFF and anti-HLA antibody levels were detected as well. Patients in each group were divided into tertiles according to BAFF levels. We investigated the relationship between BAFF levels and the occurrence of anti-HLA antibodies. Pre-transplant BAFF levels showed significant association with pre-transplant sensitization, and also with early rejection (Tertile 3, 26.9% vs. Tertile 1, 11.5%; P<0.05. Post-transplant BAFF levels showed significant association with pre-transplant sensitization, but did not show association with anti-HLA antibodies and positive donor-specific antibodies at the time of biopsy. We did not find any association between post-transplant BAFF levels and allograft biopsy results, Banff scores and microvascular inflammation scores. In conclusion, pre-transplant BAFF levels are associated with pre-transplant sensitization and are useful in predicting allograft rejection. But post-transplant BAFF levels measured at the time of indication biopsy are not associated with the appearance of de novo HLA-DSA, allograft rejection, biopsy findings and other allograft outcomes.

  2. The function of BAFF on T helper cells in autoimmunity.

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    Chen, Maogen; Lin, Xiaohong; Liu, Ya; Li, Qiang; Deng, Yiling; Liu, Zhongmin; Brand, David; Guo, Zhiyong; He, Xiaoshun; Ryffel, Bernhard; Zheng, Song Guo

    2014-06-01

    B cell-activating factor belonging to the TNF family (BAFF) exerts its pathogenic role in supporting the survival and proliferation of B cells, regulating class switch recombination as well as the selection of autoreactive B cells. Overexpression of BAFF induces a dramatic expansion of activated B cells, particularly marginal zone B cells, as well as hypergammaglobulinemia, autoantibody production and immune complex deposition. However, in addition to its effect on B cells, recent work has also demonstrated that BAFF can promote T cell activation, proliferation and differentiation. In this review, we have discussed the recent progress on the function and role of BAFF on T cells and T cell-mediated diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. The function of BAFF on T helper cells in autoimmunity

    Science.gov (United States)

    Chen, Maogen; Lin, Xiaohong; Liu, Ya; Li, Qiang; Deng, Yiling; Liu, Zhongmin; Brand, David; Guo, Zhiyong; He, Xiaoshun; Ryffel, Bernhard; Zheng, Song Guo

    2014-01-01

    Summary B cell-activating factor belonging to the TNF family (BAFF) exerts its pathogenic role in supporting the survival and proliferation of B cells, regulating class switch recombination as well as the selection of autoreactive B cells. Overexpression of BAFF induces a dramatic expansion of activated B cells, particularly marginal zone B cells, as well as hypergammaglobulinemia, autoantibody production and immune complex deposition. However, in addition to its effect on B cells, recent work has also demonstrated that BAFF can promote T cell activation, proliferation and differentiation. In this review, we have discussed the recent progress on the function and role of BAFF on T cells and T cell-mediated diseases. PMID:24411564

  4. The Role of BAFF System Molecules in Host Response to Pathogens.

    Science.gov (United States)

    Sakai, Jiro; Akkoyunlu, Mustafa

    2017-10-01

    The two ligands B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) and the three receptors BAFF receptor (BAFF-R), transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA) are members of the "BAFF system molecules." BAFF system molecules are primarily involved in B cell homeostasis. The relevance of BAFF system molecules in host responses to microbial assaults has been investigated in clinical studies and in mice deficient for each of these molecules. Many microbial products modulate the expression of these molecules. Data from clinical studies suggest a correlation between increased expression levels of BAFF system molecules and elevated B cell responses. Depending on the pathogen, heightened B cell responses may strengthen the host response or promote susceptibility. Whereas pathogen-mediated increases in the expression levels of the ligands and/or the receptors appear to promote microbial clearance, certain pathogens have evolved to ablate B cell responses by suppressing the expression of TACI and/or BAFF-R on B cells. Other than its well-established role in B cell responses, the TACI-mediated activation of macrophages is also implicated in resistance to intracellular pathogens. An improved understanding of the role that BAFF system molecules play in infection may assist in devising novel strategies for vaccine development. Copyright © 2017 American Society for Microbiology.

  5. Clinical Significance of Pre- and Post-Transplant BAFF Levels in Kidney Transplant Recipients.

    Science.gov (United States)

    Min, Ji Won; Kim, Kyoung Woon; Kim, Bo-Mi; Doh, Kyoung Chan; Choi, Min Seok; Choi, Bum Soon; Park, Cheol Whee; Yang, Chul Woo; Kim, Yong-Soo; Oh, Eun-Jee; Chung, Byung Ha

    2016-01-01

    It is well known that pre-transplant B cell activating factor (BAFF) levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine. With the same serum specimen, we measured BAFF levels, and in 78 of these patients, pre-transplant BAFF and anti-HLA antibody levels were detected as well. Patients in each group were divided into tertiles according to BAFF levels. We investigated the relationship between BAFF levels and the occurrence of anti-HLA antibodies. Pre-transplant BAFF levels showed significant association with pre-transplant sensitization, and also with early rejection (Tertile 3, 26.9% vs. Tertile 1, 11.5%; PBAFF levels showed significant association with pre-transplant sensitization, but did not show association with anti-HLA antibodies and positive donor-specific antibodies at the time of biopsy. We did not find any association between post-transplant BAFF levels and allograft biopsy results, Banff scores and microvascular inflammation scores. In conclusion, pre-transplant BAFF levels are associated with pre-transplant sensitization and are useful in predicting allograft rejection. But post-transplant BAFF levels measured at the time of indication biopsy are not associated with the appearance of de novo HLA-DSA, allograft rejection, biopsy findings and other allograft outcomes.

  6. Orbital fibroblasts of Graves' orbitopathy stimulated with proinflammatory cytokines promote B cell survival by secreting BAFF.

    Science.gov (United States)

    Tang, Fen; Chen, Xiaoqing; Mao, Yuxiang; Wan, Shangtao; Ai, Siming; Yang, Huasheng; Liu, Guangming; Zou, Yusha; Lin, Miaoli; Dan, Liang

    2017-05-05

    The success of rituximab for the treatment of active Graves' orbitopathy (GO) suggests that B cells play a critical role in intraorbital inflammation. B cell activating factor (BAFF) and its homolog a proliferation-inducing ligand (APRIL) are critical for B cell survival. However, the contribution of BAFF/APRIL to GO remains unclear. We sought to determine the role of BAFF/APRIL in the orbits of GO, and found that BAFF was markedly upregulated, while APRIL was not. Additionally, cultured GO orbital fibroblasts (GO-OFs) 2 expressing BAFF were induced to produce a large amount of BAFF. In contrast, a weak APRIL expression was detected in the OFs, and they exhibited a slight response to stimulation. Notably, pretreated GO-OFs promoted B cell survival, and this effect was significantly inhibited by a BAFF-R neutralizing antibody. This study indicates that OFs from GO can express BAFF and mediate the intraorbital survival of B cells via BAFF mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. BAFF upregulates CD28/B7 and CD40/CD154 expression and promotes mouse T and B cell interaction in vitro via BAFF receptor.

    Science.gov (United States)

    Zhang, Feng; Song, Shan-Shan; Shu, Jin-Ling; Li, Ying; Wu, Yu-Jing; Wang, Qing-Tong; Chen, Jing-Yu; Chang, Yan; Wu, Hua-Xun; Zhang, Ling-Ling; Wei, Wei

    2016-08-01

    B cell-activating factor belonging to the TNF family (BAFF) is a member of TNF family and required for peripheral B cell survival and homeostasis. BAFF has been shown to promote the proliferation of T and B cells. In this study we examined whether and how BAFF mediated the interaction between mouse T and B cells in vitro. BAFF-stimulated B or T cells were co-cultured with T or B cells. The interactions between T and B cells were analyzed by measuring the expression of co-stimulatory molecules (CD28/CD80 or CD40/CD154), the proliferation and secretion of T and B cells and other factors. Two siRNAs against the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and BAFF receptor (BAFF-R) were used to identify the receptors responsible for the actions of BAFF. BAFF-stimulated B cells significantly promoted the proliferation and activity of co-cultured T cells, and increased the percentages of CD4(+)CD28(+) and CD4(+)CD154(+) T cells. Similarly, BAFF-stimulated T cells significantly promoted the proliferation and activity of co-cultured B cells, and increased CD19(+)CD80(+) and CD19(+)CD40(+)B cell subpopulations. BAFF-R siRNA-silenced B cells showed significantly lower expression of CD40 and CD80 than the control B cells. When the BAFF-R siRNA-silenced B cells were stimulated with BAFF, then co-cultured with T cells, the expression of CD28 and CD154 on T cells was not increased. TACI siRNA-silenced B cells exhibited higher expression of CD40 and CD80 than the control B cells. When the TACI siRNA-silenced B cells were stimulated with BAFF, then co-cultured with T cells, the expression of CD28 and CD154 on T cells was significantly increased. BAFF upregulates CD28/B7 and CD40/CD154 expression, and promotes the interactions between T and B cells in a BAFF-R-dependent manner.

  8. BAFF is involved in macrophage-induced bortezomib resistance in myeloma.

    Science.gov (United States)

    Chen, Jing; He, Donghua; Chen, Qingxiao; Guo, Xing; Yang, Li; Lin, Xuanru; Li, Yi; Wu, Wenjun; Yang, Yang; He, Jingsong; Zhang, Enfan; Yi, Qing; Cai, Zhen

    2017-11-02

    We aimed to characterize the role of B-cell activating factor (BAFF) in macrophage-mediated resistance of multiple myeloma (MM) cells to bortezomib (bort), and to further understand the molecular mechanisms involved in the process. First, we detected BAFF and its three receptors on myeloma cells and macrophages using the quantitative reverse transcriptase-polymerase chain reaction and flow cytometry. The secretion of BAFF was tested in patients with MM, MM cell lines, and macrophages. The ability of macrophages to protect MM cells from bort-induced apoptosis was significantly attenuated using BAFF-neutralizing antibody in the co-culture system or knocking down the expression of BAFF in macrophages with small interfering RNA. We also showed that the MM-macrophage interaction through BAFF and its receptors was primarily mediated by the activation of Src, Erk1/2, Akt, and nuclear factor kappa B signaling and the suppression of caspase activation induced by bort. Our data demonstrated that BAFF played a functional role in the macrophage-mediated resistance of MM cells to bort, suggesting that targeting BAFF may provide a basis for the molecular- and immune-targeted therapeutic approach.

  9. Expression of BAFF and BAFF-R in Follicular Lymphoma: Correlation with Clinicopathologic Characteristics and Survival Outcomes

    OpenAIRE

    Li, Ya-Jun; Jiang, Wen-Qi; Rao, Hui-Lan; Huang, Jia-Jia; Xia, Yi; Huang, Hui-Qiang; Lin, Tong-Yu; Xia, Zhong-Jun; Li, Su; Li, Zhi-Ming

    2012-01-01

    BACKGROUND: B-cell activation factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the viability and proliferation of malignant lymphoma cells. Limited information exists regarding expression profiles and the prognostic role of BAFF and BAFF-R in follicular lymphoma (FL). We sought to determine the expression profiles of BAFF and BAFF-R in FL and to evaluate the correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and outcome of FL. Correlation between ex...

  10. BAFF promotes autoantibody production via TACI-dependent activation of transitional B cells

    Science.gov (United States)

    Jacobs, Holly M.; Thouvenel, Christopher D.; Leach, Sarah; Arkatkar, Tanvi; Metzler, Genita; Scharping, Nicole E.; Kolhatkar, Nikita S.; Rawlings, David J.; Jackson, Shaun W.

    2016-01-01

    Mice overexpressing B cell activating factor of the TNF family (BAFF) develop systemic autoimmunity characterized by class-switched anti-nuclear antibodies. Transmembrane activator and CAML interactor (TACI) signals are critical for BAFF-mediated autoimmunity, but the B cell developmental subsets undergoing TACI-dependent activation in settings of excess BAFF remains unclear. We now report that, whereas surface TACI expression is usually limited to mature B cells, excess BAFF promotes the expansion of TACI-expressing transitional B cells. TACIhi transitional cells from BAFF-Tg mice are characterized by an activated, cycling phenotype; and the TACIhi cell subset is specifically enriched for autoreactivity, expresses activation-induced cytidine deaminase (AID) and T-bet and exhibits evidence of somatic hypermutation. Consistent with a potential contribution to BAFF-mediated humoral autoimmunity, TACIhi transitional B cells from BAFF-Tg mice spontaneously produce class-switched autoantibodies ex vivo. These combined findings highlight a novel mechanism whereby BAFF promotes humoral autoimmunity via direct, TACI-dependent activation of transitional B cells. PMID:27022196

  11. Cutting Edge: BAFF Promotes Autoantibody Production via TACI-Dependent Activation of Transitional B Cells.

    Science.gov (United States)

    Jacobs, Holly M; Thouvenel, Christopher D; Leach, Sarah; Arkatkar, Tanvi; Metzler, Genita; Scharping, Nicole E; Kolhatkar, Nikita S; Rawlings, David J; Jackson, Shaun W

    2016-05-01

    Mice overexpressing B cell activating factor of the TNF family (BAFF) develop systemic autoimmunity characterized by class-switched anti-nuclear Abs. Transmembrane activator and CAML interactor (TACI) signals are critical for BAFF-mediated autoimmunity, but the B cell developmental subsets undergoing TACI-dependent activation in settings of excess BAFF remain unclear. We report that, although surface TACI expression is usually limited to mature B cells, excess BAFF promotes the expansion of TACI-expressing transitional B cells. TACI(+) transitional cells from BAFF-transgenic mice are characterized by an activated, cycling phenotype, and the TACI(+) cell subset is specifically enriched for autoreactivity, expresses activation-induced cytidine deaminase and T-bet, and exhibits evidence of somatic hypermutation. Consistent with a potential contribution to BAFF-mediated humoral autoimmunity, TACI(+) transitional B cells from BAFF-transgenic mice spontaneously produce class-switched autoantibodies ex vivo. These combined findings highlight a novel mechanism through which BAFF promotes humoral autoimmunity via direct, TACI-dependent activation of transitional B cells. Copyright © 2016 by The American Association of Immunologists, Inc.

  12. Splenic abscesses.

    Science.gov (United States)

    Al-Hajjar, Nadim; Graur, Florin; Hassan, Aboul B; Molnár, Geza

    2002-03-01

    Splenic abscesses are rare entities (autopsy incidence between 0.14-0.7%). The most frequent etiology is the septic emboli seeding from bacterial endocarditis (about 20% of cases) or other septic foci (typhoid fever, malaria, urinary tract infections, osteomielitis, otitis). The treatment of splenic abscesses was until recently splenectomy with antibiotherapy. The actual trends are more conservative (mini invasive or non-invasive) because the immunologic role of the spleen has been better understood over the last year

  13. BAFF promotes proliferation of human mesangial cells through interaction with BAFF-R

    OpenAIRE

    Zheng, Nuoyan; Wang, Donxian; Ming, Hongyan; Zhang, Haiqing; Yu, Xueqing

    2015-01-01

    Background B cell activating factor belonging to the TNF family (BAFF) is vital for B cell survival, proliferation and activation. Evidence indicates that BAFF is systemically or locally increased in glomerulonephritis (e.g. lupus nephritis, IgA nephropathy). However, the effect of BAFF on human mesangial cells is not known. Methods The impact of BAFF on the proliferation of a human mesangial cell line in vitro was investigated. The expression of BAFF receptor (BAFF-R) and downstream signal t...

  14. Changes in Blood B Cell-Activating Factor (BAFF) Levels in Multiple Sclerosis: A Sign of Treatment Outcome.

    Science.gov (United States)

    Kannel, Karin; Alnek, Kristi; Vahter, Liina; Gross-Paju, Katrin; Uibo, Raivo; Kisand, Kalle V

    2015-01-01

    Multiple sclerosis (MS) is mediated primarily by autoreactive T cells. However, evidence suggesting the involvement of humoral immunity in brain diseases has increased interest in the role of B cells and their products during MS pathogenesis. The major survival factor for B cells, BAFF has been shown to play a role in several autoimmune conditions. Elevated BAFF levels have been reported in MS animal model and during MS relapse in patients. Moreover, disease-modifying treatments (DMT) reportedly influence blood BAFF levels in MS patients, but the significance of these changes remains unclear. The present study addresses how blood BAFF levels are associated with the clinical course of relapsing-remitting MS and the effectiveness of DMT and short-term steroid treatment. During a prospective longitudinal follow-up of 2.3 years, BAFF was measured in the blood of 170 MS patients in the stable phase and within 186 relapses. BAFF levels were significantly higher in MS patients compared to healthy controls. However, stable MS patients without relapses exhibited significantly higher BAFF levels than relapsing patients. Treatment with interferon-β and immunosuppressants raised BAFF blood levels. Interestingly, a similar effect was not seen in patients treated with glatiramer acetate. Short-term treatment with high doses of intravenous methylprednisolone did not significantly alter plasma BAFF levels in 65% of relapsing-remitting MS patients. BAFF were correlated weakly but significantly with monocyte and basophil counts, but not with other blood cell types (neutrophils, lymphocytes, or eosinophils) or inflammatory biomarkers. To our knowledge, this is the first report demonstrating that higher blood BAFF levels may reflect a more stable and effective MS treatment outcome. These results challenge hypotheses suggesting that elevated blood BAFF levels are associated with more severe disease presentation and could explain the recent failure of pharmaceutical trials targeting

  15. Changes in Blood B Cell-Activating Factor (BAFF Levels in Multiple Sclerosis: A Sign of Treatment Outcome.

    Directory of Open Access Journals (Sweden)

    Karin Kannel

    Full Text Available Multiple sclerosis (MS is mediated primarily by autoreactive T cells. However, evidence suggesting the involvement of humoral immunity in brain diseases has increased interest in the role of B cells and their products during MS pathogenesis. The major survival factor for B cells, BAFF has been shown to play a role in several autoimmune conditions. Elevated BAFF levels have been reported in MS animal model and during MS relapse in patients. Moreover, disease-modifying treatments (DMT reportedly influence blood BAFF levels in MS patients, but the significance of these changes remains unclear. The present study addresses how blood BAFF levels are associated with the clinical course of relapsing-remitting MS and the effectiveness of DMT and short-term steroid treatment. During a prospective longitudinal follow-up of 2.3 years, BAFF was measured in the blood of 170 MS patients in the stable phase and within 186 relapses. BAFF levels were significantly higher in MS patients compared to healthy controls. However, stable MS patients without relapses exhibited significantly higher BAFF levels than relapsing patients. Treatment with interferon-β and immunosuppressants raised BAFF blood levels. Interestingly, a similar effect was not seen in patients treated with glatiramer acetate. Short-term treatment with high doses of intravenous methylprednisolone did not significantly alter plasma BAFF levels in 65% of relapsing-remitting MS patients. BAFF were correlated weakly but significantly with monocyte and basophil counts, but not with other blood cell types (neutrophils, lymphocytes, or eosinophils or inflammatory biomarkers. To our knowledge, this is the first report demonstrating that higher blood BAFF levels may reflect a more stable and effective MS treatment outcome. These results challenge hypotheses suggesting that elevated blood BAFF levels are associated with more severe disease presentation and could explain the recent failure of pharmaceutical

  16. Effect of glucocorticoid treatment on BAFF and APRIL expression in patients with immune thrombocytopenia (ITP).

    Science.gov (United States)

    Kamhieh-Milz, Julian; Ghosoun, Nuha; Sterzer, Viktor; Salama, Abdulgabar

    2018-03-01

    Immune thrombocytopenic purpura (ITP) is an idiopathic bleeding disorder. B cell activating factor (BAFF) and 'A proliferation-inducing ligand' (APRIL) have regulatory effects on B and T cells and may represent relevant factors in the pathogenesis of ITP. Serum levels and gene expression were investigated in ITP patients. Both BAFF and APRIL serum levels were significantly elevated in active ITP. However, gene expression analysis revealed both factors to have a tendency toward downregulation. Glucocorticoid treatment significantly reduced BAFF but not APRIL serum levels, which may be mediated by differences in transcription factor binding sites. The glucocorticoid receptor binding site is present in the BAFF promotor region, but not in the APRIL promotor region. Prednisolone in combination with vitamin D3 may be effective in reducing APRIL serum levels. In conclusion, glucocorticoid treatment exerts different regulatory effects on both BAFF and APRIL, whereas antioxidant supplementation may also be beneficial in reducing serum levels. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Pretransplant serum BAFF levels are associated with pretransplant HLA immunization and renal allograft survival.

    Science.gov (United States)

    Friebus-Kardash, Justa; Wilde, Benjamin; Keles, Deniz; Heinold, Andreas; Kribben, Andreas; Witzke, Oliver; Heinemann, Falko Markus; Eisenberger, Ute

    2018-04-01

    The essential function of B cell-activating factor (BAFF) is regulating the survival and differentiation of B cells. The link between pretransplant BAFF levels and pretransplant alloimmunization and its value to predict subsequent acute antibody-mediated rejection (AMR) and outcome after renal transplantation is not fully understood. Objective of our retrospective single-center study was to determine, by ELISA analysis of pretransplant serum BAFF levels in 249 patients undergoing renal transplantation, association between preformed anti-human leukocyte antigen (HLA) antibodies, occurrence of acute antibody mediated rejection (AMR) and renal allograft survival. Pretransplant serum BAFF levels were significantly higher in presensitized recipients with anti-HLA antibodies (3262±2796pg/ml) than in recipients without occurrence of anti-HLA antibodies (2252±1425pg/ml; pBAFF levels correlated with cumulative MFI values of anti-HLA antibodies (r=0.2966, p=0.0025). Patients with high pretransplant BAFF levels (≥2137pg/ml) experienced significantly lower allograft survival rates compared to low pretransplant BAFF levels (80% vs. 91%; p=0.01). Coexistence of high pretransplant BAFF levels and posttransplant AMR was associated with the worst allograft survival rates (56%). Relative risk (RR) for allograft loss was associated with high serum BAFF levels (RR 2.3; p=0.02), presence of anti-HLA antibodies (RR 2.5; p=0.007) or anti-HLA -donor-specific antibodies (DSAs) (RR 2.6; p=0.003) before transplant and AMR post transplant (RR 2.5; p=0.007). AMR was the strongest independent risk factor for allograft failure (RR 2.6; p=0.03). Elevated pretransplant serum BAFF levels negatively affect renal allograft survival and represent a risk factor for allosensitization and subsequent AMR. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Signals from activation of B-cell receptor with anti-IgD can override the stimulatory effects of excess BAFF on mature B cells in vivo.

    Science.gov (United States)

    Nguyen, Tue G; Morris, Jonathan M

    2014-09-01

    The selection and maturation of B-cell clones are critically determined by tonic signals from activated B cell receptors (BCR) and survival signals from BAFF cytokine. These finely tuned and coordinated signals provide a net positive signal that can promote the selection, maturation, proliferation and differentiation of a developing B cell. Stimulation with an anti-IgD antibody can also activate BCR but can lead to depletion and an arrest of mature B-cell development in vivo. It is not known whether survival signals from excess BAFF can override the suppressive effects of treatment with anti-IgD on mature B cells in vivo. Herein, we examined the effects of co-treatment of BAFF and anti-IgD on the mature B-cell compartment and antibody production in vivo by treating mice with either 1mg/kg BAFF or anti-IgD alone or in combination for 3 consecutive days. We found that co-treatment with anti-IgD significantly abrogated these stimulatory effects of BAFF treatment on splenic CD19+ B cells as well as mature CD19+IgD(hi)IgM+ B cells in vivo. Anti-IgD down-regulated the expression of the BCR complex (mIgM, mIgD and CD19) and the BAFF receptor TACI without regard to the presence of BAFF. Anti-IgD treatment also significantly negated BAFF-induced IgM production in vivo. Both BAFF and anti-IgD could individually stimulate IL-10 synthesis in B cells but did not affect one another. Taken together, our data suggest that activation of BCR with an anti-IgD antibody can override the stimulatory effects from excess BAFF on B cell proliferation and antibody production by down-regulating the expression of BCR complex and BAFF receptors. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Aberrant Expression of Functional BAFF-System Receptors by Malignant B-Cell Precursors Impacts Leukemia Cell Survival

    Science.gov (United States)

    Maia, Sara; Pelletier, Marc; Ding, Jixin; Hsu, Yen-Ming; Sallan, Stephen E.; Rao, Sambasiva P.; Nadler, Lee M.; Cardoso, Angelo A.

    2011-01-01

    Despite exhibiting oncogenic events, patient's leukemia cells are responsive and dependent on signals from their malignant bone marrow (BM) microenvironment, which modulate their survival, cell cycle progression, trafficking and resistance to chemotherapy. Identification of the signaling pathways mediating this leukemia/microenvironment interplay is critical for the development of novel molecular targeted therapies. We observed that primary leukemia B-cell precursors aberrantly express receptors of the BAFF-system, BAFF-R, BCMA, and TACI. These receptors are functional as their ligation triggers activation of NF-κB, MAPK/JNK, and Akt signaling. Leukemia cells express surface BAFF and APRIL ligands, and soluble BAFF is significantly higher in leukemia patients in comparison to age-matched controls. Interestingly, leukemia cells also express surface APRIL, which seems to be encoded by APRIL-δ, a novel isoform that lacks the furin convertase domain. Importantly, we observed BM microenvironmental cells express the ligands BAFF and APRIL, including surface and secreted BAFF by BM endothelial cells. Functional studies showed that signals through BAFF-system receptors impact the survival and basal proliferation of leukemia B-cell precursors, and support the involvement of both homotypic and heterotypic mechanisms. This study shows an unforeseen role for the BAFF-system in the biology of precursor B-cell leukemia, and suggests that the target disruption of BAFF signals may constitute a valid strategy for the treatment of this cancer. PMID:21687682

  20. Aberrant expression of functional BAFF-system receptors by malignant B-cell precursors impacts leukemia cell survival.

    Directory of Open Access Journals (Sweden)

    Sara Maia

    Full Text Available Despite exhibiting oncogenic events, patient's leukemia cells are responsive and dependent on signals from their malignant bone marrow (BM microenvironment, which modulate their survival, cell cycle progression, trafficking and resistance to chemotherapy. Identification of the signaling pathways mediating this leukemia/microenvironment interplay is critical for the development of novel molecular targeted therapies.We observed that primary leukemia B-cell precursors aberrantly express receptors of the BAFF-system, BAFF-R, BCMA, and TACI. These receptors are functional as their ligation triggers activation of NF-κB, MAPK/JNK, and Akt signaling. Leukemia cells express surface BAFF and APRIL ligands, and soluble BAFF is significantly higher in leukemia patients in comparison to age-matched controls. Interestingly, leukemia cells also express surface APRIL, which seems to be encoded by APRIL-δ, a novel isoform that lacks the furin convertase domain. Importantly, we observed BM microenvironmental cells express the ligands BAFF and APRIL, including surface and secreted BAFF by BM endothelial cells. Functional studies showed that signals through BAFF-system receptors impact the survival and basal proliferation of leukemia B-cell precursors, and support the involvement of both homotypic and heterotypic mechanisms.This study shows an unforeseen role for the BAFF-system in the biology of precursor B-cell leukemia, and suggests that the target disruption of BAFF signals may constitute a valid strategy for the treatment of this cancer.

  1. Cutting Edge: BAFF Overexpression Reduces Atherosclerosis via TACI-Dependent B Cell Activation.

    Science.gov (United States)

    Jackson, Shaun W; Scharping, Nicole E; Jacobs, Holly M; Wang, Shari; Chait, Alan; Rawlings, David J

    2016-12-15

    Patients with systemic lupus erythematosus exhibit accelerated atherosclerosis, a chronic inflammatory disease of the arterial wall. The impact of B cells in atherosclerosis is controversial, with both protective and pathogenic roles described. For example, natural IgM binding conserved oxidized lipid epitopes protect against atherosclerosis, whereas anti-oxidized low-density lipoprotein (oxLDL) IgG likely promotes disease. Because BAFF promotes B cell class-switch recombination and humoral autoimmunity, we hypothesized that excess BAFF would accelerate atherosclerosis. In contrast, BAFF overexpression markedly reduced hypercholesterolemia and atherosclerosis in hyperlipidemic mice. BAFF-mediated atheroprotection required B cells and was associated with increased protective anti-oxLDL IgM. Surprisingly, high-titer anti-oxLDL IgM production and reduced atherosclerosis was dependent on the BAFF family receptor transmembrane activator and CAML interactor. In summary, we identified a novel role for B cell-specific, BAFF-dependent transmembrane activator and CAML interactor signals in atherosclerosis pathogenesis, of particular relevance to the use of BAFF-targeted therapies in systemic lupus erythematosus. Copyright © 2016 by The American Association of Immunologists, Inc.

  2. Cigarette smoke inhibits BAFF expression and mucosal immunoglobulin A responses in the lung during influenza virus infection.

    Science.gov (United States)

    Wang, Jianmiao; Li, Qinghai; Xie, Jungang; Xu, Yongjian

    2015-03-14

    It is incompletely understood how cigarette smoke (CS) exposure affects lung mucosal immune responses during viral respiratory infections. B cell activating factor belonging to the tumor necrosis factor family (BAFF) plays an important role in the induction of secretory immunoglobulin A (S-IgA) which is the main effector of the mucosal immune system. We therefore investigated the effects of CS exposure on BAFF expression and S-IgA responses in the lung during influenza virus infection. Mice were exposed to CS and/or infected with influenza virus. Bronchoalveolar lavage fluid and lung compartments were analyzed for BAFF expression, influenza-specific S-IgA level and histological changes. Lung B cells were isolated and the activation-induced cytidine deaminase (Aicda) expression was determined. BEAS-2B cells were treated with CS extract (CSE), influenza virus, interferon beta or N-acetylcysteine and BAFF expression was measured. CS inhibited BAFF expression in the lung, particularly after long-term exposure. BAFF and S-IgA levels were increased during influenza virus infection. Three-month CS exposure prior to influenza virus infection resulted in reduced BAFF and S-IgA levels in the lung as well as augmented pulmonary inflammation on day 7 after infection. Prior CS exposure also caused decreased Aicda expression in lung B cells during infection. Neutralization of BAFF in the lung resulted in reduced S-IgA levels during influenza virus infection. CSE inhibited virus-mediated BAFF induction in a dose-dependent manner in BEAS-2B cells, while this inhibition of BAFF by CSE was prevented by pretreatment with the antioxidant N-acetylcysteine. Our findings indicate that CS may hinder early mucosal IgA responses in the lung during influenza virus infection through oxidative inhibition of BAFF, which might contribute to the increased incidence and severity of viral infections in smokers.

  3. HIV-1-triggered release of type I IFN by plasmacytoid dendritic cells induces BAFF production in monocytes.

    Science.gov (United States)

    Gomez, Alejandro M; Ouellet, Michel; Tremblay, Michel J

    2015-03-01

    HIV-1 infection leads to numerous B cell abnormalities, including hypergammaglobulinemia, nonspecific B cell activation, nonspecific class switching, increased cell turnover, breakage of tolerance, increased immature/transitional B cells, B cell malignancies, as well as a loss of capacity to generate and maintain memory, all of which contribute to a global impairment of the immune humoral compartment. Several cytokines and soluble factors, which are increased in sera of HIV-1-infected individuals, have been suggested to directly or indirectly contribute to these B cell dysfunctions, and one of these is the B cell-activating factor (BAFF). We report in this study that HIV-1 (X4- and R5-tropic) upregulates BAFF expression and secretion by human monocytes. Moreover, we show that the virus-mediated production of BAFF by monocytes relies on a type I IFN response by a small percentage of plasmacytoid dendritic cells (pDCs) present in the monocyte cultures. HIV-1-induced type I IFN by pDCs triggers BAFF production in both classical and intermediate monocytes, but not in nonclassical monocytes, which nonetheless display a very strong basal BAFF production. We report also that basal BAFF secretion was higher in monocytes obtained from females compared with those from male donors. This study provides a novel mechanistic explanation for the increased BAFF levels observed during HIV-1 infection and highlights the importance of pDC/monocyte crosstalk to drive BAFF secretion. Copyright © 2015 by The American Association of Immunologists, Inc.

  4. Dual functional BAFF receptor aptamers inhibit ligand-induced proliferation and deliver siRNAs to NHL cells

    Science.gov (United States)

    Zhou, Jiehua; Tiemann, Katrin; Chomchan, Pritsana; Alluin, Jessica; Swiderski, Piotr; Burnett, John; Zhang, Xizhe; Forman, Stephen; Chen, Robert; Rossi, John

    2013-01-01

    The B-cell–activating factor (BAFF)-receptor (BAFF-R) is restrictedly expressed on B-cells and is often overexpressed in B-cell malignancies, such as non-Hodgkin’s lymphoma. On binding to its ligand BAFF, proliferation and cell survival are increased, enabling cancer cells to proliferate faster than normal B-cells. Nucleic acid aptamers can bind to target ligands with high specificity and affinity and may offer therapeutic advantages over antibody-based approaches. In this study, we isolated several 2′-F–modified RNA aptamers targeting the B-cell–specific BAFF-R with nanomolar affinity using in vitro SELEX technology. The aptamers efficiently bound to BAFF-R on the surface of B-cells, blocked BAFF-mediated B-cell proliferation and were internalized into B-cells. Furthermore, chimeric molecules between the BAFF-R aptamer and small interfering RNAs (siRNAs) were specifically delivered to BAFF-R expressing cells with a similar efficiency as the aptamer alone. We demonstrate that a signal transducer and activator of transcription 3 (STAT3) siRNA delivered by the BAFF-R aptamer was processed by Dicer and efficiently reduced levels of target mRNA and protein in Jeko-1 and Z138 human B-cell lines. Collectively, our results demonstrate that the dual-functional BAFF-R aptamer–siRNA conjugates are able to deliver siRNAs and block ligand mediated processes, suggesting it might be a promising combinatorial therapeutic agent for B-cell malignancies. PMID:23470998

  5. Transgenic overexpression of BAFF regulates the expression of ...

    Indian Academy of Sciences (India)

    GFP-2A-BAFF/His recombinant plasmid was constructed by inserting a 2A peptide between the green fluorescent protein (GFP) and BAFF sequences. Functional GFP and BAFF proteins were expressed separately and confirmed in HeLa cells.

  6. B-cell activating factor BAFF reflects patients' immunological risk profile after kidney transplantation.

    Science.gov (United States)

    Schuster, A; Jung, B; Hofbauer, J; Kühne, L; Zecher, D; Banas, B; Bergler, T

    2017-12-01

    The B-cell activating factor BAFF plays an important role in the development and maturation of B-lymphocytes, which can contribute to the generation of donor-specific antibodies and thus may influence graft function and graft survival. Inconsistent data on the role of BAFF levels after renal transplantation for the formation of donor-specific antibodies and the contribution for allograft rejection exist. The aim of the current study was to determine to what extent the degree of pre-immunization is reflected by each patient's BAFF levels before transplantation and in the follow-up. Furthermore, the impact of BAFF on allograft rejection frequency as well as severity and resulting allograft function over time was analyzed. Additionally, the impact of viral infections on BAFF levels after transplantation - as a potential confounder - was examined. For this purpose, a group of pre-sensitized patients (PRA>0%, (52±24% on average), n=40) was compared with non-sensitized patients (PRA=0%, n=62) and in a subsequent analysis stratification in accordance to the detected BAFF level was performed. Pre-sensitized patients had significantly higher BAFF levels before transplantation and suffered significantly more often from early steroid-resistant, mainly antibody-mediated rejections. A result which was confirmed also in highly sensitized patients with PRA levels >50%. Additionally, in the follow-up patients with either rising BAFF levels over time or BAFF levels above the median also had significantly more often antibody mediated rejections. Additionally, patients with BAFF levels above detected median even displayed impaired creatinine values as well as an induced eGFR slope up to month 48 after transplantation. The occurrence of viral infections (CMV, BKV) was only an additional influencing factor in the absence of concomitant allograft rejections. Therefore, the B-cell proliferation factor BAFF appears not only to reflect the immunological risk profile of patients in the

  7. B Cell Activating Factor (BAFF) and BAFF Receptor Expression in Autoimmune and Nonautoimmune Thyroid Diseases.

    Science.gov (United States)

    Campi, Irene; Tosi, Delfina; Rossi, Stefania; Vannucchi, Guia; Covelli, Danila; Colombo, Federico; Trombetta, Elena; Porretti, Laura; Vicentini, Leonardo; Cantoni, Gianmaria; Currò, Nicola; Beck-Peccoz, Paolo; Bulfamante, Gaetano; Salvi, Mario

    2015-09-01

    The B cell activating factor (BAFF) is a member of the tumor necrosis factor family, which controls the survival/proliferation of B cells and is involved in the pathogenesis of a number of autoimmune diseases. The objective of the present study was to investigate the expression of BAFF and BAFF receptor (BAFF-R) in the thyroid tissue of patients affected with autoimmune thyroid disorders (AITD) or multinodular goiter (MNG) compared with those with normal thyroids. Immunohistochemistry was performed using a panel of antibodies against BAFF, BAFF-R, CD3, CD4, CD8, CD20, CD34, CD79a, CD1a, CD68, and CD163 on the thyroid sections of 27 patients affected with Graves' disease (GD), 23 with Hashimoto's thyroiditis (HT), 16 with nontoxic nodular goiter (NTG), and 15 with toxic nodular goiter (TG), submitted to total thyroidectomy between 2000 and 2011. The overall BAFF-R expression in thyrocytes was weak and not different in AITD and MNG. Conversely, a stronger BAFF expression was observed in MNG compared with AITD. BAFF and BAFF-R expression in the infiltrating lymphocytes was higher in AITD compared with MNG. Interestingly, in lymphocytes of follicular-like structures observed in HT, BAFF and BAFF-R were localized in the germinal center or in the mantle, respectively. This study shows that BAFF and BAFF-R are expressed in the thyrocytes derived from patients with either AITD or MNG, in addition to the expected expression of BAFF and its receptor in the infiltrating immune cells of GD and HT. These findings suggest a possible involvement of BAFF and its receptors in the pathophysiology of AITD.

  8. SYK inhibition thwarts the BAFF - B-cell receptor crosstalk and thereby antagonizes Mcl-1 in chronic lymphocytic leukemia.

    Science.gov (United States)

    Paiva, Cody; Rowland, Taylor A; Sreekantham, Bhargava; Godbersen, Claire; Best, Scott R; Kaur, Prabhjot; Loriaux, Marc M; Spurgeon, Stephen E F; Danilova, Olga V; Danilov, Alexey V

    2017-11-01

    Although small molecule inhibitors of B-cell receptor-associated kinases have revolutionized therapy in chronic lymphocytic leukemia (CLL), responses are incomplete. Pro-survival signaling emanating from the microenvironment may foster therapeutic resistance of the malignant B cells resident in the protective lymphoid niches. B-cell activating factor (BAFF) is critical to the survival of both healthy and neoplastic B cells. However, the pro-survival pathways triggered by BAFF have not been fully characterized. Here we show that BAFF elicited resistance to spontaneous and drug-induced apoptosis in stromal co-cultures, induced activation of both canonical and non-canonical NFκB signaling pathways, and triggered B-cell receptor signaling in CLL cells, independently of IGHV mutational status. SYK, a proximal kinase in the B-cell receptor signaling cascade, acted via STAT3 to bolster transcription of the anti-apoptotic protein Mcl-1, thereby contributing to apoptosis resistance in BAFF-stimulated cells. SYK inhibitor entospletinib downregulated Mcl-1, abrogating BAFF-mediated cell survival. BAFF-B-cell receptor crosstalk in neoplastic B cells was mediated by SYK interaction with TRAF2/TRAF3 complex. Thus, SYK inhibition is a promising therapeutic strategy uniquely poised to antagonize crosstalk between BAFF and B-cell receptor, thereby disrupting the pro-survival microenvironment signaling in chronic lymphocytic leukemia. Copyright© Ferrata Storti Foundation.

  9. Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers.

    Science.gov (United States)

    Figgett, William A; Deliyanti, Devy; Fairfax, Kirsten A; Quah, Pin Shie; Wilkinson-Berka, Jennifer L; Mackay, Fabienne

    2015-07-01

    B cell-activating factor of the TNF family (BAFF) is an essential B cell survival factor. However, high levels of BAFF promote systemic lupus erythematosus (SLE) in mice and humans. Belimumab (anti-human BAFF) limits B cell survival and is approved for use in patients with SLE. Surprisingly, the efficacy of rituximab (anti-human CD20) in SLE remains controversial, despite depleting B cells more potently than belimumab. This raises the question of whether B cell depletion is really the mechanism of action of belimumab. In BAFF transgenic mice, SLE development is T cell-independent but relies on innate activation of B cells via TLRs, and TLR expression is modulated by the BAFF receptor TACI. Here, we show that loss of TACI on B cells protected against BAFF-mediated autoimmune manifestations while preserving B cells, suggesting that loss of BAFF signaling through TACI rather than loss of B cells may underpin the effect of belimumab in the clinic. Therefore, B cell-sparing blockade of TACI may offer a more specific and safer therapeutic alternative to broad B cell depletion in SLE. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Increased BAFF expression in nasal polyps is associated with local IgE production, Th2 response and concomitant asthma.

    Science.gov (United States)

    Dilidaer; Zheng, Yan; Liu, Zhuofu; Hu, Xianting; Zhang, Jia; Hu, Li; Han, Miaomiao; Wang, Dehui; Li, Huabin

    2017-04-01

    B-cell activating factor of the TNF family is critical for the survival and maturation of B cells and play a role in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP). In this study, nasal tissues were enrolled from 25 CRSwNP patients (asthmatic, 16; non-asthmatic, 9), 12 CRSsNP patients and ten control subjects, respectively. The immunoreactivity of BAFF, CD20 and CD138 were examined using immunohistochemistry staining. The mRNA expression of BAFF, CD20, εGLT, AID, GATA3 and CRTH2 were examined using real-time RT-PCR. The protein levels of BAFF, IL-5 and IgE were measured using ELISA assays and the Unicap system, respectively. We found the numbers of BAFF+ cells, CD20+ cells (B cells) and CD138+ cells (plasma cells) were significantly increased in polyp tissues compared with control groups. The concentrations of BAFF, IgE and IL-5 in tissue homogenates were also significantly increased in polyp tissues compared with control groups, and the BAFF protein level in the polyp homogenates was significantly associated with the IgE and IL-5 levels and with concomitant asthma in CRSwNP patients. Our findings indicate that BAFF expression is significantly increased in CRSwNP patients and may orchestrate inflammatory load in polyp tissues by regulating T and B cell-mediated response.

  11. BAFF- and TACI-Dependent Processing of BAFFR by ADAM Proteases Regulates the Survival of B Cells.

    Science.gov (United States)

    Smulski, Cristian R; Kury, Patrick; Seidel, Lea M; Staiger, Hannah S; Edinger, Anna K; Willen, Laure; Seidl, Maximilan; Hess, Henry; Salzer, Ulrich; Rolink, Antonius G; Rizzi, Marta; Schneider, Pascal; Eibel, Hermann

    2017-02-28

    B cell activating factor (BAFF) provides B cells with essential survival signals. It binds to three receptors: BAFFR, TACI, and BCMA that are differentially expressed by B cell subsets. BAFFR is early expressed in circulating B cells and provides key signals for further maturation. Here, we report that highly regulated BAFFR processing events modulate BAFF responses. BAFFR processing is triggered by BAFF binding in B cells co-expressing TACI and it is executed by the metalloproteases ADAM10 and ADAM17. The degree of BAFF oligomerization, the expression of ADAM proteins in different B cell subsets, and the activation status of the cell determine the proteases involved in BAFFR processing. Inhibition of ADAM10 augments BAFF-dependent survival of primary human B cells, whereas inhibition of ADAM17 increases BAFFR expression levels on germinal center B cells. Therefore, BAFF-induced processing of BAFFR regulates BAFF-mediated B cell responses in a TACI-dependent manner. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. A BAFF receptor His159Tyr mutation in Sjögren's syndrome-related lymphoproliferation.

    Science.gov (United States)

    Papageorgiou, Aristea; Mavragani, Clio P; Nezos, Andrianos; Zintzaras, Elias; Quartuccio, Luca; De Vita, Salvatore; Koutsilieris, Michael; Tzioufas, Athanasios G; Moutsopoulos, Haralampos M; Voulgarelis, Michael

    2015-10-01

    To study the prevalence, clinical associations, and functional implications of the His159Tyr mutation of the BAFF receptor (BAFF-R) in patients with Sjögren's syndrome (SS). The BAFF-R His159Tyr mutation was evaluated using polymerase chain reaction (PCR)-based assays in 247 patients with SS (of whom 70 had SS complicated by lymphoma [SS-lymphoma]), 145 with systemic lupus erythematosus (SLE), and 101 with rheumatoid arthritis (RA), as well as 180 healthy controls. Real-time PCR and Western blotting were performed for the quantification of both NF-κB1 and NF-κB2 messenger RNA (mRNA) transcript and protein levels in isolated B cells from patients with SS-lymphoma carrying the mutation (SS-lymphoma-BAFF-RHis159Tyr -derived B cells) compared to B cells from patients with SS-lymphoma who were not carriers of the mutation and healthy controls. Both the SS-lymphoma and SS-nonlymphoma patient subgroups exhibited significantly higher frequencies of the His159Tyr BAFF-R mutation compared to healthy controls (8.6% of SS-lymphoma patients and 6.2% of SS-nonlymphoma patients versus 1.7% of healthy controls; P = 0.02 and P = 0.04, respectively). The corresponding frequencies of the His159Tyr BAFF-R mutation in SLE and RA patients were 3.5% and 3%, respectively. Of interest, 71.4% of the SS patients with mucosa-associated lymphoid tissue (MALT) lymphoma who were between the ages of 31 and 40 years at disease onset were mutation carriers. The generalized odds ratio for the development of SS-related MALT lymphoma in the younger age at onset (age BAFF-R mutation was 6.1 (95% confidence interval 2.0-18.7) (P BAFF-RHis159Tyr -derived B cells. This study identifies an increased prevalence of the BAFF-R His159Tyr mutation in patients with SS, particularly in those with SS complicated by MALT lymphoma whose disease onset occurred at a younger age. BAFF-RHis159Tyr -mediated activation of the alternate NF-κB pathway might contribute to the pathogenesis of SS

  13. Expression of BAFF and BAFF-R in Follicular Lymphoma: Correlation with Clinicopathologic Characteristics and Survival Outcomes

    Science.gov (United States)

    Rao, Hui-Lan; Huang, Jia-Jia; Xia, Yi; Huang, Hui-Qiang; Lin, Tong-Yu; Xia, Zhong-Jun; Li, Su; Li, Zhi-Ming

    2012-01-01

    Background B-cell activation factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the viability and proliferation of malignant lymphoma cells. Limited information exists regarding expression profiles and the prognostic role of BAFF and BAFF-R in follicular lymphoma (FL). We sought to determine the expression profiles of BAFF and BAFF-R in FL and to evaluate the correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and outcome of FL. Correlation between expression levels of BAFF detected by immunohistochemical (IHC) and serum levels of BAFF was also evaluated. Methods Paraffin-embedded specimens from 115 patients were immunohistochemically examined for BAFF and BAFF-R expression. Expression levels were dichotomized into low versus high categories based on immunostaining intensity. The correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and patient outcome was assessed. Serum levels of BAFF in 35 of the 115 patients with IHC data were measured by Enzyme-linked Immunosorbent assay (ELISA). Results BAFF and BAFF-R were expressed in 88.7% (102/115) and 87.8% (101/115) of the cases, respectively. BAFF expression was significantly correlated with only one clinicopathologic feature: Ann Arbor stage. No significant correlation was found between expression levels of BAFF detected by IHC and serum levels of BAFF detected by ELISA. High expression of BAFF-R, but not BAFF, was significantly correlated with inferior progression-free survival (PFS; P = 0.013) and overall survival (OS; P = 0.03). High expression of BAFF-R, bulky disease, and elevated lactate dehydrogenase were correlated with inferior PFS and OS in multivariate analysis. A prognostic scoring system incorporating these 3 risk factors identified 3 distinct prognostic groups with 5-year PFS of 59.4%, 41.9%, and 10.7% and OS of 91.3%, 79.7%, and 45.8%, respectively. Conclusions Most patients with FL variably express BAFF and BAFF-R. High

  14. ΔBAFF, an Alternate Splice Isoform That Regulates Receptor Binding and Biopresentation of the B Cell Survival Cytokine, BAFF*

    OpenAIRE

    Gavin, Amanda L; Aït-Azzouzene, Djemel; Ware, Carl F.; Nemazee, David

    2003-01-01

    The tumor necrosis family member BAFF is limiting for the survival of follicular B lymphocytes, but excessive BAFF signaling can lead to autoimmunity, suggesting that its activity must be tightly regulated. We have identified a conserved alternate splice isoform of BAFF, called ΔBAFF, which lacks 57 nt encoding the A–A1 loop and is co-expressed with BAFF in many mouse and human myeloid cells. Mouse ΔBAFF appears on the plasma membrane, but unlike BAFF it is inefficiently released by proteolys...

  15. The Unknown Aspect of BAFF: Inducing IL-35 Production by a CD5+CD1dhiFcγRIIbhiRegulatory B-Cell Subset in Lupus.

    Science.gov (United States)

    Zhang, Yamin; Li, Jun; Zhou, Nuoya; Zhang, Yi; Wu, Min; Xu, Jian; Shen, Chen; An, Xiangjie; Shen, Guanxin; Yang, Ming; Zhang, Chun; Tao, Juan

    2017-12-01

    IL-35 is a critical immunosuppressive cytokine that plays an important role in various autoimmune diseases. The purpose of this study was to determine whether BAFF, a key pathogenic factor in systemic lupus erythematosus, also a dichotomous regulator for B-cell immune responses, has an effect on IL-35-producing regulatory B cells and their underlying mechanisms in lupus. We found that exogenous BAFF could induce IL-35 production by splenic B cells from MRL-Fas lpr/lpr mice. BAFF-induced IL-35-producing B cells were mainly from the marginal zone B-cell subset and exhibited a CD5 + CD1d hi FcγRIIb hi phenotype. These IL-35-producing regulatory B-cell subsets exhibited regulatory effects on both CD4 + CD25 - T cells and CD4 + CD25 + regulatory T cells. We further identified that BAFF-TACI interaction could induce the production of IL-35 through the classical NF-κB1 pathway. In vivo study also showed that BAFF could facilitate IL-35 secretion in marginal zone B cells, whereas anti-BAFF treatment could decrease the frequency of IL-35-producing CD5 + CD1d hi FcγRIIb hi B cells in MRL-Fas lpr/lpr mice. We showed that BAFF could induce IL-35 production by a unique CD5 + CD1d hi FcγRIIb hi regulatory B-cell subset mainly through TACI activation in lupus, providing an advanced understanding of the regulatory effect of BAFF in autoimmune diseases. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. The interplay of IL-21 and BAFF in the formation and maintenance of human B cell memory

    Directory of Open Access Journals (Sweden)

    Jodi eKarnell

    2012-01-01

    Full Text Available To date, IL-21 stands out as the most influential cytokine for human B cell activation and differentiation. Indeed, when compared to other important B cell-tropic cytokines such as IL-2, IL-4, IL-6 and IL-10, IL-21 is clearly the most potent in terms of its ability to influence humoral immune responses in humans. IL-21 has wide reaching actions in determining how B cells will respond to co-stimulation ranging from induction of cell death upon BCR cross-linking to potent induction of class switch recombination and plasma cell differentiation when CD40 molecules are co-engaged. Another crucial B cell factor, exemplified in recent clinical trials, is BAFF/BLys. BAFF plays a critical role in the survival of human B cells and plasma blasts and influences B cell expansion and migration. Recent evidence has shown that IL-21 and BAFF can work in concert to promote and perhaps maintain humoral immunity in humans. Notably, BAFF has the unique ability to substitute for CD40L activities in regard to IL-21-costimulation and differentiation of a specific B cell subpopulation located in the human splenic marginal zone. However, and perhaps surprisingly, BAFF signals do not have the capability to override IL-21-driven cell death events when BCR is engaged. In stark contrast, anti-CD40 ligation of B cells co-activated with IL-21 and anti-IgM not only reverses this aforementioned activation-induced cell death, but transforms this death signal into one that drives plasma cell differentiation. Here we will discuss these two critical B cell factors, IL-21 and BAFF, and their distinct and complimentary effects on human B cell responses.

  17. Development of a Novel BAFF Responsive Cell Line Suitable for Detecting Bioactive BAFF and Neutralizing Antibodies against BAFF-Pathway Inhibiting Therapeutics

    OpenAIRE

    Hu, Jenny; Yu, Yanbin; Han, Hong; Civoli, Francesca; Zhuang, Yao; Thomas, John; Swanson, Steve; Jing, Shuqian; Gupta, Shalini

    2014-01-01

    BAFF has a critical role in B-cell survival, maturation and function, which makes its pathway a prime therapeutic target for various autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and Sjögren’s syndrome. A cell-based assay that measures the functional activity of BAFF is required for many high throughput purposes, such as lead target screening and BAFF quantification. We report here the development of a sensitive BAFF responsive cell line via stable tra...

  18. MiR-30a-3p negatively regulates BAFF synthesis in systemic sclerosis and rheumatoid arthritis fibroblasts.

    Directory of Open Access Journals (Sweden)

    Ghada Alsaleh

    Full Text Available We evaluated micro (mi RNA-mediated regulation of BAFF expression in fibroblasts using two concomitant models: (i synovial fibroblasts (FLS isolated from healthy controls (N or Rheumatoid Arthritis (RA patients; (ii human dermal fibroblasts (HDF isolated from healthy controls (N or Systemic Sclerosis (SSc patients. Using RT-qPCR and ELISA, we first showed that SScHDF synthesized and released BAFF in response to Poly(I:C or IFN-γ treatment, as previously observed in RAFLS, whereas NHDF released BAFF preferentially in response to IFN-γ. Next, we demonstrated that miR-30a-3p expression was down regulated in RAFLS and SScHDF stimulated with Poly(I:C or IFN-γ. Moreover, we demonstrated that transfecting miR-30a-3p mimic in Poly(I:C- and IFN-γ-activated RAFLS and SScHDF showed a strong decrease on BAFF synthesis and release and thus B cells survival in our model. Interestingly, FLS and HDF isolated from healthy subjects express higher levels of miR-30a-3p and lower levels of BAFF than RAFLS and SScHDF. Transfection of miR-30a-3p antisense in Poly(I:C- and IFN-γ-activated NFLS and NHDF upregulated BAFF secretion, confirming that this microRNA is a basal repressors of BAFF expression in cells from healthy donors. Our data suggest a critical role of miR-30a-3p in the regulation of BAFF expression, which could have a major impact in the regulation of the autoimmune responses occurring in RA and SSc.

  19. Context-Specific BAFF-R Signaling by the NF-κB and PI3K Pathways

    Directory of Open Access Journals (Sweden)

    Julia Jellusova

    2013-11-01

    Full Text Available BAFF is a soluble factor required for B cell maturation and survival. BAFF-R signals via the noncanonical NF-κB pathway regulated by the TRAF3/NIK/IKK1 axis. We show that deletion of Ikk1 during early B cell development causes a partial impairment in B cell maturation and BAFF-dependent survival, but inactivation of Ikk1 in mature B cells does not affect survival. We further show that BAFF-R employs CD19 to promote survival via phosphatidylinositol 3-kinase (PI3K, and that coinactivation of Cd19 and Ikk1 causes a profound block in B cell maturation at the transitional stage. Consistent with a role for PI3K in BAFF-R function, inactivation of PTEN mediates a partial rescue of B cell maturation and function in Baff−/− animals. Elevated PI3K signaling also circumvents BAFF-dependent survival in a spontaneous B cell lymphoma model. These findings indicate that the combined activities of PI3K and IKK1 drive peripheral B cell differentiation and survival in a context-dependent manner.

  20. Context-specific BAFF-R signaling by the NF-κB and PI3K pathways

    Science.gov (United States)

    Jellusova, Julia; Miletic, Ana V.; Cato, Matthew H.; Lin, Wai-Wai; Hu, Yinling; Bishop, Gail A.; Shlomchik, Mark J.; Rickert, Robert C.

    2014-01-01

    Summary BAFF is a soluble factor required for B cell maturation and survival. BAFF-R signals via the non-canonical NF-κB pathway regulated by the TRAF3/NIK/IKK1 axis. We show that deletion of Ikk1 during early B cell development causes a partial impairment in B cell maturation and BAFF-dependent survival, but inactivation of Ikk1 in mature B cells does not affect survival. We further show that BAFF-R employs CD19 to promote survival via PI3K, and that co-inactivation of Cd19 and Ikk1 causes a profound block in B cell maturation at the transitional stage. Consistent with a role for PI3K in BAFF-R function, inactivation of PTEN mediates a partial rescue of B cell maturation and function in Baff−/− animals. Elevated PI3K signaling also circumvents BAFF-dependent survival in a spontaneous B cell lymphoma model. These findings indicate that the combined activities of PI3K and IKK1 drive peripheral B cell differentiation and survival in a context-dependent manner. PMID:24239354

  1. The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B cells

    Science.gov (United States)

    Saulep-Easton, Damien; Vincent, Fabien B.; Quah, Pin Shie; Wei, Andrew; Ting, Stephen B.; Croce, Carlo M.; Tam, Constantine; Mackay, Fabienne

    2015-01-01

    Interleukin (IL)-10-producing B cells (B10 cells) have emerged as important regulatory players with immunosuppressive roles. Chronic lymphocytic leukemia (CLL) B cells also secrete IL-10 and share features of B10 cells, suggesting a possible contribution of CLL B cells to immunosuppression in CLL patients. Factors controlling the emergence of B10 cells are not known. B cell-activating factor of the tumour necrosis factor (TNF) family (BAFF) is critical for B cell maturation and survival, and is implicated in the development and progression of CLL. We sought to investigate the role of BAFF in the emergence of IL-10-producing B regulatory cells in healthy donors and CLL patients. Here, we report that BAFF signaling promotes IL-10 production by CLL B cells in a mouse model of CLL and in CLL patients. Moreover, BAFF-mediated IL-10 production by normal and CLL B cells is mediated via its receptor TACI. Our work uncovered a major targetable pathway important for the generation of regulatory B cells that is detrimental to immunity in CLL. PMID:26139429

  2. B Cell-Activating Factor Regulates Different Aspects of B Cell Functionality and Is Produced by a Subset of Splenic B Cells in Teleost Fish

    Science.gov (United States)

    Tafalla, Carolina; González, Lucia; Castro, Rosario; Granja, Aitor G.

    2017-01-01

    In mammals, B cell functionality is greatly influenced by cytokines released by innate cells, such as macrophages or dendritic cells, upon the early recognition of common pathogen patterns through invariant receptors. B cell-activating factor (BAFF) is one of these innate B cell-helper signals and plays a key role in the survival and differentiation of B cells. Although, evolutionarily, teleost fish constitute the first animal group in which adaptive immunity based on Ig receptors is present, fish still rely greatly on innate responses. In this context, we hypothesized that BAFF would play a key role in the control of B cell responses in fish. Supporting this, our results show that teleost BAFF recapitulates mammalian BAFF stimulating actions on B cells, upregulating the expression of membrane MHC II, improving the survival of fish naïve B cells and antibody-secreting cells, and increasing the secretion of IgM. Surprisingly, we also demonstrate that BAFF is not only produced in fish by myeloid cells but is also produced by a subset of splenic B cells. Thus, if this B cell-produced BAFF proves to be actively regulating this same B cell subset, our findings point to an ancient mechanism to control B cell differentiation and survival in lower vertebrates, which has been silenced in mammals in physiological conditions, but reemerges under pathological conditions, such as B cell lymphomas and autoimmune diseases. PMID:28360916

  3. BAFF promotes Th17 cells and aggravates experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Xiaohui Zhou

    Full Text Available BAFF, in addition to promoting B cell survival and differentiation, may affect T cells. The objective of this study was to determine the effect of BAFF on Th17 cell generation and its ramifications for the Th17 cell-driven disease, EAE.Th17 cells were increased in BAFF-Tg B6 (B6.BTg mice and decreased in B6.Baff(-/- mice. Th17 cells in B6.Baff(-/- mice bearing a BAFF Tg (B6.Baff(-/-.BTg mice were identical to those in B6.BTg mice, indicating that membrane BAFF is dispensable for Th17 cell generation as long as soluble BAFF is plentiful. In T + non-T cell criss-cross co-cultures, Th17 cell generation was greatest in cultures containing B6.BTg T cells and lowest in cultures containing B6.Baff(-/- T cells, regardless of the source of non-T cells. In cultures containing only T cells, Th17 cell generation followed an identical pattern. CD4(+ cell expression of CD126 (IL-6R α chain was increased in B6.BTg mice and decreased in B6.Baff(-/- mice, and activation of STAT3 following stimulation with IL-6 + TGF-β was also greatest in B6.BTg cells and lowest in B6.Baff(-/- cells. EAE was clinically and pathologically most severe in B6.BTg mice and least severe in B6.Baff(-/- mice and correlated with MOG(35-55 peptide-induced Th17 cell responses.Collectively, these findings document a contribution of BAFF to pathogenic Th17 cell responses and suggest that BAFF antagonism may be efficacious in Th17 cell-driven diseases.

  4. Comparative genomic of the BAFF and BAFF-like genes and immune response to bacteria of miiuy croaker (Miichthys miiuy).

    Science.gov (United States)

    Meng, Fanqiang; Sun, Yuena; Xu, Tianjun

    2015-03-01

    As a member of the tumor necrosis factor (TNF) family, B cell activating factor (BAFF), also known as TNF ligand superfamily member 13B (TNF13B), playing a critical role in enhancing immune responses. BAFF is a central cytokine for B-cell survival, proliferation, maturation and immunoglobulin secretion. In the present study, we describe the identification of the miiuy croaker BAFF (designed MmBAFF) and BAFF-like (designed MmBAFF-like) genes. The cDNA of MmBAFF contains an open reading frame (ORF) of 795 nucleotides that are translated into a predicted 264 amino acids. The ORF of MmBAFF-like consists of 705 bases encoding 234 amino acids. Amino acid sequence comparison indicated that MmBAFF and MmBAFF-like possessed the TNF signatures, a predicted transmembrane domain, three conserved cysteine residues and a putative furin protease cleavage site, which were the typical characteristics of TNF gene in mammals and birds. The predicted three-dimensional (3D) structure of the MmBAFF and MmBAFF-like monomer analyzed by comparative protein modeling revealed that they were very similar to human counterpart. Comparative genomic analysis revealed that the locations of MmBAFF and MmBAFF-like genes are conserved among the bony fish. Phylogenetic analysis shows the MmBAFF is most closely related to other teleost BAFFs with the highest similarity to Epinephelus awoara. And BAFF-like cluster get together first to BAFF cluster than three closely related TNF superfamily (TNFSF) members. Real-time quantitative PCR analysis shows the MmBAFF and MmBAFF-like transcripts are expressed in a wide range of tissues with the highest expression in skin and lymphoid tissue spleen. Upon induction by Vibrio anguillarum, their expressions are significantly upregulated in liver, spleen and kidney as compared to phosphate-buffered saline injected control fish. The association of increased BAFF expression after bacterial infection suggests that it plays a potentially important role in immune system

  5. Assessment of splenic function

    NARCIS (Netherlands)

    de Porto, A.P.N.A.; Lammers, A.J.J.; Bennink, R.J.; ten Berge, R.J.M.; Speelman, P.; Hoekstra, J.B.L.

    2010-01-01

    Hyposplenic patients are at risk of overwhelming post-splenectomy infection (OPSI), which carries mortality of up to 70%. Therefore, preventive measures are warranted. However, patients with diminished splenic function are difficult to identify. In this review we discuss immunological,

  6. Postsplenectomy splenic activity.

    Science.gov (United States)

    Orda, R; Barak, J; Baron, J; Spirer, Z; Wiznitzer, T

    1981-01-01

    Evidence of recurring activity of splenic tissue was investigated in patients who had undergone splenectomies. Methods included technetium 99m sulfur colloid scan, serum tuftsin assay, serum immunoglobulin concentration, blood cell counts, and search for Howell-Jolly bodies. Positive scans were observed together with normal levels of tuftsin in 54% of the patients. In 46% of the patients, no splenic activity was detected by scanning and low levels of tuftsin were noticed. The difference in tuftsin levels between the two groups was statistically significant. Howell-Jolly bodies and decreased serum levels of IgM featured all patients. The possible application of combined splenic scan and tuftsin assessment for screening recurring splenic activity in the postsplenectomy population at great risk is suggested. Images Fig. 1. Fig. 2. PMID:7305494

  7. Transcriptional and post-transcriptional mechanisms of BAFF-receptor dysregulation in human B lineage malignancies

    OpenAIRE

    Mihalcik, Stephen A; Tschumper, Renee C; Jelinek, Diane F

    2010-01-01

    Together, circulating BAFF and dominant receptor BAFF-R homeostatically regulate the humoral immune system. Consistently aberrant BAFF-R expression in leukemic cells reveals an intimate connection of these cells' malignant physiology to the BAFF/BAFF-R axis and also provides an additional survival mechanism to the expressing cells. In this study, we used primary cells and cell lines to interrogate the mechanisms underlying aberrant BAFF-R expression in precursor B acute lymphoblastic leukemia...

  8. Splenic epithelial cyst

    International Nuclear Information System (INIS)

    Yousuf, M.; Jalali, U.

    2011-01-01

    Cysts of spleen are rare entities. Congenital splenic cysts are even more uncommon comprising of only 10% of benign non-parasitic cysts. We report a case of 22 years old female who presented with history of 2 years abdominal pain and gradual distension. Ultrasound and computed tomography (CT) both were suggestive of splenic cyst. Laboratory tests show thrombocytopenia with platelets count of 97000 per cubic millimeter and anemia with hemoglobin 8.7 gram per deciliter. Serological tests were negative for parasitic infection. Splenectomy was done and the weight of the spleen was found to be 1.5 kilogram. Histopathological findings are consistent with splenic epithelial cyst. The aetiology, diagnostic modalities and treatment options are discussed in the case report. (author)

  9. The Expression of BAFF Is Controlled by IRF Transcription Factors.

    Science.gov (United States)

    Sjöstrand, Maria; Johansson, Alina; Aqrawi, Lara; Olsson, Tomas; Wahren-Herlenius, Marie; Espinosa, Alexander

    2016-01-01

    Patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) are typically characterized by the presence of autoantibodies and an IFN-signature. The strength of the IFN-signature positively correlates with disease severity, suggesting that type I IFNs are active players in these diseases. BAFF is a cytokine critical for development and proper selection of B cells, and the targeting of BAFF has emerged as a successful treatment strategy of SLE. Previous reports have suggested that BAFF expression is directly induced by type I IFNs, but the precise mechanism for this remains unknown. In this article, we demonstrate that BAFF is a bona fide ISG and that IFN regulatory factors (IRFs) control the expression of BAFF. We identify IRF1 and IRF2 as positive regulators of BAFF transcription and IRF4 and IRF8 as potent repressors; in addition, we have mapped the precise binding site for these factors in the BAFF promoter. IFN-β injections induced BAFF expression mainly in neutrophils and monocytes, and BAFF expression in neutrophils from pSS patients strongly correlated with the strength of the IFN-signature. In summary, we show that BAFF expression is directly induced by type I IFNs via IRF1 and IRF2, whereas IRF4 and IRF8 are negative regulators of BAFF expression. These data suggest that type I IFN blockade in SLE and pSS patients will lead to downregulation of BAFF and a consequential reduction of autoreactive B cell clones and autoantibodies. Copyright © 2015 by The American Association of Immunologists, Inc.

  10. Splenic injury after colonoscopy

    DEFF Research Database (Denmark)

    Petersen, C.R.; Adamsen, S.; Gocht-Jensen, P.

    2008-01-01

    Splenic injury is a rare and serious complication of colonoscopy. The most likely mechanism is tension on the splenocolic ligament and adhesions. Eight cases were identified among claims for compensation submitted to the Danish Patient Insurance Association during the period 1992-2006, seven...

  11. Postcesarean Splenic Torsion

    Directory of Open Access Journals (Sweden)

    Yu-Hui Huang

    2006-09-01

    Conclusion: Splenic torsion is a rare cause of acute abdominal pain during pregnancy or postpartum, and the symptoms vary depending on the degree of torsion. Early involvement of many complementary specialty services enabled early recognition of this rare entity and timely definitive treatment.

  12. Ruptured Splenic Artery Aneurysm

    African Journals Online (AJOL)

    1974-05-04

    May 4, 1974 ... Radiological confirmation of the commonness of the condition found at coeliac angiography,' adds further support for a high autopsy incidence. The unusual preponderance of females with splenic artery aneurysms3.•.• cannot be explained on the basis of aetiology, as they are most often caused by arterio- ...

  13. Serum BAFF and thyroid autoantibodies in autoimmune thyroid disease.

    Science.gov (United States)

    Lin, Jiunn-Diann; Wang, Yuan-Hung; Fang, Wen-Fang; Hsiao, Chia-Jung; Chagnaadorj, Amarzaya; Lin, Yuh-Feng; Tang, Kam-Tsun; Cheng, Chao-Wen

    2016-11-01

    This study investigated the association of serum B-lymphocyte activating factor (BAFF) levels with autoimmune thyroid disease (AITD) in a Chinese population. We enrolled 221 patients with AITD [170 patients with Graves' disease (GD), 51 patients with Hashimoto's thyroiditis (HT)], and 124 healthy controls. Serum BAFF levels, thyroid function and thyroid autoantibody (TAb) levels, including of thyroid-stimulating hormone receptor antibody (TSHRAb), anti-thyroid peroxidase antibody (Anti-TPO Ab), and antithyroglobulin antibody (ATA), were measured at baseline. Serum BAFF levels were higher in the GD, HT, and AITD groups than in the control group. Significant correlations were observed between BAFF and TSHRAb levels (r=0.238, p=0.018), between BAFF and Anti-TPO Ab levels (p=0.038), and between BAFF and ATA titers (p=0.025) in women but not in men. In addition, serum BAFF levels were significantly associated with free thyroxine (r=0.430, p=0.004) and TSHRAb (r=0.495, p=0.001) levels in women with active GD but not in those with inactive GD. Serum BAFF levels are increased in GD, HT, and AITD. The correlation between serum BAFF and TAb levels exhibits a dimorphic pattern, particularly in active GD. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. No evidence that soluble TACI induces signalling via membrane-expressed BAFF and APRIL in myeloid cells.

    Directory of Open Access Journals (Sweden)

    Josquin Nys

    Full Text Available Myeloid cells express the TNF family ligands BAFF/BLyS and APRIL, which exert their effects on B cells at different stages of differentiation via the receptors BAFFR, TACI (Transmembrane Activator and CAML-Interactor and/or BCMA (B Cell Maturation Antigen. BAFF and APRIL are proteins expressed at the cell membrane, with both extracellular and intracellular domains. Therefore, receptor/ligand engagement may also result in signals in ligand-expressing cells via so-called "reverse signalling". In order to understand how TACI-Fc (atacicept technically may mediate immune stimulation instead of suppression, we investigated its potential to activate reverse signalling through BAFF and APRIL. BAFFR-Fc and TACI-Fc, but not Fn14-Fc, reproducibly stimulated the ERK and other signalling pathways in bone marrow-derived mouse macrophages. However, these effects were independent of BAFF or APRIL since the same activation profile was observed with BAFF- or APRIL-deficient cells. Instead, cell activation correlated with the presence of high molecular mass forms of BAFFR-Fc and TACI-Fc and was strongly impaired in macrophages deficient for Fc receptor gamma chain. Moreover, a TACI-Fc defective for Fc receptor binding elicited no detectable signal. Although these results do not formally rule out the existence of BAFF or APRIL reverse signalling (via pathways not tested in this study, they provide no evidence in support of reverse signalling and point to the importance of using appropriate specificity controls when working with Fc receptor-expressing myeloid cells.

  15. Immune complexes induce TNF-α and BAFF production from U937 cells by HMGB1 and RAGE.

    Science.gov (United States)

    Gao, X-J; Qu, Y-Y; Liu, X-W; Zhu, M; Ma, C-Y; Jiao, Y-L; Cui, B; Chen, Z-J; Zhao, Y-R

    2017-04-01

    This study investigated the effects of immune complexes (ICs) on tumor necrosis factor α (TNF-α) and B cell-activating factor (BAFF) production from U937 cells and further explored the mechanism. U937 cells were incubated with necrosis supernatant or systemic lupus erythematosus (SLE) sera alone, or their combination. The expression of TNF-α and BAFF was determined by Real-time polymerase chain reaction and enzyme-linked immunosorbent assay. High mobility group box protein 1(HMGB1) A-box was produced by gene recombination. HMGB1 A-box and anti-receptor for advanced glycation end products (RAGE) antibody were adopted in the blocking experiments. The importance of DNA for cytokine induction was investigated by DNase treatment. The combination of necrosis supernatant and SLE sera induced the expression of TNF-α and BAFF significantly increased compared to necrosis supernatant or SLE sera alone. Recombinant HMGB1 A-box protein was purified, and TNF-α and BAFF production, which were induced by this combination, was blocked via HMGB1 A-box and anti-RAGE antibody. Moreover, we found that DNA component is important for the immunostimulatory activity of this combination. ICs containing DNA can promote TNF-α and BAFF production in U937 cells, and this process can be mediated by HMGB1 and RAGE. One possible mechanism of increasing BAFF production in SLE is proposed in this study whereby B cell activation, antibody production and ICs stimulated monocytes may create a vicious cycle that leads to B cell hyperactivity, which can be of importance for SLE etiopathogenesis.

  16. Expression of BAFF-R, but not BAFF, is an independent prognostic factor in diffuse large B-cell lymphoma patients treated with R-CHOP.

    Science.gov (United States)

    Wang, Yu; Li, Ya-Jun; Jiang, Wen-Qi; Rao, Hui-Lan; Huang, Jia-Jia; Xia, Yi; Bi, Xiwen; Sun, Peng; Huang, Hui-Qiang; Lin, Tong-Yu; Guan, Zhong-Zhen; Li, Zhi-Ming

    2015-11-01

    B-cell activating factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the progression of malignant B-cells. The aim of the present study was to evaluate the expression profiles and the clinical significance of BAFF and BAFF-R in diffuse large B-cell lymphoma (DLBCL). Paraffin-embedded specimens from 136 patients with newly diagnosed DLBCL, treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP), were examined for BAFF and BAFF-R expression by immunohistochemistry. BAFF and BAFF-R were expressed in 72.1 % (98/136) and 47.1 % (64/136) of the DLBCL tissues, respectively. Negative BAFF-R expression was significantly correlated with elevated serum lactate dehydrogenase (LDH) levels (P = 0.036), an International Prognostic Index (IPI) score of 2 or higher (P BAFF-R expression than in those with negative BAFF-R expression (73.4 vs. 56.9 %, P = 0.045). Negative expression of BAFF-R, but not of BAFF, was significantly associated with inferior progression-free survival (PFS; P = 0.020) and overall survival (OS; P = 0.028). Only negative BAFF-R expression was correlated with inferior PFS and OS in multivariate analysis (P = 0.049 and 0.040, respectively). Taken together, our results showed that the majority and approximate one-half of patients with DLBCL were positive for BAFF and BAFF-R, respectively. Negative expression of BAFF-R, but not of BAFF, could be an independent risk factor for PFS and OS in patients with DLBCL treated with standard R-CHOP.

  17. Splenic artery aneurysm.

    Science.gov (United States)

    Tcbc-Rj, Rui Antônio Ferreira; Ferreira, Myriam Christina Lopes; Ferreira, Daniel Antônio Lopes; Ferreira, André Gustavo Lopes; Ramos, Flávia Oliveira

    2016-01-01

    Splenic artery aneurysms - the most common visceral artery aneurysms - are found most often in multiparous women and in patients with portal hypertension. Indications for treatment of splenic artery aneurysm or pseudoaneurysm include specific symptoms, female gender and childbearing age, presence of portal hypertension, planned liver transplantation, a pseudoaneurysm of any size, and an aneurysm with a diameter of more than 2.5cm. Historically, the treatment of splenic artery aneurysm has been surgical ligation of the splenic artery, ligation of the aneurysm, or aneurysmectomy with or without splenectomy, depending on the aneurysm location. There are other percutaneous interventional techniques. The authors present a case of a splenic artery aneurysm in a 51-year-old woman, detected incidentally. RESUMO Aneurismas da artéria esplênica - os aneurismas arteriais viscerais mais comuns - são encontrados mais frequentemente em mulheres multíparas e em pacientes com hipertensão portal. As indicações para o seu tratamento incluem sintomas específicos, sexo feminino e idade fértil, presença de hipertensão portal, paciente em fila de transplante hepático, um pseudoaneurisma de qualquer tamanho, e um aneurisma com um diâmetro superior a 2,5cm. Historicamente, o tratamento do aneurisma da artéria esplênica tem sido a ligadura cirúrgica da artéria esplênica, a ligadura do aneurisma ou a aneurismectomia, com ou sem esplenectomia, dependendo do local do aneurisma. Existem outras técnicas intervencionistas percutâneas. Os autores apresentam o caso de um aneurisma de artéria esplênica em uma mulher de 51 anos de idade, diagnosticado incidentalmente.

  18. B cell activating factor (BAFF) and BAFF receptors: fakes and facts.

    Science.gov (United States)

    Ferraccioli, G; Gremese, E

    2017-12-01

    Analysis of B cell activating factor (BAFF) receptors before and after B cell depletion therapy (BCDT) might offer a clue to the understanding of whether some B cell subsets may represent useful biomarkers of biological and clinical responses. Among the BAFF receptors in a cohort of rheumatoid arthritis (RA) patients, the AA have shown, by fluorescence activated cell sorter (FACS) analysis of median fluorescence intensity (MFI), that transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA) do not change, whereas the most important, BAFF receptor 3 (BR3), appears to be decreased before as well as after BCDT in all B cell subsets but not in plasmablasts, the most important subset, depleted by BCDT. © 2017 British Society for Immunology.

  19. BAFF induces spleen CD4{sup +} T cell proliferation by down-regulating phosphorylation of FOXO3A and activates cyclin D2 and D3 expression

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Fang; Chen, Rongjing [Department of Orthodontics, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China); Liu, Baojun [Laboratory of Lung, Inflammation and Cancers, Huashan Hospital, Fudan University, Shanghai (China); Zhang, Xiaoping [Department of Nuclear Medicine, Shanghai 10th People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Han, Junli; Wang, Haining [Department of General Dentistry, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China); Shen, Gang [Department of Orthodontics, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China); Tao, Jiang, E-mail: taojiang2012@yahoo.cn [Department of General Dentistry, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Firstly analyze the mechanism of BAFF and anti-CD3 co-stimulation on purified mouse splenic CD4{sup +} T cells. Black-Right-Pointing-Pointer Carrying out siRNA technology to study FOXO3A protein function. Black-Right-Pointing-Pointer Helpful to understand the T cell especially CD4{sup +} T cell's role in immunological reaction. -- Abstract: The TNF ligand family member 'B cell-activating factor belonging to the TNF family' (BAFF, also called BLyS, TALL-1, zTNF-4, and THANK) is an important survival factor for B and T cells. In this study, we show that BAFF is able to induce CD4{sup +} spleen T cell proliferation when co-stimulated with anti-CD3. Expression of phosphorylated FOXO3A was notably down-regulated and cyclins D2 and D3 were up-regulated and higher in the CD4{sup +} T cells when treated with BAFF and anti-CD3, as assessed by Western blotting. Furthermore, after FOXO3A was knocked down, expression of cyclin D1 was unchanged, compared with control group levels, but the expression of cyclins D2 and D3 increased, compared with the control group. In conclusion, our results suggest that BAFF induced CD4{sup +} spleen T cell proliferation by down-regulating the phosphorylation of FOXO3A and then activating cyclin D2 and D3 expression, leading to CD4{sup +} T cell proliferation.

  20. A loop region of BAFF controls B cell survival and regulates recognition by different inhibitors.

    Science.gov (United States)

    Vigolo, Michele; Chambers, Melissa G; Willen, Laure; Chevalley, Dehlia; Maskos, Klaus; Lammens, Alfred; Tardivel, Aubry; Das, Dolon; Kowalczyk-Quintas, Christine; Schuepbach-Mallepell, Sonia; Smulski, Cristian R; Eslami, Mahya; Rolink, Antonius; Hummler, Edith; Samy, Eileen; Fomekong Nanfack, Yves; Mackay, Fabienne; Liao, Maofu; Hess, Henry; Jiang, Xuliang; Schneider, Pascal

    2018-03-23

    The B cell survival factor (TNFSF13B/BAFF) is often elevated in autoimmune diseases and is targeted in the clinic for the treatment of systemic lupus erythematosus. BAFF contains a loop region designated the flap, which is dispensable for receptor binding. Here we show that the flap of BAFF has two functions. In addition to facilitating the formation of a highly active BAFF 60-mer as shown previously, it also converts binding of BAFF to TNFRSF13C (BAFFR) into a signaling event via oligomerization of individual BAFF-BAFFR complexes. Binding and activation of BAFFR can therefore be targeted independently to inhibit or activate the function of BAFF. Moreover, structural analyses suggest that the flap of BAFF 60-mer temporarily prevents binding of an anti-BAFF antibody (belimumab) but not of a decoy receptor (atacicept). The observed differences in profiles of BAFF inhibition may confer distinct biological and clinical efficacies to these therapeutically relevant inhibitors.

  1. BAFF-R Specific Activation of TRAF6 and the PI3K-Pathway in Lymphoma B Cells

    OpenAIRE

    Secreto, Frank; Manske, Michelle; Price-Troska, Tammy; Ziesmer, Steven; Hodge, Lucy S.; Ansell, Stephen M.; Cerhan, James R.; Novak, Anne J.

    2014-01-01

    BAFF-R is the primary BAFF receptor that is responsible for promoting B-cell development and survival. Malignant B-cells exploit the BAFF/BAFF receptor system and high serum BAFF levels or genetic alterations in BAFF receptors have been found in B-cell cancers. BAFF signaling impacts pro-survival pathways, however, other than NF-κB2, little is known about the specific pathways activated by individual BAFF receptors. Using a novel BAFF-R expression model we now demonstrate that activation of B...

  2. Coil embolization of the splenic artery: impact on splenic volume.

    Science.gov (United States)

    Preece, Stephen R; Schriber, Stacey M; Choudhury, Kingshuk R; Suhocki, Paul V; Smith, Tony P; Kim, Charles Y

    2014-06-01

    To determine the impact of coil embolization of the splenic artery on splenic volume based on computed tomography (CT) imaging. Splenic artery embolization (SAE) was performed in 148 consecutive patients over an 8-year period in an institutional review board-approved retrospective study. Of these, 60 patients (36 men; mean age, 49 y) had undergone contrast-enhanced CT before and after SAE with a mean time interval of 355 days. Pre- and postembolization splenic volumes were calculated with volume-rendering software. Presence of Howell-Jolly bodies was ascertained on laboratory tests. A trauma control group consisted of 39 patients with splenic laceration and follow-up CT but no splenic intervention. SAE in trauma patients resulted in an insignificant decrease in mean spleen size from 224 cm(3) to 190 cm(3) (P = .222). However, postembolization splenic volume was significantly smaller than follow-up volume in the trauma control group (353 cm(3); P Howell-Jolly bodies after SAE. No patients required repeat embolization or splenectomy. Coil embolization of the splenic artery resulted in a modest but significant decrease in splenic volume when performed distally; proximal embolization resulted in an insignificant volume change. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

  3. BAFF level increased in patients with autoimmune hemolytic anemia.

    Science.gov (United States)

    Zhao, Yu-Bing; Li, Jun-Min; Wei, Bei-Wen; Xu, Zi-Zhen

    2015-01-01

    BAFF (B-cell activating factor of the TNF family), an important regulator of B-cell, has been observed to be over-expressed in a variety of autoimmune diseases. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease occurred when antibodies directed against autologous red blood cells. We assessed serum levels of BAFF in AIHA patients with different serological characteristics. Serum BAFF levels were measured in 44 AIHA patients with different direct antiglobulin test (DAT) results and 25 healthy controls. The correlation of BAFF expression with DAT results and serological characteristics was assessed. Serum levels of BAFF in AIHA patients were significantly higher than in healthy subjects (AIHA: 1382.7 ± 1412.8 pg/ml, healthy control: 725.0 ± 415.7 pg/ml, P = 0.0057). Serum BAFF levels were significantly higher in patients with IgG(+)C3(+) or IgG(+) than healthy controls (DAT: negative) (P = 0.012, 0.004, respectively). No significant correlations were presented between serum BAFF levels and four serological parameters: hemoglobine, percentage of reticulocyte, total serum bilirubin, and lactate dehydrogenase. AIHA patients present higher serum BAFF levels than healthy controls, especially for those of IgG(+)C3(+) DAT result. This might lead to a new approach of AIHA treatment.

  4. Characterization of Lamprey BAFF-like Gene: Evolutionary Implications.

    Science.gov (United States)

    Das, Sabyasachi; Sutoh, Yoichi; Hirano, Masayuki; Han, Qifeng; Li, Jianxu; Cooper, Max D; Herrin, Brantley R

    2016-10-01

    BAFF (TNF superfamily [TNFSF] 13B/Blys) and APRIL (TNFSF13) are important regulatory factors for lymphocyte activation and survival in mammals. A BAFF/APRIL-like relative called BAFF- and APRIL-like molecule (BALM) has also been identified in cartilaginous and bony fishes, and we report in this study a BAFF-like gene in lampreys. Our phylogenetic analysis of these genes and a related TNFSF12 gene called TNF-like weak inducer of apoptosis (TWEAK) suggest that, whereas an ancestral homolog of BAFF and APRIL was already present in a common ancestor of jawed and jawless vertebrates, TWEAK evolved early on in the jawed vertebrate lineage. Like mammalian BAFF and APRIL, the lamprey BAFF-like gene is expressed in T-like, B-like, and innate immune cells. The predicted protein encoded by this BAFF-like gene in lampreys exhibits higher sequence similarity with mammalian BAFF than APRIL. Correspondingly, we find BAFF orthologs in all of the jawed vertebrate representatives that we examined, although APRIL and/or BALM orthologs are not identifiable in certain jawed vertebrates. For example, BALM is not identifiable in tetrapods, and APRIL is not identifiable in several bony fishes or in birds, the latter of which also lack a TWEAK-like gene. Our analysis further suggests that a hybrid molecule called TWE-PRIL, which is a product of an in-genomic fusion between APRIL and TWEAK genes evolved early in mammalian evolution. Copyright © 2016 by The American Association of Immunologists, Inc.

  5. BAFF-driven autoimmunity requires CD19 expression.

    Science.gov (United States)

    Fairfax, Kirsten A; Tsantikos, Evelyn; Figgett, William A; Vincent, Fabien B; Quah, Pin Shie; LePage, Mélanie; Hibbs, Margaret L; Mackay, Fabienne

    2015-08-01

    B cell activating factor of the tumor necrosis factor family (BAFF or BLyS) is a critical factor for B cell survival and maturation. BAFF-transgenic (BAFF-Tg) mice develop autoimmunity that resembles systemic lupus erythematosus (SLE) in a T cell-independent but MyD88-dependent manner, implicating toll-like receptor (TLR) signaling. The specific B cell subtypes that make pro-inflammatory autoantibodies in BAFF-Tg mice are TLR-activated innate B cells known as marginal zone (MZ) and B1 B cells. These cells infiltrate the salivary glands and kidneys of diseased BAFF-Tg mice. However, loss of B1a or MZ B cells does not protect BAFF-Tg mice against disease, suggesting that B1b B cells might be the important pathogenic B cell subset. To test this hypothesis, we have generated BAFF-Tg mice that retained follicular B cells, but are deficient in B1a, B1b and MZ B cells, by crossing BAFF-Tg mice to CD19-deficient mice (BTg-CD19(-/-)). The BTg-CD19(-/-) mice did not produce autoantibodies and were protected from splenomegaly, kidney pathology and all signs of autoimmunity. This work suggests that B1b B cells, rather than MZ or B1a B cells, are sufficient and possibly required for the development of autoimmunity. Loss of the majority of innate-like B cells was able to protect BAFF-Tg mice from developing disease, so we can now conclude that autoimmunity induced by excessive BAFF production requires B1b B cells and CD19 signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. The effects of Jieduquyuzishen prescription-treated rat serum on the BAFF/BAFF-R signal pathway.

    Directory of Open Access Journals (Sweden)

    De-Hong Wu

    Full Text Available Systemic lupus erythematosus (SLE is a chronic inflammatory disease mainly characterized by B cell hyperactivity. Glucocorticoid (GC is widely used in SLE for its potent anti-inflammatory and immunosuppressive effects. Despite its important clinical efficacy, high-dose or long-term use of GC can cause severe side effects, such as osteoporosis, osteonecrosis, cataracts, hyperglycemia, coronary heart disease and cognitive impairment. Our early clinical studies have shown that Jieduquyuzishen prescription (JP can effectively reduce the adverse effects and improve the curative effect of GC in the treatment of SLE. The BAFF/BAFF-R signaling pathway plays an important role in the development of SLE and has been regarded as a potential target for the therapy of SLE. In this study, we attempt to investigate the effect of JP on the BAFF/BAFF-R signaling pathway to explore the mechanism of JP in reducing the toxicity and enhancing the efficacy of GC. YAC-1 cells, isolated rat peripheral blood lymphocytes, polymorphonuclear neutrophils and spleen lymphocytes were treated with drug-containing serum. The results of RT-PCR, Western blot and dual-luciferase reporter gene assays indicate that either JP or GC can inhibit the mBAFF-induced up-regulation of BAFF, BAFF-R, Bcl-2, IL-10 and NF-κB in YAC-1 cells and WEHI-231 cells. Furthermore, MTS, flow cytometry and CFSE results reveal that the proliferation and survival of lymphocytes activated by mBAFF are suppressed by JP, GC and their combination. Contrary to GC, JP can reduce the apoptosis and raise the survival of polymorphonuclear neutrophils and can't increase the apoptosis of the peripheral blood lymphocytes and spleen lymphocytes. Therefore, it is possible that JP can down-regulate the BAFF/BAFF-R signaling pathway as effectively as GC, which may result in the dosage reduction of GC, thus decreasing the toxicity and improving the efficacy of GC-based treatment of SLE.

  7. Splenic abscess: a rare presentation

    Directory of Open Access Journals (Sweden)

    Mohit Bhatia

    2015-01-01

    Full Text Available Splenic abscess is a rare clinical entity with an incidence of 0.2-0.7% in autopsy-based studies. When untreated, splenic abscess is associated with nearly 100% mortality; in treated patients, the mortality rate is 16.6% during the first 90 days. It mostly occurs in patients with neoplasia, immunodeficiency, trauma, diabetes or splenic infarct. The incidence of splenic abscess is thought to be growing because of the increase in the number of immunocompromised patients who are particularly at risk for this disease and also because of the widespread use of diagnostic modalities. However, the optimal treatment for this remains unclear. We present a case of a 42-year-old man diagnosed with multiloculated splenic abscess and was subjected to splenectomy.

  8. Increased levels of BAFF in patients with systemic lupus erythematosus are associated with acute-phase reactants, independent of BAFF genetics: a case-control study.

    Science.gov (United States)

    Eilertsen, Gro Ø; Van Ghelue, Marijke; Strand, Harald; Nossent, Johannes C

    2011-12-01

    To determine whether increased levels of B-cell activating factor (BAFF) in patients with SLE are due to disease activity or genetic variations in the promoter region of the BAFF gene and BAFF gene expression. The case-control study included 101 SLE patients and 111 healthy controls. Five single nucleotide polymorphisms (SNPs) in the BAFF promoter region were investigated by melting point analysis: c.-2841 (T > C), c.-2704 (T > C), c.-2701 (A > T), c.-871 (C > T) and c.-514 (A > G). BAFF mRNA levels were determined by real-time PCR (BAFF-RQ) and serum BAFF (s-BAFF) levels were measured by ELISA. Independent predictors that might be correlated with increased s-BAFF in SLE patients were analysed by multivariate regression methods. RESULTS; Although s-BAFF levels were increased in SLE patients (1.73 vs 0.98 ng/μl, P acute-phase responses, CRP and haemoglobin, but probably not dependent on BAFF genotype or expression. This indicates that s-BAFF production occurs at sites of inflammation.

  9. Growth of Murine Splenic Tissue Is Suppressed by Lymphotoxin β-Receptor Signaling (LTβR) Originating from Splenic and Non-Splenic Tissues

    DEFF Research Database (Denmark)

    Milićević, Novica M; Nohroudi, Klaus; Schmidt, Friederike

    2016-01-01

    LTβR signaling. Two-dimensional differential gel electrophoresis and subsequent mass spectrometry of stromal splenic tissue was applied to screen for potential factors mediating the LTβR dependent suppressive activity. Thus, LTβR dependent growth suppression is involved in regulating the size...

  10. B cell activation factor (BAFF) is a novel adipokine that links obesity and inflammation

    OpenAIRE

    Kim, Yu-Hee; Choi, Bong-Hyuk; Cheon, Hyae-Gyeong; Do, Myoung-Sool

    2009-01-01

    B cell activation factor (BAFF) is a novel member of the TNF ligand superfamily, mainly produced by myeloid cells. BAFF has been shown to participate in B-cell survival and B- and T-cell maturation. BAFF expression in adipocytes has been recently demonstrated. In the current study, we verified that BAFF expression is increased during adipocyte differentiation. BAFF expression was augmented by TNF-α treatment and was decreased by rosiglitazone treatment. BAFF secretion in lean and in ob/ob mic...

  11. BAFF-neutralizing interaction of belimumab related to its therapeutic efficacy for treating systemic lupus erythematosus.

    Science.gov (United States)

    Shin, Woori; Lee, Hyun Tae; Lim, Heejin; Lee, Sang Hyung; Son, Ji Young; Lee, Jee Un; Yoo, Ki-Young; Ryu, Seong Eon; Rhie, Jaejun; Lee, Ju Yeon; Heo, Yong-Seok

    2018-03-23

    BAFF, a member of the TNF superfamily, has been recognized as a good target for autoimmune diseases. Belimumab, an anti-BAFF monoclonal antibody, was approved by the FDA for use in treating systemic lupus erythematosus. However, the molecular basis of BAFF neutralization by belimumab remains unclear. Here our crystal structure of the BAFF-belimumab Fab complex shows the precise epitope and the BAFF-neutralizing mechanism of belimumab, and demonstrates that the therapeutic activity of belimumab involves not only antagonizing the BAFF-receptor interaction, but also disrupting the formation of the more active BAFF 60-mer to favor the induction of the less active BAFF trimer through interaction with the flap region of BAFF. In addition, the belimumab HCDR3 loop mimics the DxL(V/L) motif of BAFF receptors, thereby binding to BAFF in a similar manner as endogenous BAFF receptors. Our data thus provides insights for the design of new drugs targeting BAFF for the treatment of autoimmune diseases.

  12. Transgenic overexpression of BAFF regulates the expression of ...

    Indian Academy of Sciences (India)

    LI ZHANG

    GFP-2A-BAFF/His recombinant plasmid was constructed by ... vided novel insight into further exploration of modulating adaptive immunity and studying autoimmune diseases caused by ... major role in the survival, proliferation and differentiation.

  13. BAFF Promotes Th17 Cells and Aggravates Experimental Autoimmune Encephalomyelitis

    Science.gov (United States)

    Lan, Qin; Wang, Julie; Su, Wenru; Han, Yuan-Ping; Fan, Huimin; Liu, Zhongmin; Stohl, William; Zheng, Song Guo

    2011-01-01

    Background BAFF, in addition to promoting B cell survival and differentiation, may affect T cells. The objective of this study was to determine the effect of BAFF on Th17 cell generation and its ramifications for the Th17 cell-driven disease, EAE. Methodology/Principal Findings Th17 cells were increased in BAFF-Tg B6 (B6.BTg) mice and decreased in B6.Baff−/− mice. Th17 cells in B6.Baff−/− mice bearing a BAFF Tg (B6.Baff−/−.BTg mice) were identical to those in B6.BTg mice, indicating that membrane BAFF is dispensable for Th17 cell generation as long as soluble BAFF is plentiful. In T + non-T cell criss-cross co-cultures, Th17 cell generation was greatest in cultures containing B6.BTg T cells and lowest in cultures containing B6.Baff−/− T cells, regardless of the source of non-T cells. In cultures containing only T cells, Th17 cell generation followed an identical pattern. CD4+ cell expression of CD126 (IL-6R α chain) was increased in B6.BTg mice and decreased in B6.Baff−/− mice, and activation of STAT3 following stimulation with IL-6 + TGF-β was also greatest in B6.BTg cells and lowest in B6.Baff−/− cells. EAE was clinically and pathologically most severe in B6.BTg mice and least severe in B6.Baff−/− mice and correlated with MOG35–55 peptide-induced Th17 cell responses. Conclusions/Significance Collectively, these findings document a contribution of BAFF to pathogenic Th17 cell responses and suggest that BAFF antagonism may be efficacious in Th17 cell-driven diseases. PMID:21897850

  14. Gingival crevicular fluid and serum levels of APRIL, BAFF and TNF-alpha in rheumatoid arthritis and osteoporosis patients with periodontal disease.

    Science.gov (United States)

    Gümüş, Pinar; Buduneli, Eralp; Biyikoğlu, Başak; Aksu, Kenan; Saraç, Fulden; Buduneli, Nurcan; Lappin, David F

    2013-10-01

    This study was performed to evaluate gingival crevicular fluid (GCF) and serum levels of a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF) and compare this to differences between TNF-alpha levels in rheumatoid arthritis (RA), osteoporosis (OPR) and systemically healthy women with periodontal disease (SH). Gingival crevicular fluid (GCF) and serum samples were obtained before any periodontal intervention from 17 RA, 19 OPR patients and 13 SH women with periodontitis. Full-mouth clinical periodontal measurements were recorded. APRIL, BAFF and TNF-α levels were determined by ELISA. Statistical analysis was performed using multivariate analysis, ANOVA and Spearman correlation. Pocket depths differed in site-specific comparisons, but otherwise clinical measurements were similar in the three study groups. Multivariate least squares regression ANOVA adjusted for age and for plaque index indicated that total amounts of TNF-α and concentrations of TNF-α, BAFF and APRIL were significantly greater in the RA patients than in the SH group (p<0.05), and GCF concentrations of BAFF were greater in OPR patients than in SH. Serum TNF-α and BAFF were significantly higher in the RA group compared to SH (p<0.05) and serum TNF-α was greater in RA than in OPR (p<0.05). APRIL and BAFF correlated with RANKL levels in GCF and serum (p<0.05). Despite long-term usage of anti-inflammatory drugs in the RA and OPR patients, increased TNF-family cytokines, might suggest that these patients have a propensity to overproduce these inflammatory mediators but whether this results from greater disease activity or contribute to greater disease activity remains moot. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. CT appearance of splenic abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Kondo, Mariko; Sakai, Kunio [Niigata Univ. (Japan). School of Medicine; Shiina, Makoto; Sasage, Akira; Saito, Akira

    1995-04-01

    CT findings in 13 cases with malignant splenic lesions (7, malignant lymphoma ; 6, metastatic tumor) and 25 cases with non-malignant lesions (9, infarction ; 5, abscess ; 5, cyst ; 3, hematoma ; 1, hemangioma ; 1, sarcoidosis ; 1, lymphangioma) were described. Although CT was useful in localization of splenic lesions, there were usually nonspecific CT findings to each lesion. So CT findings outside the spleen and clinical course were considered to be important for differential diagnosis. (author).

  16. Profile of BAFF and its receptors' expression in lupus nephritis is associated with pathological classes.

    Science.gov (United States)

    Suso, J P; Posso-Osorio, I; Jiménez, C A; Naranjo-Escobar, J; Ospina, F E; Sánchez, A; Cañas, C A; Tobón, G J

    2018-04-01

    Background/Objective B-cell activating factor (BAFF) plays an important role in the pathogenesis of systemic lupus erythematosus. However, the role of BAFF in lupus nephritis (LN) is not understood. Our aim was to evaluate the expression of BAFF and its three receptors in renal biopsy samples from patients with LN and investigate a relationship with pathological class. Methods We conducted a prospective descriptive study (2011-2014) on 52 kidney biopsy samples from patients with LN. Immunohistochemistry for BAFF, its receptors (transmembrane activator and calcium modulator and cyclophilin ligand interaction (TACI), protein maturation of B cells (BCMA), and BAFF-receptor (BAFF-R)), and CD20 expression was performed. Samples were scored according to the percentage of cells with positive expression. Results In class II LN, BAFF-R and TACI were not expressed, whereas BCMA and BAFF were lowly expressed in the interstitial inflammatory infiltrates. Proliferative class III/IV had elevated BAFF expression in the glomeruli, and TACI was expressed in interstitial inflammatory infiltrates and the glomeruli. Interestingly, the class IV cases with vasculopathy ( n = 4) had endothelial BAFF expression, which was not visible in thrombotic microangiopathy ( n = 4). Class V was characterized by low BAFF expression in interstitial inflammatory infiltrates and by BAFF, TACI, and BCMA expression in the glomeruli. BAFF expression was associated with inflammatory scores and CD20 positive infiltrates, mainly in class IV. Conclusions Expression patterns of BAFF and its receptors differ according to LN class. Our study provides evidence that BAFF could be used as a routine marker in LN biopsies and to determine which patients will benefit from anti-BAFF therapy.

  17. Stoichiometry of Heteromeric BAFF and APRIL Cytokines Dictates Their Receptor Binding and Signaling Properties*

    Science.gov (United States)

    Schuepbach-Mallepell, Sonia; Das, Dolon; Willen, Laure; Vigolo, Michele; Tardivel, Aubry; Lebon, Luc; Kowalczyk-Quintas, Christine; Nys, Josquin; Smulski, Cristian; Zheng, Timothy S.; Maskos, Klaus; Lammens, Alfred; Jiang, Xuliang; Hess, Henry; Tan, Seng-Lai; Schneider, Pascal

    2015-01-01

    The closely related TNF family ligands B cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) serve in the generation and maintenance of mature B-lymphocytes. Both BAFF and APRIL assemble as homotrimers that bind and activate several receptors that they partially share. However, heteromers of BAFF and APRIL that occur in patients with autoimmune diseases are incompletely characterized. The N and C termini of adjacent BAFF or APRIL monomers are spatially close and can be linked to create single-chain homo- or hetero-ligands of defined stoichiometry. Similar to APRIL, heteromers consisting of one BAFF and two APRILs (BAA) bind to the receptors B cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) but not to the BAFF receptor (BAFFR). Heteromers consisting of one APRIL and two BAFF (ABB) bind to TACI and BCMA and weakly to BAFFR in accordance with the analysis of the receptor interaction sites in the crystallographic structure of ABB. Receptor binding correlated with activity in reporter cell line assays specific for BAFFR, TACI, or BCMA. Single-chain BAFF (BBB) and to a lesser extent single-chain ABB, but not APRIL or single-chain BAA, rescued BAFFR-dependent B cell maturation in BAFF-deficient mice. In conclusion, BAFF-APRIL heteromers of different stoichiometries have distinct receptor-binding properties and activities. Based on the observation that heteromers are less active than BAFF, we speculate that their physiological role might be to down-regulate BAFF activity. PMID:25953898

  18. Isolated splenic peliosis in an immunocompromised patient

    African Journals Online (AJOL)

    cited by Gushiken1). Isolated splenic peliosis is extremely rare, and most cases are associated with peliosis hepatis. Establishing the incidence of splenic peliosis is difficult, since the condition usually remains asymptomatic or is discovered ...

  19. Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases.

    Science.gov (United States)

    Samy, Eileen; Wax, Stephen; Huard, Bertrand; Hess, Henry; Schneider, Pascal

    2017-01-02

    The B cell-stimulating molecules, BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand), are critical factors in the maintenance of the B cell pool and humoral immunity. In addition, BAFF and APRIL are involved in the pathogenesis of a number of human autoimmune diseases, with elevated levels of these cytokines detected in the sera of patients with systemic lupus erythematosus (SLE), IgA nephropathy, Sjögren's syndrome, and rheumatoid arthritis. As such, both molecules are rational targets for new therapies in B cell-driven autoimmune diseases, and several inhibitors of BAFF or BAFF and APRIL together have been investigated in clinical trials. These include the BAFF/APRIL dual inhibitor, atacicept, and the BAFF inhibitor, belimumab, which is approved as an add-on therapy for patients with active SLE. Post hoc analyses of these trials indicate that baseline serum levels of BAFF and BAFF/APRIL correlate with treatment response to belimumab and atacicept, respectively, suggesting a role for the two molecules as predictive biomarkers. It will, however, be important to refine future testing to identify active forms of BAFF and APRIL in the circulation, as well as to distinguish between homotrimer and heteromer configurations. In this review, we discuss the rationale for dual BAFF/APRIL inhibition versus single BAFF inhibition in autoimmune disease, by focusing on the similarities and differences between the physiological and pathogenic roles of the two molecules. A summary of the preclinical and clinical data currently available is also presented.

  20. Therapeutic Effects of PADRE-BAFF Autovaccine on Rat Adjuvant Arthritis

    Directory of Open Access Journals (Sweden)

    Guo-dong Feng

    2014-01-01

    Full Text Available B cell activating factor (BAFF is a cytokine of tumor necrosis factor family mainly produced by monocytes and dendritic cells. BAFF can regulate the proliferation, differentiation, and survival of B lymphocytes by binding with BAFF-R on B cell membrane. Accumulating evidences showed that BAFF played crucial roles and was overexpressed in various autoimmune diseases such as systemic lupus erythematous (SLE and rheumatoid arthritis (RA. This suggests that BAFF may be a therapeutic target for these diseases. In the present study, we developed a BAFF therapeutic vaccine by coupling a T helper cell epitope AKFVAAWTLKAA (PADRE to the N terminus of BAFF extracellular domains (PADRE-BAFF and expressed this fusion protein in Escherichia coli. The purified vaccine can induce high titer of neutralizing BAFF antibodies and ameliorate the syndrome of complete Freund’s adjuvant (CFA induced rheumatoid arthritis in rats. Our data indicated that the BAFF autovaccine may be a useful candidate for the treatment of some autoimmune diseases associated with high level of BAFF.

  1. Expression of BAFF and BR3 in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    J.H. Duan

    2016-03-01

    Full Text Available The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE. Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3 on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (P<0.01. The percentage of BR3 on B lymphocytes was downregulated in the active SLE group compared with the stable SLE group and controls (P<0.01. BAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (P<0.01. The percentage of BR3 on B lymphocytes was lower in patients who were positive for proteinuria than in those who were negative (P<0.01. The BAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment.

  2. Exploring BAFF: its expression, receptors and contribution to the immunopathogenesis of Sjögren's syndrome.

    Science.gov (United States)

    Thompson, Nicolyn; Isenberg, David A; Jury, Elizabeth C; Ciurtin, Coziana

    2016-09-01

    SS is an autoimmune condition characterized by exocrine gland destruction, autoantibody production, immune complex deposition and systemic complications associated with lymphocytic infiltration of many organs. Genetic, environmental and viral factors play a role in disease aetiology, however, the exact mechanisms driving the immunopathogenesis of SS remain uncertain. Here we discuss a role for B cell activating factor (BAFF), whereby B cell hyperactivity and increased BAFF secretion observed in patients and animal models of the disease can be explained by the altered expression of cell-specific BAFF/BAFF receptor (BAFF-R) variants in several immune cell types. Understanding the role of BAFF/BAFF-R heterogeneity in SS pathogenesis could help to facilitate new treatment strategies for patients. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Serum BAFF and APRIL levels in patients with autoimmune hemolytic anemia and their clinical significance.

    Science.gov (United States)

    Xu, Zi-Zhen; Zhao, Bing-Bing; Xiong, Hong; Wei, Bei-Wen; Wang, Ye-Fei

    2015-10-01

    B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play crucial roles in B cell development, survival, and antibody production. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease that occurs when antibodies target autologous red blood cells. Here, we analyzed the serum levels of BAFF and APRIL and their respective clinical associations in patients with AIHA. Serum BAFF and APRIL levels in patients with AIHA were significantly higher (P BAFF and APRIL levels were significantly augmented in patients with lower hemoglobin levels (hemoglobin was 480 IU/mL). Glucocorticoid treatment dramatically reduced serum levels of BAFF and APRIL. Thus, serum BAFF and APRIL levels may reflect the clinical activity of this disease. Our results indicate that analysis of serum concentrations of BAFF and APRIL potentially represents a useful tool for the assessment of AIHA disease activity and progression.

  4. BAFF inhibition: a new class of drugs for the treatment of autoimmunity

    Science.gov (United States)

    Liu, Zheng; Davidson, Anne

    2011-01-01

    BAFF (BLyS) and APRIL are TNF-like cytokines that support survival and differentiation of B cells. Recent studies have discovered a role for BAFF in augmenting both innate and adaptive immune responses as well as in collaborating with other inflammatory cytokines to promote the activation and differentiation of effector immune cells. BAFF is an important pathogenic factor in lupus mouse models and BAFF inhibition successfully delays disease onset in these mice, although the responsiveness to BAFF inhibition varies among different strains. These results have led to the development of inhibitors targeting BAFF and APRIL in humans. An anti-BAFF antibody has shown significant but modest efficacy in two Phase III clinical trials for moderately active SLE and other inhibitors are being developed or at early stages of clinical testing. PMID:21333645

  5. The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity.

    Science.gov (United States)

    Vincent, Fabien B; Saulep-Easton, Damien; Figgett, William A; Fairfax, Kirsten A; Mackay, Fabienne

    2013-06-01

    The BAFF system plays a key role in the development of autoimmunity, especially in systemic lupus erythematosus (SLE). This often leads to the assumption that BAFF is mostly a B cell factor with a specific role in autoimmunity. Focus on BAFF and autoimmunity, driven by pharmaceutical successes with the recent approval of a novel targeted therapy Belimumab, has relegated other potential roles of BAFF to the background. Far from being SLE-specific, the BAFF system has a much broader relevance in infection, cancer and allergy. In this review, we provide the latest views on additional roles of the BAFF system in health and diseases, as well as an update on BAFF and autoimmunity, with particular focus on current clinical trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Splenic irradiation for hairy cell leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Al-Moundhri, A.; Graham, P.H. [St George Hospital, Kogarah, NSW, (Australia). Department of Radiation Oncology

    1997-11-01

    Splenic irradiation in the management of hairy cell leukaemia is previously unreported. A case is presented here to illustrate that splenic irradiation may be a useful addition to systemic therapies. It achieved local splenic and blood picture response and remission similar to splenectomy without any significant toxicity. (authors). 7 refs., 2 figs.

  7. Large primary splenic cyst: A laparoscopic technique.

    LENUS (Irish Health Repository)

    Geraghty, M

    2009-01-01

    Splenic cysts are rare lesions with around 800 cases reported in the world literature. Traditionally splenectomy was the treatment of choice. However, with the recognition of the important immunological function of the spleen, new techniques to preserve splenic function have been developed. This case emphasizes that in selected cases splenic preservation is appropriate.

  8. Splenic conservation in children with splenic injury at Nnewi - South ...

    African Journals Online (AJOL)

    Hitherto, the mode of treatment has been towards resuscitation and splenectomy but over the past one and half decades, the trend moved to conserve. Objective: We therefore review the management of splenic injuries in children over the past ten years as well as highlight management problems. Patients and Methods: ...

  9. Primary splenic torsion in a Boston terrier

    International Nuclear Information System (INIS)

    Ohta, H.; Takagi, S.; Murakami, M.; Sasaki, N.; Yoshikawa, M.; Nakamura, K.; Hwang, S.J.; Yamasaki, M.; Takiguchi, M.

    2009-01-01

    A 7-year-old female Boston terrier was referred to Hokkaido University Veterinary Teaching Hospital with a history of hemoglobinuria and anemia for several days. Abdominal radiographs showed splenomegaly, and ultrasonography revealed a hypoechoic splenic parenchyma with interspersed linear echoes consistent with the ultrasonographic appearance of splenic torsion. Ultrasonography and computed tomography (CT) indicated a C-shaped spleen. Exploratory laparotomy confirmed the diagnosis of splenic torsion. A splenectomy was performed, and the dog recovered well without complications. This is the first report of splenic torsion in Boston terriers, and the usefulness of ultrasonographic and CT findings of the splenic torsion was also confirmed

  10. Primary splenic torsion in a Boston terrier.

    Science.gov (United States)

    OHTA, Hiroshi; TAKAGI, Satoshi; MURAKAMI, Masahiro; SASAKI, Noboru; YOSHIKAWA, Muneyoshi; NAKAMURA, Kensuke; HWANG, Shiang-Jyi; YAMASAKI, Masahiro; TAKIGUCHI, Mitsuyoshi

    2009-11-01

    A 7-year-old female Boston terrier was referred to Hokkaido University Veterinary Teaching Hospital with a history of hemoglobinuria and anemia for several days. Abdominal radiographs showed splenomegaly, and ultrasonography revealed a hypoechoic splenic parenchyma with interspersed linear echoes consistent with the ultrasonographic appearance of splenic torsion. Ultrasonography and computed tomography (CT) indicated a C-shaped spleen. Exploratory laparotomy confirmed the diagnosis of splenic torsion. A splenectomy was performed, and the dog recovered well without complications. This is the first report of splenic torsion in Boston terriers, and the usefulness of ultrasonographic and CT findings of the splenic torsion was also confirmed.

  11. Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore.

    Science.gov (United States)

    Howe, H S; Thong, B Y H; Kong, K O; Chng, H H; Lian, T Y; Chia, F L; Tay, K S S; Lau, T C; Law, W G; Koh, E T; Leung, B P

    2017-09-01

    To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies. © 2017 British Society for

  12. Association of variants in BAFF (rs9514828 and rs1041569) and BAFF-R (rs61756766) genes with the risk of chronic lymphocytic leukemia.

    Science.gov (United States)

    Jasek, Monika; Bojarska-Junak, Agnieszka; Wagner, Marta; Sobczyński, Maciej; Wołowiec, Dariusz; Roliński, Jacek; Karabon, Lidia; Kuśnierczyk, Piotr

    2016-10-01

    The B-cell activator factor (BAFF)/BAFF receptor (BAFF-R) axis seems to play an important role in the development and progression of chronic lymphocytic leukemia (CLL). Here, we investigated the association of eight single nucleotide polymorphisms (SNPs) in the BAFF (TNFSF13B) and BAFF-R (TNFRSF13C) genes with risk of sporadic CLL in a group of 439 CLL patients and 477 controls. We also examined the correlation between selected SNPs and CLL clinical parameters as well as BAFF plasma levels and intracellular BAFF expression. Our results point to a possible association between the rs9514828 (CT vs. CC + TT; OR = 0.74; CI 95 % = 0.57; 0.97; p = 0.022) and rs1041569 (AT vs. AA + TT; OR = 0.72; CI 95 % = 0.54; 0.95; p = 0.021) of BAFF gene and rs61756766 (CC vs. CT; OR = 2.03; CI 95 % = 1.03; 3.99; p = 0.03) of BAFF-R gene and CLL risk. Additionally, we observed that homozygotes rs1041569 AA and TT had a slightly higher risk (HR = 1.12) for the need of treatment in comparison to AT heterozygotes. In conclusion, our results indicate that SNPs in BAFF and BAFF-R genes may be considered as potential CLL risk factors.

  13. BAFF is decreased in the cerebrospinal fluid of multiple sclerosis at clinical onset.

    Science.gov (United States)

    Puthenparampil, M; Miante, S; Federle, L; Zanetta, C; Toffanin, E; Ruggero, S; Rinaldi, F; Gallo, P

    2016-08-15

    B-cells are thought to play a relevant role in multiple sclerosis (MS) pathology. BAFF (B cell activating factor of the TNF family) is a B-cell survival factor constitutively produced inside the CNS by astrocytes. We studied the intrathecal synthesis of BAFF in MS at clinical onset. Paired serum and cerebrospinal fluid (CSF) specimens from 40 clinically isolated syndromes (CIS) suggestive of MS or early relapse-onset MS (eRRMS) and from 18 healthy controls (HC) were analysed. Patients were classified based on the detection of oligoclonal IgG bands in the CSF (IgGOB+ and IgGOB-). BAFF was detected by highly sensitive ELISA and its ratio (CSF-BAFF/serum-BAFF, QBAFF) and Index (QBAFF/QAlb, BAFF-Index) were calculated. IgGOB+ presented lower CSF concentrations of BAFF compared to both HC and IgGOB- (pBAFF Index was significantly lower in IgGOB+ compared to both HC and IgGOB- (pBAFF index and IgGIF (r: -0.4, pBAFF in IgGOB+ at clinical onset suggest the absorption of this factor by intrathecally recruited B cells since the early disease phases. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. BAFF activation of the ERK5 MAP kinase pathway regulates B cell survival.

    Science.gov (United States)

    Jacque, Emilie; Schweighoffer, Edina; Tybulewicz, Victor L J; Ley, Steven C

    2015-06-01

    B cell activating factor (BAFF) stimulation of the BAFF receptor (BAFF-R) is essential for the homeostatic survival of mature B cells. Earlier in vitro experiments with inhibitors that block MEK 1 and 2 suggested that activation of ERK 1 and 2 MAP kinases is required for BAFF-R to promote B cell survival. However, these inhibitors are now known to also inhibit MEK5, which activates the related MAP kinase ERK5. In the present study, we demonstrated that BAFF-induced B cell survival was actually independent of ERK1/2 activation but required ERK5 activation. Consistent with this, we showed that conditional deletion of ERK5 in B cells led to a pronounced global reduction in mature B2 B cell numbers, which correlated with impaired survival of ERK5-deficient B cells after BAFF stimulation. ERK5 was required for optimal BAFF up-regulation of Mcl1 and Bcl2a1, which are prosurvival members of the Bcl-2 family. However, ERK5 deficiency did not alter BAFF activation of the PI3-kinase-Akt or NF-κB signaling pathways, which are also important for BAFF to promote mature B cell survival. Our study reveals a critical role for the MEK5-ERK5 MAP kinase signaling pathway in BAFF-induced mature B cell survival and homeostatic maintenance of B2 cell numbers. © 2015 Jacque et al.

  15. Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice.

    Science.gov (United States)

    Morissette, Mathieu C; Gao, Yang; Shen, Pamela; Thayaparan, Danya; Bérubé, Jean-Christophe; Paré, Peter D; Brandsma, Corry-Anke; Hao, Ke; Bossé, Yohan; Ettinger, Rachel; Herbst, Ronald; Humbles, Alison A; Kolbeck, Roland; Zhong, Nanshan; Chen, Rongchang; Stämpfli, Martin R

    2016-12-01

    Emerging evidence suggests that autoimmune processes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. We observed that BAFF levels were elevated in smokers and mice exposed to cigarette smoke. In mice, BAFF expression was rapidly induced in the lungs following 4 days of cigarette smoke exposure and remained elevated following 8 and 24 weeks of exposure. Alveolar macrophages were the major source of BAFF Blockade of BAFF using a BAFF receptor-Fc (BAFFR-Fc) construct prevented pulmonary ANA and TLT formation when delivered concurrent with cigarette smoke exposure. Under these conditions, no impact on lung inflammation was observed. However, administration of BAFFR-Fc following smoking cessation markedly reduced the number of TLTs and ANA levels and, of note, reduced pulmonary neutrophilia. Altogether, this study shows for the first time a central role of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggests that BAFF blockade following smoking cessation could have beneficial effects on persistent inflammatory processes.In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. Data presented show that BAFF plays a central role in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggest a therapeutic potential for BAFF blockade in limiting autoimmune processes associated with smoking. © 2016 The Authors. Physiological

  16. Up-regulated BAFF and BAFF receptor expression in patients with intractable temporal lobe epilepsy and a pilocarpine-induced epilepsy rat model.

    Science.gov (United States)

    Ma, Limin; Li, Ruohan; Huang, Hao; Yuan, Jinxian; Ou, Shu; Xu, Tao; Yu, Xinyuan; Liu, Xi; Chen, Yangmei

    2017-05-01

    Some studies have suggested that BAFF and BAFFR are highly expressed in the central nervous system (CNS) and participate in inflammatory and immune associated diseases. However, whether BAFF and BAFFR are involved in the pathogenesis of epilepsy remains unknown. This study aimed to investigate the expression of BAFF and BAFFR proteins in the brains of patients with temporal lobe epilepsy (TLE) and in a pilocarpine-induced rat model of TLE to identify possible roles of the BAFF-BAFFR signaling pathway in epileptogenesis. Real-time quantitative polymerase chain reaction (RT-qPCR), western blot, immunohistochemistry, and double-immunofluorescence were performed in this study. The results showed that BAFF and BAFFR expression levels were markedly up-regulated in intractable TLE patients and TLE rats. Moreover, BAFF and BAFFR proteins mainly highly expressed in the membranes and cytoplasms of the dendritic marker MAP2 in the cortex and hippocampus. Therefore, the significant increased in BAFF and BAFFR protein expression in both TLE patients and rats suggest that BAFF and BAFFR may play important roles in regulating the pathogenesis of epilepsy. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  17. Computed tomography of splenic infarcts

    Energy Technology Data Exchange (ETDEWEB)

    Triller, J.; Bona, E.; Barbier, P.

    1985-04-01

    Splenic infarcts are represented by wedge-shaped, oval or linear areas. Haemorrhagic infarcts are characterised by being hyperdense. Disseminated infarction occurs predominantly in myeloproliferative diseases. During the early stages, the infarct appears as an ill-defined hypodense defect, with non-homogeneous contrast enhancement. During the acute and sub-acute stage, the density of the infarct is low and there is no contrast enhancement. During the chronic stage, its density increases and there is slight contrast enhancement. Complications following splenic infarcts, such as abscesses, bleeding and rupture can be demonstrated by CT with great accuracy. Problems in differential diagnosis may occur if there are atypical manifestations of the infarct, with respect to abscess or leukaemic infiltrations.

  18. BAFF and BAFF receptor levels correlate with B cell subset activation and redistribution in controlled human malaria infection

    NARCIS (Netherlands)

    Scholzen, A.; Teirlinck, A.C.; Bijker, E.M.; Roestenberg, M.; Hermsen, C.C.; Hoffman, S.L.; Sauerwein, R.W.

    2014-01-01

    Characteristic features of Plasmodium falciparum malaria are polyclonal B cell activation and an altered composition of the blood B cell compartment, including expansion of CD21(-)CD27(-) atypical memory B cells. BAFF is a key cytokine in B cell homeostasis, but its potential contribution to the

  19. Characterization of BAFF and APRIL subfamily receptors in rainbow trout (Oncorhynchus mykiss). Potential role of the BAFF / APRIL axis in the pathogenesis of proliferative kidney disease.

    Science.gov (United States)

    Granja, Aitor G; Holland, Jason W; Pignatelli, Jaime; Secombes, Christopher J; Tafalla, Carolina

    2017-01-01

    Proliferative kidney disease (PKD) is a parasitic infection of salmonid fish characterized by hyper-secretion of immunoglobulins in response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In this context, we hypothesized that the BAFF/APRIL axis, known to play a major role in B cell differentiation and survival in mammals, could be affected by the parasite and consequently be involved in the apparent shift in normal B cell activity. To regulate B cell activity, BAFF and APRIL bind to transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), whereas BAFF also binds to BAFF receptor (BAFF-R). In teleost fish, although some BAFF and APRIL sequences have been reported, their receptors have not been identified. Thus, as a first step in the current work, we have identified homologues to mammalian TACI, BCMA and BAFF-R in rainbow trout (Oncorhynchus mykiss), that constitute the first report of BAFF and APRIL receptor sequences in fish. Subsequently we studied the transcriptional modulation of BAFF, APRIL, and the fish-specific related cytokine, BALM and their putative receptors in fish naturally exposed to T. bryosalmonae. Finally, to gain further insights on the functional role that these cytokines play during the course of PKD, we have studied their effect on the survival of kidney IgM+ B cells and on immunoglobulin transcription. Our results support the premise that the BAFF / APRIL axis could play an important role during PKD, which may open the possibility of new therapeutic treatments against the disease.

  20. Characterization of BAFF and APRIL subfamily receptors in rainbow trout (Oncorhynchus mykiss. Potential role of the BAFF / APRIL axis in the pathogenesis of proliferative kidney disease.

    Directory of Open Access Journals (Sweden)

    Aitor G Granja

    Full Text Available Proliferative kidney disease (PKD is a parasitic infection of salmonid fish characterized by hyper-secretion of immunoglobulins in response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In this context, we hypothesized that the BAFF/APRIL axis, known to play a major role in B cell differentiation and survival in mammals, could be affected by the parasite and consequently be involved in the apparent shift in normal B cell activity. To regulate B cell activity, BAFF and APRIL bind to transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI and B cell maturation antigen (BCMA, whereas BAFF also binds to BAFF receptor (BAFF-R. In teleost fish, although some BAFF and APRIL sequences have been reported, their receptors have not been identified. Thus, as a first step in the current work, we have identified homologues to mammalian TACI, BCMA and BAFF-R in rainbow trout (Oncorhynchus mykiss, that constitute the first report of BAFF and APRIL receptor sequences in fish. Subsequently we studied the transcriptional modulation of BAFF, APRIL, and the fish-specific related cytokine, BALM and their putative receptors in fish naturally exposed to T. bryosalmonae. Finally, to gain further insights on the functional role that these cytokines play during the course of PKD, we have studied their effect on the survival of kidney IgM+ B cells and on immunoglobulin transcription. Our results support the premise that the BAFF / APRIL axis could play an important role during PKD, which may open the possibility of new therapeutic treatments against the disease.

  1. Stoichiometry of Heteromeric BAFF and APRIL Cytokines Dictates Their Receptor Binding and Signaling Properties.

    Science.gov (United States)

    Schuepbach-Mallepell, Sonia; Das, Dolon; Willen, Laure; Vigolo, Michele; Tardivel, Aubry; Lebon, Luc; Kowalczyk-Quintas, Christine; Nys, Josquin; Smulski, Cristian; Zheng, Timothy S; Maskos, Klaus; Lammens, Alfred; Jiang, Xuliang; Hess, Henry; Tan, Seng-Lai; Schneider, Pascal

    2015-06-26

    The closely related TNF family ligands B cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) serve in the generation and maintenance of mature B-lymphocytes. Both BAFF and APRIL assemble as homotrimers that bind and activate several receptors that they partially share. However, heteromers of BAFF and APRIL that occur in patients with autoimmune diseases are incompletely characterized. The N and C termini of adjacent BAFF or APRIL monomers are spatially close and can be linked to create single-chain homo- or hetero-ligands of defined stoichiometry. Similar to APRIL, heteromers consisting of one BAFF and two APRILs (BAA) bind to the receptors B cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) but not to the BAFF receptor (BAFFR). Heteromers consisting of one APRIL and two BAFF (ABB) bind to TACI and BCMA and weakly to BAFFR in accordance with the analysis of the receptor interaction sites in the crystallographic structure of ABB. Receptor binding correlated with activity in reporter cell line assays specific for BAFFR, TACI, or BCMA. Single-chain BAFF (BBB) and to a lesser extent single-chain ABB, but not APRIL or single-chain BAA, rescued BAFFR-dependent B cell maturation in BAFF-deficient mice. In conclusion, BAFF-APRIL heteromers of different stoichiometries have distinct receptor-binding properties and activities. Based on the observation that heteromers are less active than BAFF, we speculate that their physiological role might be to down-regulate BAFF activity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Is it worth investigating splenic function in patients with celiac disease?

    Science.gov (United States)

    Di Sabatino, Antonio; Brunetti, Laura; Carnevale Maffè, Gabriella; Giuffrida, Paolo; Corazza, Gino Roberto

    2013-01-01

    Celiac disease, an immune-mediated enteropathy induced in genetically susceptible individuals by the ingestion of gluten, is the most frequent disorder associated with splenic hypofunction or atrophy. Defective splenic function affects more than one-third of adult patients with celiac disease, and it may predispose to a higher risk of infections by encapsulated bacteria and thromboembolic and autoimmune complications, particularly when celiac patients have concomitant pre-malignant and malignant complications (refractory celiac disease, ulcerative jejunoileitis and enteropathy-associated T-cell lymphoma). However, the clinical management of patients with celiac disease does not take into account the evaluation of splenic function, and in patients with high degree of hyposplenism or splenic atrophy the prophylactic immunization with specific vaccines against the polysaccharide antigens of encapsulated bacteria is not currently recommended. We critically re-evaluate clinical and diagnostic aspects of spleen dysfunction in celiac disease, and highlight new perspectives in the prophylactic management of infections in this condition. PMID:23613624

  3. Expression of BAFF and BR3 in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Duan, J H; Jiang, Y; Mu, H; Tang, Z Q

    2016-03-01

    The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF) and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE). Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3) on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (PBAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (PBAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment.

  4. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2017-12-01

    Full Text Available Paeoniflorin-6′-O-benzene sulfonate (code: CP-25 was the chemistry structural modifications of Paeoniflorin (Pae. CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF or Tumor necrosis factor alpha (TNF-alpha. CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19+ B cells, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+ B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  5. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents.

    Science.gov (United States)

    Zhang, Feng; Shu, Jin-Ling; Li, Ying; Wu, Yu-Jing; Zhang, Xian-Zheng; Han, Le; Tang, Xiao-Yu; Wang, Chen; Wang, Qing-Tong; Chen, Jing-Yu; Chang, Yan; Wu, Hua-Xun; Zhang, Ling-Ling; Wei, Wei

    2017-01-01

    Paeoniflorin-6'- O -benzene sulfonate (code: CP-25) was the chemistry structural modifications of Paeoniflorin (Pae). CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF) or Tumor necrosis factor alpha (TNF-alpha). CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19 + B cells, CD19 + CD20 + B cells, CD19 + CD27 + B cells and CD19 + CD20 + CD27 + B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  6. Splenic function after angioembolization for splenic trauma in children and adults: A systematic review

    NARCIS (Netherlands)

    Schimmer, J. A. G.; van der Steeg, A. F. W.; Zuidema, W. P.

    2016-01-01

    Splenic artery embolization (SAE), proximal or distal, is becoming the standard of care for traumatic splenic injury. Theoretically the immunological function of the spleen may be preserved, but this has not yet been proven. A parameter for measuring the remaining splenic function must therefore be

  7. Escherichia coli clearance after splenic autotransplants

    International Nuclear Information System (INIS)

    Marques, R.G.; Petroianu, A.; Oliveira, M.B.N.; Bernardo-Filho, M.; Portela, M.C.

    2002-01-01

    Background: Splenic autotransplantation seems to be the only alternative for preservation of splenic tissue, after total splenectomy. The present study was carried out to analyze Escherichia coli depuration by mononuclear phagocyte system organs after total splenectomy and splenic autotransplantation. Methods: We utilized an experimental model including young and adult Wistar rats, of both sexes, submitted to total splenectomy and splenic autotransplantation. The evaluation method was intravenous inoculation of a suspension of Escherichia coli labeled with technetium-99m. We analyzed bacteria uptake by mononuclear phagocyte system organs and bacteria remnant in the bloodstream. Results: There was no difference between young and adult animals in bacteria uptake by mononuclear phagocyte system organs. In the comparison of groups, it was found out that the mean percent uptake by spleen and liver of animals in the control group was higher than that observed for animals with splenic implants. However, bacteria uptake in the lung was higher in the splenic implant group than in the control group. Although spleen bacteria uptake in the control group animals has been higher than that of animals in the splenic implant group, the remnant bacteria in the bloodstream was similar. Animals submitted to isolated total splenectomy showed higher bacteria remnant in the bloodstream than animals of the control group or the group submitted to total splenectomy combined with splenic autotransplantation. Conclusion: Our results indicate that autogenous splenic implant is efficacious in bacteria depuration in rats, by means of their macrophages phagocytosis. In addition, it does not modify bacteria removal function of liver and lung

  8. Deletion of muscarinic type 1 acetylcholine receptors alters splenic lymphocyte functions and splenic noradrenaline concentration.

    Science.gov (United States)

    Hainke, Susanne; Wildmann, Johannes; Del Rey, Adriana

    2015-11-01

    The existence of interactions between the immune and the sympathetic nervous systems is well established. Noradrenaline can promote or inhibit the immune response, and conversely, the immune response itself can affect noradrenaline concentration in lymphoid organs, such as the spleen. It is also well known that acetylcholine released by pre-ganglionic neurons can modulate noradrenaline release by the postsynaptic neuron. The spleen does not receive cholinergic innervation, but it has been reported that lymphocytes themselves can produce acetylcholine, and express acetylcholine receptors and acetylcholinesterase. We found that the spleen of not overtly immunized mice in which muscarinic type 1 acetylcholine receptors have been knocked out (M1KO) has higher noradrenaline concentrations than that of the wildtype mice, without comparable alterations in the heart, in parallel to a decreased number of IgG-producing B cells. Splenic lymphocytes from M1KO mice displayed increased in vitro-induced cytotoxicity, and this was observed only when CD4(+) T cells were present. In contrast, heterozygous acetylcholinesterase (AChE+/-) mice, had no alterations in splenic noradrenaline concentration, but the in vitro proliferation of AChE+/- CD4(+) T cells was increased. It is theoretically conceivable that reciprocal effects between neuronally and non-neuronally derived acetylcholine and noradrenaline might contribute to the results reported. Our results emphasize the need to consider the balance between the effects of these mediators for the final immunoregulatory outcome. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Role of BAFF in pediatric patients with allergic rhinitis during sublingual immunotherapy.

    Science.gov (United States)

    Luo, Renzhong; Liu, Wenlong; Wang, Jie; Chen, Yanqiu; Sun, Changzhi; Zhou, Lifeng; Li, Yan; Deng, Li

    2014-08-01

    Sublingual immunotherapy (SLIT) is the only therapeutic option for allergic rhinitis (AR) that modifies the immunological process to an allergen, rather than treating symptoms simply. However, its regulatory mechanisms are largely unknown. B-cell-activating factor of the TNF family (BAFF) plays very important roles in the development, differentiation, and proliferation of B cells and T cells. The aim of this study was to identify the role of BAFF during SLIT in pediatric patients with AR. Seventy-two house dust mite (HDM)-sensitized pediatric patients with AR were enrolled in this study. Thirty-six pediatric patients received HDM allergen extract for SLIT and 36 pediatric patients received placebo. Serum and nasal aspirate of different time points during treatment was collected and used for enzyme-linked immunosorbent assay (ELISA) of BAFF and related cytokines, respectively. Peripheral blood mononuclear cells were collected and stimulated by HDM allergen with or without rhBAFF after 12 months of treatment. Our results showed that the expression of BAFF protein decreased during the SLIT treatment compared with that in the placebo group after 6 months of therapy, and this trend lasted for 12 months. The decreased BAFF expression was positively related to Th2 cytokines and increased IL-10 expression. BAFF was also related to local production of IgA. In vitro experiments showed that BAFF can promote Th2 cytokines and inhibit IL-10 expression by PBMCs. During SLIT, BAFF expression was decreased and related to low Th2 cytokine expression and enhanced IL-10 expression. Besides, BAFF may contribute to local production of IgA. Our results suggested that BAFF may be an important biomarker during SLIT. Authors' summary. Sublingual immunotherapy (SLIT) is the only therapeutic option for allergic rhinitis (AR) that modifies the immunological process to an allergen, rather than simply treating symptoms. However, its regulatory mechanisms are largely unknown. B

  10. Serum B cell-activating factor (BAFF) level in connective tissue disease associated interstitial lung disease.

    Science.gov (United States)

    Hamada, Tsutomu; Samukawa, Takuya; Kumamoto, Tomohiro; Hatanaka, Kazuhito; Tsukuya, Go; Yamamoto, Masuki; Machida, Kentaro; Watanabe, Masaki; Mizuno, Keiko; Higashimoto, Ikkou; Inoue, Yoshikazu; Inoue, Hiromasa

    2015-09-30

    Interstitial lung diseases (ILDs) are common in patients with connective tissue diseases (CTDs). Although the diagnosis of an underlying CTD in ILD (CTD-ILD) affects both prognosis and treatment, it is sometimes difficult to distinguish CTD-ILD from chronic fibrosing interstitial pneumonia (CFIP). B cell-activating factor belonging to the tumour necrosis factor family (BAFF) plays a crucial role in B cell development, survival, and antibody production. We examined serum levels of BAFF, surfactant protein D (SP-D), and Krebs von den Lungen-6 (KL-6) in 33 patients with CTD-ILD, 16 patients with undifferentiated CTD-ILD, 19 patients with CFIP, and 26 healthy volunteers. And we analysed the relationship between serum BAFF levels and pulmonary function, as well as the expression of BAFF in the lung tissue of patients with CTD-ILD. Serum levels of BAFF were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. However, there were no significant differences in serum levels of SP-D and KL-6. Furthermore, serum BAFF levels in CTD-ILD patients were inversely correlated with pulmonary function. BAFF was strongly expressed in the lungs of CTD-ILD patients, but weakly in normal lungs. This is the first study to demonstrate that serum BAFF levels were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. Furthermore, serum BAFF levels were correlated with pulmonary function. We consider that serum BAFF levels in patients with CTD-ILD reflect the presence of ILDs disease activity and severity. These finding suggest that BAFF may be a useful marker for distinguishing CTD-ILD from CFIP.

  11. Targeting the splicing of mRNA in autoimmune diseases: BAFF inhibition in Sjögren's syndrome as a proof of concept

    NARCIS (Netherlands)

    Roescher, N.; Vosters, J. L.; Alsaleh, G.; Dreyfus, P.; Jacques, S.; Chiocchia, G.; Sibilia, J.; Tak, P. P.; Chiorini, J. A.; Mariette, X.; Gottenberg, Jacques-Eric

    2014-01-01

    BAFF (B-cell-activating factor of the tumor necrosis factor family), a pivotal cytokine for B-cell activation, is overexpressed by salivary gland (SG) epithelial cells in primary Sjogren's syndrome (pSS). ΔBAFF, a physiological inhibitor of BAFF, is a minor alternative splice variant of BAFF. A U7

  12. The strength of the antibody response to the nematode Ascaris lumbricoides inversely correlates with levels of B-Cell Activating Factor (BAFF)

    OpenAIRE

    Bornacelly, Adriana; Mercado, Dilia; Acevedo, Nathalie; Caraballo, Luis

    2014-01-01

    Background B-Cell Activating Factor (BAFF) is a cytokine regulating antibody production. Polymorphisms in the gene encoding BAFF were associated with the antibody response to Ascaris but not to mite allergens. In the present study we evaluated the relationship between BAFF and specific antibodies against Ascaris and mites in 448 controls and 448 asthmatics. Soluble BAFF was measured by ELISA and BAFF mRNA by qPCR. Surface expression of BAFF and its receptor (BAFF-R) was analyzed by flow cytom...

  13. Splenic Tuberculosis Presenting as Ascites in Immunocompetant ...

    African Journals Online (AJOL)

    Tuberculosis can involve any part of the gastrointestinal tract from mouth to anus, the peritoneum and the pancreatobiliary system. Here we report a case of splenic tuberculosis in a 60-year-old man who presented with ascitis. Splenic tuberculosis is an unusual clinical presentation, especially in immunocompetent patients.

  14. Splenic abscess due to Salmonella enteritidis

    Directory of Open Access Journals (Sweden)

    Hatice Çabadak

    2012-02-01

    Full Text Available Splenic abscess is a very rare complication of non-typhoidal Salmonella infections. We report a case of splenic abscess caused by Salmonella enteritidis. The patient is a 63-year-old woman with diabetes mellitus and underwent splenectomy. This case suggests that the patients with comorbities are at increased risk for invasive infections in non-typhoidal Salmonella infections.

  15. Splenic irradiation in HIV-related thrombocytopenia

    International Nuclear Information System (INIS)

    Leung, J.T.; Kuan, R.

    1996-01-01

    Splenic irradiation has been used in patients with HIV-related thrombocytopenia. This retrospective review deals with four patients treated with low dose splenic irradiation. All patients had an increase in platelet count and tolerated the treatment without side effects. However, the treatment response lasted for several months only. 9 refs., 1 tab

  16. Molecular characterization and evolutionary analysis of horse BAFF-R, a tumor necrosis factor receptor related to B-cell survival.

    Science.gov (United States)

    Wu, Haitao; Chen, Shanshan; Liu, Meng; Xu, Xingzhou; Ji, Xuemei; Gao, Kai; Tian, Aiying; Ke, Zhen; Zhang, Jianrong; Zhao, Bo; Zhang, Shuangquan

    2014-01-01

    B-cell survival depends on signals induced by B-cell activating factor (BAFF) that binds to the BAFF receptor (BAFF-R). Herein, a BAFF-R homolog was identified in a horse (Equus caballus). The horse BAFF-R gene, located on chromosome 28, spans 1444 base pairs and encodes a 183-amino acid protein. The protein is structurally conserved, in which the DxL motif plays an important role in binding to BAFF. Furthermore, the horse BAFF-R extracellular domain was expressed and purified, which specifically bound to His6-sBAFF and had the capability of blocking the function of His6-sBAFF in vitro. Finally, evolutionary analyses indicated that some codon sites of BAFF-R evolve with positive selection and that the genetic relationship among a horse, Chiroptera, and Caniformia are the closest. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. B cell-independent contribution of BAFF to murine autoimmune disease.

    Science.gov (United States)

    Stohl, William; Banfalvi, Agnes

    2016-11-01

    BAFF blockade is efficacious in murine and human SLE. Whereas the attendant reduction in B cells contributes to the efficacy, it remains unresolved whether a B cell-independent component also contributes. Since accurate assessment of a B cell-independent component can only be made in a B cell-independent autoimmune disease, we investigated MOG 35-55 -induced EAE in C57BL/6 mice. Neither pharmacologic neutralization nor genetic elimination of BAFF affected disease, nor did elimination of APRIL (with or without elimination of BAFF) or constitutive over-expression of BAFF. Eliminating BAFF had no effect on disease even in mice that were genetically manipulated to maintain greater-than-normal numbers of B cells. However, elimination of BAFF in B cell-deficient mice dramatically reduced disease, thereby unmasking a B cell-independent contribution of BAFF to an autoimmune disease. Our findings raise the plausibility that BAFF contributes to SLE not only through effects on B cells but through B cell-independent pathways as well. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Significance of BAFF/APRIL Expression and Their Receptors in Pediatric Patients With Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Sun, Baolan; Li, Lin; Xu, Meiyu; Wang, Xudong; Wang, Feng; Ni, Hongbing

    2016-04-01

    In this study, we investigated the mRNA expression and protein levels of B-cell activating factor (BAFF)/a proliferation-inducing ligand (APRIL) and their receptors in acute lymphoblastic leukemia (ALL) cell lines and pediatric patients with ALL using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. The location and level of the BAFF/APRIL proteins in ALL cell lines were also detected by immunofluorescence cytochemistry and flow cytometry. Correlations between plasma protein levels of BAFF/APRIL and primary clinical parameters were analyzed. We found that BAFF/APRIL was highly expressed in pediatric ALL patients and ALL cell lines. The BAFF/APRIL proteins were located on the cell membrane, and the proportion of positive cells and mean fluorescence intensity were significantly higher than in the healthy control group (PBAFF/APRIL and their receptors in untreated ALL children were significantly higher than in healthy controls (PBAFF/APRIL were positively correlated with the white blood cell count, lactate dehydrogenase, and serum ferritin. Abnormal levels of BAFF/APRIL in pediatric ALL suggest that BAFF/APRIL are associated with the development and progression of ALL in children and may provide information for the development of BAFF-based and APRIL-based targeted therapies.

  19. Potential role of serum BAFF as a biomarker in HIV infection.

    Science.gov (United States)

    Carbone, Javier; Calahorra, Leticia; Navarro, Joaquin; Sarmiento, Elizabeth

    2015-04-01

    We evaluated the potential role of serum B-cell activating factor (BAFF) as a biomarker in HIV infection and analyzed the relationship between BAFF concentration and the immunophenotypic activation status of T-cells. We tested the hypothesis that higher serum BAFF concentrations are associated with risk for development of AIDS in HIV positive individuals. Forty-one HIV patients (CDC category A 17, category B 24) were evaluated retrospectively. Serum BAFF concentrations were assessed using a commercial enzyme-linked immunosorbent assay. Cox regression was used to estimate the probability for development of AIDS. Patients with higher BAFF concentrations (> 2100 pg/mL) were at greater risk of developing AIDS (relative hazard 5.69; p = 0.0033). BAFF levels were independently associated with risk of AIDS after adjustment by clinical risk factors. Serum BAFF was correlated with activated T-cell subsets and with neopterin levels. BAFF is a good candidate for further evaluation as a nonspecific surrogate marker in HIV infection.

  20. IFN type I and II induce BAFF secretion from human decidual stromal cells.

    Science.gov (United States)

    Lundell, Anna-Carin; Nordström, Inger; Andersson, Kerstin; Lundqvist, Christina; Telemo, Esbjörn; Nava, Silvia; Kaipe, Helen; Rudin, Anna

    2017-01-06

    B cell activating factor (BAFF) is a critical cytokine for maturation of immature B cells. In murine lymph nodes, BAFF is mainly produced by podoplanin-expressing stromal cells. We have previously shown that circulating BAFF levels are maximal at birth, and that farmers' children exhibit higher BAFF levels in cord blood than non-farmers' children. Here, we sought to investigate whether maternal-derived decidual stromal cells from placenta secrete BAFF and examine what factors could stimulate this production. We found that podoplanin is expressed in decidua basalis and in the underlying villous tissue as well as on isolated maternal-derived decidual stromal cells. Decidual stromal cells produced BAFF when stimulated with IFN-γ and IFN-α, and NK cells and NK-T-like cells competent of IFN-γ production were isolated from the decidua. Finally, B cells at different maturational stages are present in decidua and all expressed BAFF-R, while stromal cells did not. These findings suggest that decidual stromal cells are a cellular source of BAFF for B cells present in decidua during pregnancy.

  1. Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice

    NARCIS (Netherlands)

    Morissette, Mathieu C; Gao, Yang; Shen, Pamela; Thayaparan, Danya; Bérubé, Jean-Christophe; Paré, Peter D; Brandsma, Corry-Anke; Hao, Ke; Bossé, Yohan; Ettinger, Rachel; Herbst, Ronald; Humbles, Alison A; Kolbeck, Roland; Zhong, Nanshan; Chen, Rongchang; Stämpfli, Martin R

    2016-01-01

    Emerging evidence suggests that autoimmune processes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and

  2. Embolization Therapy for Traumatic Splenic Lacerations

    Energy Technology Data Exchange (ETDEWEB)

    Dasgupta, Niloy; Matsumoto, Alan H., E-mail: ahm4d@virginia.edu; Arslan, Bulent; Turba, Ulku C.; Sabri, Saher; Angle, John F. [University of Virginia Health System, Division of Vascular and Interventional Radiology, Department of Radiology (United States)

    2012-08-15

    Purpose: This study was designed to evaluate the clinical success, complications, and transfusion requirements based on the location of and agents used for splenic artery embolization in patients with splenic trauma. Methods: A retrospective study was performed of patients with splenic trauma who underwent angiography and embolization from September 2000 to January 2010 at a level I trauma center. Electronic medical records were reviewed for demographics, imaging data, technical aspects of the procedure, and clinical outcomes. Results: Fifty patients were identified (34 men and 16 women), with an average age of 48 (range, 16-80) years. Extravasation was seen on initial angiography in 27 (54%) and was absent in 23 (46%). All 27 patients with extravasation were embolized, and 18 of 23 (78.2%) without extravasation were embolized empirically. Primary clinical success was similar (>75%) across all embolization locations, embolic agents, and grades of laceration treated. Of 45 patients treated, 9 patients (20%) were embolized in the main splenic artery, 34 (75.6%) in the splenic hilum, and 2 (4.4%) were embolized in both locations. Partial splenic infarctions developed in 47.3% treated in the splenic hilum compared with 12.5% treated in the main splenic artery. There were four (8.9%) mortalities: two occurred in patients with multiple critical injuries and two from nonbleeding etiologies. Conclusions: Embolization of traumatic splenic artery injuries is safe and effective, regardless of the location of treatment. Embolization in splenic hilar branches may have a higher incidence of infarction. The grade of laceration and agents used for embolotherapy did not impact the outcomes.

  3. Proximal Versus Distal Splenic Artery Embolisation for Blunt Splenic Trauma: What is the Impact on Splenic Immune Function?

    International Nuclear Information System (INIS)

    Foley, P. T.; Kavnoudias, H.; Cameron, P. U.; Czarnecki, C.; Paul, E.; Lyon, S. M.

    2015-01-01

    PurposeTo compare the impact of proximal or distal splenic artery embolisation versus that of splenectomy on splenic immune function as measured by IgM memory B cell levels.Materials and MethodsPatients with splenic trauma who were treated by splenic artery embolisation (SAE) were enrolled. After 6 months splenic volume was assessed by CT, and IgM memory B cells in peripheral blood were measured and compared to a local normal reference population and to a post-splenectomy population.ResultsOf the 71 patients who underwent embolisation, 38 underwent proximal embolisation, 11 underwent distal embolisation, 22 patients were excluded, 1 had both proximal and distal embolisation, 5 did not survive and 16 did not return for evaluation. There was a significant difference between splenectomy and proximal or distal embolisation and a trend towards greater preservation of IgM memory B cell number in those with distal embolisation—a difference that could not be attributed to differences in age, grade of injury or residual splenic volume.ConclusionIgM memory B cell levels are significantly higher in those treated with SAE compared to splenectomy. Our data provide evidence that splenic embolisation should reduce immunological complications of spleen trauma and suggest that distal embolisation may maintain better function

  4. Proximal Versus Distal Splenic Artery Embolisation for Blunt Splenic Trauma: What is the Impact on Splenic Immune Function?

    Energy Technology Data Exchange (ETDEWEB)

    Foley, P. T., E-mail: pfoley@doctors.org.uk [The Canberra Hospital, Department of Medical Imaging (Australia); Kavnoudias, H., E-mail: h.kavnoudias@alfred.org.au [The Alfred Hospital, Radiology Research Unit, Radiology Department (Australia); Cameron, P. U., E-mail: paul.cameron@unimelb.edu.au [The Alfred Hospital, Infectious Diseases Unit (Australia); Czarnecki, C., E-mail: caroline.czarnecki@gmail.com [Royal Melbourne Hospital, Radiology Department (Australia); Paul, E., E-mail: eldho.paul@monash.edu [Monash University, Department of Epidemiology & Preventive Medicine, School of Public Health and Preventive Medicine, Alfred Hospital (Australia); Lyon, S. M., E-mail: lyonsey@optusnet.com.au [Melbourne Endovascular (Australia)

    2015-10-15

    PurposeTo compare the impact of proximal or distal splenic artery embolisation versus that of splenectomy on splenic immune function as measured by IgM memory B cell levels.Materials and MethodsPatients with splenic trauma who were treated by splenic artery embolisation (SAE) were enrolled. After 6 months splenic volume was assessed by CT, and IgM memory B cells in peripheral blood were measured and compared to a local normal reference population and to a post-splenectomy population.ResultsOf the 71 patients who underwent embolisation, 38 underwent proximal embolisation, 11 underwent distal embolisation, 22 patients were excluded, 1 had both proximal and distal embolisation, 5 did not survive and 16 did not return for evaluation. There was a significant difference between splenectomy and proximal or distal embolisation and a trend towards greater preservation of IgM memory B cell number in those with distal embolisation—a difference that could not be attributed to differences in age, grade of injury or residual splenic volume.ConclusionIgM memory B cell levels are significantly higher in those treated with SAE compared to splenectomy. Our data provide evidence that splenic embolisation should reduce immunological complications of spleen trauma and suggest that distal embolisation may maintain better function.

  5. Determinants of splenectomy in splenic injuries following blunt ...

    African Journals Online (AJOL)

    Introduction. The management of splenic injuries has shifted from splenectomy to splenic preservation owing to the risk of overwhelming post-splenectomy infection (OPSI). This study aimed to identify the factors that determine splenectomy in patients with isolated splenic injuries, with a view to increasing the rate of splenic ...

  6. Splenic tuberculosis. Report of twelve cases

    International Nuclear Information System (INIS)

    Adil, A.; Chikhaoui, N.; Ousehal, A.; Kadiri, R.

    1995-01-01

    Tuberculosis of the spleen is not exceptional. The authors report ten cases which occurred with a predominance in young male adults. All patients had at least one other site of tuberculosis without any HIV infection. All patients had focal splenic lesions in the form of scattered hypo-echogenic and hypodense nodules. These nodules had a pseudo-tumor appearance in one case. CT-guided puncture was performed in one case. Splenic tuberculosis is not as rare as is sometimes thought. The CT-guided splenic puncture is now performed routinely and remains the ideal diagnostic approach. (authors). 9 refs., 5 figs

  7. Splenic injuries in athletes: a review.

    Science.gov (United States)

    Gannon, Elizabeth H; Howard, Thomas

    2010-01-01

    Splenic injuries can be challenging to the sports medicine physician. While these injuries are not common among athletes, they can have serious, potentially fatal consequences if not properly diagnosed and managed in a prompt and timely fashion. Currently, there are no evidence-based guidelines on returning athletes to previous levels of activity after sustaining a splenic injury. In addition, there is no consensus on follow-up imaging after injury. This article discusses the evaluation of athletes with blunt abdominal trauma for splenic injury, including the imaging, management, and current return-to-play guidelines.

  8. Characteristics of BAFF and APRIL factor expression in multiple myeloma and clinical significance.

    Science.gov (United States)

    Pan, Jing; Sun, Yuanyuan; Zhang, Ning; Li, Jianming; Ta, Fangxin; Wei, Wei; Yu, Shanshan; Ai, Limei

    2017-09-01

    The characteristics of the proliferation of B-cell activating factor (BAFF) and the proliferation-inducing ligand (APRIL) mRNA expression in mononuclear cell in multiple myeloma patients were detected, and the correlation was analyzed between the BAFF and APRIL concentrations in plasma and tumor burden parameters of multiple myeloma. Bone marrow samples from 60 patients with multiple myeloma and 20 healthy persons taken as controls, were collected. Bone marrow mononuclear cells (BMMCs) were harvested, and plasma was extracted. BAFF and APRIL mRNA expression was quantified using real-time fluorescent quantitative PCR in the BMMCs. ELISA was used to detect the characteristics of gene and protein expression of BAFF and APRIL in KM3 cell line. The BAFF and APRIL mRNA expression in initial treatment group, remission group and non-remission group were markedly higher than that in control group (PBAFF concentration in multiple myeloma (P=0.0027). In conclusion, for the gene and protein expression of BAFF and APRIL in patients with multiple myeloma, the initial treatment group and non-remission are higher than control and remission group. The higher the stage was, the more the factors were expressed. Characteristics of expression of BAFF and APRIL may be used as a new index to evaluate the prognosis of multiple myeloma.

  9. Chicoric acid suppresses BAFF expression in B lymphocytes by inhibiting NF-κB activity.

    Science.gov (United States)

    Chen, Lingxi; Huang, Gang; Gao, Min; Shen, Xiaodong; Gong, Wei; Xu, Zhizhen; Zeng, Yijun; He, Fengtian

    2017-03-01

    B cell activating factor belonging to the TNF family (BAFF) plays a critical role in the pathogenesis of autoimmune diseases. The inhibition of BAFF expression is an emerging therapeutic approach for these disorders. Chicoric acid (CA), a bioactive phytochemical found in several widely used traditional medicinal plants, has significant anti-inflammatory activity and anti-arthritic effects. However, the role of CA in modulation of BAFF expression remains unknown. In this study, we demonstrated that CA reduced BAFF expression in human B lymphocyte cell lines and decreased the DNA-binding activity of nuclear factor-κB (NF-κB) in the BAFF promoter region. Furthermore, CA inhibited both the nuclear translocation of p65 (the subunit of NF-κB) and the phosphorylation of IκBα (inhibitor of NF-κB). These results suggest that CA suppresses BAFF expression by inhibiting NF-κB activity, and CA may serve as a novel therapeutic agent to down-regulate excessive BAFF expression in autoimmune diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Inhibition of B cell activating factor (BAFF) in the management of systemic lupus erythematosus (SLE).

    Science.gov (United States)

    Stohl, William

    2017-06-01

    The anti-BAFF monoclonal antibody, belimumab, was approved 5+ years ago by the US Food and Drug Administration for the treatment of adult SLE patients. Although BAFF is now a proven therapeutic target in SLE, the limited clinical efficacy both in the clinical trials setting and in 'real-life' experience begs for further therapeutic improvement. Areas covered: In addition to belimumab, three other BAFF antagonists (atacicept, blisibimod, tabalumab) that biologically differ from belimumab are being or have been evaluated in SLE late-stage clinical trials. Literature search was performed using the search words/phrases, 'BAFF', 'BLyS', 'APRIL', 'BCMA', 'TACI', 'BR3', 'belimumab', 'atacicept', 'blisibimod', 'tabalumab', 'lupus clinical trial' along with papers from the author's personal library. Expert commentary: The reasons underlying current lack of enthusiasm among clinicians for BAFF antagonism are discussed, and speculation if offered regarding the use of a BAFF antagonist as part of sequential therapy and regarding the utility of individual or pairs of BAFF receptors as therapeutic targets.

  11. [Laparoscopic cleavage in splenic symptomatic cyst].

    Science.gov (United States)

    Fernández-López, Antonio-José; Candel-Arenas, Marifé; González-Valverde, Francisco-Miguel; Luján-Martínez, Delia; Medina-Manuel, Esther; Albarracín Marín-Blázquez, Antonio

    2017-12-01

    Splenic cysts are rare diseases that are diagnosed incidentally during imaging studies. When cysts are recognized, surgical treatment is recommended adapted to the particular case, depending on the size and location of the cyst and the age of the patient in order to avoid dangerous complications such as spleen rupture or cyst infection with abscess. We report 2patients with symptomatic splenic epidermoid cyst treated by laparoscopic cleavage. Laparoscopic cleavage is a surgical option for splenic cyst, with the goal of reducing postoperative complications while preserving splenic function. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  12. The strength of the antibody response to the nematode Ascaris lumbricoides inversely correlates with levels of B-Cell Activating Factor (BAFF).

    Science.gov (United States)

    Bornacelly, Adriana; Mercado, Dilia; Acevedo, Nathalie; Caraballo, Luis

    2014-06-07

    B-Cell Activating Factor (BAFF) is a cytokine regulating antibody production. Polymorphisms in the gene encoding BAFF were associated with the antibody response to Ascaris but not to mite allergens. In the present study we evaluated the relationship between BAFF and specific antibodies against Ascaris and mites in 448 controls and 448 asthmatics. Soluble BAFF was measured by ELISA and BAFF mRNA by qPCR. Surface expression of BAFF and its receptor (BAFF-R) was analyzed by flow cytometry. Individuals with specific IgE levels to Ascaris >75th percentile had lower levels of soluble BAFF; those with specific IgG levels to Ascaris >75th percentile had reduced BAFF mRNA. Total IgE and specific IgE to mites were not related to BAFF levels. There were no differences in soluble BAFF or mRNA levels between asthmatics and controls. There was an inverse relationship between the cell-surface expression of BAFF-R on CD19+ B cells and BAFF levels at the transcriptional and protein level. These findings suggest that differences in BAFF levels are related to the strength of the antibody response to Ascaris.

  13. The strength of the antibody response to the nematode Ascaris lumbricoides inversely correlates with levels of B-Cell Activating Factor (BAFF)

    Science.gov (United States)

    2014-01-01

    Background B-Cell Activating Factor (BAFF) is a cytokine regulating antibody production. Polymorphisms in the gene encoding BAFF were associated with the antibody response to Ascaris but not to mite allergens. In the present study we evaluated the relationship between BAFF and specific antibodies against Ascaris and mites in 448 controls and 448 asthmatics. Soluble BAFF was measured by ELISA and BAFF mRNA by qPCR. Surface expression of BAFF and its receptor (BAFF-R) was analyzed by flow cytometry. Results Individuals with specific IgE levels to Ascaris >75th percentile had lower levels of soluble BAFF; those with specific IgG levels to Ascaris >75th percentile had reduced BAFF mRNA. Total IgE and specific IgE to mites were not related to BAFF levels. There were no differences in soluble BAFF or mRNA levels between asthmatics and controls. There was an inverse relationship between the cell-surface expression of BAFF-R on CD19+ B cells and BAFF levels at the transcriptional and protein level. Conclusions These findings suggest that differences in BAFF levels are related to the strength of the antibody response to Ascaris. PMID:24906685

  14. Splenic abscess: successful non-surgical therapy.

    Science.gov (United States)

    Jolobe, O. M.; Melnick, S. C.

    1983-01-01

    A 57-year-old man with splenic abscess, demonstrated by isotope scanning, ultrasonography and computerized axial tomography (CAT scan) during the course of a septicaemic illness resulting from culture-positive bacterial endocarditis, was successfully treated with antibiotics alone, resolution of the abscess being confirmed by 2 further scans. This is the second case report of successful conservative treatment of splenic abscess. Images Fig. 1 Fig. 2 PMID:6634547

  15. Splenic irradiation in chronic myeloid leukemia

    International Nuclear Information System (INIS)

    Hukku, S.; Baboo, H.A.; Venkataratnam, S.; Vidyasagar, M.S.; Patel, N.L.

    1983-01-01

    Results of splenic irradiation as the initial and only method of treatment are reported in 25 patients with chronic myeloid leukemia. Peripheral remission was induced in all the patients. Induction was achieved after a short period of 11 to 30 days in the majority of the patients, the longest period being 40 days. Several patients were in remission 9 months after treatment. The results are compared with those obtained by chemotherapy. Some advantages of splenic irradiation over chemotherapy are emphasized. (Auth.)

  16. Transgenic overexpression of BAFF regulates the expression of immune-related genes in zebrafish, Danio rerio.

    Science.gov (United States)

    Zhang, Li; Liu, Chao; Zhou, Xin; Xie, Ying; Su, Libo; Geng, Qi; Liu, Binghui; Liu, Shufeng

    2016-12-01

    The B-cell activating factor (BAFF) is a member of tumour necrosis factor (TNF) superfamily that specifically regulates B lymphocyte proliferation and survival. Excess BAFF leads to overproduction of antibodies for secretion, anti-dsDNA antibodies and a lupus-like syndrome in mice. To investigate whether transgenic overexpression of the zebrafish BAFF leads to immunoglobulin changes and/or early maturing of the immune system, a Tol2-GFP-2A-BAFF/His recombinant plasmid was constructed by inserting a 2A peptide between the green fluorescent protein (GFP) and BAFF sequences. Functional GFP and BAFF proteins were expressed separately and confirmed in HeLa cells. The relative expression of immune-related genes (IgLC-1, IgLC-2, IgLC-3, IgD, IgM and IL-4), early lymphoid markers (Ikaros, Rag-1 and TCRAC), and the protooncogene Bcl-2 were evaluated by quantitative polymerase chain reaction (PCR) in F0 founder of transgenic zebrafish juveniles and adults. Ectopic expression of BAFF in adults was confirmed using Western blots and was shown to upregulate IgLC-1, IgLC-2, IgD, IgM, IgZ/T, Ikaros, Rag-1, TCRAC, IL-4 and Bcl-2 expression in juveniles on day 21 and IgLC-1, IgLC-2, IgD, IgM,IgZ/T, Rag-1, TCRAC and Bcl-2 expression in zebrafish three months postfertilization. The relative titers of specific IgM against Edwardsiella tarda WED were assessed using modified enzyme-linked immunosorbent assay (ELISA) with the whole body homogenate of zebrafish and demonstrated a significant increase in BAFF-transgenic group. Therefore, our findings provided novel insight into further exploration of modulating adaptive immunity and studying autoimmune diseases caused by regulating BAFF.

  17. Overexpression of the Cytokine BAFF and Autoimmunity Risk.

    Science.gov (United States)

    Steri, Maristella; Orrù, Valeria; Idda, M Laura; Pitzalis, Maristella; Pala, Mauro; Zara, Ilenia; Sidore, Carlo; Faà, Valeria; Floris, Matteo; Deiana, Manila; Asunis, Isadora; Porcu, Eleonora; Mulas, Antonella; Piras, Maria G; Lobina, Monia; Lai, Sandra; Marongiu, Mara; Serra, Valentina; Marongiu, Michele; Sole, Gabriella; Busonero, Fabio; Maschio, Andrea; Cusano, Roberto; Cuccuru, Gianmauro; Deidda, Francesca; Poddie, Fausto; Farina, Gabriele; Dei, Mariano; Virdis, Francesca; Olla, Stefania; Satta, Maria A; Pani, Mario; Delitala, Alessandro; Cocco, Eleonora; Frau, Jessica; Coghe, Giancarlo; Lorefice, Lorena; Fenu, Giuseppe; Ferrigno, Paola; Ban, Maria; Barizzone, Nadia; Leone, Maurizio; Guerini, Franca R; Piga, Matteo; Firinu, Davide; Kockum, Ingrid; Lima Bomfim, Izaura; Olsson, Tomas; Alfredsson, Lars; Suarez, Ana; Carreira, Patricia E; Castillo-Palma, Maria J; Marcus, Joseph H; Congia, Mauro; Angius, Andrea; Melis, Maurizio; Gonzalez, Antonio; Alarcón Riquelme, Marta E; da Silva, Berta M; Marchini, Maurizio; Danieli, Maria G; Del Giacco, Stefano; Mathieu, Alessandro; Pani, Antonello; Montgomery, Stephen B; Rosati, Giulio; Hillert, Jan; Sawcer, Stephen; D'Alfonso, Sandra; Todd, John A; Novembre, John; Abecasis, Gonçalo R; Whalen, Michael B; Marrosu, Maria G; Meloni, Alessandra; Sanna, Serena; Gorospe, Myriam; Schlessinger, David; Fiorillo, Edoardo; Zoledziewska, Magdalena; Cucca, Francesco

    2017-04-27

    Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).

  18. VAV1 and BAFF, via NFκB pathway, are genetic risk factors for myasthenia gravis

    DEFF Research Database (Denmark)

    Avidan, Nili; Le Panse, Rozen; Harbo, Hanne F

    2014-01-01

    confirmation loci were genotyped in 1177 EOMG patients and 814 controls, from nine European centres. RESULTS: ALLELE FREQUENCY DIFFERENCES WERE FOUND IN FOUR NOVEL LOCI: CD86, AKAP12, VAV1, B-cell activating factor (BAFF), and tumor necrosis factor-alpha (TNF-α), and these differences were consistent in all...... are novel and of interest as VAV1 is a key signal transducer essential for T- and B-cell activation, and BAFF is a cytokine that plays important roles in the proliferation and differentiation of B-cells. Moreover, we noted striking epistasis between the predisposing VAV1 and BAFF haplotypes; they conferred...

  19. BAFF/APRIL system in pediatric OMS: relation to severity, neuroinflammation, and immunotherapy.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; McGee, Nathan R; Travelstead, Anna L; Colliver, Jerry A; Ness, Jayne M; Ransohoff, Richard M

    2013-01-16

    B-cell dysregulation has been implicated but not fully characterized in pediatric opsoclonus-myoclonus syndrome (OMS), a neuroblastoma-associated neuroinflammatory disorder. To assess the role of B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), two critical B cell-modulating cytokines, as potential biomarkers of disease activity and treatment biomarkers in OMS. Soluble BAFF and APRIL were measured in cerebrospinal fluid (CSF) and serum by ELISA in 433 children (296 OMS, 109 controls, 28 other inflammatory neurological disorders (OIND)). BAFF-R receptors on circulating CD19+ B cells were measured by flow cytometry. A blinded scorer rated motor severity on the OMS Evaluation Scale. Immunotherapies were evaluated cross-sectionally and longitudinally. The mean CSF BAFF concentration, which was elevated in untreated OMS and OIND, correlated with OMS severity category (P = 0.006), and reduction by adrenocorticotropic hormone or corticotropin (ACTH) (-61%) or corticosteroids (-38%) was seen at each level of severity. In contrast, CSF APRIL was normal in OMS and OIND and unaffected by immunotherapy. When the entire OMS dataset was dichotomized into 'high' versus 'normal' CSF BAFF concentration, the phenotype of the high group included greater motor severity and number of CSF oligoclonal bands, and a higher concentration of inflammatory chemokines CXCL13 and CXCL10 in CSF and CXCL9 and CCL21 in serum. Serum APRIL was 6.7-fold higher in the intravenous immunoglobulins (IVIg) group, whereas serum BAFF was 2.6-fold higher in the rituximab group. The frequency of B cell BAFF-R expression was similar in untreated and treated OMS. Longitudinal studies of CSF BAFF revealed a significant decline in ACTH-treated patients (with or without rituximab) (P OMS displayed heterogeneity in CSF BAFF expression, which met many but not all criteria as a potential biomarker of disease activity. We speculate that CSF BAFF may have more utility in a biomarker panel

  20. Use of radionuclide techniques for assessment of splenic function and detection of splenic remnants

    International Nuclear Information System (INIS)

    Ganguly, S.; Sinha, S.; Sarkar, B.R.; Basu, S.; Ghosh, S.

    1998-01-01

    Full text: The spleen is often involved in hematological malignancies; it is also the site of RBC destruction in thalassemia and ITP. In latter cases, splenectomy is often performed and postoperatively, detection of functioning splenic remnants affect the prognosis adversely. In this study, we assessed the usefulness of radionuclide techniques in : a) assessment of splenic function in primarily non-splenic diseases (benign or malignant), and b) detection of splenic remnant after splenectomy. 12 patients of splenomegaly and 5 patients after splenectomy underwent splenic imaging; imaging was performed using both 99m Tc-sulphur colloid (with first pass) and 99m Tc labelled heat denatured RBCs as tracers. Thus splenic perfusion, morphology and RBC trapping functions were all assessed. The colloid images usually matched the RBC images except in 2 cases where photogenic areas (presumably infarcts) were visualized on RBC scans that were missed on colloid scans. Three of the post splenectomy cases revealed functioning splenic remnants, which was also better visualized on RBC scans. It is concluded that radionuclide imaging could be used regularly for assessing function of spleen, or detecting splenic remnants

  1. Spontaneous Splenic Rupture in Melanoma

    Directory of Open Access Journals (Sweden)

    Hadi Mirfazaelian

    2014-01-01

    Full Text Available Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.

  2. Antibodies That Block or Activate Mouse B Cell Activating Factor of the Tumor Necrosis Factor (TNF) Family (BAFF), Respectively, Induce B Cell Depletion or B Cell Hyperplasia*

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Schuepbach-Mallepell, Sonia; Vigolo, Michele; Willen, Laure; Tardivel, Aubry; Smulski, Cristian R.; Zheng, Timothy S.; Gommerman, Jennifer; Hess, Henry; Gottenberg, Jacques-Eric; Mackay, Fabienne; Donzé, Olivier

    2016-01-01

    B cell activating factor of the TNF family (BAFF), also known as B lymphocyte stimulator, is a ligand required for the generation and maintenance of B lymphocytes. In this study, the ability of different monoclonal antibodies to recognize, inhibit, or activate mouse BAFF was investigated. One of them, a mouse IgG1 named Sandy-2, prevented the binding of BAFF to all of its receptors, BAFF receptor, transmembrane activator and calcium modulating ligand interactor, and B cell maturation antigen, at a stoichiometric ratio; blocked the activity of mouse BAFF on a variety of cell-based reporter assays; and antagonized the prosurvival action of BAFF on primary mouse B cells in vitro. A single administration of Sandy-2 in mice induced B cell depletion within 2 weeks, down to levels close to those observed in BAFF-deficient mice. This depletion could then be maintained with a chronic treatment. Sandy-2 and a previously described rat IgG1 antibody, 5A8, also formed a pair suitable for the sensitive detection of endogenous circulating BAFF by ELISA or using a homogenous assay. Interestingly, 5A8 and Sandy-5 displayed activities opposite to that of Sandy-2 by stimulating recombinant BAFF in vitro and endogenous BAFF in vivo. These tools will prove useful for the detection and functional manipulation of endogenous mouse BAFF and provide an alternative to the widely used BAFF receptor-Fc decoy receptor for the specific depletion of BAFF in mice. PMID:27451394

  3. CsBAFF, a Teleost B Cell Activating Factor, Promotes Pathogen-Induced Innate Immunity and Vaccine-Induced Adaptive Immunity.

    Directory of Open Access Journals (Sweden)

    Yun Sun

    Full Text Available B cell activating factor (BAFF is a member of the tumor necrosis factor family that is known to play an important role in B cell activation, proliferation, and differentiation in mammals. However, studies of BAFF in teleosts are very limited and its function, in particular that under in vivo conditions, is essentially unknown. In this study, we conducted in vivo as well as in vitro functional analyses of a BAFF homologue (CsBAFF from the teleost fish tongue sole (Cynoglossus semilaevis. CsBAFF is composed of 261 residues and shares moderate sequence identities with known BAFFs of other teleosts. CsBAFF expression was most abundant in immune organs and was upregulated during bacterial infection. Purified recombinant CsBAFF (rCsBAFF bound to tongue sole lymphocytes and promoted cellular proliferation and survival. The results of an in vivo study showed that CsBAFF overexpression in tongue sole significantly enhanced macrophage activation and reduced bacterial infection in fish tissues, whereas knockdown of CsBAFF expression resulted in increased bacterial dissemination and colonization in fish tissues. Furthermore, vaccination studies showed that CsBAFF enhanced the immunoprotection of a DNA vaccine and augmented the production of specific serum antibodies. Taken together, these results provide the first in vivo evidence to indicate that teleost BAFF is an immunostimulator that significantly contributes to the innate antibacterial immune response and vaccine-induced adaptive immune response.

  4. Determinants of splenectomy in splenic injuries following blunt abdominal trauma.

    Science.gov (United States)

    Akinkuolie, A A; Lawal, O O; Arowolo, O A; Agbakwuru, E A; Adesunkanmi, A R K

    2010-02-01

    The management of splenic injuries has shifted from splenectomy to splenic preservation owing to the risk of overwhelming post-splenectomy infection (OPSI). This study aimed to identify the factors that determine splenectomy in patients with isolated splenic injuries, with a view to increasing the rate of splenic preservation. Files of 55 patients managed for isolated splenic injuries from blunt abdominal trauma between 1998 and 2007 were retrospectively analysed using a pro forma. Management options were classified into nonoperative, operative salvage and splenectomy. The majority of patients suffered splenic injury as a result of motor vehicle accident (MVA) trauma or falls. Splenectomy was undertaken in 33 (60%) patients, 12 (22%) had non-operative management, and operative salvage was achieved in 10 (18%) patients. Significant determinants of splenectomy were grade of splenic injury, hierarchy of the surgeon, and hierarchy of the assistant. MVA injury and falls accounted for the vast majority of blunt abdominal trauma in this study. The rate and magnitude of energy transferred versus splenic protective mechanisms at the time of blunt abdominal trauma seems to determine the grade of splenic injury. Interest in splenic salvage surgery, availability of technology that enables splenic salvage surgery, and the experience of the surgeon and assistant appear to determine the surgical management. Legislation on vehicle safety and good parental control may reduce the severity of splenic injury in blunt abdominal trauma. When surgery is indicated, salvage surgery should be considered in intermediate isolated splenic injury to reduce the incidence of OPSI.

  5. Involvement of BAFF and APRIL in Resistance to Apoptosis of Acute Myeloid Leukemia.

    Science.gov (United States)

    Bolkun, Lukasz; Grubczak, Kamil; Schneider, Gabriela; Zembko, Paula; Radzikowska, Urszula; Singh, Paulina; Kloczko, Janusz; Ratajczak, Mariusz Z; Moniuszko, Marcin; Eljaszewicz, Andrzej

    2016-01-01

    B-cell activation factor of the TNF family (BAFF), and a proliferation-inducing ligand (APRIL), two members of the tumour necrosis factor (TNF) superfamily, beyond playing a significant role in normal B-cell development, promote survival and proliferation of malignant B cells. Both ligands interact with 3 receptors: BAFF-R, specific to BAFF, and TACI and BCMA which are shared by both BAFF and APRIL. Here we wished to investigate the potential role of these proteins in resistance of acute myeloid leukaemia (AML) blasts to apoptosis. We found that the levels of both mRNA and proteins of APRIL, BAFF and their receptors were expressed in leukaemic cells of 24 newly diagnosed, untreated AML patients. We also demonstrated that patients who did not further respond to induction therapy (NR) presented with significantly higher baseline APRIL and BAFF expression on AML blasts as compared to these subjects who, after induction, achieved complete remission (CR) following induction therapy. Moreover, we observed striking differences in baseline levels of BCMA between CR and NR patients as we did not find detectable expression of this receptor in the latter group of patients. Interestingly, we found that AML blasts collected at baseline from NR patients cultured in presence of exogenous BAFF and APRIL were significantly more resistant to spontaneous or drug-induced apoptosis as compared with cells derived from CR patients. Altogether, our data confirm that BAFF and APRIL signaling play important role in AML pathogenesis and susceptibility to cytotoxic therapy while measuring of BCMA expression on AML cells can become a novel prognostic factor for chemotherapy response.

  6. Mice overexpressing BAFF develop a commensal flora–dependent, IgA-associated nephropathy

    Science.gov (United States)

    McCarthy, Douglas D.; Kujawa, Julie; Wilson, Cheryl; Papandile, Adrian; Poreci, Urjana; Porfilio, Elisa A.; Ward, Lesley; Lawson, Melissa A.E.; Macpherson, Andrew J.; McCoy, Kathy D.; Pei, York; Novak, Lea; Lee, Jeannette Y.; Julian, Bruce A.; Novak, Jan; Ranger, Ann; Gommerman, Jennifer L.; Browning, Jeffrey L.

    2011-01-01

    B cell activation factor of the TNF family (BAFF) is a potent B cell survival factor. BAFF overexpressing transgenic mice (BAFF-Tg mice) exhibit features of autoimmune disease, including B cell hyperplasia and hypergammaglobulinemia, and develop fatal nephritis with age. However, basal serum IgA levels are also elevated, suggesting that the pathology in these mice may be more complex than initially appreciated. Consistent with this, we demonstrate here that BAFF-Tg mice have mesangial deposits of IgA along with high circulating levels of polymeric IgA that is aberrantly glycosylated. Renal disease in BAFF-Tg mice was associated with IgA, because serum IgA was highly elevated in nephritic mice and BAFF-Tg mice with genetic deletion of IgA exhibited less renal pathology. The presence of commensal flora was essential for the elevated serum IgA phenotype, and, unexpectedly, commensal bacteria–reactive IgA antibodies were found in the blood. These data illustrate how excess B cell survival signaling perturbs the normal balance with the microbiota, leading to a breach in the normal mucosal-peripheral compartmentalization. Such breaches may predispose the nonmucosal system to certain immune diseases. Indeed, we found that a subset of patients with IgA nephropathy had elevated serum levels of a proliferation inducing ligand (APRIL), a cytokine related to BAFF. These parallels between BAFF-Tg mice and human IgA nephropathy may provide a new framework to explore connections between mucosal environments and renal pathology. PMID:21881212

  7. Autotransplantation for treatment of severe splenic lesions.

    Science.gov (United States)

    Resende, Vivian; Petroianu, Andy; Junior, Wilson C T

    2002-10-01

    The aim of the study was to evaluate clinical and laboratory variables in patients undergoing spleen autotransplantation. We studied 29 patients with severe trauma of the spleen and its pedicle. Of these, 20 underwent autotransplantation (group I) and 9 underwent total splenectomy without preservation of splenic tissue (group II). Twenty-two additional subjects with an intact spleen were used as controls (group III). Immediate and late postoperative complications were investigated. Laboratory counts were performed during the late postoperative period (red blood cells, hemoglobin, white blood cells, platelets, and Howell-Jolly bodies). To investigate the immunological profiles of patients we performed B- and T-lymphocyte counts and determined IgA, IgG, and IgM levels. All patients underwent splenic scintigraphy with technetium 99m sulfur colloid. Groups I and III did not present abnormal blood bodies, and their hematological and immunological patterns were normal. Group II showed increased numbers of Howell-Jolly bodies and low IgM levels. Splenic scintigraphy indicated the viability and filtering function of the splenic remnant in group I. Autotransplantation is a good option to maintain splenic function when total splenectomy is necessary.

  8. BAFF and APRIL expression as an autoimmune signature of membranous nephropathy.

    Science.gov (United States)

    Han, Seung Seok; Yang, Seung Hee; Jo, Hyung Ah; Oh, Yun Jung; Park, Minkyoung; Kim, Joo Young; Lee, Hajeong; Lee, Jung Pyo; Lee, Sang-Ho; Joo, Kwon Wook; Lim, Chun Soo; Kim, Yon Su; Kim, Dong Ki

    2018-01-09

    Based on the fact that B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have a regulatory role in B cell biology, excessive levels of these cytokines can promote autoimmune pathogenesis. However, the expression and implication remain unresolved in cases of membranous nephropathy (MN). The plasma BAFF levels of the primary MN patients were higher than those of healthy controls but lower than those of secondary MN patients, whereas the APRIL levels were similar between the MN patients and healthy controls. The BAFF levels were higher in relapse cases, whereas the APRIL levels were higher in the patients who did not experience remission compared with the counterpart patients. The ectopic expression of BAFF and APRIL was observed in the glomeruli or circulating B cells of MN patients, and this high expression trend was similar to that of lupus patients. Expression profile of BAFF and APRIL in MN is similar to that of other autoimmune disease, which affects the kidney outcomes. Plasma BAFF and APRIL levels were measured upon kidney biopsy in patients with primary ( n = 89) and secondary MN ( n = 13), and the results were compared with the levels in healthy controls ( n = 111). The kidney outcomes (e.g., remission and relapse) were traced for the median of 3 years. Aberrant expression of the cytokines was evaluated in the kidney and circulating B cells using immunohistochemistry and flow cytometry analyses, respectively.

  9. BAFF Expression is Modulated by Female Hormones in Human Immune Cells.

    Science.gov (United States)

    Drehmer, Manuela N; Suterio, Dalila G; Muniz, Yara C N; de Souza, Iliada R; Löfgren, Sara E

    2016-10-01

    Among several autoimmune diseases, one of the main risk factors is the female gender, and much consideration has been given to the involvement of female hormones in their etiology. B-cell activating factor (BAFF) is a key factor in survival and maturation of B cells and is overexpressed in several autoimmune patients although the mechanism behind this feature is unclear. In murine models, BAFF expression could be upregulated by exogenous estrogen treatment in splenocytes; however, no evidence of this relationship was available in humans. Here, leukocytes from healthy male and female individuals were collected and cultivated in the presence or absence of estrogen or progesterone. BAFF gene expression was accessed by quantitative PCR and compared between treated and untreated group of cells. In the presence of estrogen, BAFF expression was upregulated by more than 5 times in both genders. When exposed to progesterone, the female-originated cells showed increased expression, while the cells of male origin a significant downregulation of BAFF. Our results suggest that female hormones can modulate the expression of BAFF, a key cytokine in autoimmune pathways, in human immune cells. These data might contribute to the understanding of the etiology as well as the gender bias featured by several autoimmune disorders.

  10. VNAR single-domain antibodies specific for BAFF inhibit B cell development by molecular mimicry.

    Science.gov (United States)

    Häsler, Julien; Flajnik, Martin F; Williams, Gareth; Walsh, Frank S; Rutkowski, J Lynn

    2016-07-01

    B cell-activating factor (BAFF) plays a dominant role in the B cell homeostasis. However, excessive BAFF promotes the development of autoreactive B-cells and several antibodies have been developed to block its activity. Bispecific antibodies with added functionality represent the next wave of biologics that may be more effective in the treatment of complex autoimmune disease. The single variable domain from the immunoglobulin new antigen receptor (VNAR) is one of the smallest antibody recognition units that could be combined with monospecific antibodies to develop bispecific agents. We isolated a panel of BAFF-binding VNARs with low nM potency from a semi-synthetic phage display library and examined their functional activity. The anti-BAFF VNARs blocked the binding of BAFF to all three of its receptors (BR3, TACI and BCMA) and the presence of the conserved DXL receptor motif found in the CDR3 regions suggests molecular mimicry as the mechanism of antagonism. One clone was formatted as an Fc fusion for functional testing and it was found to inhibit both mouse and human BAFF with equal potency ex vivo in a splenocyte proliferation assay. In mice, subchronic administration reduced the number of immature and transitional intermediates B cells and mature B cell subsets. These results indicate that VNAR single domain antibodies function as selective B-cell inhibitors and offer an alternative molecular format for targeting B-cell disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Enriched environment and stress exposure influence splenic B lymphocyte composition.

    Science.gov (United States)

    Gurfein, Blake T; Hasdemir, Burcu; Milush, Jeffrey M; Touma, Chadi; Palme, Rupert; Nixon, Douglas F; Darcel, Nicholas; Hecht, Frederick M; Bhargava, Aditi

    2017-01-01

    Prolonged chronic stress has deleterious effects on immune function and is associated with numerous negative health outcomes. The spleen harbors one-fourth of the body's lymphocytes and mediates both innate and adaptive immune responses. However, the subset of splenic lymphocytes that respond, either adaptively or maladaptively, to various stressors remains largely unknown. Here we investigated the effects of unpredictable chronic mild stress (CMS) exposure on spleen composition in male mice housed in two different caging conditions: standard caging (Cntl) and enriched environment (EE). EE-caged mice exhibited the greatest absolute number of splenocytes and CMS exposure significantly lowered splenocyte numbers in both caging conditions. Glucocorticoid production, measured by mean fecal corticosterone metabolites (FCM), was significantly lower in EE-caged mice vs. Cntl-caged mice. Surprisingly, CMS exposure resulted in an increase in mean FCM in EE-caged mice, but no significant change in Cntl-caged mice. CMS altered the splenic B:T lymphocyte ratio; it reduced the frequency of B cells, but increased the frequency of T cells in EE-caged mice. Splenocyte number and B:T lymphocyte ratio showed a negative relationship with mean FCM. EE-caged mice had a lower frequency of immature and germinal B cells than Cntl-caged mice. CMS markedly increased the frequency of immature and marginal zone B cells, but decreased the frequency of follicular B cells in both caging conditions. Mean FCM correlated positively with frequency of immature, marginal zone and germinal center B cells, but negatively with frequency of follicular B cells. To conclude, splenic immune cells, particularly B lymphocyte composition, are modulated by caging environment and stress and may prime mice differently to respond to immune challenges.

  12. Serum BAFF levels, Methypredsinolone therapy, Epstein-Barr Virus and Mycobacterium avium subsp. paratuberculosis infection in Multiple Sclerosis patients.

    Science.gov (United States)

    Mameli, Giuseppe; Cocco, Eleonora; Frau, Jessica; Arru, Giannina; Caggiu, Elisa; Marrosu, Maria Giovanna; Sechi, Leonardo A

    2016-07-07

    Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease.

  13. Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseases.

    Science.gov (United States)

    Matsushita, Takashi; Hasegawa, Minoru; Matsushita, Yukiyo; Echigo, Takeshi; Wayaku, Takamasa; Horikawa, Mayuka; Ogawa, Fumihide; Takehara, Kazuhiko; Sato, Shinichi

    2007-02-01

    Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma.

  14. The value of MDCT in diagnosis of splenic artery aneurysms

    International Nuclear Information System (INIS)

    Sun Cong; Liu Cheng; Wang Ximing; Wang Daoping

    2008-01-01

    Objective: To evaluate the clinical value of multiple detector computed tomography (MDCT) in the diagnosis and planning the treatment of splenic aneurysms. Methods: Eight cases with splenic artery aneurysms (SAA) were retrospectively reviewed. Sixty four-slice spiral CT scans were performed. Intravenous contrast material was injected at 4 ml/s, and arterial and venous phase images were obtained. Subsequently, arterial phase images were analyzed and made for CT angiography. The diagnosis was made by using axial and reconstructive images. All of the patients were also performed Doppler color echocardiography. Results: All patients showed splenic artery and splenic artery aneurysms clearly with CT arterial phase images. Among them, six patients had splenic artery aneurysms, one had giant splenic artery aneurysms (GSAA) and one had splenic artery pseudoaneurysms. Ultrasound examination only diagnosed six of them. Conclusion: MDCT is a noninvasive and valuable method in diagnosis of splenic artery aneurysms and has high value in determination of treatment plan

  15. The value of MDCT in diagnosis of splenic artery aneurysms

    Energy Technology Data Exchange (ETDEWEB)

    Sun Cong [Shandong University, Shandong Provincial Medical Imaging Institute, Road jing-wu No. 324, Jinan, Shandong 250021 (China)], E-mail: suncong03@163.com; Liu Cheng; Wang Ximing; Wang Daoping [Shandong University, Shandong Provincial Medical Imaging Institute, Road jing-wu No. 324, Jinan, Shandong 250021 (China)

    2008-03-15

    Objective: To evaluate the clinical value of multiple detector computed tomography (MDCT) in the diagnosis and planning the treatment of splenic aneurysms. Methods: Eight cases with splenic artery aneurysms (SAA) were retrospectively reviewed. Sixty four-slice spiral CT scans were performed. Intravenous contrast material was injected at 4 ml/s, and arterial and venous phase images were obtained. Subsequently, arterial phase images were analyzed and made for CT angiography. The diagnosis was made by using axial and reconstructive images. All of the patients were also performed Doppler color echocardiography. Results: All patients showed splenic artery and splenic artery aneurysms clearly with CT arterial phase images. Among them, six patients had splenic artery aneurysms, one had giant splenic artery aneurysms (GSAA) and one had splenic artery pseudoaneurysms. Ultrasound examination only diagnosed six of them. Conclusion: MDCT is a noninvasive and valuable method in diagnosis of splenic artery aneurysms and has high value in determination of treatment plan.

  16. Changing treatment of pediatric splenic trauma

    International Nuclear Information System (INIS)

    Kakkasseril, J.S.; Stewart, D.; Cox, J.A.; Gelfand, M.

    1982-01-01

    A review of splenic injuries at Cincinnati Children's Hospital Medical Center from July 1978 to June 1980 revealed this form of injury in 29 patients. Treatment without surgery was successful in 21 patients. Seven patients required operation. One patient died shortly after admission of severe associated injuries. All patients admitted with blunt abdominal trauma were initially treated conservatively. If the clinical state improved, after transfusions if necessary, or remained stable and there were no objective signs of further blood loss, conservative therapy was continued. Liver-spleen scans were obtained on an urgent basis to confirm the diagnosis of splenic injury in patients who did not undergo surgery. No complications of treatment without surgery were recognized. The satisfactory outcome in these patients suggests that there is a place for treatment without surgery in some children with splenic injury

  17. The (re)generation of splenic tissue

    Science.gov (United States)

    Hovius, J W R; Verberne, H J; Bennink, R J; Blok, W L

    2010-01-01

    A 48-year-old man with a history of a traumatic splenic rupture followed by splenectomy at the age of 5 years was referred to the outpatient clinic with markedly elevated liver enzymes. He was diagnosed with alcoholic liver cirrhosis. Ultrasound of the upper abdomen revealed hepatomegaly and suggested a central mass in the liver. Subsequent MRI of the abdomen did not show a hepatic mass, but revealed multiple intraperitoneal and retroperitoneal ovoid structures with a maximum diameter of 3 cm. A peripheral blood smear did not reveal Howell-Jolly bodies suggesting intact splenic function. The diagnosis splenosis—that is, autotransplantation of splenic tissue after iatrogenic/traumatic rupture of the spleen—was considered and confirmed by SPECT-CT with technetium-99m (99mTc) labelled heat-denatured autologous red blood cells. PMID:22778202

  18. Hyperferritinemia in dogs with splenic hemangiosarcoma.

    Science.gov (United States)

    Chikazawa, Seishiro; Hori, Yasutomo; Hoshi, Fumio; Kanai, Kazutaka; Ito, Naoyuki; Higuchi, Seiichi

    2013-11-01

    Serum ferritin concentration increases in dogs in association with various diseases. In this study, we measured serum ferritin levels in dogs with splenic masses, using a sandwich ELISA assay. Eleven dogs with hemangiosarcoma (HSA), six with hematoma, 1 with hemangioma and 3 with lymphoma were enrolled. All dogs with HSA had serum ferritin concentrations above the normal limit (1,357 ng/ml, mean + 2× standard deviation of normal). Increased serum ferritin concentrations have also been observed in few cases of hematoma, hemangioma and lymphoma. Therefore, hyperferritinemia is not specific for splenic HSA, but may have clinical usefulness as a sensitive test for the disease. Further evaluation of serum ferritin concentrations in dogs with splenic HSA is needed.

  19. Splenic mass with remote trauma history: a management dilemma.

    LENUS (Irish Health Repository)

    McCarthy, C J

    2011-03-02

    BACKGROUND: Delayed presentation of splenic trauma is a well described entity. METHOD: We report two patients who presented with splenic abnormality found incidentally on imaging for other medical problems. A remote history of splenic trauma was elicited during clinical evaluation; 18 months in one patient and 11 years in the second patient. Both patients underwent surgical exploration. CONCLUSIONS: Radiological investigations could not reassure us that the splenic abnormalities were benign, and their management was the subject of some debate.

  20. Splenic mass with remote trauma history: a management dilemma.

    LENUS (Irish Health Repository)

    McCarthy, C J

    2012-02-01

    BACKGROUND: Delayed presentation of splenic trauma is a well described entity. METHOD: We report two patients who presented with splenic abnormality found incidentally on imaging for other medical problems. A remote history of splenic trauma was elicited during clinical evaluation; 18 months in one patient and 11 years in the second patient. Both patients underwent surgical exploration. CONCLUSIONS: Radiological investigations could not reassure us that the splenic abnormalities were benign, and their management was the subject of some debate.

  1. Determinants of splenectomy in splenic injuries following blunt ...

    African Journals Online (AJOL)

    Discussion. MVA injury and falls accounted for the vast majority of blunt abdominal trauma in this study. The rate and magnitude of energy transferred versus splenic protective mechanisms at the time of blunt abdominal trauma seems to determine the grade of splenic injury. Interest in splenic salvage surgery, availability of ...

  2. Complicated congenital splenic cyst: Saved by a splenunculus

    Directory of Open Access Journals (Sweden)

    Karia Nina

    2011-01-01

    Full Text Available A 12-year-old girl presented with a large congenital splenic cyst complicated by Salmonella organisms. After failure of conservative management and percutaneous drainage, a splenectomy was performed. An incidental splenunculus was preserved. On follow up the splenunculus had increased to normal splenic size and there was no evidence of Howell-Jolly bodies, suggesting normal splenic function.

  3. Drainage of Splenic Abscess: A Case Report | Kombo | Nigerian ...

    African Journals Online (AJOL)

    ... and was managed by tube drainage. His post operative recovery was uneventful. Conclusion: Tube drainage of the splenic abscess is encouraged if there is easy access to the abscess and there is evidence of residual splenic tissue in the critically ill patient. Key Word: Tube drainage, splenic abscess, splenectomy.

  4. Investigations of a rabbit (Oryctolagus cuniculus model of systemic lupus erythematosus (SLE, BAFF and its receptors.

    Directory of Open Access Journals (Sweden)

    Jiahui Yang

    2009-12-01

    Full Text Available B-cell activation factor belonging to the tumor necrosis factor family (BAFF is a major contributor to survival of B lymphocytes during development and maturation. A relationship between circulating BAFF levels and disease activity has been reported in patients with the autoimmune disease Systemic Lupus Erythematosus (SLE. Clinical trials targeting BAFF or its receptors are currently in progress. In order to further characterize a rabbit (Oryctolagus cuniculus model of SLE, we investigated the expression of BAFF and its receptors in non-inbred, pedigreed rabbits derived from breeding and selection based on autoantibody responses. We immunized rabbits related to previous groups that developed autoantibodies and inflammatory responses after immunizations with peptides synthesized on multiple antigen-branched polylysine backbones. Blood and sera collected before immunization and after boosts were used for health monitoring, analyses of serum autoantibody responses by ELISA and immunofluorescence. Peripheral blood mononuclear cells (PBMC were studied by flow cytometry and were the source of mRNA for quantitative PCR analyses. We hypothesized that BAFF mRNA expression and serum BAFF levels measured indirectly through BAFF receptor binding might increase in autoantibody-producing rabbits. Immunized rabbits developed elevated levels of leucocyte populations, anti-nuclear, anti-dsDNA and other autoantibodies. BR3 mRNA levels in total PBMC decreased and BAFF levels remained low and unchanged in most immunized rabbits. By flow cytometry, percentages of BAFF positive cells decreased. Percentages of transmembrane activator and CAML interactor (TACI decreased in most rabbits from all the immunized groups. The rabbit is an important model for human autoimmune and infectious diseases, and a high quality draft rabbit genome assembly was recently completed. Human disease models developed in non-inbred pedigreed animals are better able to reflect the complexities

  5. BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    2013-10-01

    Full Text Available Primary biliary cirrhosis (PBC is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

  6. BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo; Hu, Mintao [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Zhang, Peng [Nanjing Medical University, Nanjing, Jiangsu (China); Cao, Hong [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Wang, Yongzhen [The Second Hospital of Nanjing, Nanjing, Jiangsu (China); Wang, Zheng; Su, Tingting [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China)

    2013-05-10

    Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

  7. The effect of BAFF inhibition on autoreactive B cell selection in murine SLE.

    Science.gov (United States)

    Boneparth, Alexis; Woods, Megan; Huang, Weiqing; Akerman, Meredith; Lesser, Martin; Davidson, Anne

    2016-02-12

    The goal of this study was to determine how BAFF availability influences selection of the autoreactive B cell repertoire in NZB/W and NZW/BXSB lupus prone mice bearing the site-directed heavy chain transgene 3H9 that encodes for anti-dsDNA and anti-CL autoantibodies. We used a bone marrow chimera system in which autoreactive 3H9 transgenic B cells were allowed to mature in competition with wild type cells and could be identified by GFP fluorescence. The light chain repertoire associated with the 3H9 heavy chain in naïve and antigen-activated B cell subsets was assessed using single cell PCR. We found that deletion of autoreactive transgenic B cells occurred in the bone marrow of both strains regardless of BAFF availability and there were only modest and physiologically non-relevant effects on the naïve B cell repertoire. BAFF inhibition had different effects on selection of the germinal center repertoire in the two strains. In the NZW/BXSB strain, BAFF inhibition phenocopied the loss of one TLR7 allele in that it influenced the selection of 3H9 encoded autoreactive B cells in the germinal center but did not prevent somatic mutation. In the NZB/W strain BAFF inhibition did not alter the selection of 3H9 encoded B cells in the germinal center but it influenced selection of a subset of germinal center cells into the plasma cell compartment. Our data underscore the complexity of regulation of the autoreactive B cell repertoire by BAFF and may help to explain the heterogeneity of responses observed after BAFF inhibition in humans.

  8. Association of BAFF with PI3K/Akt/mTOR signaling in lupus nephritis.

    Science.gov (United States)

    Ge, Fengmei; Wang, Fangfang; Yan, Xiuqing; Li, Zhao; Wang, Xuebin

    2017-11-01

    Systemic lupus erythematosus is a connective tissue disease characterized by autoimmune inflammation, which leads to specific and nonspecific immune disorders with the formation of various autoantibodies by activated B cells. B‑cell‑activating factor (BAFF) is secreted by macrophages and activated T cells, and is responsible for the proliferation, maturation and differentiation of B cells. However, the mechanism of BAFF involvement in lupus nephritis (LN) remains unclear. The aim of the present study was to investigate the association between BAFF and phosphoinositide 3‑kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling in order to elucidate the pathogenesis of LN. In the present study, 18 patients with LN and 20 controls were included. The clinical data were analyzed and plasma levels of BAFF were measured using an ELISA. The mRNA and protein levels of BAFF, phosphorylated (p)‑PI3K, p‑Akt and p‑mTOR in kidney tissues were measured using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting. Plasma BAFF levels were significantly increased in patients with LN compared with the controls (PBAFF, p‑PI3K, p‑Akt and p‑mTOR in kidney tissue were significantly increased in patients with LN compared with the controls (all PBAFF in the kidney tissues of patients with LN were positively correlated with the levels of p‑PI3K, p‑Akt and p‑mTOR. The results of the present study revealed a correlation between BAFF and the PI3K/Akt/mTOR signaling pathway, and it is hypothesized that they are involved in the pathogenesis of LN.

  9. Splenectomy for solitary splenic metastasis of ovarian cancer

    International Nuclear Information System (INIS)

    Koh, Yang Seok; Kim, Jung Chul; Cho, Chol Kyoon

    2004-01-01

    Splenic metastases occur in rare cases with a few case reports of patients in the literature. Generally, splenic metastases mean late dissemination of a disease. Solitary splenic metastases from solid tumors are extremely unusual. We report a case of a patient with ovarian mucinous cystadenocarcinoma who underwent splenectomy for isolated parenchymal metastasis. Ovarian epithelial tumors comprised most of isolated splenic metastases from gynecologic tumor. When isolated splenic recurrence is suspected on image studies and serum tumor markers, intraabdominal gross findings should be examined to exclude peritoneal carcinomatosis. If only spleen was under suspicion of recurrence of ovarian cancer, splenectomy may play a therapeutic role

  10. Magnetic resonance imaging of splenic iron overload

    International Nuclear Information System (INIS)

    Arrive, L.; Thurnher, S.; Hricak, H.; Price, D.C.

    1990-01-01

    The value of magnetic resonance (MR) imaging in assessing iron overload in the spleen was retrospectively investigated in 40 consecutive patients. MR appearance, mesaure of signal intensity and T1-and T2-relaxation times were correlated with the histologically determined level of iron in the spleen in each patient. Histologic examination revealed no iron overload in 19 patients, mild iron overload in seven, moderate iron overload in six, and severe iron overload in eight. All 19 patients with no splenic iron overload and 11 of the other 21 patients with splenic iron overload were correctly identified by MR imaging (sensitivity 52%, specificity 100%, accuracy 75%). Splenic iron overload was diagnosed when a decrease of signal intensity of the spleen compared with those of adipose tissue and renal cortex was demonstrated. MR images demonstrated all eight cases of severe, three of the six cases of moderate, and none of the seven cases of mild iron overload. Only spleens with severe iron overload had a significant mean decrease in signal intensity and T1- and T2-relaxation times. Although specific, MR imaging is poorly sensitive to splenic iron overload. (author). 15 refs.; 5 figs.; 3 tabs

  11. Splenic abscess: comparison of four imaging methods

    International Nuclear Information System (INIS)

    Grant, E.; Mertens, M.A.; Mascatello, V.J.

    1979-01-01

    The diagnostic efficacy of scintiscanning (/sup 99m/Tc-sulfur colloid and 67 Ga citrate), ultrasonography, arteriography, and computed tomography are compared for imaging of a splenic abscess. It was concluded that ultrasmography, the least invasive and least expensive technique, alone would have sufficed in making the diagnosis

  12. Surgical management of splenic echinococcal disease

    Directory of Open Access Journals (Sweden)

    Meimarakis G

    2009-04-01

    Full Text Available Abstract Background Infection of the spleen with echinococcus is a rare clinical entity. Because the diagnosis of a splenic infestation with echinococcus is sometimes delayed, large hydatid cysts or pseudotumors may develop, demanding a differential surgical approach to cure the disease. Methods In a retrospective study 10 patients out of 250 with abdominal echinococcosis (4% were identified to have splenic infestation, either limited to the spleen (n = 4 or with synchronous involvement of the liver (n = 4, major omentum (n = 1, or the liver and lung (n = 1. Only one patient had alveolar echinococcosis whereas the others showed hydatid cysts of the spleen. Surgical therapy included splenectomy in 7 patients or partial cyst excision combined with omentoplasty in 3 patients. In case of liver involvement, pericystectomy was carried out simultaneously. Results There was no mortality. Postoperative complications were observed in 4 patients. Hospital stay and morbidity were not influenced when splenic procedures were combined with pericystectomies of the liver. Mean follow- up was 8.8 years and all of the patients are free of recurrence at this time. Conclusions Splenectomy should be the preferred treatment of hydatid cysts but partial cystectomy is suitable when the cysts are located at the margins of the spleen. Due to low morbidity rates, simultaneous treatment of splenic and liver hydatid cysts is recom mended.

  13. Radiological features of a symptomatic splenic hamartoma

    International Nuclear Information System (INIS)

    Thompson, S.E.; Walsh, E.A.; Cramer, B.C.; Pushpanathan, C.C.; Hollett, P.; Ingram, L.; Price, D.

    1996-01-01

    Symptomatic splenic hamartomas are rare in the pediatric age group, with only four previous reports in the literature. Splenic hamartoma has been reported as a solid homogeneous mass without calcification on CT and ultrasound (US), and only one previous report of the findings on MRI has been published. We report a case of a large symptomatic splenic hamartoma in a 14-year-old girl who presented with splenomegaly, pancytopenia and growth retardation. A solid mass with multiple punctate foci resembling calcifications was seen on US. The mass was heterogeneous and better demarcated on enhanced CT. Radiocolloid scintigraphy demonstrated uptake within the lesion, but less than that of normal spleen. The mass was isointense relative to normal splenic tissue on T1-weighted MRI (0.5 T) and of increased intensity with T2 weighting. At splenectomy, a red pulp hamartoma was identified, which contained nodules of hyalinization and necrosis thought to account for the punctate foci seen on US. (orig.). With 4 figs

  14. The (re)generation of splenic tissue

    NARCIS (Netherlands)

    Hovius, J. W. R.; Verberne, H. J.; Bennink, R. J.; Blok, W. L.

    2010-01-01

    A 48-year-old man with a history of a traumatic splenic rupture followed by splenectomy at the age of 5 years was referred to the outpatient clinic with markedly elevated liver enzymes. He was diagnosed with alcoholic liver cirrhosis. Ultrasound of the upper abdomen revealed hepatomegaly and

  15. Puzzles in practice: splenic vein thrombosis.

    Science.gov (United States)

    McIntyre, Brittany; Marsh, Melanie; Walden, Jeffrey

    2016-06-01

    This report details a 58-year-old gentleman who presented to his outpatient primary care physician's clinic several times over four weeks for ongoing epigastric pain radiating into his left flank, dry heaving, and constipation. He was presumed to have gastritis at each visit and prescribed escalating doses of proton pump inhibitors. Due to the unrelenting pain, he eventually was admitted to the hospital and diagnosed with splenic vein thrombosis after computed tomography imaging of the abdomen. Our literature search revealed that pancreatic pathology is overwhelmingly the contributing factor to splenic vein thrombosis. Our patient had prominent collateral vasculature, suggesting that his splenic vein thrombosis was chronic in nature and likely the cause of his ongoing abdominal pain. Splenic vein thrombosis is an uncommon cause of abdominal pain, but one that should be included in the treating physician's differential diagnoses when abdominal pain is ongoing despite medical therapy. Although he had no evidence of initial findings on radiography, our patient was eventually diagnosed with biopsy-proven pancreatic cancer. Our case report demonstrates how patients presenting with persistent or worsening abdominal pain despite the use of proton pump inhibitors or other acid reducing agents and potential 'red flag' findings such as decreased appetite and weight loss should be worked up for other potential sources of abdominal pathology.

  16. Radiological features of a symptomatic splenic hamartoma

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, S.E. [Department of Radiology, Janeway Child Health Centre and Memorial University of Newfoundland, Janeway Place, St. John`s, NF A1A 1R8 (Canada); Walsh, E.A. [Department of Radiology, Janeway Child Health Centre and Memorial University of Newfoundland, Janeway Place, St. John`s, NF A1A 1R8 (Canada); Cramer, B.C. [Department of Radiology, Janeway Child Health Centre and Memorial University of Newfoundland, Janeway Place, St. John`s, NF A1A 1R8 (Canada); Pushpanathan, C.C. [Department of Pathology, Janeway Child Health Centre and Memorial University of Newfoundland, St. John`s, NF (Canada); Hollett, P. [Department of Nuclear Medicine, Health Sciences Centre and Memorial University of Newfoundland, St. John`s, NF (Canada); Ingram, L. [Department of Pediatrics, Janeway Child Health Centre and Memorial University of Newfoundland, St. John`s, NF (Canada); Price, D. [Department of Surgery, Janeway Child Health Centre and Memorial University of Newfoundland, St. John`s, NF (Canada)

    1996-09-01

    Symptomatic splenic hamartomas are rare in the pediatric age group, with only four previous reports in the literature. Splenic hamartoma has been reported as a solid homogeneous mass without calcification on CT and ultrasound (US), and only one previous report of the findings on MRI has been published. We report a case of a large symptomatic splenic hamartoma in a 14-year-old girl who presented with splenomegaly, pancytopenia and growth retardation. A solid mass with multiple punctate foci resembling calcifications was seen on US. The mass was heterogeneous and better demarcated on enhanced CT. Radiocolloid scintigraphy demonstrated uptake within the lesion, but less than that of normal spleen. The mass was isointense relative to normal splenic tissue on T1-weighted MRI (0.5 T) and of increased intensity with T2 weighting. At splenectomy, a red pulp hamartoma was identified, which contained nodules of hyalinization and necrosis thought to account for the punctate foci seen on US. (orig.). With 4 figs.

  17. Overview of Nonoperative Blunt Splenic Injury Management with Associated Splenic Artery Pseudoaneurysm.

    Science.gov (United States)

    Morrison, Chet A; Gross, Brian W; Kauffman, Matthew; Rittenhouse, Katelyn J; Rogers, Frederick B

    2017-06-01

    The delayed development of splenic artery pseudoaneurysm (SAP) can complicate the nonoperative management of splenic injuries. We sought to determine the utility of repeat imaging in diagnosing SAP in patients managed nonoperatively without angioembolization. We hypothesized that a significant rate of SAPs would be found in this population on repeat imaging. Patients undergoing nonoperative splenic injury management from January 2011 to June 2015 were queried from the trauma registry. Rates of repeat imaging, angioembolization, readmission, and SAP development were analyzed. Further, subanalyses investigating the incidence of SAP in patients managed nonoperatively without angioembolization were conducted. A total of 133 patients met inclusion criteria. Repeat imaging rate was 40 per cent, angioembolization rate was 26 per cent, and readmission rate was 6 per cent. Within the study population, nine SAPs were found (8/9 in patients with splenic injury grade ≥III). Of these nine SAPs, three (33%) were identified on initial scans and embolized, whereas six (67%) were found on repeat imaging in patients not initially receiving angioembolization. Splenic injuries are typically managed nonoperatively without serious complications. Our results suggest patients with splenic injuries grade ≥III managed nonoperatively without angioembolization should have repeat imaging within 48 hours to rule out the possibility of SAP.

  18. Fish-oil-derived n-3 PUFAs reduce inflammatory and chemotactic adipokine-mediated cross-talk between co-cultured murine splenic CD8+ T cells and adipocytes.

    Science.gov (United States)

    Monk, Jennifer M; Liddle, Danyelle M; De Boer, Anna A; Brown, Morgan J; Power, Krista A; Ma, David Wl; Robinson, Lindsay E

    2015-04-01

    Obese adipose tissue (AT) inflammation is characterized by dysregulated adipokine production and immune cell accumulation. Cluster of differentiation (CD) 8+ T cell AT infiltration represents a critical step that precedes macrophage infiltration. n-3 (ω-3) Polyunsaturated fatty acids (PUFAs) exert anti-inflammatory effects in obese AT, thereby disrupting AT inflammatory paracrine signaling. We assessed the effect of n-3 PUFAs on paracrine interactions between adipocytes and primary CD8+ T cells co-cultured at the cellular ratio observed in obese AT. C57BL/6 mice were fed either a 3% menhaden fish-oil + 7% safflower oil (FO) diet (wt:wt) or an isocaloric 10% safflower oil (wt:wt) control (CON) for 3 wk, and splenic CD8+ T cells were isolated by positive selection (via magnetic microbeads) and co-cultured with 3T3-L1 adipocytes. Co-cultures were unstimulated (cells alone), T cell receptor stimulated, or lipopolysaccharide (LPS) stimulated for 24 h. In LPS-stimulated co-cultures, FO reduced secreted protein concentrations of interleukin (IL)-6 (-42.6%), tumor necrosis factor α (-67%), macrophage inflammatory protein (MIP) 1α (-52%), MIP-1β (-62%), monocyte chemotactic protein (MCP) 1 (-23%), and MCP-3 (-19%) vs. CON, which coincided with a 74% reduction in macrophage chemotaxis toward secreted chemotaxins in LPS-stimulated FO-enriched co-culture-conditioned media. FO increased mRNA expression of the inflammatory signaling negative regulators monocyte chemoattractant 1-induced protein (Mcpip; +9.3-fold) and suppressor of cytokine signaling 3 (Socs3; +1.7-fold), whereas FO reduced activation of inflammatory transcription factors nuclear transcription factor κB (NF-κB) p65 and signal transducer and activator of transcription 3 (STAT3) by 27% and 33%, respectively. Finally, mRNA expression of the inflammasome components Caspase1 (-36.4%), Nod-like receptor family pyrin domain containing 3 (Nlrp3; -99%), and Il1b (-68.8%) were decreased by FO compared with CON (P

  19. B cell activating factor (BAFF) selects IL-10-B cells over IL-10+B cells during inflammatory responses.

    Science.gov (United States)

    Ma, Ning; Zhang, Yu; Liu, Qilin; Wang, Zhiding; Liu, Xiaoling; Zhu, Gaizhi; Yu, Dandan; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Wang, Tianxiao; Ma, Yuanfang; Shen, Beifen; Li, Yan; Xiao, He; Wang, Renxi

    2017-05-01

    B cell activating factor (BAFF) regulates B cell maturation, survival, function, and plays a critical pathogenic role in autoimmune diseases. It remains unclear how BAFF affects IL-10 - B cells versus regulatory B cells (Bregs) in inflammatory responses. In this study, we found that IL-10-expressing Bregs decreased in lupus-prone MRL/lpr mice and experimental allergic encephalomyelitis (EAE) mice. On blockade of the effects of BAFF with TACI-IgG, IL-10 + Bregs were upregulated in MRL/lpr and EAE mice. In addition, BAFF expanded IL-10 + B cells over IL-10 - B cells under noninflammatory conditions in vitro, whereas it expanded IL-10 - B cells over IL-10 + B cells during inflammatory responses, such as stimulation with autoantigen and LPS. Finally, the selection of IL-10 - B cells over IL-10 + B cells by BAFF was dependent on BAFF receptors (BAFFR, TACI, and BCMA) that were upregulated by inflammatory responses. This study suggests that BAFF selects IL-10 - B cells over IL-10 + regulatory B cells via BAFF receptors in inflammatory responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Interferon-beta increases systemic BAFF levels in multiple sclerosis without increasing autoantibody production

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Sellebjerg, Finn; Krakauer, Martin

    2011-01-01

    Background: Treatment with interferon-beta (IFN-beta) increases B-cell activating factor of the TNF family (BAFF) expression in multiple sclerosis (MS), raising the concern that treatment of MS patients with IFN-beta may activate autoimmune B cells and stimulate the production of MS-associated au......Background: Treatment with interferon-beta (IFN-beta) increases B-cell activating factor of the TNF family (BAFF) expression in multiple sclerosis (MS), raising the concern that treatment of MS patients with IFN-beta may activate autoimmune B cells and stimulate the production of MS......-associated autoantibodies. Objective: To investigate whether BAFF levels are associated with disease severity/activity in untreated MS patients, and to assess the effect of IFN-beta therapy on circulating BAFF and anti-myelin basic protein (MBP) autoantibody levels. Results: Twenty-three patients with relapsing......-remitting MS (RRMS) were followed longitudinally from initiation of IFN-beta therapy. Their blood levels of BAFF correlated positively at baseline with the expanded disability status scale (p

  1. IgG-immune complexes promote B cell memory by inducing BAFF1

    Science.gov (United States)

    Kang, SunAh; Keener, Amanda B.; Jones, Shannon Z.; Benschop, Robert J.; Caro-Maldonado, Alfredo; Rathmell, Jeffrey C.; Clarke, Stephen H.; Matsushima, Glenn K.; Whitmire, Jason K.; Vilen, Barbara J.

    2015-01-01

    Memory B cell responses are vital for protection against infections, but must also be regulated to prevent autoimmunity. Cognate T cell help, somatic hypermutation, and affinity maturation within germinal centers (GCs) are required for high affinity memory B cell formation; however, the signals that commit GC B cells to the memory pool remain unclear. In this study, we identify a role for IgG immune complexes (ICs), FcγRs, and BAFF during the formation of memory B cells in mice. We found that early secretion of IgG in response to immunization with a T-dependent antigen leads to IC-FcγR interactions that induce DCs to secrete BAFF which acts at or upstream of Bcl-6 in activated B cells. Loss of CD16, hematopoietic cell-derived BAFF, or blocking IC:FcγR regions in vivo diminished the expression of Bcl-6, the frequency of GC and memory B cells, and secondary antibody responses. BAFF also contributed to the maintenance and/or expansion of the Tfh population, although it was dispensable for their formation. Thus, early antibody responses contribute to the optimal formation of B cell memory through IgG-ICs and BAFF. Our work defines a new role for FcγRs in GC and memory B cell responses. PMID:26621863

  2. Expression profile of BAFF in peripheral blood from patients of IgA nephropathy: Correlation with clinical features and Streptococcus pyogenes infection.

    Science.gov (United States)

    Zheng, Nuoyan; Fan, Jinjin; Wang, Bing; Wang, Dongxian; Feng, Pinning; Yang, Qiongqiong; Yu, Xueqing

    2017-04-01

    B cells are critically important for the pathogenesis of IgA nephropathy (IgAN). The present study aimed to investigate the abundance of B cell activating factor (BAFF), which belongs to the tumor necrosis factor superfamily, in the peripheral blood of patients with IgAN. The different forms of BAFF in peripheral blood and its association with clinical features and immunological factors were analyzed. mRNA levels of BAFF and other associated genes in the peripheral blood mononuclear cells (PBMCs) of patients with IgAN and controls were analyzed by quantitative polymerase chain reaction. Cellular BAFF proteins in PBMCs and plasma soluble BAFF proteins were measured by western blot analysis and ELISA, respectively. PBMCs from patients were stimulated with Streptococcus pyogenes (S. pyogenes) ex vivo for the BAFF secretion assay. The data demonstrated that, although mRNA levels of BAFF in PBMC were not significantly increased in patients with IgAN, they were positively associated with those of a proliferation inducing ligand (APRIL), Toll‑like receptor (TLR)2, TLR4 and TLR7. The cellular BAFF protein in PBMCs was not upregulated. Plasma BAFF protein levels in patients with IgAN (n=76) were significantly decreased compared with controls. However, plasma BAFF levels were positively associated with serum creatinine, proteinuria, uric acid and group A Streptococcus infection index in patients with IgAN. In patients with IgAN, plasma BAFF concentrations were markedly higher in those with more severe renal tubular atrophy/interstitial fibrosis and global glomerulosclerosis. Furthermore, BAFF production in PBMCs of patients with IgAN was increased following S. pyogenes stimulation ex vivo. In conclusion, plasma BAFF levels in patients with IgAN were associated with renal function and disease activity. S. pyogenes infection was closely associated with BAFF production in patients with IgAN.

  3. Splenic flexure volvulus presenting with gangrene

    International Nuclear Information System (INIS)

    Machado, Norman O; Chopra, Pradeep J; Subramanian, Sureshkannan K

    2009-01-01

    Volvulus of the splenic flexure is very rare cause of colonic obstruction constituting 2% of cases of colonic segmental volvulus. Primary splenic flexure volvulus (SFV) is due to congenital absence or laxity of the phrenocolic, gastro colic, and splenocolic ligaments while secondary volvulus is due to other causes including some prior surgery releasing these ligaments. A preoperative diagnosis can be established based on the characteristic radiological findings on plain x-ray abdomen and CT scan. We present a case of SFV in a young man who presented with acute abdominal pain, and distension, and illustrate the usefulness of CT scan, and plain x-ray of the abdomen in making a preoperative diagnosis. Laparotomy revealed a gangrenous SFV, which was resected and primary anastomosis was carried out. Literature is reviewed with regards to predisposing factors, presentation, investigation, and management among the more than 32 cases reported so far. (author)

  4. The (re)generation of splenic tissue

    OpenAIRE

    Hovius, J W R; Verberne, H J; Bennink, R J; Blok, W L

    2010-01-01

    A 48-year-old man with a history of a traumatic splenic rupture followed by splenectomy at the age of 5 years was referred to the outpatient clinic with markedly elevated liver enzymes. He was diagnosed with alcoholic liver cirrhosis. Ultrasound of the upper abdomen revealed hepatomegaly and suggested a central mass in the liver. Subsequent MRI of the abdomen did not show a hepatic mass, but revealed multiple intraperitoneal and retroperitoneal ovoid structures with a maximum diameter of 3 cm...

  5. Changes in gastrosplenic circulation and splenic function after distal pancreatectomy with spleen preservation and splenic vessel excision.

    Science.gov (United States)

    Kohan, Gustavo; Ocampo, Carlos G; Zandalazini, Hugo I; Klappenbach, Roberto; Quesada, Bernabe M; Porras, Luis T Chiappetta; Rodriguez, Juan Alvarez; Oria, Alejandro S

    2013-10-01

    Distal pancreatectomy with spleen preservation and splenic vessel excision is a commonly used technique. However, it produces significant gastrosplenic circulation and splenic function changes. The aim of this work was to determine the immediate consequences on gastrosplenic circulation, late consequences on splenic function, and development of varicose veins. Thirty-five patients with pancreatic tumors and anatomical feasibility were included. Preoperative splenic circulation was evaluated by dynamic contrast-enhanced computed tomography (CT) scans. Early splenic perfusion was assessed by CT 7 days after surgery and late changes in gastrosplenic circulation 6 months after surgery. Varicose veins were evaluated by CT and endoscopy 6 months after surgery. Pitted cells and Howell-Jolly bodies were used as markers of splenic function. Postoperatory findings included changes in splenic perfusion 7 days and 6 months after surgery, development of varicose veins on CT scans and endoscopy, and detection of markers of splenic hypofunction on blood smears. Seven days after surgery, 63% of patients had some degree of splenic hypoperfusion, and 6 months after surgery, 83% of patients had normal perfusion. CT scans showed varices in 26 patients, and endoscopy revealed varicose veins in 11. Two patients experienced bleeding; markers of splenic hypofunction were found in 59% of cases.

  6. [Splenic abscess and cat-scratch disease].

    Science.gov (United States)

    Valdesoiro Navarrete, L; Pineda Solas, V; Martín Martín, C; Sanfeliu Sala, I; Cabezas Maspoch, R M; Sánchez Oespina, M

    2001-10-01

    Cat-scratch disease is caused by a Gram-negative bacillus known as Bartonella henselae. This disease is usually benign and causes regional adenitis that does not require treatment. However, some patients develop more serious atypical forms of the disease including prolonged systemic illness with hepatic and splenic abscesses.A 14-year-old girl was admitted to hospital with a 12-day history of persistent high fever and abdominal pain. Ultrasonography and computerized tomography of the abdomen revealed splenic abscesses. These findings, together with an antecedent of cat exposure, led to the suspicion of cat-scratch disease, which was confirmed by serology. The girl was treated with intramuscular ceftriaxone and clinical evolution was favorable. Splenic cat-scratch disease is infrequent. Cat-scratch disease sometimes presents as fever of unknown origin and consequently this disease should be considered in the differential diagnosis of prolonged fever. Although evolution is usually favorable, antibiotic therapy is recommended in systemic manifestations of cat-scratch disease.

  7. Pediatric blunt splenic trauma: a comprehensive review

    Energy Technology Data Exchange (ETDEWEB)

    Lynn, Karen N.; Werder, Gabriel M.; Callaghan, Rachel M.; Jafri, Zafar H. [William Beaumont Hospital, Department of Diagnostic Radiology, Royal Oak, MI (United States); Sullivan, Ashley N. [St. George' s University School of Medicine, Grenada, West Indies (Grenada); Bloom, David A. [William Beaumont Hospital, Department of Diagnostic Radiology, Royal Oak, MI (United States); William Beaumont Hospital, Section of Pediatric Radiology, Department of Radiology, Royal Oak, MI (United States)

    2009-09-15

    Abdominal trauma is a leading cause of death in children older than 1 year of age. The spleen is the most common organ injured following blunt abdominal trauma. Pediatric trauma patients present unique clinical challenges as compared to adults, including different mechanisms of injury, physiologic responses, and indications for operative versus nonoperative management. Splenic salvage techniques and nonoperative approaches are preferred to splenectomy in order to decrease perioperative risks, transfusion needs, duration/cost of hospitalization, and risk of overwhelming postsplenectomy infection. Early and accurate detection of splenic injury is critical in both adults and children; however, while imaging findings guide management in adults, hemodynamic stability is the primary determinant in pediatric patients. After initial diagnosis, the primary role of imaging in pediatric patients is to determine the level and duration of care. We present a comprehensive literature review regarding the mechanism of injury, imaging, management, and complications of traumatic splenic injury in pediatric patients. Multiple patients are presented with an emphasis on the American Association for the Surgery of Trauma organ injury grading system. Clinical practice guidelines from the American Pediatric Surgical Association are discussed and compared with our experience at a large community hospital, with recommendations for future practice guidelines. (orig.)

  8. Evaluation of splenic autotransplants by radionuclide methods

    International Nuclear Information System (INIS)

    Nawaz, K.; Nema, T.A.; Al-Mohannadi, S.; Abdel-Dayem, H.M.

    1986-01-01

    The viability of omental autotransplantation of splenic tissue after splenectomy has been disputed. The authors followed up splenic implants by imaging with either Tc-99m tin colloid or heat-damaged RBCs to determine how early implants can be visualized and whether a difference exists between patients who underwent emergency splenectomy for trauma (nine patients) and those who underwent elective splenectomy (seven patients). In the latter group, splenectomy was performed for portal hypertension in six patients and for hematologic disorder (Wiscott Aldrich syndrome) in one. All patients were imaged 2-4 weeks and 6 months after surgery. In the first group, seven implants were seen at 2-4 weeks and all nine were seen by 6 months. In the second group, only two implants were seen at 2-4 weeks and four were seen at 6 months; two implants were not visualized even at 6 months. The implant of the patient with hematologic disorder was not seen before 6 months. The authors conclude that splenic implants can be visualized bu scintigraphic methods as early as 2-4 weeks after surgery, and that by 6 months all implants from normal spleen are viable. By contrast, spleen implants placed for portal hypertension or hematologic disorders may fail

  9. CT of splenic and perisplenic abnormalities in septic patients

    International Nuclear Information System (INIS)

    Balthazar, E.J.; Hilton, S.; Naidich, D.; Megibow, A.; Levine, R.

    1985-01-01

    Splenic and perisplenic pathology, demonstrated by CT examination in 14 septic patients, was correlated with the clinical course and with surgical and pathologic findings available. Twelve patients were intravenous drug addicts and two patients developed bacteremia associated with bacterial endocarditis. The CT fingings were divided into three groups: (1) Single wedge-shaped peripherally located defects were seen in five patients; there was good response to medical therapy without other complications. (2) Larger and/or multiple, rounded or oval lesions were present in five patients; two of these patients had splenic abscesses proven on subsequent splenectomy. (3) Multiple splenic lesions and fissures associated with perisplenic and subphrenic fluid collections were seen in four patients; infected splenic infarcts, splenic fractures, and infected perisplenic hemorrhagic fluid collections were found in this group of patients. The CT examination in septic patients can reliably demonstrate splenic and perisplenic pathology, and its appearance contributes greatly to the overall clinical assessment and surgical approach

  10. CT of splenic and perisplenic abnormalities in septic patients

    Energy Technology Data Exchange (ETDEWEB)

    Balthazar, E.J.; Hilton, S.; Naidich, D.; Megibow, A.; Levine, R.

    1985-01-01

    Splenic and perisplenic pathology, demonstrated by CT examination in 14 septic patients, was correlated with the clinical course and with surgical and pathologic findings available. Twelve patients were intravenous drug addicts and two patients developed bacteremia associated with bacterial endocarditis. The CT fingings were divided into three groups: (1) Single wedge-shaped peripherally located defects were seen in five patients; there was good response to medical therapy without other complications. (2) Larger and/or multiple, rounded or oval lesions were present in five patients; two of these patients had splenic abscesses proven on subsequent splenectomy. (3) Multiple splenic lesions and fissures associated with perisplenic and subphrenic fluid collections were seen in four patients; infected splenic infarcts, splenic fractures, and infected perisplenic hemorrhagic fluid collections were found in this group of patients. The CT examination in septic patients can reliably demonstrate splenic and perisplenic pathology, and its appearance contributes greatly to the overall clinical assessment and surgical approach.

  11. Symptomatic splenic hamartoma with renal, cutaneous, and hematological abnormalities

    International Nuclear Information System (INIS)

    Kassarjian, A.; Patenaude, Y.G.; Bernard, C.; Bell, L.

    2001-01-01

    Background. There is a rare association between splenic hamartomas and hematological abnormalities with, to our knowledge, only 24 reported cases in the English literature. Patients and methods. We report a case of a splenic hamartoma in a 14-year-old boy associated with membranoproliferative glomerulonephritis, multiple lobular capillary hemangiomas of the skin, hypertension, and anemia. Following imaging with ultrasonography, MRI, and nuclear scans, a hamartoma was suspected, but malignancy could not be excluded. The lesion was removed by partial splenectomy, and pathological examination confirmed the presence of a red pulp splenic hamartoma. Results. The renal, hematological, and dermatological abnormalities resolved following removal of the splenic hamartoma. This is the first reported case of a splenic hamartoma associated with renal, cutaneous, and hematological abnormalities and only the second reported case of a symptomatic splenic hamartoma treated by partial splenectomy. (orig.)

  12. Symptomatic splenic hamartoma with renal, cutaneous, and hematological abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Kassarjian, A.; Patenaude, Y.G. [Dept. of Medical Imaging, Montreal Children' s Hospital, PQ (Canada); Bernard, C. [Dept. of Pathology, Montreal Children' s Hospital, PQ (Canada); Bell, L. [Dept. of Nephrology, Montreal Children' s Hospital, PQ (Canada)

    2001-02-01

    Background. There is a rare association between splenic hamartomas and hematological abnormalities with, to our knowledge, only 24 reported cases in the English literature. Patients and methods. We report a case of a splenic hamartoma in a 14-year-old boy associated with membranoproliferative glomerulonephritis, multiple lobular capillary hemangiomas of the skin, hypertension, and anemia. Following imaging with ultrasonography, MRI, and nuclear scans, a hamartoma was suspected, but malignancy could not be excluded. The lesion was removed by partial splenectomy, and pathological examination confirmed the presence of a red pulp splenic hamartoma. Results. The renal, hematological, and dermatological abnormalities resolved following removal of the splenic hamartoma. This is the first reported case of a splenic hamartoma associated with renal, cutaneous, and hematological abnormalities and only the second reported case of a symptomatic splenic hamartoma treated by partial splenectomy. (orig.)

  13. Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus.

    Science.gov (United States)

    Salazar-Camarena, D C; Ortiz-Lazareno, P C; Cruz, A; Oregon-Romero, E; Machado-Contreras, J R; Muñoz-Valle, J F; Orozco-López, M; Marín-Rosales, M; Palafox-Sánchez, C A

    2016-05-01

    B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) signaling pathways regulate B-cell survival through interactions with their receptors BAFF-R, TACI and BCMA. We evaluated the association of these ligands/receptors on B-cell subsets according to clinical manifestations of systemic lupus erythematosus (SLE). BAFF and APRIL serum concentrations were measured in 30 SLE patients by enzyme-linked immunosorbent assay. The BAFF-R, TACI and BCMA expression was analyzed on each B cell subset (CD19 + CD27-CD38-/ + naïve; CD19 + CD27 + CD38-/ + memory; CD19 + CD27-CD38 + + immature and CD19 + CD27 + CD38 + + plasma cells) by flow cytometry, and compared among patients with different clinical manifestations as well as healthy controls (HCs). Serum BAFF and APRIL levels were high in SLE patients and correlated with the Mex-SLEDAI disease activity index (r = 0.584; p = 0.001 and r = 0.456; p = 0.011, respectively). The SLE patients showed an increased proportion of memory and plasma B cells (p < 0.05). BAFF-R, TACI and BCMA expression in SLE patients was decreased in almost all B cell subsets compared to HCs (p < 0.05). A lower BCMA expression was associated with severe disease activity, glomerulonephritis, serositis and hemolytic anemia (p < 0.01). BCMA expression showed a negative correlation with Mex-SLEDAI score (r = -0.494, p = 0.006). Decreased BCMA expression on peripheral B cells according to severe disease activity suggests that BCMA plays an important regulating role in B-cell hyperactivity and immune tolerance homeostasis in SLE patients. © The Author(s) 2015.

  14. Case of microgastria in association with splenic-gonadal fusion

    Energy Technology Data Exchange (ETDEWEB)

    Mandell, G.A.; Alavi, A.; Heyman, S.; Ziegler, M.M.

    1983-03-01

    Microgastria is a rare congenital anomaly usually associated with asplenia. In this 2 1/2-year-old presenting with left hydrocele and inguinal hernia multiple accessory spleens were found in the inguinal-scrotal region compatible with splenic-gonadal fusion. sup(99m)Tc-sulfur colloid scanning is helpful in microgastria searching for the presence of splenic tissue and in splenic-gonadal fusion for the location of accessory heterotopic spleens.

  15. Association of splenic and renal infarctions in acute abdominal emergencies

    Energy Technology Data Exchange (ETDEWEB)

    Romano, Stefania E-mail: stefromano@libero.it; Scaglione, Mariano; Gatta, Gianluca; Lombardo, Patrizia; Stavolo, Ciro; Romano, Luigia; Grassi, Roberto

    2004-04-01

    Introduction: Splenic and renal infarctions are usually related to vascular disease or haematologic abnormalities. Their association is infrequent and rarely observed in trauma. In this study, we analyze our data to look at the occurrence of renal and splenic infarctions based on CT findings in a period of 4 years. Materials and Methods: We retrospectively reviewed the imaging findings of 84 patients admitted to our Department of Diagnostic Imaging from June 1998 to December 2002, who underwent emergency abdominal spiral CT examination and in whom there was evidence of splenic and/or renal infarction. Results: We found 40 cases of splenic infarction and 54 cases of renal infarction, associated in 10 patients. In 26 patients, there was also evidence of intestinal infarction. A traumatic origin was found in 19 cases; non-traumatic causes were found in 65 patients. Association between renal and splenic infarction in the same patient was related to trauma in two cases. Conclusions: Although renal and splenic infarctions are a common manifestation of cardiac thromboembolism, other systemic pathologies, infections or trauma may lead to this occurrence. Renal infarction may be clinically and/or surgically managed with success in most cases. There are potential complications in splenic infarction, such as development of pseudocysts, abscesses, hemorrhage, subcapsular haematoma or splenic rupture; splenectomy in these cases may be necessary. Some patients with splenic and/or renal infarction may be clinically asymptomatic. The high accuracy of CT examination is needed to allow a correct evaluation of infarcted organs.

  16. Serial Changes of the Splenic Volume after Traumatic Intraperitoneal Hemorrhage

    International Nuclear Information System (INIS)

    Park, Hyun Jin; Lee, Young Hwan; Jung, Kyung Jae

    2010-01-01

    We wanted to evaluate the serial changes of the splenic volume in patients with traumatic intraperitoneal hemorrhage. 20 consecutive patients with traumatic intraperitoneal hemorrhage and who underwent initial CT, early follow-up CT within 30 days and late follow- up CT examinations thereafter were included in this study. The volume of the spleen on each CT examination was measured and the relative splenic volume (RSV) on the initial and early follow-CT examinations was calculated on the basis of the splenic volume on the late follow-up CT. The hemoperitoneum score was calculated on the basis of the size of the intraperitoneal hemorrhage. The average RSVs of the initial and early follow-up CT were 62.0% and 133.3%, respectively, and all the patients showed an increase of the splenic and relative splenic volumes on the early follow-up CT, as compared with those on the initial CT. Initial splenic contraction was seen in 18 patients (90.0%) and early splenomegaly was seen in 14 patients (70.0%). Patients with initial splenic contraction and early splenomegaly were the most common (12 patient, 60.0%). Initial physiologic splenic contraction was seen in most of the patients with hemoperitoneum, and thereafter early splenomegaly was commonly seen before normalization of the splenic volume

  17. B cell activating factor of the tumor necrosis factor family (BAFF behaves as an acute phase reactant in acute pancreatitis.

    Directory of Open Access Journals (Sweden)

    Georg Pongratz

    Full Text Available To determine if B cell activating factor of the tumor necrosis factor family (BAFF acts as an acute phase reactant and predicts severity of acute pancreatitis.40 patients with acute pancreatitis were included in this single center cohort pilot study. Whole blood and serum was analyzed on day of admission and nine consecutive days for BAFF, c-reactive protein (CRP, interleukin-6 (IL-6, procalcitonin (PCT, and leucocyte numbers. Different severity Scores (Ranson, APACHE II, SAPS II, SAPS III and the clinical course of the patient (treatment, duration of stay, duration ICU were recorded.Serum BAFF correlates with CRP, an established marker of severity in acute pancreatitis at day of admission with a timecourse profil similar to IL-6 over the first nine days. Serum BAFF increases with Ranson score (Kruskal-Wallis: Chi2 = 10.8; p = 0.03 similar to CRP (Kruskal-Wallis: Chi2 = 9.4; p = 0.05 . Serum BAFF, IL-6, and CRP levels are elevated in patients that need intensive care for more than seven days and in patients with complicated necrotizing pancreatitis. Discriminant analysis and receiver operator characteristics show that CRP (wilks-lambda = 0.549; ROC: AUC 0.948 and BAFF (wilks-lambda = 0.907; ROC: AUC 0.843 serum levels at day of admission best predict severe necrotizing pancreatitis or death, outperforming IL-6, PCT, and number of leucocytes.This study establishes for the first time BAFF as an acute phase reactant with predictive value for the course of acute pancreatitis. BAFF outperforms established markers in acute pancreatitis, like IL-6 and PCT underscoring the important role of BAFF in the acute inflammatory response.

  18. B cell activating factor of the tumor necrosis factor family (BAFF) behaves as an acute phase reactant in acute pancreatitis.

    Science.gov (United States)

    Pongratz, Georg; Hochrinner, Hannah; Straub, Rainer H; Lang, Stefanie; Brünnler, Tanja

    2013-01-01

    To determine if B cell activating factor of the tumor necrosis factor family (BAFF) acts as an acute phase reactant and predicts severity of acute pancreatitis. 40 patients with acute pancreatitis were included in this single center cohort pilot study. Whole blood and serum was analyzed on day of admission and nine consecutive days for BAFF, c-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and leucocyte numbers. Different severity Scores (Ranson, APACHE II, SAPS II, SAPS III) and the clinical course of the patient (treatment, duration of stay, duration ICU) were recorded. Serum BAFF correlates with CRP, an established marker of severity in acute pancreatitis at day of admission with a timecourse profil similar to IL-6 over the first nine days. Serum BAFF increases with Ranson score (Kruskal-Wallis: Chi2 = 10.8; p = 0.03) similar to CRP (Kruskal-Wallis: Chi2 = 9.4; p = 0.05 ). Serum BAFF, IL-6, and CRP levels are elevated in patients that need intensive care for more than seven days and in patients with complicated necrotizing pancreatitis. Discriminant analysis and receiver operator characteristics show that CRP (wilks-lambda = 0.549; ROC: AUC 0.948) and BAFF (wilks-lambda = 0.907; ROC: AUC 0.843) serum levels at day of admission best predict severe necrotizing pancreatitis or death, outperforming IL-6, PCT, and number of leucocytes. This study establishes for the first time BAFF as an acute phase reactant with predictive value for the course of acute pancreatitis. BAFF outperforms established markers in acute pancreatitis, like IL-6 and PCT underscoring the important role of BAFF in the acute inflammatory response.

  19. Antibodies That Block or Activate Mouse B Cell Activating Factor of the Tumor Necrosis Factor (TNF) Family (BAFF), Respectively, Induce B Cell Depletion or B Cell Hyperplasia.

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Schuepbach-Mallepell, Sonia; Vigolo, Michele; Willen, Laure; Tardivel, Aubry; Smulski, Cristian R; Zheng, Timothy S; Gommerman, Jennifer; Hess, Henry; Gottenberg, Jacques-Eric; Mackay, Fabienne; Donzé, Olivier; Schneider, Pascal

    2016-09-16

    B cell activating factor of the TNF family (BAFF), also known as B lymphocyte stimulator, is a ligand required for the generation and maintenance of B lymphocytes. In this study, the ability of different monoclonal antibodies to recognize, inhibit, or activate mouse BAFF was investigated. One of them, a mouse IgG1 named Sandy-2, prevented the binding of BAFF to all of its receptors, BAFF receptor, transmembrane activator and calcium modulating ligand interactor, and B cell maturation antigen, at a stoichiometric ratio; blocked the activity of mouse BAFF on a variety of cell-based reporter assays; and antagonized the prosurvival action of BAFF on primary mouse B cells in vitro A single administration of Sandy-2 in mice induced B cell depletion within 2 weeks, down to levels close to those observed in BAFF-deficient mice. This depletion could then be maintained with a chronic treatment. Sandy-2 and a previously described rat IgG1 antibody, 5A8, also formed a pair suitable for the sensitive detection of endogenous circulating BAFF by ELISA or using a homogenous assay. Interestingly, 5A8 and Sandy-5 displayed activities opposite to that of Sandy-2 by stimulating recombinant BAFF in vitro and endogenous BAFF in vivo These tools will prove useful for the detection and functional manipulation of endogenous mouse BAFF and provide an alternative to the widely used BAFF receptor-Fc decoy receptor for the specific depletion of BAFF in mice. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Functions of the splenic remnant after subtotal splenectomy for treatment of severe splenic injuries.

    Science.gov (United States)

    Resende, Vivian; Petroianu, Andy

    2003-04-01

    To evaluate the clinical and laboratory characteristics of patients submitted to subtotal splenectomy during the immediate and late postoperative period. The study was conducted on 34 patients, 25 of whom were submitted to subtotal splenectomy (group I), and 9 to total splenectomy without preservation of splenic tissue (group II), and on 22 patients with intact spleens (group III, control). The immediate and late postoperative complications were investigated. Hematological examinations were performed during the late postoperative period (red cell count, hemoglobin, platelets, total and segmented leukocytes, lymphocytes, and Howell-Jolly bodies). Immunoglobulins (IgA, IgM, and IgG) and total T lymphocytes (TTL), active T lymphocytes (ATL), and B lymphocytes were also determined. Splenic scintigraphy with (99m)Tc colloidal sulfur was performed. Groups I and III did not presented abnormal blood bodies and their hematological and immunological pattern were normal. None of the groups showed leukocytosis or thrombocytosis. Howell-Jolly bodies were observed only in group II, which also showed reduced IgM levels. Scintigraphy showed filtering splenic tissue in group I. We conclude that subtotal splenectomy is a good surgical alternative for serious distal spleen lesion or when the main splenic pedicle is injured.

  1. Spontaneous splenic rupture in pregnancy: a case report | Makwe ...

    African Journals Online (AJOL)

    Spontaneous splenic rupture in pregnancy is a rare condition, associated with very high maternal mortality rate and fetal wastage. It is frequently misdiagnosed at presentation. We report a case of a 33-year-old, gravida 2, para 1 lady at 29 weeks' gestation with spontaneous splenic rupture, which was initially diagnosed as ...

  2. Fatal splenic rupture in Ehlers-Danlos syndrome.

    OpenAIRE

    Harris, S. C.; Slater, D. N.; Austin, C. A.

    1985-01-01

    A fatal case of Ehlers-Danlos syndrome (Type IV) is described. Autopsy revealed splenic rupture that had resulted from spontaneous haemorrhage into the splenic parenchyma. This is a previously unrecorded complication of Ehlers-Danlos syndrome and should be considered in the differential diagnosis of chest and abdominal pain in patients with this condition.

  3. The pattern and management outcomes of splenic injuries in the ...

    African Journals Online (AJOL)

    Background: In the last decade or so, the management of splenic injuries has undergone a lot of debate and changes including refinement of the indications for non-operative management (NOM). The aims of this retrospective study are: to characterize the pattern of splenic injuries in the Abha region of Saudi Arabia; ...

  4. Blunt Splenic Trauma in Children : Are We Too Careful?

    NARCIS (Netherlands)

    De Jong, W. J. J.; Nellensteijn, D. R.; ten Duis, H. J.; Albers, M. J. I. J.; El Moumni, M.; Hulscher, J. B. F.

    Introduction: There has been a shift from operative treatment (OT) to non-operative treatment (NOT) of splenic injury. We evaluated the outcomes of treatment of pediatric patients with blunt splenic trauma in our hospital, with special focus on the outcomes after NOT. Patients and Methods: The data

  5. artery splenic entIty Aneurysm of the controversial

    African Journals Online (AJOL)

    1983-01-08

    Jan 8, 1983 ... An abdominal aortogram and a coeliac arteriogram revealed a splenic artery aneurysm measuring approximarely 3 cm in diameter. Ar elecrive laparotomy, a calcified non-ruptured aneurysm of the splenic artery embedded in the rail of the pancreas and situared 5 cm from rhe hilum of rhe spleen was ...

  6. artery splenic entIty Aneurysm of the controversial

    African Journals Online (AJOL)

    1983-01-08

    Jan 8, 1983 ... methods of diagnosis of splenic artery aneur~sms have been exrenslvely revIewed III prevIOus pubhcations, 9 this commu- nication reports the successful elective resection of a non- ruptured, calcified splenic artery aneurysm. Case report. A 60-year-old White woman was admitted to Tygerberg Hospi-.

  7. Splenic abscess in children: A report of three patients | Rattan ...

    African Journals Online (AJOL)

    Splenic abscess is uncommon in paediatric age group. It usually occurs in conditions of disseminated infective focus. Conventional treatment of abscess is incision and drainage, although splenectomy or splenic conservation is alternative. In this report, we are presenting case summaries of three patients suffering from ...

  8. Splenic arteriovenous fistula treated with percutaneous transarterial embolization

    DEFF Research Database (Denmark)

    Madsen, M.A.; Frevert, S.; Madsen, P.L.

    2008-01-01

    Splenic arteriovenous fistula is a rare complication following splenectomy. We report a case of a large splenic arteriovenous fistula 23 years after splenectomy in a 50-year old male with abdominal pain, gastro-intestinal bleeding, ascites, diarrhoea, dyspnoea, portal hypertension and heart failure...

  9. Complicated congenital splenic cyst: Saved by a splenunculus ...

    African Journals Online (AJOL)

    A 12-year-old girl presented with a large congenital splenic cyst complicated by Salmonella organisms. After failure of conservative management and percutaneous drainage, a splenectomy was performed. An incidental splenunculus was preserved. On follow up the splenunculus had increased to normal splenic size and ...

  10. Spontaneous resolution of splenic infarcts after distal splenorenal ...

    African Journals Online (AJOL)

    Background: In cases of portal hypertension with splenic infarcts, splenectomy with proximal splenorenal shunt has been recommended. We are sharing our experience with distal splenorenal shunt in these cases contrary to the popular belief. Materials and Methods: Splenic infarcts were graded as mild, moderate and ...

  11. Selective Binding BAFF/APRIL by the In and Outside Conservative Region of BCMA.

    Science.gov (United States)

    Zheng, Chang; Zhang, Xiaojuan; Zhao, Zhen; Hao, Xiaofei; Wei, Jing; Sun, Jian

    2017-01-01

    BAFF and APRIL are members of TNF superfamily. They play vital roles in the pathogenesis of autoimmune diseases. BCMA, a receptor, shows higher affinity for APRIL than for BAFF. Previous studies found that ligand binding specificity of BCMA may be determined by sequence outside DxL motif. Investigate the contribution of a segment outside the DxL motif of BCMA for binding with ligands. In this study, the conservative region of BCMA was divided into two segments: BCMA1 (NEYFDSLLHACIPC), a segment of the DXL motif and BCMA2 (QLRCSSNTPPLT), a segment outside of the DXL motif. Two peptides corresponding to the two segments were synthesized and their contribution to the ligands binding were detected by competitive ELISA. BCMA1-Fc fusion protein was also constructed, purified and analyzed by indirect and competitive ELISA. BCMA2 had no inhibiting effect on the interaction of BCMA-Fc and BCMA1-Fc with BAFF, but, it inhibited 22.5% and 15.2% of the interaction of BCMA-Fc and BCMA1-Fc with mAPRIL respectively. The binding rates of BCMA1-Fc for BAFF were 91.7%, but 80.6% for mAPRIL, suggesting that BCMA1-Fc without BCMA2, bound BAFF well and less efficiently to mAPRIL. These results suggest that BCMA2 outside of the conservative DxL motif of BCMA may play an important role in the binding selectivity to its ligands. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Fingolimod induces BAFF and expands circulating transitional B cells without activating memory B cells and plasma cells in multiple sclerosis.

    Science.gov (United States)

    Miyazaki, Yusei; Niino, Masaaki; Takahashi, Eri; Suzuki, Masako; Mizuno, Masanori; Hisahara, Shin; Fukazawa, Toshiyuki; Amino, Itaru; Nakano, Fumihito; Nakamura, Masakazu; Akimoto, Sachiko; Minami, Naoya; Fujiki, Naoto; Doi, Shizuki; Shimohama, Shun; Terayama, Yasuo; Kikuchi, Seiji

    2018-02-01

    Patients with multiple sclerosis (MS) who are treated with fingolimod have an increased proportion of transitional B cells in the circulation, but the underlying mechanism is not known. We hypothesized that B cell-activating factor of the tumor necrosis factor family (BAFF) is involved in the process. Compared with healthy controls and untreated MS patients, fingolimod-treated MS patients had significantly higher serum concentrations of BAFF, which positively correlated with the proportions and the absolute numbers of transitional B cells in blood. Despite the elevated concentrations of BAFF in fingolimod-treated MS patients, serum levels of soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor, and B cell maturation antigen were not elevated. Our results show that fingolimod induces BAFF in the circulation and expands transitional B cells, but does not activate memory B cells or plasma cells in MS, which is favorable for the treatment of this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. [Giant splenic cyst in a teenager girl: Case report].

    Science.gov (United States)

    Martínez Torres, Beatriz; Medina García, Manuel; Zafra Anta, Miguel Ángel; García Muñoz-Najar, Alejandro José; Tardío Dovao, Juan C

    2017-06-01

    Giant nonparasitic splenic epidermoid cysts are relatively uncommon. These lesions can lead abdominal pain, but most of then are asymptomatic, and they are discovered incidentally. We report a 13-y old female with a giant splenic epidermoid cystic, given the special interest of diagnostic and therapeutic decision-making of this rare entity. A 13-y old female with clinical history of abdominal pain since the last two months. On physical examination a firm, tender mass was palpable in left hypochondrium. Diagnosis of a large cystic splenic mass was made based on ultrasound and abdominal computed tomography scan. Splenectomy was performed, and histopathological-immunohistochemistry studies revealed findings suggestive of primary epithelial cyst. The post-operative clinical course was satisfactory and uneventful. Treatment of giant nonparasitic splenic cysts is surgical. Preserve splenic parenchyma must be the aim in an individualized decision-making. The different types of surgical modalities will be according to the diagnosis and clinical situation (cyst size, age, comorbidities).

  14. BAFF knockout improves systemic inflammation via regulating adipose tissue distribution in high-fat diet-induced obesity.

    Science.gov (United States)

    Kim, Do-Hwan; Do, Myoung-Sool

    2015-01-16

    Obesity is recognized as a chronic low-grade inflammatory state due to adipose tissue expansion being accompanied by an increase in the production of proinflammatory adipokines. Our group is the first to report that B-cell-activating factor (BAFF) is produced from adipocytes and functions as a proinflammatory adipokine. Here, we investigated how loss of BAFF influenced diet-induced obesity in mice by challenging BAFF(-/-) mice with a high-fat diet for 10 weeks. The results demonstrated that weight gain in BAFF(-/-) mice was >30% than in control mice, with a specific increase in the fat mass of the subcutaneous region rather than the abdominal region. Expression of lipogenic genes was examined by quantitative real-time PCR, and increased lipogenesis was observed in the subcutaneous adipose tissue (SAT), whereas lipogenesis in the epididymal adipose tissue (EAT) was reduced. A significant decrease in EAT mass resulted in the downregulation of inflammatory gene expression in EAT, and more importantly, overall levels of inflammatory cytokines in the circulation were reduced in obese BAFF(-/-) mice. We also observed that the macrophages recruited in the enlarged SAT were predominantly M2 macrophages. 3T3-L1 adipocytes were cultured with adipose tissue conditioned media (ATCM), demonstrating that EAT ATCM from BAFF(-/-) mice contains antilipogenic and anti-inflammatory properties. Taken together, BAFF(-/-) improved systemic inflammation by redistributing adipose tissue into subcutaneous regions. Understanding the mechanisms by which BAFF regulates obesity in a tissue-specific manner would provide therapeutic opportunities to target obesity-related chronic diseases.

  15. Laparoscopy of a splenic flexure volvulus

    Directory of Open Access Journals (Sweden)

    Yuichi Sesumi

    2017-09-01

    Full Text Available Splenic flexure volvulus (SFV is a very rare condition that is unlikely to be suspected even when a patient has repeated episodes of abdominal pain and dyschezia. We describe the case of SFV diagnosed and treated laparoscopically in the non-volvulus condition. A 14-year-old boy with no medical history had severe left upper abdominal pain and dyschezia for approximately 1 year. Although contrast enema examination revealed no characteristic findings of volvulus, such as a bird-beak sign, a redundant part of the colon was found to be the site of abdominal pain. We suspected that this part of the colon was the cause of the left upper abdominal pain and performed laparoscopic exploration. The colon at the splenic flexure formed a long loop and was predisposed to twisting; therefore, we performed resection and functional anastomosis of this redundant colon. The postoperative course was uneventful, and the left upper abdominal pain and dyschezia did not recur. Laparoscopic exploration can play a role in patients who are suspected to have recurrent colonic volvulus with radiographic evidence of a redundant portion of the colon, as indicated in our case.

  16. Splenic function in chronic myelogenous leukemia

    International Nuclear Information System (INIS)

    Covas, D.T.; Zago, M.A.

    1987-01-01

    Spleen function was evaluated by measurement of the clearance of autologous heat-damaged 99m Tc-labelled erythrocytes from the circulation and into the spleen and the enumeration of pitted erythrocytes by interference contrast microscopy, and the spleen area was determined by scintillation scanning. All measurements were performed on 12 patients with chronic myelogenous leukemia and compared with 10 controls with apparently normal spleens, 6 splenectomized subjects and 9 patients with a reactive splenomegaly. Patients with CML had spleen function test results similar to normal controls in spite of having enlarged spleens whose projection area did not differ from that of the patients with reactive splenomegaly. Thus, patients with CML have a decreased spleen function per unit volume and signs of splenic hypofunction in the peripheral blood. The reduction of spleen function per unit volume in CML is the result of a severe decrease of the splenic blood perfusion which could result from the combined effects of the myeloid metaplasia and the increased whole-blood viscosity due to high white-cell counts. (author)

  17. Medical image of the week: splenic infarction

    Directory of Open Access Journals (Sweden)

    Casey DJ

    2016-08-01

    Full Text Available No abstract available. Article truncated after 150 words. A 52-year-old Hispanic woman with a past medical history significant for Type 1 Diabetes Mellitus, hypertension, and rheumatoid arthritis presented with left upper quadrant pain for one day. Her review of systems was positive for bloating, severe epigastric and left upper quadrant tenderness that radiated to the back and left shoulder, nausea with non-bilious emesis, and diarrhea for one day prior to admission. Physical exam only revealed epigastric and left upper quadrant tenderness to light palpation without rebound or guarding. Abdominal computed tomography of the abdomen demonstrated a new acute or subacute splenic infarct with no clear evidence of an embolic source in the abdomen or pelvis (Figure 1. Echocardiogram with bubble study and contrast did not demonstrate valve abnormalities, cardiac mass, vegetation, valve or wall motion abnormalities and no evidence of patent foramen ovale. Splenic infarction should be suspected when patients present with sharp, acute left upper quadrant pain ...

  18. Systemic lupus erythematosus and splenic abscess

    International Nuclear Information System (INIS)

    Guarnizo Z, Pilar; Ramirez R, Francisco Alejandro; Ramirez G, Luis Alberto

    2006-01-01

    Systemic lupus erythematosus is an autoimmune disease in which there is an increase risk of infections by common germ as by opportunistic germs. This fact is explained by the alterations in the humoral and cellular immunity, and phagocytic mononuclear system due to the disease and the immunosuppressive therapy use for its treatment. Multiple infectious processes have been describes in patients with SLE and within them, the splenic abscess, although in few cases. Usually its presence is associated with an underlying disease such as sepsis or peritonitis, with multiple outcomes. Due to its low frequency as well as the unusual presentation, we reported a case of a solitary splenic abscess documented by ultrasound in a teenager with SLE and immunosuppressive treatment, without any underlying infection, who presents with fever, abdominal pain, leucocytosis and elevation of acute phase reactants. He received antibiotic therapy with clindamycin and ceftriaxone and percutaneous drainage of the abscess guided by ultrasound and sent to culture in which grew non-typificable anaerobe germs, with a favorable evolution after 5 year of follow up

  19. Non-operative management for penetrating splenic trauma : how far can we go to save splenic function?

    NARCIS (Netherlands)

    Spijkerman, Roy; Teuben, Michel Paul Johan; Hoosain, Fatima; Taylor, Liezel Phyllis; Hardcastle, Timothy Craig; Blokhuis, Taco Johan|info:eu-repo/dai/nl/231997841; Warren, Brian Leigh; Leenen, Luke Petrus Hendrikus|info:eu-repo/dai/nl/071390596

    2017-01-01

    BACKGROUND: Selective non-operative management (NOM) for the treatment of blunt splenic trauma is safe. Currently, the feasibility of selective NOM for penetrating splenic injury (PSI) is unclear. Unfortunately, little is known about the success rate of spleen-preserving surgical procedures. The aim

  20. Enhanced anti-tumor therapeutic efficacy of DNA vaccine by fusing the E7 gene to BAFF in treating human papillomavirus-associated cancer.

    Science.gov (United States)

    Wu, Chao-Chih; Wu, Fang-Cih; Hsu, Yun-Tin; Hsiao, Yu-Chia; Yang, Yuh-Cheng; Chang, C Allen; Chang, Chih-Long

    2017-05-16

    B-cell-activating factor (BAFF) belongs to the tumor necrosis factor family that not only stimulates B and T cells but also counteracts immune tolerance. BAFF is also a type II membrane protein, which is secreted through the endoplasmic reticulum (ER)-Golgi apparatus pathway. Fusing an antigen to BAFF might enhance the presentation of major histocompatibility complex class I molecules. These characteristics represent an opportunity to enhance the antitumor effects of DNA vaccines. Therefore, we fused BAFF to human papillomavirus type 16 E7 as a DNA vaccine and evaluated its antitumor effects. We found that this vaccine increased E7-specific CD8+ T-cell immune responses, engendered major antitumor effects against E7-expressing tumors, and prolonged the survival of the immunized mice. Interestingly, vaccinating B-cell-deficient mice with BAFF-E7 revealed considerable E7-specific CD8+ T-cell immune responses, suggesting that B cells do not contribute to this immune response. Image analysis through confocal fluorescence microscopy revealed that fusing BAFF to E7 targeted the protein to the ER, but not BAFF lacking 128 N-terminal residues that generated a lower number of E7-specific CD8+ T cells in the vaccinated mice. Our data indicated that the ER-targeting characteristic of BAFF is the main factor improving the potency of DNA vaccines.

  1. Splenic hypofunction in the nephrotic syndrome of childhood

    Energy Technology Data Exchange (ETDEWEB)

    McVicar, M.I.; Chandra, M.; Margouleff, D.; Zanzi, I.

    1986-05-01

    The reticuloendothelial system, including the spleen, subserves important immunologic functions. Loss of splenic function results in an increased incidence of severe bacterial infections and is accompanied by thrombocytosis. Several nephrotic children were noted to have remarkably high platelet counts and predisposition to bacterial infection with encapsulated organisms. We, therefore, investigated the splenic function of nine children with primary nephrotic syndrome and measured the phagocytic function of the spleen by sequestration of Technetium-99-labelled heat-treated autologous RBC, administered intravenously. Four children had decreased splenic function. Repeat studies performed in two of these children after remission of the nephrotic syndrome gave normal results. There were six episodes of bacterial infection (3 peritonitis, 1 septic arthritis, 1 cellulitis, and 1 Escherichia coli urinary tract infection) among the four patients with decreased splenic function. There were no episodes of bacterial infection among the five nephrotic children with normal splenic function. Nephrotic patients with decreased splenic function had significantly increased platelet counts (921,000 +/- 196,000; mean +/- SEM) compared to those with normal function (435,000 +/- 46,000; P less than 0.001). Our findings suggest the possibility that some nephrotic children may have decreased splenic function in association with increased susceptibility to bacterial infections.

  2. Bacterial phagocytosis by macrophage of autogenous splenic implant

    Directory of Open Access Journals (Sweden)

    Marques R. G.

    2003-01-01

    Full Text Available Autogenous splenic implant seems to be the only alternative for preservation of splenic tissue after total splenectomy. This work was carried out to analyze the morphologic regeneration of autotransplanted splenic tissue in Wistar rats and to determine the bacterial phagocytic function of their macrophages. We utilized an experimental model with thirty-two rats, of both sexes, submitted to total splenectomy combined with autotransplantation in greater omentum of slices of the whole spleen mass. The animals were divided into two groups: I - young rats weighing 100 to 150 g; and II - adult rats weighing 250 to 300 g. Sixteen weeks later animals were intravenously inoculated with a suspension of Escherichia coli AB1157. Twenty minutes after inoculation, the animals were sacrificed and the splenic autotransplants were removed for morphological study. There was regeneration of autotransplanted splenic tissue in all animals. A similar morphological aspect among all animals was observed, with splenic tissue showing red and white pulps, lymphoid follicles, and marginal zone, with a moderate architectural disarrangement. Macrophages containing gram-negative bacterial aggregates as well as macrophages with hemosiderin pigments within the cytoplasm were observed. Blood vessels showed preserved walls, with no signs of vasculitis or thrombosis. The present results suggest that autogenous splenic implants in the greater omentum of the rat acquire the macro- and microscopic architecture of a normal spleen, with reduced dimensions, and preserve bacterial phagocyte function.

  3. Trypanosoma brucei Co-opts NK Cells to Kill Splenic B2 B Cells.

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    Deborah Frenkel

    2016-07-01

    Full Text Available After infection with T. brucei AnTat 1.1, C57BL/6 mice lost splenic B2 B cells and lymphoid follicles, developed poor parasite-specific antibody responses, lost weight, became anemic and died with fulminating parasitemia within 35 days. In contrast, infected C57BL/6 mice lacking the cytotoxic granule pore-forming protein perforin (Prf1-/- retained splenic B2 B cells and lymphoid follicles, developed high-titer antibody responses against many trypanosome polypeptides, rapidly suppressed parasitemia and did not develop anemia or lose weight for at least 60 days. Several lines of evidence show that T. brucei infection-induced splenic B cell depletion results from natural killer (NK cell-mediated cytotoxicity: i B2 B cells were depleted from the spleens of infected intact, T cell deficient (TCR-/- and FcγRIIIa deficient (CD16-/- C57BL/6 mice excluding a requirement for T cells, NKT cell, or antibody-dependent cell-mediated cytotoxicity; ii administration of NK1.1 specific IgG2a (mAb PK136 but not irrelevant IgG2a (myeloma M9144 prevented infection-induced B cell depletion consistent with a requirement for NK cells; iii splenic NK cells but not T cells or NKT cells degranulated in infected C57BL/6 mice co-incident with B cell depletion evidenced by increased surface expression of CD107a; iv purified NK cells from naïve C57BL/6 mice killed purified splenic B cells from T. brucei infected but not uninfected mice in vitro indicating acquisition of an NK cell activating phenotype by the post-infection B cells; v adoptively transferred C57BL/6 NK cells prevented infection-induced B cell population growth in infected Prf1-/- mice consistent with in vivo B cell killing; vi degranulated NK cells in infected mice had altered gene and differentiation antigen expression and lost cytotoxic activity consistent with functional exhaustion, but increased in number as infection progressed indicating continued generation. We conclude that NK cells in T. brucei

  4. [Functions of the splenic remnant after subtotal splenectomy for treatment of severe splenic injuries].

    Science.gov (United States)

    Resende, Viviam; Petroianu, Andy

    2002-01-01

    To evaluate clinical and laboratory variables in patients submitted to subtotal splenectomy. 34 patients with severe trauma of the spleen and its pedicle were studied: 25 patients were submitted to subtotal splenectomy, preserving only the upper pole of the spleen (Group I), 9 were submitted to total splenectomy (Group II), and other 22 people with intact spleen were the control (Group III). Immediate and late postoperative complications were investigated. Laboratory exams were performed in the late postoperative period (red blood cells, hemoglobin, white blood cells, platelets and Howell-Jolly bodies). We studied the B- and T-lymphocyte counts and the immunoglobulins A, G and M (IgA, IgG and IgM) levels. Splenic scintigraphy with technetium 99mTc sulfur colloid was carried out on all patients. Group II presented Howell-Jolly bodies increased and low level of immunoglobulin M. The splenic scintigraphy demonstrated the viability and the filtering function of the splenic remnant in Group I. Subtotal splenectomy is a surgical alternative technique for treatment of severe distal injuries of the spleen or when its main vessels are damaged.

  5. Splenic Involvement in Hereditary Hemorrhagic Telangiectasia

    Directory of Open Access Journals (Sweden)

    Susumu Takamatsu

    2016-01-01

    Full Text Available A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities.

  6. Unusual CT and MR Imaging Characteristics of Splenic Lymphoma

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    Chhavi Kaushik

    2011-01-01

    Full Text Available Lymphoma is the most common malignancy of the spleen. The imaging features of splenic lymphoma are nonspecific and mostly lymphomas present as a diffusely enlarged spleen. Focal lesions are described but remain of low density or intensity on CT or MRI, respectively. We describe a histologically proven case of splenic lymphoma that showed an atypical hyperdense/hyperenhancing appearance on imaging suspicious for a vascular pathology. To the best of our knowledge and based on review of English literature, such an appearance of splenic lymphoma is extremely unusual and rare.

  7. Isolated splenic metastasis from a thymic carcinoma: A case report.

    Science.gov (United States)

    Chen, Dongmei; Meng, Xiangying; Zhao, Yaowei; Wu, Shikai

    2016-09-01

    Thymic carcinomas are rare tumors that arise in the anterior mediastinum. Most of these malignancies develop local metastases limited in the thorax. Splenic metastases from thymic carcinomas are extremely rare. Here we report a case of isolated splenic metastasis from a 38-year-old female patient with Stage IV thymic carcinoma, who was treated with chemoradiotherapy. At twenty-2 months follow-up, the patient was found to have an isolated spleen metastasis, which was treated by Cyberknife with a reduced size of the metastasis, representing a partial response. Although splenic metastasis is a rare phenomenon, physicians need to be aware of the possibility of such metastases.

  8. Bacterial clearance after total splenectomy and splenic autotransplantation in rats

    Energy Technology Data Exchange (ETDEWEB)

    Marques, R.G. E-mail: rmarques@uerj.br; Petroianu, Andy; Oliveira, M.B.N. de; Bernardo-Filho, M.; Boasquevisque, E.M.; Portela, M.C

    2002-12-01

    Wistar rats submitted to isolated total splenectomy or total splenectomy combined with splenic autotransplantation were inoculated with {sup 99m}technetium-labeled Escherichia coli. Measurement of isotope uptake in the organs of the mononuclear phagocytic system showed a greater bacterial bloodstream clearance in rats with splenic autotransplantation. Although uptake of bacteria in the spleen was higher in the control group, the number of bacteria remaining in the bloodstream did not differ between groups. These results indicate that splenic autotransplantation preserves the phagocytic function of the spleen.

  9. Bacterial clearance after total splenectomy and splenic autotransplantation in rats

    International Nuclear Information System (INIS)

    Marques, R.G.; Petroianu, Andy; Oliveira, M.B.N. de; Bernardo-Filho, M.; Boasquevisque, E.M.; Portela, M.C.

    2002-01-01

    Wistar rats submitted to isolated total splenectomy or total splenectomy combined with splenic autotransplantation were inoculated with 99m technetium-labeled Escherichia coli. Measurement of isotope uptake in the organs of the mononuclear phagocytic system showed a greater bacterial bloodstream clearance in rats with splenic autotransplantation. Although uptake of bacteria in the spleen was higher in the control group, the number of bacteria remaining in the bloodstream did not differ between groups. These results indicate that splenic autotransplantation preserves the phagocytic function of the spleen

  10. CLINICAL VALUE OF BAFF AND APRIL CONCENTRATIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS

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    T. A. Panafidina

    2016-01-01

    Full Text Available Systemic lupus erythematosus (SLE is characterized by the pathological activation and differentiation of B lymphocytes. The B-lymphocyte stimulator (BLyS, also known as B cell-activating factor of the tumor necrosis factor family (BAFF, and its homologue, a proliferation-inducing ligand (APRIL, belong to the ligands of the tumor necrosis factor (TNF family and play a key role in B-lymphocyte selection and survival.Objective: to determine serum BAFF and APRIL concentrations in patients with SLE and a relationship of the clinical and laboratory parameters of the disease to the level of these cytokines.Subjects and methods. The investigation enrolled 73 patients (62 women and 11 men; median age, 30.0 [28.0; 46.0] years with SLE (disease duration, 5.0 [1.5; 11.0] years and its high activity (the median SLEDAI-2K scores of 8 [2; 13].Involvement of the kidneys and joints were found in 40 and 36% of cases, respectively; there were hematologic disorders in 38%, antinuclear factor (ANF in 94.5%, and anti-double stranded DNA antibodies in 77%. The concurrent antiphospholipid syndrome was detected in 15% of the patients. 66% of the patients took glucocorticoids (GCs (the median dose was 10 [0; 15] mg/day, calculated with reference to prednisolone, 42% received cytotoxic drugs (cyclophosphamide, mycophenolate mofetil, azathioprine; 12% used biological agents (BAs; 31.5% received no therapy at enrolment in the investigation. Serum BAFF and APRIL concentrations were estimated using an enzyme immunoassay.Results and discussion. The concentrations of BAFF and APRIL did not differ essentially in the patients with SLE and in the controls: the median level of BAFF was 0.02 [0.01; 0.64] and 0.02 [0.01; 0.03] ng/ml; that of APRIL was 2.09 [0.01; 3.80] and 0.01 [0.01; 4.16] ng/ml, respectively. The elevated concentration of BAFF (>0.82 ng/ml was revealed in 5.5% of the patients with SLE and that of APRIL (>5.96 ng/ml in 4.1%. There was a positive correlation between

  11. Blood stage Plasmodium falciparum antigens induce T cell independent immunoglobulin production via B cell activation factor of the TNF family (BAFF) pathway.

    Science.gov (United States)

    Kumsiri, Ratchanok; Potup, Pachuen; Chotivanich, Kesinee; Petmitr, Songsak; Kalambaheti, Thareerat; Maneerat, Yaowapa

    2010-12-01

    T independent (TI) antigens (Ags) activate monocytes to produce a cytokine, termed B cell activation factor (BAFF), involved in immunoglobulin (Ig) production. This study aimed to investigate whether the soluble schizont fraction of Plasmodium falciparum antigen (sPfAg) and hemozoin (HZ) could act as TI Ag to induce P. falciparum (Pf) specific Ig production via BAFF pathway. Co-cultures of monocytes and naïve B cells from 6 healthy donors were stimulated with sPfAg (10mg/ml) or HZ (10μM). At interval times, the expressions of BAFF on activated monocytes, BAFF receptor (BAFF-R) and proliferation nuclear Ag in activated B cells were determined by flow cytometry. The soluble BAFF (sBAFF), total and specific IgG levels in the supernatants were assessed by enzyme-linked immunosorbent assay (ELISA). The finding revealed both sPfAg and HZ could activate monocytes to express BAFF on surface and release sBAFF in the supernatant within 72h of stimulation. The B cells responded to specific activation, indicated by BAFF-R expression on the surface within 72h, marked proliferation on day 7, and final production of total and specific IgG during days 7-12. Comparing to sPfAg, HZ stimulated monocyte and B cell co-culture to express higher levels of BAFF and sBAFF during 24-48h, more BAFF-R on HZ activated B cells within 24h and induced marked proliferation of B cells with higher Pf specific IgG level. However, stimulation with sPfAg showed a more significant correlation between BAFF expression on the activated monocytes at 72h and the Pf specific IgG level on day 12 (r=0.961, p=0.039, Pearson Correlation). In conclusion, it is possible that both sPfAg and HZ stimulated B cells to produce specific IgG with BAFF involvement. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Data for the crystal structure of APRIL–BAFF–BAFF heterotrimer

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    Klaus Maskos

    2016-03-01

    Full Text Available The TNF family ligands B cell activation factor (BAFF and a proliferation-inducing ligand (APRIL modulate B cell function by forming homotrimers and heterotrimers. To determine the structure of a heterotrimer of BAFF and APRIL, these ligands were expressed as a single chain protein in HEK 293 cells, purified by affinity and size exclusion chromatographies, and crystallized. Crystals belonging to the orthorhombic crystal system with a space group of C2221 diffracted to 2.43 Å. Initial structural solution was obtained by the molecular replacement method, and the structure was further refined to an R factor of 0.179 and free R factor of 0.234. The atomic coordinates and structure factors have been deposited into the Protein Data Bank (accession code 4ZCH.

  13. Serum BAFF in Indian patients with IIM: a retrospective study reveals novel clinico-phenotypic associations in children and adults.

    Science.gov (United States)

    Gupta, Latika; Chaurasia, Smriti; Srivastava, Puja; Dwivedi, Sanjay; Lawrence, Able; Misra, Ramnath

    2018-03-07

    We studied the serum levels of B cell survival factors BAFF and APRIL in patients with idiopathic inflammatory myositis (IIM) and their relation with clinical and autoantibodies. Seventy-five patients (51 females and 24 males) with IIM (Bohan and Peter's criteria 1975) and 25 healthy adults were analyzed for BAFF, APRIL and IL-17 by ELISA, and myositis-specific and associated antibodies (MSA and MAA) using line immunoblot assay. Of the 75 patients, 59 were adults, 42 had Dermatomyositis (DM), and 17 had Polymyositis. Median disease duration was 5 (3-12) months. BAFF levels were higher in IIM than healthy controls [p = 0.001], and in children with jDM than adults [p = 0.026]. BAFF levels were higher in adults with arthritis [p = 0.018], weight loss [p = 0.007], and PAH [p = 0.004]. Among the various MSAs, lowest levels were seen in those with anti-SRP [p = 0.043]. Median follow-up duration was 145 patient years. Twelve patients relapsed, while nine were in drug-free remission. BAFF were similar between these groups. Serum APRIL levels were elevated in limited number of patients with myositis, and the levels did not differ amongst the clinico-serologic phenotypes. IL-17 levels were higher in individuals positive for anti-SRP [p = 0.028]. Serum BAFF levels are elevated in IIM, more so in children. BAFF levels may be useful as biomarker for PAH and arthritis. Anti-SRP positivity is associated with elevated IL-17 levels suggesting role in pathogenesis.

  14. BAFF and APRIL from Activin A-Treated Dendritic Cells Upregulate the Antitumor Efficacy of Dendritic Cells In Vivo.

    Science.gov (United States)

    Shurin, Michael R; Ma, Yang; Keskinov, Anton A; Zhao, Ruijing; Lokshin, Anna; Agassandian, Marianna; Shurin, Galina V

    2016-09-01

    The members of the TGFβ superfamily play a key role in regulating developmental and homeostasis programs by controlling differentiation, proliferation, polarization, and survival of different cell types. Although the role of TGFβ1 in inflammation and immunity is well evident, the contribution of other TGFβ family cytokines in the modulation of the antitumor immune response remains less documented. Here we show that activin A triggers SMAD2 and ERK1/2 pathways in dendritic cells (DC) expressing type I and II activin receptors, and upregulates production of the TNFα family cytokines BAFF (TALL-1, TNFSF13B) and APRIL (TALL-2, TNFSF13A), which is blocked by SMAD2 and ERK1/2 inhibitors, respectively. BAFF and APRIL derived from activin A-treated DCs upregulate proliferation and survival of T cells expressing the corresponding receptors, BAFF-R and TACI. In vivo, activin A-stimulated DCs demonstrate a significantly increased ability to induce tumor-specific CTLs and inhibit the growth of melanoma and lung carcinoma, which relies on DC-derived BAFF and APRIL, as knockdown of the BAFF and APRIL gene expression in activin A-treated DCs blocks augmentation of their antitumor potential. Although systemic administration of activin A, BAFF, or APRIL for the therapeutic purposes is not likely due to the pluripotent effects on malignant and nonmalignant cells, our data open a novel opportunity for improving the efficacy of DC vaccines. In fact, a significant augmentation of the antitumor activity of DC pretreated with activin A and the proven role of DC-derived BAFF and APRIL in the induction of antitumor immunity in vivo support this direction. Cancer Res; 76(17); 4959-69. ©2016 AACR. ©2016 American Association for Cancer Research.

  15. Increased levels of BAFF and APRIL related to human active pulmonary tuberculosis.

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    Kai Liu

    Full Text Available BACKGROUND: Despite great efforts to improve diagnosis and treatment, tuberculosis (TB remains a major health problem worldwide, especially in developing countries. Lack of concrete immune markers is still the obstacle to properly evaluate active TB. Therefore, identification of more validated biomarkers and phenotypic signatures is imperative. In particular, T cell-related biomarkers are more significant. METHODOLOGY: To understand the nature of CD4(+ T cell-derived signatures involved in infection and disease development, we examined and analyzed whole genome expression profiles of purified CD4(+ T cells from healthy individuals (HD, two distinct populations with latent infection (with low or high IFN-γ levels, LTB(L/LTB(H and untreated TB patients. Following, we validated the expression profiles of genes in the peripheral CD4(+ T cells from each group and examined secretion levels of distinct cytokines in serum and pleural effusion. PRINCIPAL FINDINGS: Our bio-informatic analyses indicate that the two latent populations and clinical TB patients possess distinct CD4(+ T cell gene expression profiles. Furthermore, The mRNA and protein expression levels of B cell activating factor (BAFF, which belongs to the TNF family, and a proliferation-inducing ligand (APRIL were markedly up-regulated at the disease stage. In particular, the dramatic enhancement of BAFF and APRIL in the pleural effusion of patients with tuberculosis pleurisy suggests that these proteins may present disease status. In addition, we found that the BAFF/APRIL system was closely related to the Th1 immune response. Our study delineates previously unreported roles of BAFF and APRIL in the development of tuberculosis, and these findings have implications for the diagnosis of the disease. Our study also identifies a number of transcriptional signatures in CD4(+ T cells that have the potential to be utilized as diagnostic and prognostic tools to combat the tuberculosis epidemic.

  16. US and CT findings in splenic focal lesions in AIDS

    International Nuclear Information System (INIS)

    Schinina, V.; Rizzi, E.B.; Mazzuoli, G.; Bibbolilno, C.; David, V.

    2000-01-01

    To evaluate the role of US and CT in focal splenic lesions in AIDS patients in relation to etiology. Material and Methods: A total of 66 patients with AIDS and focal splenic lesions were examined with sonography. CT with administration of contrast medium was performed in 12 cases. Results: Of the focal splenic lesions, 67% were correlated with an infective pathology with prevalence of Mycobacteria tuberculosis (75%), 26% were neoplastic and 6% splenic infarcts. The lesions were hypoechoic in 60% of the cases, while 10% were hypoanechoic and 1% anechoic. At CT, all lesions appeared hypodense, even after i.v. administration of contrast medium. Conclusion: The combination of echographic reports and clinical and laboratory data allows for a diagnosis that can be confirmed, and making a decision for effective therapy of AIDS is possible. CT does not provide any additional information

  17. A case of posttraumatic splenic translocation into the thorax

    International Nuclear Information System (INIS)

    Sosnowski, P.; Sikorski, L.; Ziemianski, A.

    1993-01-01

    A case of the left diaphragmatic hernia due to blunt thoracic and abdominal trauma is presented. Characteristic radiological signs of splenic translocation into the thorax contributed to quick diagnosis and immediate surgical intervention. (author)

  18. Aneurysm of the splenic artery - a entity controversial | du Toit ...

    African Journals Online (AJOL)

    The case of an asymptomatic, calcified, arteriosclerotic, intact splenic artery aneurysm in a 60-year-old woman is presented. The diagnosis was confirmed by selective coeliac arteriography and the aneurysm was successfully resected with preservation of the spleen.

  19. Melioidosis Presenting with Isolated Splenic Abscesses: A Case Report

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    Chun-Yu Lin

    2007-08-01

    Full Text Available Splenic abscesses caused by Burkholderia pseudomallei are rarely reported in Taiwan. Here we report a middle-aged man who presented with fever, chills, and general malaise for several days. Abdominal echo revealed isolated splenic abscesses and he received antibiotics treatment according to the initial blood culture result, Serratia marcescens. However, fever did not subside. Then he was referred to our hospital and meropenem was prescribed. Fever subsided 5 days after the beginning of meropenem administration. Repeated fine-needle aspiration of splenic abscesses drained out the pus, which was cultured as B. pseudomallei. He was finally diagnosed as a case of melioidosis based on microbiological evidence. Physicians must take melioidosis into consideration when splenic abscesses are encountered clinically.

  20. Splenic Operations In A Teaching Hospital, South-Western Nigeria ...

    African Journals Online (AJOL)

    %. Conclusion: As trauma is the most common indication for operations on the spleen, spleen conservation should be practiced more often where open procedures are indicated. Keywords: Splenic operations, Spleen conservation surgery, ...

  1. Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus

    Science.gov (United States)

    Price, Jordan V.; Haddon, David J.; Kemmer, Dodge; Delepine, Guillaume; Mandelbaum, Gil; Jarrell, Justin A.; Gupta, Rohit; Balboni, Imelda; Chakravarty, Eliza F.; Sokolove, Jeremy; Shum, Anthony K.; Anderson, Mark S.; Cheng, Mickie H.; Robinson, William H.; Browne, Sarah K.; Holland, Steven M.; Baechler, Emily C.; Utz, Paul J.

    2013-01-01

    Autoantibodies against cytokines, chemokines, and growth factors inhibit normal immunity and are implicated in inflammatory autoimmune disease and diseases of immune deficiency. In an effort to evaluate serum from autoimmune and immunodeficient patients for Abs against cytokines, chemokines, and growth factors in a high-throughput and unbiased manner, we constructed a multiplex protein microarray for detection of serum factor–binding Abs and used the microarray to detect autoantibody targets in SLE. We designed a nitrocellulose-surface microarray containing human cytokines, chemokines, and other circulating proteins and demonstrated that the array permitted specific detection of serum factor–binding probes. We used the arrays to detect previously described autoantibodies against cytokines in samples from individuals with autoimmune polyendocrine syndrome type 1 and chronic mycobacterial infection. Serum profiling from individuals with SLE revealed that among several targets, elevated IgG autoantibody reactivity to B cell–activating factor (BAFF) was associated with SLE compared with control samples. BAFF reactivity correlated with the severity of disease-associated features, including IFN-α–driven SLE pathology. Our results showed that serum factor protein microarrays facilitate detection of autoantibody reactivity to serum factors in human samples and that BAFF-reactive autoantibodies may be associated with an elevated inflammatory disease state within the spectrum of SLE. PMID:24270423

  2. Howell-Jolly bodies. A clue to splenic infarction.

    Science.gov (United States)

    Larrimer, J H; Mendelson, D S; Metz, E N

    1975-06-01

    A 74-year-old woman with secondary erythrocytosis was found to have Howell-Jolly bodies in peripheral blood erythrocytes following acute splenic infarction. The Howell-Jolly bodies were a transitory finding and disappeared six days after the infarction, although the spleen remained abnormal by isotope scanning for several weeks. Careful inspection of the peripheral blood film may be an aid in the diagnosis of acute splenic infarction.

  3. Splenic Pregnancy: A New Minimally Invasive Approach to Treatment

    International Nuclear Information System (INIS)

    Klang, Eyal; Keddel, Nicholas; Inbar, Yael; Rimon, Uri; Amitai, Michal

    2016-01-01

    The spleen is a rare site of abdominal ectopic pregnancy. In a review of the literature, we found 16 published cases of primary splenic pregnancies. Of the cases identified, all received surgical intervention, with one case successfully treated with laparoscopic methotrexate injection, and the rest underwent splenectomy. We would like to present a case of primary splenic pregnancy in a 35-year-old woman successfully treated with percutaneous image-guided injection of methotrexate and KCl.

  4. Splenic Pregnancy: A New Minimally Invasive Approach to Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Klang, Eyal, E-mail: eyalkla@hotmail.com; Keddel, Nicholas; Inbar, Yael; Rimon, Uri; Amitai, Michal [Tel Hashomer Hospital, The Chaim Sheba Medical Center, Department of Radiology (Israel)

    2016-09-15

    The spleen is a rare site of abdominal ectopic pregnancy. In a review of the literature, we found 16 published cases of primary splenic pregnancies. Of the cases identified, all received surgical intervention, with one case successfully treated with laparoscopic methotrexate injection, and the rest underwent splenectomy. We would like to present a case of primary splenic pregnancy in a 35-year-old woman successfully treated with percutaneous image-guided injection of methotrexate and KCl.

  5. Splenic simulation by left hepatic lobe following splenectomy

    International Nuclear Information System (INIS)

    Noel, A.; Harbert, J.C.

    1984-01-01

    Remodeling of the liver following splenectomy may simulate hypertrophy of an accessory spleen on sulfur colloid scans. Two patients are reported. In one case splenic simulation is attributed to unusual hepatic scarring confirmed at autopsy. In the second the unusual configuration appears to have been caused by molding of the liver. The clinician should be aware of possible splenic simulation in postsplenectomy patients suspected of hypersplenism

  6. The presence of B-cell activating factor (BAFF) in umbilical cord blood in both healthy and pre-eclamptic pregnancies and in human breast milk.

    Science.gov (United States)

    Bienertova-Vasku, Julie; Zlamal, Filip; Tomandl, Josef; Hodicka, Zuzana; Novak, Jan; Splichal, Zbynek; Ventruba, Pavel; Thon, Vojtech; Vasku, Anna

    2015-06-01

    B-cell activating factor (BAFF) is an important immune regulator that was recently reported to be secreted by placenta. The aim of the study was to investigate the presence of BAFF in umbilical cord blood, maternal serum, and breast milk in normal and in pre-eclamptic pregnancies. Pairs of maternal serum/umbilical cord blood were obtained from 12 pre-eclamptic and 34 physiological pregnancies. Another cohort of 10 healthy lactating women was established that was followed up for 6 months following delivery to investigate BAFF levels in breast milk. BAFF levels in maternal peripheral blood were significantly higher in physiological pregnancies than in pre-eclamptic pregnancies (p BAFF in breast milk during the 6-month post-partum period of breastfeeding. In this study, we demonstrate that BAFF levels are significantly lower in maternal peripheral blood in pre-eclamptic pregnancies. We also report the consistent presence of BAFF in breast milk in healthy women. More research into the role of BAFF in pregnancy, and during breastfeeding, is imperative. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Increase of Intracellular BAFF in B Cells of Sjögren’s Patients Is Not Affected by Decrease of BAFFR

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    Jan Krejsek

    2015-07-01

    Full Text Available The presence of a broad spectrum of autoantibodies in Sjögren’s syndrome (SjS patients is the result of abnormal B-cell regulation that can be at least partially explained by abnormal BAFF/BAFFR regulation. The objective of this study was to determine both membrane and intracellular expression of BAFF/BAFFR in monocytes and B-cells in peripheral blood of 19 primary Sjögren’s syndrome patients and 20 healthy controls using flow cytometry. We also measured sBAFF in serum. Compared to healthy controls, both surface and intracellular expression of BAFF was significantly increased in monocytes and B-cells of SjS patients. Also serum sBAFF level was elevated. Expression of BAFFR on B-cells of SjS patients was surprisingly decreased, but there was no clear increase or decrease within monocytes. Our results indicate that activated monocytes communicate with B-cells via BAFF and BAFFR, so that B-cells are stimulated, but BAFF is also produced to stimulate cells in autocrine way. The decrease of BAFFR expression in SjS patients suggests that there is the mechanism that attempts to take over in order to balance the high level of BAFF.

  8. BAFF overexpression increases lymphocytic infiltration in Sjögren's target tissue, but only inefficiently promotes ectopic B-cell differentiation.

    Science.gov (United States)

    Ding, Jian; Zhang, Wei; Haskett, Scott; Pellerin, Alex; Xu, Shanqin; Petersen, Britta; Jandreski, Luke; Hamann, Stefan; Reynolds, Taylor L; Zheng, Timothy S; Mingueneau, Michael

    2016-08-01

    B-cell activating factor (BAFF) levels are increased in rheumatoid arthritis, lupus and primary Sjögren's syndrome (pSS). However, BAFF contribution to pathogenesis is not completely understood. In pSS, immune infiltration of the salivary and lacrimal glands leads to xerostomia and xerophtalmia. Glandular B cell hyperactivation, differentiation into germinal center (GC)-like structures and plasma cell accumulation are histopathological hallmarks that were attributed to increased BAFF. Here, we experimentally tested this hypothesis by overexpressing BAFF in a mouse model of pSS. BAFF overexpression enhanced lymphocytic infiltration and MHCII expression on B cells. Increased BAFF also induced B cell differentiation into GC B cells within the autoimmune target tissue. However, even in these conditions, GC B cells only accounted for BAFF is not efficiently promoting ectopic GC formation in pSS and warranting further investigation of therapeutics targeting both BAFF and the related TNF-family member APRIL. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Prune belly syndrome, splenic torsion, and malrotation: a case report.

    Science.gov (United States)

    Tran, Sifrance; Grossman, Eric; Barsness, Katherine A

    2013-02-01

    An 18 year old male with a history of prune belly syndrome (PBS) presented with acute abdominal pain and palpable left upper quadrant mass. Computed tomography (CT) of the abdomen revealed a medialized spleen with a "whirl sign" in the splenic vessels, consistent with splenic torsion. Coincidentally, the small bowel was also noted to be on the right side of the abdomen, while the colon was located on the left, indicative of malrotation. Emergent diagnostic laparoscopy confirmed splenic torsion and intestinal malrotation. Successful laparoscopic reduction of the splenic torsion was achieved, however, conversion to an open procedure by a vertical midline incision was necessary owing to the patient's unique anatomy. Open splenopexy with a mesh sling and Ladd's procedure were subsequently performed. Malrotation and wandering spleen are known, rare associated anomalies in PBS; however, both have not been reported concurrently in a patient with PBS in the literature. In patients with PBS, acute abdominal pain, and an abdominal mass, high clinical suspicion for gastrointestinal malformations and prompt attention can result in spleen preservation and appropriate malrotation management. We present a case of a teenager who presented with a history of PBS, acute abdominal pain, and a palpable abdominal mass. The patient was found to have splenic torsion and intestinal malrotation. The clinical findings, diagnostic imaging, and surgical treatment options of splenic torsion are reviewed. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. [Isolated splenic metastases from cervical cancer: a rare entity].

    Science.gov (United States)

    Villalón-López, José Sebastián; Souto-del Bosque, Rosalía; Montañez-Lugo, Juan Ignacio; Chávez-González, Bruno

    2014-01-01

    Splenic metastases from solid tumors are a rare event with an incidence of only 2.9% to 9%. Splenic metastases from cervical cancer are a rare entity. Only a few cases have been reported of isolated spleen metastases from cervical cancer. We present the case of a 76-year-old woman with moderately differentiated endocervical adenocarcinoma stromal and endocervical invasion. Clinical stage was Ib1 and Ca-125 values of 150 U. She was managed with hysterectomy and pelvic lymphadenectomy. She received pelvic radiotherapy (45 Gy) followed 24 Gy of brachytherapy. Two years later she presented with abdominal pain. Abdominal computed tomography showed two splenic parenchymal lesions without disease in the remainder of the abdominal cavity and chest with a Ca-125 of 2,733 U. The patient is submitted to splenectomy. Histopathology demonstrates splenic metastases of well-differentiated adenocarcinoma from the endocervix. Immunohistochemical stain showed positivity from carcinoembryonic antigen; estrogen and progesterone receptors are negative. Ca-125 level 8 weeks after surgery was 16 U/ml. The patient received six cycles of adjuvant chemotherapy with paclitaxel and cisplatin. At 12 months follow-up the patient is alive and without evidence of tumor activity. The spleen is an uncommon site of metastasis. Splenectomy is considered the appropriate treatment in order to avoid complications such as splenic rupture and splenic vein thrombosis as well as to improve pain control from splenomegaly. Twelve months after surgery our patient is alive and without evidence of tumor activity.

  11. CP-25 attenuates the inflammatory response of fibroblast-like synoviocytes co-cultured with BAFF-activated CD4(+) T cells.

    Science.gov (United States)

    Jia, Xiaoyi; Wei, Fang; Sun, Xiaojing; Chang, Yan; Xu, Shu; Yang, Xuezhi; Wang, Chun; Wei, Wei

    2016-08-02

    Total glucosides of paeony (TGP) is the first anti-inflammatory immune regulatory drug approved for the treatment of rheumatoid arthritis in China. A novel compound, paeoniflorin-6'-O-benzene sulfonate (code CP-25), comes from the structural modification of paeoniflorin (Pae), which is the effective active ingredient of TGP. The aim of the present study is to investigate the effect of CP-25 on adjuvant arthritis (AA) fibroblast-like synoviocytes (FLS) co-cultured with BAFF-activated CD4(+) T cells and the expression of BAFF-R in CD4(+) T cells. The mRNA expression of BAFF and its receptors was assessed by qPCR. The expression of BAFF receptors in CD4(+) T cells was analyzed by flow cytometry. The effect of CP-25 on AA rats was evaluated by their joint histopathology. The cell culture growth of thymocytes and FLS was detected by cell counting kit (CCK-8). The concentrations of IL-1β, TNF-α, and IL-6 were measured by Enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of BAFF and BAFF-R were enhanced in the mesenteric lymph nodes of AA rats, TACI expression was reduced, and BCMA had no change. The expression of BAFF-R in CD4(+) T cells was also enhanced. CP-25 alleviated the joint histopathology and decreased the expression of BAFF-R in CD4(+) T cells from AA rats in vivo. In vitro, CP-25 inhibited the abnormal cell culture growth of BAFF-stimulated thymocytes and FLS. In the co-culture system, IL-1β, IL-6 and TNF-α production was enhanced by FLS co-cultured with BAFF-activated CD4(+) T cells. Moreover, BAFF-stimulated CD4(+) T cells promoted the cell culture growth of FLS. The addition of CP-25 decreased the expression of BAFF-R in CD4(+) T cells and inhibited the cell culture growth and cytokine secretion ability of FLS co-cultured with BAFF-activated CD4(+) T cells. The present study indicates that CP-25 may repress the cell culture growth and cytokine secretion ability of FLS, and its inhibitory effects might be associated with its ability

  12. A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells

    Directory of Open Access Journals (Sweden)

    Jonathan V. Almaden

    2014-12-01

    Full Text Available BAFF, an activator of the noncanonical NFκB pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NFκB family member RelB is required ex vivo for B cell maturation, but cRel is required for proliferation. Combined molecular network modeling and experimentation revealed Nfkb2 p100 as a pathway switch; at moderate p100 synthesis rates in maturing B cells, BAFF fully utilizes p100 to generate the RelB:p52 dimer, whereas at high synthesis rates, p100 assembles into multimeric IκBsome complexes, which BAFF neutralizes in order to potentiate cRel activity and B cell expansion. Indeed, moderation of p100 expression or disruption of IκBsome assembly circumvented the BAFF requirement for full B cell expansion. Our studies emphasize the importance of p100 in determining distinct NFκB network states during B cell biology, which causes BAFF to have context-dependent functional consequences.

  13. A pathway switch directs BAFF signaling to distinct NFκB transcription factors in maturing and proliferating B cells.

    Science.gov (United States)

    Almaden, Jonathan V; Tsui, Rachel; Liu, Yi C; Birnbaum, Harry; Shokhirev, Maxim N; Ngo, Kim A; Davis-Turak, Jeremy C; Otero, Dennis; Basak, Soumen; Rickert, Robert C; Hoffmann, Alexander

    2014-12-24

    BAFF, an activator of the noncanonical NFκB pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NFκB family member RelB is required ex vivo for B cell maturation, but cRel is required for proliferation. Combined molecular network modeling and experimentation revealed Nfkb2 p100 as a pathway switch; at moderate p100 synthesis rates in maturing B cells, BAFF fully utilizes p100 to generate the RelB:p52 dimer, whereas at high synthesis rates, p100 assembles into multimeric IκBsome complexes, which BAFF neutralizes in order to potentiate cRel activity and B cell expansion. Indeed, moderation of p100 expression or disruption of IκBsome assembly circumvented the BAFF requirement for full B cell expansion. Our studies emphasize the importance of p100 in determining distinct NFκB network states during B cell biology, which causes BAFF to have context-dependent functional consequences. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Proximal splenic artery embolization for blunt splenic injury: clinical, immunologic, and ultrasound-Doppler follow-up.

    Science.gov (United States)

    Bessoud, Bertrand; Duchosal, Michel A; Siegrist, Claire-Anne; Schlegel, Susanna; Doenz, Francesco; Calmes, Jean-Marie; Qanadli, Salah D; Schnyder, Pierre; Denys, Alban

    2007-06-01

    To evaluate the clinical, US (ultrasound)-Doppler and hematologic findings after proximal splenic artery embolization (PSAE) for blunt injury. From August 1998 to February 2003, 37 patients (28 men and 9 women; 20-89 years old, mean 40 years) underwent PSAE for blunt injuries. One patient required secondary splenectomy after PSAE. Early complications were investigated during the hospital stay. Delayed follow-up included review of the outpatient records, telephone interview, consultation, US-Doppler splenic study, Howell-Jolly body search, and serum antibody titer determinations (pneumococcus and Haemophilus influenzae B). No early postprocedural complications were depicted. Ten patients were lost on follow-up. Two patients had a telephone interview that revealed no complication. Twenty-four patients were examined 6 to 63 (mean 26) months after the embolization. No late complication was reported. Splenic measurements were in the normal range: length (53-110 mm; mean, 73), width (49-110 mm; 76), thickness (26-56 mm; 38), volume (61-508 mL; 226), standard ellipsoid formula volume (32-265 mL; 118), corrected volume (29-238 mL; 106), and splenic volumetric index (2.3-18.8; 8.4). The spleen was homogeneous in 23 patients (96%). Intrasplenic vascularization was present and splenic vein was patent in all patients. Howell-Jolly bodies were found in two patients. All patients (24 of 24) evaluated for exposure-driven immunity against Haemophilus Influenza b had sufficient immunity. Seventeen of the 18 patients (94%) evaluated for exposure-driven immunity against pneumococcus had sufficient immunity. Five of the six patients (83%) evaluated for pneumococcus vaccine response had a sufficient response. Proximal splenic artery embolization in blunt splenic injuries is a well-tolerated technique without major long-term impact on the splenic anatomy and immune function.

  15. Diagnosis of splenic involvement in Hodgkin's disease by radionuclide evaluation of splenic contraction in response to adrenaline

    International Nuclear Information System (INIS)

    Osadchaya, T.I.; Vasilo, N.I.; Baisogolov, G.D.

    1980-01-01

    Splenic contraction in response to adrenaline was studied by a radionuclidic technique in 33 patients who then underwent exploratory laparotomy and splenectomy. The decrease in splenic size was estimated by the percent diminution of spleen area from the baseline scan, and was found to be significantly less (P < 0.001) in the group of patients with Hodgkins's involvement of the spleen. Possible applications of the test for diagnostic purposes are discussed

  16. BAFF (B cell activating factor) transcript level in peripheral blood of patients with SLE is associated with same-day disease activity as well as global activity over the next year.

    Science.gov (United States)

    Zollars, Eric; Bienkowska, Jadwiga; Czerkowicz, Julie; Allaire, Norm; Ranger, Ann M; Magder, Laurence; Petri, Michelle

    2015-01-01

    Quantitating gene expression is a potential method of developing biomarkers in systemic lupus erythematosus (SLE). Because of the known pathological role of B cell activating factor (BAFF) in SLE, we explored the association between BAFF gene expression and clinical activity in SLE. A total of 275 patients with SLE completed this phase of a prospective observational study. At entry into the study, the BAFF gene expression levels were determined in peripheral blood RNA. Serum concentration of BAFF protein was also measured. We then determined clinical associations with SLE disease history, SLE activity on the same day and SLE activity over the course of the next year. Elevated BAFF gene expression was associated with a history of more leucopenia and serologically with more autoantibodies (anti-dsDNA, anti-Sm, anti-Ro, anti-La and anti-RNP) and low complement. Patients with higher amounts of BAFF transcript had higher measured levels of clinical disease activity. Initial high levels of BAFF gene expression also predicted increased disease activity over the course of the next year. In contrast, serum concentration of BAFF protein was not strongly associated with same-day global disease activity or with future disease activity. BAFF gene expression level is associated with clinical and serological SLE activity on the same day and predictive of clinical activity over the next year. BAFF gene expression is a better measure and predictor of SLE disease activity than the serum BAFF protein level.

  17. Isolated Retroperitoneal Hydatid Cyst Invading Splenic Hilum

    Directory of Open Access Journals (Sweden)

    Safak Ozturk

    2014-01-01

    Full Text Available Introduction. Hydatid disease (HD is an infestation that is caused by the larval stage of Echinococcus granulosus. The liver is affected in approximately two-thirds of patients, the lungs in 25%, and other organs in a small proportion. Primary retroperitoneal hydatid cyst is extremely rare. The most common complaint is abdominal pain; however, the clinical features of HD may be generally dependent on the location of the cyst. Case Presentation. A 43-year-old female was admitted with the complaint of abdominal pain. Her physical examination was normal. Computed tomography (CT revealed a 17 × 11 cm cystic lesion, with a thick and smooth wall that is located among the left liver lobe, diaphragm, spleen, tail of the pancreas, and transverse colon and invading the splenic hilum. Total cystectomy and splenectomy were performed. Pathological examination was reported as cyst hydatid. Discussion. Cysts in the peritoneal cavity are mainly the result of the spontaneous or traumatic rupture of concomitant hepatic cysts or surgical inoculation of a hepatic cyst. Serological tests contribute to diagnosis. In symptomatic and large hydatid peritoneal cysts, surgical resection is the only curative treatment. Total cystectomy is the gold standard. Albendazole or praziquantel is indicated for inoperable and disseminated cases. Percutaneous aspiration, injection, and reaspiration (PAIR technique is another nonsurgical option.

  18. Pathway of Toll-like receptor 7/B cell activating factor/B cell activating factor receptor plays a role in immune thrombocytopenia in vivo.

    Directory of Open Access Journals (Sweden)

    Qing Yang

    Full Text Available Immune thrombocytopenia (ITP is an autoimmune disorder characterized by anti-platelet autoantibody-mediated platelet destruction. Antigen-presenting cell (APC dysfunction is considered to play crucial roles in ITP. However, how APC affects autoreactive B cells in ITP is still unknown. Using a mouse model of immune thrombocytopenia, we demonstrated an increase in levels of TLR7 in splenic mononuclear cells (SMCs. Using both TLR7 agonist and TLR7 silencing lentivirus, we found stimulation of TLR7 decreased platelet counts and increased levels of platelet-associated IgG (PAIgG in ITP mice, which correlates TLR7 with platelet destruction by autoantibodies. Levels of serum BAFF increased significantly in ITP mice and stimulation of TLR7 promoted secretion of BAFF. Among the three BAFF receptors, only BAFF receptor (BAFF-R increased in ITP mice. However, activation of TLR7 showed no effect on the expression of BAFF receptors. These findings indicate that upregulation of TLR7 may augment BAFF secretion by APC and through ligation of BAFF-R promote autoreactive B cell survival and thus anti-platelet autoantibody production. The pathway of TLR7/BAFF/BAFF-R provides us with an explanation of how activation of APC affects autoantibody production by B cells in ITP and thus might provide a reasonable therapeutic strategy for ITP.

  19. The reevaluation of plain roentgenological study in isolated splenic injury

    International Nuclear Information System (INIS)

    Kang, Seong Ihn; Ko, Seung Sook; Kim, Kil Jeong; Oh, Jae Hee; Kim, Young Chul

    1986-01-01

    The spleen is the most common intraabdominal organ injured in blunt trauma. Although physical signs and symptoms, coupled with abdominal paracentesis and peritoneal lavage confirm intraabdominal injury, but isolated splenic injury especially delayed rupture, the diagnosis and clinical course is variable. We are reevaluation of plain roentgenologic findings for the light of early diagnosis of isolated splenic injury. 24 patients of the autopsy and surgically proven isolated splenic injury at Chosun University Hospital in the period from 1980 January to 1986 June were analyzed plain roentgenogram retrospectively. The results were as follows: 1. Male patients predominate, constitution 87.5%. Incidence has been greatest in second to fourth decade. 2. Mode of trauma causing isolated splenic injury is most common in motor vehicle accident and others are fall down, struck by fist, blow to object, uncertain blunt trauma. 3. Delayed rupture of spleen occurred in 2 cases (8.3%). 4. Common patterns of splenic injury is simple laceration that involves both the capsule and the parenchyma and a laceration that involves the splenic pedicle. 5. Plain chest roentgenographic findings were abnormal in 4 cases (16.7%). The most common plain abdominal roentgenographic findings was the evidence of intaabdominal fluid in 21 cases (87.5%). The others are included in order of frequency; gastric dilatation, prominent mucosal folds on greater curvature of the stomach, evidence of pelvic fluid, displacement of stomach to the right or downward, mass density in the region of spleen. 6. No relationship can be shown between patterns of injury, time lapse after trauma and plain roentgenological findings. But the evidence of intraabdominal fluid is most important in the light of early diagnosis. 7. Diagnosis of splenic injury may be most helpful that in combination with clinical history, clinical symptoms and signs and plain film findings. In delayed rupture, diagnostic value of serial examination

  20. Splenic Artery Embolization for the Treatment of Gastric Variceal Bleeding Secondary to Splenic Vein Thrombosis Complicated by Necrotizing Pancreatitis: Report of a Case

    Directory of Open Access Journals (Sweden)

    Hee Joon Kim

    2016-01-01

    Full Text Available Splenic vein thrombosis is a relatively common finding in pancreatitis. Gastric variceal bleeding is a life-threatening complication of splenic vein thrombosis, resulting from increased blood flow to short gastric vein. Traditionally, splenectomy is considered the treatment of choice. However, surgery in necrotizing pancreatitis is dangerous, because of severe inflammation, adhesion, and bleeding tendency. In the Warshaw operation, gastric variceal bleeding is rare, even though splenic vein is resected. Because the splenic artery is also resected, blood flow to short gastric vein is not increased problematically. Herein, we report a case of gastric variceal bleeding secondary to splenic vein thrombosis complicated by necrotizing pancreatitis successfully treated with splenic artery embolization. Splenic artery embolization could be the best treatment option for gastric variceal bleeding when splenectomy is difficult such as in case associated with severe acute pancreatitis or associated with severe adhesion or in patients with high operation risk.

  1. Impact of developmental lead exposure on splenic factors

    International Nuclear Information System (INIS)

    Kasten-Jolly, Jane; Heo, Yong; Lawrence, David A.

    2010-01-01

    Lead (Pb) is known to alter the functions of numerous organ systems, including the hematopoietic and immune systems. Pb can induce anemia and can lower host resistance to bacterial and viral infections. The anemia is due to Pb's inhibition of hemoglobin synthesis and Pb's induction of membrane changes, leading to early erythrocyte senescence. Pb also increases B-cell activation/proliferation and skews T-cell help (Th) toward Th2 subset generation. The specific mechanisms for many of the Pb effects are, as yet, not completely understood. Therefore, we performed gene expression analysis, via microarray, on RNA from the spleens of developmentally Pb-exposed mice, in order to gain further insight into these Pb effects. Splenic RNA microarray analysis indicated strong up-regulation of genes coding for proteolytic enzymes, lipases, amylase, and RNaseA. The data also showed that Pb affected the expression of many genes associated with innate immunity. Analysis of the microarray results via GeneSifter software indicated that Pb increased apoptosis, B-cell differentiation, and Th2 development. Direct up-regulation by Pb of expression of the gene encoding the heme-regulated inhibitor (HRI) suggested that Pb can decrease erythropoiesis by blocking globin mRNA translation. Pb's high elevation of digestive/catabolizing enzymes could generate immunogenic self peptides. With Pb's potential to induce new self-peptides and to enhance the expression of caspases, cytokines, and other immunomodulators, further evaluation of Pb's involvement in autoimmune phenomena, especially Th2-mediated autoantibody production, and alteration of organ system activities is warranted.

  2. The BAFF / APRIL axis plays an important role in virus-induced peritoneal responses in rainbow trout.

    Science.gov (United States)

    Soleto, Irene; Abós, Beatriz; Castro, Rosario; González, Lucia; Tafalla, Carolina; Granja, Aitor G

    2017-05-01

    IgM + B cells have been recently demonstrated to be key regulators of peritoneal inflammation in teleost, as a large number of them occupy the peritoneal cavity after 48 h of antigenic stimulation. Despite this, the number of studies addressing the mechanism through which this cell population expands and differentiates in response to stimuli has been scarcely addressed. Because the BAFF/APRIL axis is known to play a major role in B cell survival and differentiation in mammals, we hypothesized that it could be affected in the peritoneal cavity in response to an inflammatory stimulus. To verify this hypothesis, we studied how BAFF, APRIL and the fish-specific related cytokine BALM as well as their putative receptors are regulated in rainbow trout after intraperitoneal (i.p.) injection of viral hemorrhagic septicemia virus (VHSV). When the transcriptional analysis was performed in total cells from the peritoneum, we observed that VHSV provoked an up-regulation of both BAFF and BAFF receptor (BAFF-R) mRNA levels. However, when we examined how isolated peritoneal IgM + B cells were transcriptionally affected by VHSV i.p. injection, we found that APRIL, BALM and the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) were also up-regulated in response to the virus. IgM - cells, on the other hand, only up-regulated BALM transcription in response to VHSV. Finally, to gain further insight on the role that these cytokines play in the peritoneum, we have studied their effect on the survival of peritoneal IgM + B cells. This work demonstrates a key role for the BAFF/APRIL axis in the peritoneal inflammatory response and contributes to further understanding how IgM + B cells are regulated at this specific peripheral site. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Sonographic Measurement of Normal Splenic Length in Korean Adults

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Sang Bum; Cheon, Byung Kook; Kim, Jong Min; Oh, Kyung Seoung; Jung, Gyoo Sik; Huh, Jin Do; Joh, Young Duk [Kosin University College of Medicine, Busan (Korea, Republic of)

    1996-12-15

    To establish upper limit of normal splenic length of Korean adults on ultrasonography and to determice the degree of interobserver and intraobserver variation. Ultrasonographic scans were performed to measure the maximum length of spleen in 105 of 150 adults selected by convenience sampling. Remained 45 cases with any conditions that could alter splenic size were excluded from this study. The maximum length of spleen was measured and correlated with body surface area, patient height, weight, age and sex. In 31 of the 105 adults we evaluated the interobserver and intraobserver variations in sonographic measurements of splenic length obtained by three radiologists in blind fashion. The mean splenic length in 105 adults was 8.56cm ({+-} 0.95). The splenic length positively correlated with body surface area, patient height and weight (P <0.001), and negatively correlated with patient age (P < 0.01). Male spleen (8.87 cm {+-} 1.07) was longer than female spleen (8.35 cm {+-} 0.81) (P < 0.05). The following guidelines are proposed for the upper limit of normal splenic length at different groups of body surface area: no longer than 10 cm at 1.20{approx}1.59 m{sup 2}, 11 cm at1.60{approx}1.79 m{sup 2}, and 12 cm at 1.80{approx}1.99 m{sup 2}. The mean interobserver variation between any two radiologists ranged from 0.32 cm ({+-} 0.29) to 0.39 cm ({+-} 0.33) and interobserver variations were within 1 cm in 96%. The mean intraobserver variations were within 0.5 cm in 91%. The splenic length closely correlated with body surface area, patient height, weight and age. Particularly the upper limit of normal splenic length changed according to body surface area. Interobserver variation about 1 cm and intraobserver variation about 0.5 cm should be considered in the measurement of the splenic length on ultrasonography

  4. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction....... From the perspective of mediatization research, the most important effect of the media stems from their embeddedness in culture and society....

  5. A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells

    OpenAIRE

    Jonathan V. Almaden; Rachel Tsui; Yi C. Liu; Harry Birnbaum; Maxim N. Shokhirev; Kim A. Ngo; Jeremy C. Davis-Turak; Dennis Otero; Soumen Basak; Robert C. Rickert; Alexander Hoffmann

    2014-01-01

    SUMMARY BAFF, an activator of the noncanonical NF?B pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NF?B family member RelB is required ex vivo for B cell maturation, but cRel is required for proliferation. Combined molecular network modeling and experimentation revealed Nfkb2 p100 as a pathway switch; at moderate p100 synthesis rates in maturing B cells, BAFF fully utilizes p100 to generate the RelB:p52 dimer, wh...

  6. Spontaneous splenic rupture in Waldenstrom's macroglobulinemia: a case report

    Directory of Open Access Journals (Sweden)

    Charakidis Michail

    2010-09-01

    Full Text Available Abstract Introduction We report the case of a patient with Waldenstrom's macroglobulinemia complicated by spontaneous splenic rupture. Case presentation A 49-year-old Caucasian woman was referred to our emergency department by her general practitioner following a three-week history of malaise, night sweats, six kilograms of weight loss, intermittent nausea and vomiting, progressive upper abdominal pain and easy bruising. On the fourth day following her admission, she had a rapid clinical deterioration, with subsequent radiological investigations revealing a splenic rupture. Her morphology, biochemistry, flow cytometry and histology were strongly suggestive of Waldenstrom's macroglobulinemia. Conclusions Spontaneous splenic rupture is not an expected complication of low-grade lymphoplasmacytic lymphomas, such as Waldenstrom's macroglobulinemia. To the best of our knowledge, this is the only reported case of early spontaneous splenic rupture due to Waldenstrom's macroglobulinemia. Our case highlights that despite the typical disease course of low-grade hematological malignancies, signs and symptoms of imminent splenic rupture should be considered when formulating a clinical assessment.

  7. Exogenous and endogenous angiogenic stimuli do not augment splenic autotransplantation.

    Science.gov (United States)

    Power, Richard E; Kay, Elaine W; Bouchier-Hayes, David

    2002-01-01

    To find out if angiogenic stimulation improves the ability of the spleen to regenerate. Experimental study. Teaching hospital, Republic of Ireland. 27 male Sprague-Dawley rats. Each spleen was removed and half was reimplanted in the greater omentum. The rats were randomised into three groups of 9 each: the first (control) group was given no stimulation; the second had the implanted spleen sutured into the omentum with 6/0 polypropylene; and in the third group the implanted spleen was injected with human recombinant vascular endothelial growth factor (VEGF) 500 microg. Clearance of Howell-Jolly bodies, and the weight and histological appearance of the splenic remnant at 3 months. The splenic remnant was significantly larger at 3 months in the control group (p = 0.0006). Histological examination of the tissue from the control group showed that it was architecturally similar to that of normal functioning spleen, whereas the tissue from the two treated groups contained less lymphoid tissue and showed widespread acute and chronic inflammatory changes. There was a significantly greater clearance of Howell-Jolly bodies (an index of splenic function) from the peripheral blood of the control group (p = 0.0009). The excellent recovery of the splenic remnant in the control group suggests that the procedure of splenic autotransplantation might warrant further consideration and study.

  8. Ultrasound-guided percutaneous core needle biopsy of splenic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Park, SangIk; Shin, Yong Moon; Won, Hyung Jin; Kim, Pyo Nyun; Lee, Moon Gyu [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2017-05-15

    To evaluate the safety and efficacy of ultrasound-guided percutaneous core needle biopsy of splenic lesions. This retrospective study included 30 patients who underwent percutaneous core needle biopsy of their splenic lesions using 18- or 20-gauge needles between January 2001 and July 2016 in a single tertiary care center. The characteristics of the splenic lesions were determined by reviewing the ultrasound and computed tomography examinations. Acquisition rate and diagnostic accuracy were calculated, using pathologic results of the splenectomy specimen, clinical course and/or imaging follow-up as a reference standard. Post-procedure complications were identified from electronic medical records, laboratory findings and computed tomography images. Seventy-three specimens were obtained from the 30 patients and splenectomy was performed in 2 patients. Twenty-nine of the 30 patients had focal splenic lesions, while the remaining patient had homogeneous splenomegaly. Acquisition rate and diagnostic accuracy were 80.0% (24/30) and 76.7% (23/30), respectively. Perisplenic hemorrhage without hemodynamic instability developed in one patient. Ultrasound-guided percutaneous core needle biopsy of splenic lesions is a safe method for achieving a histopathologic diagnosis and can be considered as an alternative to splenectomy in patients with a high risk of splenectomy-related complications.

  9. Percutaneous Treatment of Splenic Cystic Echinococcosis: Results of 12 Cases

    Energy Technology Data Exchange (ETDEWEB)

    Akhan, Okan, E-mail: akhano@tr.net; Akkaya, Selçuk, E-mail: selcuk.akkaya85@gmail.com [Hacettepe University, Department of Radiology, School of Medicine (Turkey); Dağoğlu, Merve Gülbiz, E-mail: drmgkartal@gmail.com [Istanbul University, Department of Radiology, Istanbul School of Medicine (Turkey); Akpınar, Burcu, E-mail: burcu-akpinar@yahoo.com [Hacettepe University, Department of Radiology, School of Medicine (Turkey); Erbahçeci, Aysun, E-mail: aysunerbahceci@yahoo.com [Istanbul Bakirkoy Dr. Sadi Konuk Education and Research Hospital, Department of Radiology (Turkey); Çiftçi, Türkmen, E-mail: turkmenciftci@yahoo.com [Hacettepe University, Department of Radiology, School of Medicine (Turkey); Köroğlu, Mert, E-mail: mertkoroglu@hotmail.com [Antalya Education and Research Hospital, Department of Radiology (Turkey); Akıncı, Devrim, E-mail: akincid@hotmail.com [Hacettepe University, Department of Radiology, School of Medicine (Turkey)

    2016-03-15

    PurposeCystic echinococcosis (CE) in the spleen is a rare disease even in endemic regions. The aim of this study was to examine the efficacy of percutaneous treatment for splenic CE.Materials and MethodsTwelve patients (four men, eight women) with splenic CE were included in this study. For percutaneous treatment, CE1 and CE3A splenic hydatid cysts were treated with either the PAIR (puncture, aspiration, injection, respiration) technique or the catheterization technique.ResultsEight of the hydatid cysts were treated with the PAIR technique and four were treated with catheterization. The volume of all cysts decreased significantly during the follow-up period. No complication occurred in seven of 12 patients. Abscess developed in four patients. Two patients underwent splenectomy due to cavity infection developed after percutaneous treatment, while the spleen was preserved in 10 of 12 patients. Total hospital stay was between 1 and 18 days. Hospital stay was longer and the rate of infection was higher in the catheterization group. Follow-up period was 5–117 months (mean, 44.8 months), with no recurrence observed.ConclusionThe advantages of the percutaneous treatment are its minimal invasive nature, short hospitalization duration, and its ability to preserve splenic tissue and function. As the catheterization technique is associated with higher abscess risk, we suggest that the PAIR procedure should be the first percutaneous treatment option for splenic CE.

  10. Splenic Artery Pseudoaneurysm Presenting as Massive Hematemesis: A Diagnostic Dilemma

    Directory of Open Access Journals (Sweden)

    Peeyush Varshney

    2014-01-01

    Full Text Available Introduction. Splenic artery Pseudoaneurysm, a complication of chronic pancreatitis, presenting as massive hematemesis is a rare presentation. Case Report. We present a case of 38-year-old male admitted with chief complaints of pain in the upper abdomen and massive hematemesis for the last 15 days. On examination there was severe pallor. On investigating the patient, Hb was 4.0 gm/dL, upper GI endoscopy revealed a leiomyoma in fundus of stomach, and EUS Doppler also supported the UGI findings. On further investigation of the patient, CECT of the abdomen revealed a possibility of distal pancreatic carcinoma encasing splenic vessels and infiltrating the adjacent structure. FNA taken at the time of EUS was consistent with inflammatory pathology. Triple phase CT of the abdomen revealed a splenic artery pseudoaneurysm with multiple splenic infarcts. After resuscitation we planned an emergency laparotomy; splenic artery pseudoaneurysm densely adherent to adjacent structures and associated with distal pancreatic necrosis was found. We performed splenectomy with repair of the defect in the stomach wall and necrosectomy. Postoperative course was uneventful and patient was discharged on day 8. Conclusion. Pseudoaneurysm can be at times a very difficult situation to manage; options available are either catheter embolisation if patient is vitally stable, or otherwise, exploration.

  11. Ultrasound-guided percutaneous core needle biopsy of splenic lesions

    International Nuclear Information System (INIS)

    Park, SangIk; Shin, Yong Moon; Won, Hyung Jin; Kim, Pyo Nyun; Lee, Moon Gyu

    2017-01-01

    To evaluate the safety and efficacy of ultrasound-guided percutaneous core needle biopsy of splenic lesions. This retrospective study included 30 patients who underwent percutaneous core needle biopsy of their splenic lesions using 18- or 20-gauge needles between January 2001 and July 2016 in a single tertiary care center. The characteristics of the splenic lesions were determined by reviewing the ultrasound and computed tomography examinations. Acquisition rate and diagnostic accuracy were calculated, using pathologic results of the splenectomy specimen, clinical course and/or imaging follow-up as a reference standard. Post-procedure complications were identified from electronic medical records, laboratory findings and computed tomography images. Seventy-three specimens were obtained from the 30 patients and splenectomy was performed in 2 patients. Twenty-nine of the 30 patients had focal splenic lesions, while the remaining patient had homogeneous splenomegaly. Acquisition rate and diagnostic accuracy were 80.0% (24/30) and 76.7% (23/30), respectively. Perisplenic hemorrhage without hemodynamic instability developed in one patient. Ultrasound-guided percutaneous core needle biopsy of splenic lesions is a safe method for achieving a histopathologic diagnosis and can be considered as an alternative to splenectomy in patients with a high risk of splenectomy-related complications

  12. B-cell activating factor (BAFF) plasma level at the time of chronic GvHD diagnosis is a potential predictor of non-relapse mortality.

    Science.gov (United States)

    Saliba, R M; Sarantopoulos, S; Kitko, C L; Pawarode, A; Goldstein, S C; Magenau, J; Alousi, A M; Churay, T; Justman, H; Paczesny, S; Reddy, P; Couriel, D R

    2017-07-01

    Biological markers for risk stratification of chronic GvHD (cGvHD) could improve the care of patients undergoing allogeneic hematopoietic stem cell transplantation. Increased plasma levels of B-cell activating factor (BAFF), chemokine (C-X-C motif) ligand 9 (CXCL9) and elafin have been associated with the diagnosis, but not with outcome in patients with cGvHD. We evaluated the association between levels of these soluble proteins, measured by ELISA at the time of cGvHD diagnosis and before the initiation of therapy, with non-relapse-mortality (NRM). Based on the log-transformed values, factor levels were divided into tertiles defined respectively as low, intermediate, and high levels. On univariable analysis, BAFF levels were significantly associated with NRM, whereas CXCL9 and elafin levels were not. Both low (⩽2.3 ng/mL, hazard ratio (HR)=5.8, P=0.03) and high (>5.7 ng/mL, HR=5.4, P=0.03) BAFF levels were associated with a significantly higher NRM compared with intermediate BAFF level. The significant effect of high or low BAFF levels persisted in multivariable analysis. A subset of cGvHD patients had persistently low BAFF levels. In conclusion, our data show that BAFF levels at the time of cGvHD diagnosis are associated with NRM, and also are potentially useful for risk stratification. These results warrant confirmation in larger studies.

  13. Soluble BAFF Level Is Not Correlated to Mycobacterium avium Subspecies Paratuberculosis Antibodies and Increases After Interferon-β Therapy in Multiple Sclerosis Patients.

    Science.gov (United States)

    Mameli, Giuseppe; Cossu, Davide; Caggiu, Elisa; Arru, Giannina; Niegowska, Magdalena; Cocco, Eleonora; Frau, Jessica; Marrosu, Maria Giovanna; Sechi, Leonardo A

    2016-09-01

    B cells are being recognized as one of the major players in the pathogenesis of multiple sclerosis (MS). The B cell activating factor (BAFF) system plays an essential role in B cell homeostasis and function in the periphery. Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to MS in Sardinia. Antibodies against a MAP surface protein, MAP_2694, have been found significantly associated to MS patients, and this response was modified by interferon-β therapy. Increased BAFF levels following IFN-β therapy have been also described in MS patients. In this study, we evaluated whether soluble BAFF levels are comparable in men and women affected by MS and performed a correlation of the reported BAFF increase in MS patients under IFN-β therapy with changes of humoral response against MAP_2694. For these reasons, we investigated 44 MS patients before and after IFN-β therapy. A significant difference of BAFF levels was found between men and women with MS; moreover, we confirmed that IFN-β therapy strongly induces BAFF serum levels, but this was not related to the modification of immunological response against MAP_2694. In conclusion, our study highlights that IFN-β therapy induces the potent B cell survival factor BAFF without alterations of the humoral immune response against MAP.

  14. High expression levels of BLyS/BAFF by blood dendritic cells and granulocytes are associated with B-cell dysregulation in SIV-infected rhesus macaques.

    Science.gov (United States)

    Poudrier, Johanne; Soulas, Caroline; Chagnon-Choquet, Josiane; Burdo, Tricia; Autissier, Patrick; Oskar, Kathryn; Williams, Kenneth C; Roger, Michel

    2015-01-01

    Dendritic cells (DCs) modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF). In recent longitudinal studies involving HIV-1-infected individuals with different rates of disease progression, we have shown that DCs were altered in number and phenotype in the context of HIV-1 disease progression and B-cell dysregulations were associated with increased BLyS/BAFF expression in plasma and by blood myeloid DCs (mDCs) in rapid and classic progressors but not in HIV-1-elite controllers (EC). Suggesting that the extent to which HIV-1 disease progression is controlled may be linked to BLyS/BAFF expression status and the capacity to orchestrate B-cell responses. Herein, longitudinal analyses of simian immunodeficiency virus (SIV)-infected rhesus macaques also revealed increased expression of BLyS/BAFF by blood mDCs as soon as day 8 and throughout infection. Strikingly, granulocytes presented the highest BLyS/BAFF expression profile in the blood of SIV-infected macaques. BLyS/BAFF levels were also increased in plasma and correlated with viral loads. Consequently, these SIV-infected animals had plasma hyperglobulinemia and reduced blood B-cell numbers with altered population frequencies. These data underscore that BLyS/BAFF is associated with immune dysregulation in SIV-infected rhesus macaques and suggest that BLyS/BAFF is a key regulator of immune activation that is highly conserved among primates. These findings emphasize the potential importance of this SIV-infected primate model to test whether blocking excess BLyS/BAFF has an effect on the overall inflammatory burden and immune restoration.

  15. High expression levels of BLyS/BAFF by blood dendritic cells and granulocytes are associated with B-cell dysregulation in SIV-infected rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Johanne Poudrier

    Full Text Available Dendritic cells (DCs modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF. In recent longitudinal studies involving HIV-1-infected individuals with different rates of disease progression, we have shown that DCs were altered in number and phenotype in the context of HIV-1 disease progression and B-cell dysregulations were associated with increased BLyS/BAFF expression in plasma and by blood myeloid DCs (mDCs in rapid and classic progressors but not in HIV-1-elite controllers (EC. Suggesting that the extent to which HIV-1 disease progression is controlled may be linked to BLyS/BAFF expression status and the capacity to orchestrate B-cell responses. Herein, longitudinal analyses of simian immunodeficiency virus (SIV-infected rhesus macaques also revealed increased expression of BLyS/BAFF by blood mDCs as soon as day 8 and throughout infection. Strikingly, granulocytes presented the highest BLyS/BAFF expression profile in the blood of SIV-infected macaques. BLyS/BAFF levels were also increased in plasma and correlated with viral loads. Consequently, these SIV-infected animals had plasma hyperglobulinemia and reduced blood B-cell numbers with altered population frequencies. These data underscore that BLyS/BAFF is associated with immune dysregulation in SIV-infected rhesus macaques and suggest that BLyS/BAFF is a key regulator of immune activation that is highly conserved among primates. These findings emphasize the potential importance of this SIV-infected primate model to test whether blocking excess BLyS/BAFF has an effect on the overall inflammatory burden and immune restoration.

  16. Effect of ghrelin on regulation of splenic sympathetic nerve discharge.

    Science.gov (United States)

    Balivada, Sivasai; Pawar, Hitesh N; Montgomery, Shawnee; Kenney, Michael J

    2016-12-01

    Ghrelin influences immune system function and modulates the sympathetic nervous system; however, the contribution of ghrelin to neural-immune interactions is not well-established because the effect of ghrelin on splenic sympathetic nerve discharge (SND) is not known. This study tested the hypothesis that central ghrelin administration would inhibit splenic SND in anesthetized rats. Rats received intracerebroventricular (ICV) injections of ghrelin (1nmol/kg) or aCSF. Lumbar SND recordings provided a non-visceral nerve control. The ICV ghrelin administration significantly increased splenic and lumbar SND, whereas mean arterial pressure (MAP) was not altered. These findings provide fundamental information regarding the nature of sympathetic-immune interactions. Published by Elsevier B.V.

  17. A Case of Ruptured Splenic Artery Aneurysm in Pregnancy

    Directory of Open Access Journals (Sweden)

    Elizabeth K. Corey

    2014-01-01

    Full Text Available Background. Rupture of a splenic artery aneurysm is rare complication of pregnancy that is associated with a significant maternal and fetal mortality. Case. A multiparous female presented in the third trimester with hypotension, tachycardia, and altered mental status. A ruptured splenic artery aneurysm was discovered at the time of laparotomy and cesarean delivery. The patient made a full recovery following resection of the aneurysm. The neonate survived but suffered severe neurologic impairment. Conclusion. The diagnosis of ruptured splenic artery aneurysm should be considered in a pregnant woman presenting with signs of intra-abdominal hemorrhage. Early intervention by a multidisciplinary surgical team is key to preserving the life of the mother and fetus.

  18. Unusual long-term complications of a splenic cyst.

    LENUS (Irish Health Repository)

    Ward, E V M

    2012-02-01

    Splenic cysts are relatively uncommon, and are usually asymptomatic. They are benign, typically treated conservatively and followed up with ultrasound examination, with few reported complications. We report a case of a simple splenic cyst that was followed up on imaging over a seven-year period. During that time, the cyst gradually enlarged from 5 cm to 12 cm in diameter, however the patient remained asymptomatic. After seven years, the patient was admitted with abdominal pain and a pelvic mass. The spleen was located within the pelvis, which was felt to be due to the weight of the cyst which caused the spleen to migrate out of its normal position. This case illustrates an extremely unusual complication, and suggests that while most splenic cysts may be managed conservatively, enlarging cysts may be prone to gravitational effects and prophylactic treatment should be considered.

  19. SOLITARY SPLENIC METASTASIS OF COLON CANCER: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Sh. Hashemzadeh M. Safari

    2004-11-01

    Full Text Available Although splenic metastasis is fairly common in disseminated cancer, solitary splenic metastasis in the absence of diffuse dissemination is rare. We report a case of 44 year-old man who developed isolated splenic metastasis of colon cancer. The patient had undergone right sided hemicolectomy for colon cancer in 1988. In 2001, he underwent reoperation because of local recurrence of tumor in the anastomotic site. The patient was admitted to our hospital on Sep 2003 with abdominal pain. Chest X-ray was normal. Abdominal CT scan showed a large cystic lesion in the spleen. Splenectomy was performed for the patient. The spleen was enlarged, firm and irregular. Histological examination showed metastatic mucinous adenocarcinoma. Based on this case, we recommend that clinicians consider possibility of metastasis in cystic lesions of spleen, especially in patients with a history of a malignant disease.

  20. Unusual long-term complications of a splenic cyst.

    LENUS (Irish Health Repository)

    Ward, E V M

    2010-01-01

    Splenic cysts are relatively uncommon, and are usually asymptomatic. They are benign, typically treated conservatively and followed up with ultrasound examination, with few reported complications. We report a case of a simple splenic cyst that was followed up on imaging over a seven-year period. During that time, the cyst gradually enlarged from 5 cm to 12 cm in diameter, however the patient remained asymptomatic. After seven years, the patient was admitted with abdominal pain and a pelvic mass. The spleen was located within the pelvis, which was felt to be due to the weight of the cyst which caused the spleen to migrate out of its normal position. This case illustrates an extremely unusual complication, and suggests that while most splenic cysts may be managed conservatively, enlarging cysts may be prone to gravitational effects and prophylactic treatment should be considered.

  1. Analysis of Associations of Human BAFF Gene Polymorphisms with Autoimmune Thyroid Diseases.

    Directory of Open Access Journals (Sweden)

    Jiunn-Diann Lin

    Full Text Available The B-lymphocyte-activating factor (BAFF is associated with B-cell functions, and gene polymorphisms of the BAFF have been linked to autoimmune diseases (AIDs. In this study, we explored possible associations of two BAFF single-nucleotide polymorphisms (SNPs, rs1041569 and rs2893321, with autoimmune thyroid diseases (AITDs in an ethnic Chinese population.In total, 319 Graves' disease (GD, 83 Hashimoto's thyroiditis (HT patients, and 369 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism and direct sequencing were used to genotype rs2893321 and rs1041569.There was a significant difference in frequencies of the G allele and AG+GG genotype of rs2893321 between the GD and control groups (p = 0.013, odds ratio (OR = 0.76, and p = 0.017, OR = 0.68, respectively and between the AITD and control groups (p = 0.009, OR = 0.76, and, p = 0.014, OR = 0.69, respectively. The AA genotype of rs2893321 was associated with low titers of the thyroid-stimulating hormone receptor antibody (TSHRAb (p = 0.015 in males but not in females. The AA genotype of rs2893321 was associated with the presence of two different types of thyroid autoantibody (TAb (TSHRAb and Hashimoto's autoantibody (anti-thyroglobulin or anti-microsomal antibody in females and with that of one type in males.rs2893321 may be a susceptible genetic variant for the development of GD and AITDs. Associations of rs2893321 with susceptibility to GD and AITDs and the correlation between rs2893321 and TAb exhibit a dimorphic pattern. Additional studies with larger sample sizes are required to confirm our findings.

  2. Splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia

    International Nuclear Information System (INIS)

    Gratwohl, A.; Hermans, J.; Biezen, A.V.

    1996-01-01

    A total of 229 patients with chronic myeloid leukaemia (CML) in chronic phase were randomized between 1986 and 1990 to receive or not receive additional splenic irradiation as part of their conditioning prior to bone marrow transplantation (BMT). Both groups, 115 patients with and 114 patients without splenic irradiation, were very similar regarding distribution of age, sex, donor/recipient sex combination, conditioning, graft-versus-host disease (GvHD) prevention method and blood counts at diagnosis or prior to transplant. 135 patients (59%) are alive as of October 1995 with a minimum follow-up of 5 years. 52 patients have relapsed (23%), 26 patients in the irradiated, 26 patients in the non-irradiated group (n.s.) with a relapse incident at 6 years of 28%. The main risk factor for relapse was T-cell depletion as the method for GvHD prevention, and an elevated basophil count in the peripheral blood prior to transplant. Relapse incidence between patients with or without splenic irradiation was no different in patients at high risk for relapse, e.g. patients transplanted with T-cell-depleted marrows (P = n.s.) and in patients with low risk for relapse, e.g. patients transplanted with non-T-cell-depleted transplants and basophil counts 3% basophils in peripheral blood). In this patient group, relapse incidence was 11% at 6 years with splenic irradiation but 32% in the non-irradiated group (P = 0.05). Transplant-related mortality was similar whether patients received splenic irradiation or not. This study suggests an advantage in splenic irradiation prior to transplantation for CML in this subgroup of patients and illustrates the need for tailored therapy. (Author)

  3. Preserved splenic function after angioembolisation of high grade injury.

    Science.gov (United States)

    Skattum, Jorunn; Titze, Thomas Larsen; Dormagen, Johann Baptist; Aaberge, Ingeborg S; Bechensteen, Anne Grete; Gaarder, Per Ivar; Gaarder, Christine; Heier, Hans Erik; Næss, Pål Aksel

    2012-01-01

    After introducing splenic artery embolisation (SAE) in the institutional treatment protocol for splenic injury, we wanted to evaluate the effects of SAE on splenic function and assess the need for immunisation in SAE treated patients. 15 SAE patients and 14 splenectomised (SPL) patients were included and 29 healthy blood donors volunteered as controls. Clinical examination, medical history, general blood counts, immunoglobulin quantifications and flowcytometric analysis of lymphocyte phenotypes were performed. Peripheral blood smears from all patients and controls were examined for Howell-Jolly (H-J) bodies. Abdominal doppler, gray scale and contrast enhanced ultrasound (CEUS) were performed on all the SAE patients. Leukocyte and platelet counts were elevated in both SAE and SPL individuals compared to controls. The proportion of memory B-lymphocytes did not differ significantly from controls in either group. In the SAE group total IgA, IgM and IgG levels as well as pneumococcal serotype specific IgG and IgM antibody levels did not differ from the control group. In the SPL group total IgA and IgG Pneumovax(®) (PPV23) antibody levels were significantly increased, and 5 of 12 pneumococcal serotype specific IgGs and IgMs were significantly elevated. H-J bodies were only detected in the SPL group. CEUS confirmed normal sized and well perfused spleens in all SAE patients. In our study non-operative management (NOM) of high grade splenic injuries including SAE, was followed by an increase in total leukocyte and platelet counts. Normal levels of immunoglobulins and memory B cells, absence of H-J bodies and preserved splenic size and intraparenchymal blood flow suggest that SAE has only minor impact on splenic function and that immunisation probably is unnecessary. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Insulin radioreceptor assay on murine splenic leukocytes and peripheral erythrocytes

    International Nuclear Information System (INIS)

    Shimizu, F.; Kahn, R.

    1982-01-01

    Insulin radioreceptor assays were developed using splenic leukocytes and peripheral erythrocytes from individual mice. Splenic leukocytes were prepared using an NH 4 Cl buffer which did not alter insulin binding, but gave much higher yields than density gradient methods. Mouse erythrocytes were isolated from heparinized blood by three passages over a Boyum gradient, and a similar buffer was used to separate cells from free [ 125 I]iodoinsulin at the end of the binding incubation. Insulin binding to both splenic leukocytes and peripheral erythrocytes had typical pH, temperature, and time dependencies, and increased linearly with an increased number of cells. Optimal conditions for the splenic leukocytes (6 x 10 7 /ml) consisted of incubation with [ 125 I]iodoinsulin at 15 C for 2 h in Hepes buffer, pH 8.0. In cells from 20 individual mice, the specific [ 125 I]iodoinsulin binding was 2.6 +/- 0.1% (SEM), and nonspecific binding was 0.3 +/- 0.04% (10.6% of total binding). Erythrocytes (2.8 x 10 9 /ml) were incubated with [ 125 ]iodoinsulin at 15 C for 2 h in Hepes buffer, pH 8.2. In cells from 25 individual mice, the specific [ 125 I]iodoinsulin binding was 4.5 +/- 0.2%, and nonspecific binding was 0.7 +/- 0.03% (13.6% of total binding). In both splenic leukocytes and peripheral erythrocytes, analysis of equilibrium binding data produced curvilinear Scatchard plots with approximately 3500 binding sites/leukocyte and 20 binding sites/erythrocyte. These data demonstrate that adequate numbers of splenic leukocytes and peripheral erythrocytes can be obtained from individual mice to study insulin binding in a precise and reproducible manner

  5. Splenic rupture after screening colonoscopy: case report and literature review.

    Science.gov (United States)

    DuCoin, Christopher; Acholonu, Emeka; Ukleja, Andrew; Cellini, Florencia; Court, Ismael; Dabage, Nemer; Szomstein, Samuel; Rosenthal, Raul J

    2010-02-01

    Splenic rupture is a rare complication after colonoscopy, and to date there are only 46 reported cases in the English-language literature. Presented is a case report of splenic rupture after screening colonoscopy that resulted in laparotomy and splenectomy within 24 hours of the original procedure. The article covers the hypothesized mechanisms of injury, various precautions to take during colonoscopy, suggested diagnostic algorithm, determining factors in treatment, and vaccine regimen. The article concludes by stating that as the number of colonoscopies increase, so will the prevalence of associated complications, and that physicians are encouraged to understand this paradigm shift.

  6. CT-guided percutaneous treatment of solitary pyogenic splenic abscesses

    Energy Technology Data Exchange (ETDEWEB)

    Pombo, F. [Dept. of Radiology, Hospital Juan Canalejo, La Coruna (Spain); Suarez, I. [Dept. of Radiology, Hospital Juan Canalejo, La Coruna (Spain); Marini, M. [Dept. of Radiology, Hospital Juan Canalejo, La Coruna (Spain); Arrojo, L. [Dept. of Radiology, Hospital Juan Canalejo, La Coruna (Spain); Echaniz, A. [Dept. of Internal Medicine, Hospital Juan Canalejo, La Coruna (Spain)

    1991-08-01

    Six patients with solitary pyogenic splenic abscesses treated by CT-guided percutaneous drainage (by catheter or needle), are presented. There were 3 unilocular, purely intrasplenic abscesses and 3 complex lesions with loculations and perisplenic involvement. Percutaneous drainage and intravenous antibiotics were curative in 4 patients. In the other 2, who had multiloculated abscesses, despite initially successful drainage, splenectomy was performed because of intractable left upper quadrant pain in one case and persistent fever and drainage of pus after 30 days in the other. These patients also developed large, sterile left pleural effusions. Solitary pyogenic splenic abscesses - particularly if uniloculated - can be effectively treated by CT-guided percutaneous drainage. (orig.)

  7. Observation Versus Embolization in Patients with Blunt Splenic Injury After Trauma: A Propensity Score Analysis

    NARCIS (Netherlands)

    Olthof, Dominique C.; Joosse, Pieter; Bossuyt, Patrick M. M.; de Rooij, Philippe P.; Leenen, Loek P. H.; Wendt, Klaus W.; Bloemers, Frank W.; Goslings, J. Carel

    2016-01-01

    Non-operative management (NOM) is the standard of care in hemodynamically stable patients with blunt splenic injury after trauma. Splenic artery embolization (SAE) is reported to increase observation success rate. Studies demonstrating improved splenic salvage rates with SAE primarily compared SAE

  8. Observation Versus Embolization in Patients with Blunt Splenic Injury After Trauma : A Propensity Score Analysis

    NARCIS (Netherlands)

    Olthof, Dominique C.; Joosse, Pieter; Bossuyt, Patrick M. M.; de Rooij, Philippe P.; Leenen, Loek P. H.; Wendt, Klaus W.; Bloemers, Frank W.; Goslings, J. Carel

    Non-operative management (NOM) is the standard of care in hemodynamically stable patients with blunt splenic injury after trauma. Splenic artery embolization (SAE) is reported to increase observation success rate. Studies demonstrating improved splenic salvage rates with SAE primarily compared SAE

  9. Salmonella sepsis following posttraumatic splenectomy and implantation of autologous splenic tissue

    DEFF Research Database (Denmark)

    Schrøder, H M; Hovendal, C

    1985-01-01

    A severe complication following implantation of autologous splenic tissue occurred in a 51-year-old man. Indirect injury to abdomen resulted in a lesion of the splenic artery. Following splenectomy and reimplantation of splenic tissue into three pouches, a severe Salmonella sepsis developed within...

  10. Molecular detection of vector-borne pathogens in blood and splenic samples from dogs with splenic disease.

    Science.gov (United States)

    Movilla, Rebeca; Altet, Laura; Serrano, Lorena; Tabar, María-Dolores; Roura, Xavier

    2017-03-13

    The spleen is a highly perfused organ involved in the immunological control and elimination of vector-borne pathogens (VBP), which could have a fundamental role in the pathogenesis of splenic disease. This study aimed to evaluate certain VBP in samples from dogs with splenic lesions. Seventy-seven EDTA-blood and 64 splenic tissue samples were collected from 78 dogs with splenic disease in a Mediterranean area. Babesia spp., Bartonella spp., Ehrlichia/Anaplasma spp., Hepatozoon canis, Leishmania infantum, hemotropic Mycoplasma spp. and Rickettsia spp. were targeted using PCR assays. Sixty EDTA-blood samples from dogs without evidence of splenic lesions were included as a control group. More than half (51.56%) of the biopsies (33/64) were consistent with benign lesions and 48.43% (31/64) with malignancy, mostly hemangiosarcoma (25/31). PCR yielded positive results in 13 dogs with spleen alterations (16.67%), for Babesia canis (n = 3), Babesia gibsoni (n = 2), hemotropic Mycoplasma spp. (n = 2), Rickettsia massiliae (n = 1) and "Babesia vulpes" (n = 1), in blood; and for B. canis, B. gibsoni, Ehrlichia canis and L. infantum (n = 1 each), in spleen. Two control dogs (3.3%) were positive for B. gibsoni and H. canis (n = 1 each). Benign lesions were detected in the 61.54% of infected dogs (8/13); the remaining 38.46% were diagnosed with malignancies (5/13). Infection was significantly associated to the presence of splenic disease (P = 0.013). There was no difference in the prevalence of infection between dogs with benign and malignant splenic lesions (P = 0.69); however B. canis was more prevalent in dogs with hemangiosarcoma (P = 0.006). VBP infection could be involved in the pathogenesis of splenic disease. The immunological role of the spleen could predispose to alterations of this organ in infected dogs. Interestingly, all dogs with B. canis infection were diagnosed with hemangiosarcoma in the present survey. As previously

  11. Relationship between Circulating BAFF Serum Levels with Proliferating Markers in Patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Michael G. Alexandrakis

    2013-01-01

    Full Text Available In multiple myeloma, there are many factors influencing the growth of the malignant clone in direct and indirect manners. BAFF is a growth factor for myeloma cells. The aim of the study was to measure its circulating levels in 54 pretreatment patients, along with serum levels of other proliferation markers, such as interleukins-6, -10, and -15, CRP, and beta-2 microglobulin, as well as bone marrow plasma cell infiltration and expression of Ki-67 PI, in various stages of the disease and after effective treatment in 28 of them. Serum levels of the previously mentioned factors were measured by ELISA, whereas bone marrow plasma cell infiltration and Ki-67 expression were estimated immunohistochemically. All measured parameters were higher in pretreated myeloma patients compared to healthy population and were also increasing with the progression of the disease. They all also decreased after effective therapy. Furthermore, all pretreatment values correlated to each other. BAFF seems to be an important growth factor for myeloma plasma cells. Measuring its serum levels, along with the previously mentioned cytokines, may provide important information regarding the degree of myeloma cells’ proliferation. Therefore, they all could be used as markers of proliferation and disease activity.

  12. Spontaneous occlusion of post-traumatic splenic pseudoaneurysm: report of two cases in children

    Energy Technology Data Exchange (ETDEWEB)

    Raghavan, Ashok; Wong, Christopher Kah Fook; Lam, Albert; Stockton, Vivienne [Department of Medical Imaging, The Children' s Hospital at Westmead, Sydney (Australia)

    2004-04-01

    Conservative therapy for splenic injuries is widely advocated. The advantages of conservative therapy for splenic injuries include the preservation of splenic immune function, prevention of overwhelming post-splenectomy sepsis, and avoidance of laparotomy and its associated early and late complications. Pseudoaneurysms of the splenic artery branch are encountered because of the prevalence of conservative management and widespread use of imaging techniques in the follow-up of these cases. We report two cases of post-traumatic splenic pseudoaneurysm in children which thrombosed spontaneously, one during the diagnostic angiogram examination and another on follow-up studies. (orig.)

  13. Case Report - Isolated splenic peliosis in an immunocompromised ...

    African Journals Online (AJOL)

    Isolated splenic peliosis is an even more unusual phenomenon. Patients with AIDS may develop peliosis in association with bacillary angiomatosis. This is due to secondary infection with Bartonella henselae or a similar organism, Rochalimaea henselae. Case presentation: A 45-year-old HIV-positive man on antiretroviral ...

  14. Ectopic Splenic Tissue in the Testis: A Case Report

    African Journals Online (AJOL)

    Ectopic SplENic tiSSUE iN thE tEStiS associated with bilateral cryptorchidism and hypospadias4. Brasch et al. reported a case involving the right testis5. Ultrasonography, scintigraphy (with technetium-99m) and single positron emission computerized tomography are considered the best diagnostic tools for this condition2,3.

  15. Primary Splenic Hydatid: A Case Report | Gul | East and Central ...

    African Journals Online (AJOL)

    Hydatid disease is a parasitic infection caused mainly by Echinococcus granulosus and is a common entity in this part of the world . However, primary hydatid disease of spleen is a rare entity. We are reporting a case of a massive primary splenic hydatid cyst in a 27 yr old female, who presented with left upper quadrant ...

  16. Splenic lymphoma with villous lymphocytes: case report | Atipo ...

    African Journals Online (AJOL)

    We present the case of malignant Non-Hodgkin splenic lymphoma with villous lymphocytes regarded as atypical chronic lymphoid leukemia. This was a 62 years old male patient admitted in the Haematologic Department of Brazzaville Teaching Hospital for an enlarged spleen, anaemia and lymphocytosis. The initial ...

  17. Spontaneous splenic rupture during the recovery phase of dengue fever.

    Science.gov (United States)

    de Silva, W T T; Gunasekera, M

    2015-07-02

    Spontaneous splenic rupture is a rare but known complication of dengue fever. Previously reported cases have occurred early during the course of the disease and most cases have led to a fatal outcome. Here we report a case of spontaneous splenic rupture in a patient with dengue fever, which occurred during the recovery phase of the illness. A 28-year-old Sinhalese, Sri Lankan man presented with a history of fever, myalgia and vomiting of 4 days duration. Investigations revealed a diagnosis of dengue fever with no signs of plasma leakage. He was managed in the ward as per local protocol. During the recovery phase the patient developed severe abdominal distention with circulatory failure. Radiology revealed splenic rupture with massive amounts of abdominal free fluid. The patient was resuscitated and Emergency laparotomy with splenectomy was performed. The outcome was excellent with the patient making a complete recovery. Although splenic rupture is a known complication of dengue fever it may be manifested late in the disease process. A high degree of suspicion should be maintained and patients must be monitored even during the recovery phase of dengue fever. Early diagnosis and intervention can prevent mortality.

  18. Ruptured splenic epidermoid cyst: case report and imaging appearances

    International Nuclear Information System (INIS)

    Spencer, N.J.B.; Arthur, R.J.; Stringer, M.D.

    1996-01-01

    Traumatic rupture of a splenic epidermoid cyst is a rare but recognised cause of ''acute abdomen'' in a child. We describe such a case occurring after very minor trauma, show the influence that imaging had in making an accurate diagnosis, and discuss how this influenced clinical management. (orig.). With 1 fig

  19. Modulation of cytokine production profiles in splenic dendritic cells ...

    African Journals Online (AJOL)

    We examined the role of splenic dendritic cells in immune response to Toxoplasma gondii infection in SAG1 (P30+) transgenic mice by investigating the kinetics of intracellular cytokines expression of IL-4, IL-10, IL-12 and IFN-γ by intracellular cytokine staining (ICS) using flow cytometry, and compared the results to those of ...

  20. Sonographic Evaluation of the Splenic Length in Normal Pregnancy ...

    African Journals Online (AJOL)

    Methods: A prospective descriptive cross sectional study of the sonographic measurements of the splenic length was performed on 150 healthy normal pregnant women correlating this with the body mass index, gestational age and parity. Data were analyzed using software SPSS version 15 (SPSS Inc., Chicago, IL, USA).

  1. Dynamic alteration in splenic function during acute falciparum malaria

    Energy Technology Data Exchange (ETDEWEB)

    Looareesuwan, S.; Ho, M.; Wattanagoon, Y.; White, N.J.; Warrell, D.A.; Bunnag, D.; Harinasuta, T.; Wyler, D.J.

    1987-09-10

    Plasmodium-infected erythrocytes lose their normal deformability and become susceptible to splenic filtration. In animal models, this is one mechanism of antimalarial defense. To assess the effect of acute falciparum malaria on splenic filtration, we measured the clearance of heated /sup 51/Cr-labeled autologous erythrocytes in 25 patients with acute falciparum malaria and in 10 uninfected controls. Two groups of patients could be distinguished. Sixteen patients had splenomegaly, markedly accelerated clearance of the labeled erythrocytes (clearance half-time, 8.4 +/- 4.4 minutes (mean +/- SD) vs. 62.5 +/- 36.5 minutes in controls; P less than 0.001), and a lower mean hematocrit than did the patients without splenomegaly (P less than 0.001). In the nine patients without splenomegaly, clearance was normal. After institution of antimalarial chemotherapy, however, the clearance in this group accelerated to supernormal rates similar to those in the patients with splenomegaly, but without the development of detectable splenomegaly. Clearance was not significantly altered by treatment in the group with splenomegaly. Six weeks later, normal clearance rates were reestablished in most patients in both groups. We conclude that splenic clearance of labeled erythrocytes is enhanced in patients with malaria if splenomegaly is present and is enhanced only after treatment if splenomegaly is absent. Whether this enhanced splenic function applies to parasite-infected erythrocytes in patients with malaria and has any clinical benefit will require further studies.

  2. Primary Giant Splenic Echinococcal Cyst Treated by Laparoscopy.

    Science.gov (United States)

    Arce, Maira A; Limaylla, Himerón; Valcarcel, Maria; Garcia, Hector H; Santivañez, Saul J

    2016-01-01

    Cystic echinococcosis (CE) is a zoonosis caused by the larval stage of the dog tapeworm Echinococcus granulosus. Liver and lungs are the most commonly affected organs whereas splenic infection is rarer and its primary involvement occurs in less than 2% of abdominal CE. We report a case of primary giant splenic hydatid cyst in a 75-year-old Peruvian woman that was laparoscopically removed without any complications, perioperative prophylactic chemotherapy with albendazole 400 mg twice a day 5 days before, and 7 days after the surgical procedure was administered, postoperative recovery was uneventful, and; at her 3-month follow-up the patient remains asymptomatic and an abdominal computed tomography scan demonstrated a cystic cavity of 15 cm diameter with no daughter vesicles, neither other abdominal organ involvement. This case is in line with the existing literature on laparoscopical treatment of splenic cystic hydatid disease, suggesting that laparoscopical treatment is a safe and effective approach for large splenic hydatid cysts to be preferred to open surgical techniques. © The American Society of Tropical Medicine and Hygiene.

  3. Splenic artery embolisation for portal hypertention in children ...

    African Journals Online (AJOL)

    Background: Bleeding from esophageal varices is one of the most common causes of serious gastrointestinal haemorrhage in children. We analysed our experience with the use of splenic artery embolisation and variceal sclerotherapy for bleeding oesophageal varices. Patients and Methods: Records of all patients treated ...

  4. Spontaneous Rupture of Splenic Hemangioma in a Neonate

    OpenAIRE

    Martinez-Leo, Bruno; Vidal-Medina, Jorge; Cervantes-Ledezma, Jes?s; D?az De Le?n-Rivera, Arid; D?az-Velasco, Edith

    2016-01-01

    Spleen vascular tumors such as hemangiomas, albeit rare, can present during neonatal period with unexplained circulatory shock. We present a case of a newborn with refractory hypovolemic shock and acute abdomen that underwent emergency splenectomy due to spontaneous rupture of a splenic hemangioma.

  5. Hyposplenism: Comparison of different methods for determining splenic function

    NARCIS (Netherlands)

    Lammers, A. J. Jolanda; de Porto, Alexander P. N. A.; Bennink, Roelof J.; van Leeuwen, Ester M. M.; Biemond, Bart J.; Goslings, J. Carel; van Marle, Jan; ten Berge, Ineke J. M.; Speelman, Peter; Hoekstra, Joost B. L.

    2012-01-01

    Asplenic patients are at risk for pneumococcal sepsis. Patients with hyposplenic function, such as associated with sickle cell disease (SCD), are also at risk. However, tests to assess splenic function are either unavailable or lacking standardization. The aim of this study was to compare different

  6. Splenic abscess due to blastomycosis: scintigraphic, sonographic, and CT evaluation

    International Nuclear Information System (INIS)

    Dubuisson, R.L.; Jones, T.B.

    1983-01-01

    This paper describes the radiologic evaluation of a case of splenic abscess secondary to North American blastomycosis in a known intravenous drug abuser, a disease not believed to be previously reported in the radiologic literature. Dynamic computed tomography proved especially useful in narrowing the diagnostic possibilities and excluding vascular lesions

  7. Study of splenic irradiation in chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Guiney, M.J.; Liew, K.H.; Quong, G.G.; Cooper, I.A.

    1989-01-01

    A retrospective study was performed to assess the effect of splenic irradiation (SI) on splenomegaly, splenic pain, anemia, and thrombocytopenia in patients with chronic lymphocytic leukemia. Twenty-two patients received 32 courses of SI. Of 31 courses of SI given for splenomegaly there were 19 responders (61%). Ten courses of SI were given for splenic pain resulting in partial relief of pain in 4 courses and complete relief in 4 courses. Only 4 of 16 courses given for anemia resulted in elevations of hemoglobin of 2 g/dL or more. Of the 14 courses of SI given for thrombocytopenia there were only 2 responses with platelet counts decreasing further in another 9 courses. The median duration of response was 14 months (range: 3-116 months). There was no dose-response relationship detected for SI in CLL. Treatment related toxicity was hematologic and secondary to leucopenia and thrombocytopenia. We recommend the use of small fraction sizes of 25 cGy to 50 cGy and close monitoring of hematological parameters. Splenic irradiation effectively palliates splenomegaly and reduces spleen size in CLL. It was of limited value in correcting anemia and thrombocytopenia in this patient population

  8. Splenic concentration of bone imaging agents in functional asplenia

    International Nuclear Information System (INIS)

    Dhekne, R.D.

    1981-01-01

    Three cases of sickle cell disease associated with functional asplenia are described. The spleen was not visualized on routine Tc-99m-sulfur colloid scan. The bone scan performed with Tc-99m-phosphate compounds revealed abnormal splenic activity in all three cases. The previous case reports and the literature on this subject are reviewed

  9. Management of Splenic Injuries in a University Teaching Hospital in ...

    African Journals Online (AJOL)

    Splenectomy was the most frequently performed procedure. Challenges identified in the management of patients with splenic injuries in Nigeria include delayed presentation, underutilization of CT, unavailability of interventional radiology, inadequate ICUs, limited vaccination, discharge against medical advice and poor ...

  10. Emergency endovascular coiling of a ruptured giant splenic artery aneurysm

    DEFF Research Database (Denmark)

    Wernheden, Erika; Brenøe, Anne Sofie; Shahidi, Saeid

    2017-01-01

    Splenic artery aneurysms (SAAs) are the third most common abdominal aneurysm. Endovascular treatment of SAAs is preferred, and coiling is the most commonly used technique. Ruptured giant (>5 cm) SAAs are usually treated with open surgery including splenectomy. We present a rare case of a ruptured...

  11. Laparoscopic Splenectomy for Traumatic Splenic Injury after Screening Colonoscopy

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    Salim Abunnaja

    2012-09-01

    Full Text Available Colonoscopy is a widespread diagnostic and therapeutic procedure. The most common complications include bleeding and perforation. Splenic rupture following colonoscopy is rarely encountered and is most likely secondary to traction on the splenocolic ligament. Exploratory laparotomy and splenectomy is the most commonly employed therapeutic intervention for this injury reported in the literature. We present the case of a patient with this potentially fatal complication who was treated successfully at our institution. To our knowledge it is the first report in the literature of laparoscopic splenectomy as a successful minimally invasive treatment of splenic rupture following colonoscopy. The patient was a 62-year-old female who underwent screening colonoscopy with polypectomies at the cecum, descending colon and rectum. Immediately following the procedure she developed abdominal pain and had a syncopal episode. Clinical, laboratory and imaging findings were suggestive of hemoperitoneum and a ruptured spleen. A diagnostic laparoscopy was emergently performed and revealed a grade IV splenic laceration and hemoperitoneum. Laparoscopic splenectomy was completed safely and effectively. The patient’s postoperative recovery was uneventful. We conclude that splenic rupture after colonoscopy is a rare but dangerous complication. A high index of suspicion is required to recognize it early. Awareness of this potential complication can lead to optimal patient outcome. Laparoscopic splenectomy may be a feasible treatment option.

  12. Expression of TNF-superfamily members BAFF and APRIL in breast cancer: Immunohistochemical study in 52 invasive ductal breast carcinomas

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    Stathopoulos Efstathios N

    2008-03-01

    Full Text Available Abstract Background Recent studies suggest an association between chronic inflammation, modulating the tissue microenvironment, and tumor biology. Tumor environment consists of tumor, stromal and endothelial cells and infiltrating macrophages, T lymphocytes, and dendritic cells, producing an array of cytokines, chemokines and growth factors, accounting for a complex cell interaction and regulation of differentiation, activation, function and survival of tumor and surrounding cells, responsible for tumor progression and spreading or induction of antitumor immune responses and rejection. Tumor Necrosis Factor (TNF family members (19 ligands and 29 receptors represent a pleiotropic family of agents, related to a plethora of cellular events from proliferation and differentiation to apoptosis and tumor reduction. Among these members, BAFF and APRIL (CD257 and CD256 respectively gained an increased interest, in view of their role in cell protection, differentiation and growth, in a number of lymphocyte, epithelial and mesenchymal structures. Methods We have assayed by immunohistochemistry 52 human breast cancer biopsies for the expression of BAFF and APRIL and correlated our findings with clinicopathological data and the evolution of the disease. Results BAFF was ubiquitely expressed in breast carcinoma cells, DCIS, normal-appearing glands and ducts and peritumoral adipocytes. In contrast, APRIL immunoreactive expression was higher in non-malignant as compared to malignant breast structures. APRIL but not BAFF immunoreactivity was higher in N+ tumors, and was inversely related with the grade of the tumors. Neither parameter was related to DFS or the OS of patients. Conclusion Our data show, for the first time, an autocrine secretion of BAFF and APRIL from breast cancer cells, offering new perspectives for their role in neoplastic and normal breast cell biology and offering new perspectives for possible selective intervention in breast cancer.

  13. Antibody response to a T-cell-independent antigen is preserved after splenic artery embolization for trauma

    NARCIS (Netherlands)

    Olthof, D. C.; Lammers, A. J. J.; van Leeuwen, E. M. M.; Hoekstra, J. B. L.; ten Berge, I. J. M.; Goslings, J. C.

    2014-01-01

    Splenic artery embolization (SAE) is increasingly being used as a nonoperative management strategy for patients with blunt splenic injury following trauma. The aim of this study was to assess the splenic function of patients who were embolized. A clinical study was performed, with splenic function

  14. [Splenic auto-implant and hyperbaric oxygen therapy in rats].

    Science.gov (United States)

    Paulo, Isabel Cristina Andreatta Lemos; Silva, Alcino Lázaro da; Piras, Cláudio; Ramos, Bernardo Faria; Zanetti, Fernando Roberto; Paulo, Danilo Nagib Salomão

    2010-06-01

    To study the functional and morphological features of splenic autoimplants in rats subjected, or not, to postoperative hyperbaric oxygen therapy. One hundred and five male Wistar rats, weighing 251.6 g ± 29.5 g, were studied ot early (11th day) and late (70th day ) postoperative periods. For each period the animals were distributed in the following groups: A (n=40), splenic manipulation; B (n=65),splenic autoimplants, not treated (nt) (A11nt--n=10, B11nt--n=21, A70nt--n=10, B70nt--n=18) and treated with hyperbaric oxygen (t) ( A11t--n=10, B11t--n=15, A70t--n=10, B70t--n=11). Blood was collected for measurement of lipids and immunoglobulins, platelet and Howell-Jolly body count before and after surgery. The spleen and autoimplants were removed for histologic analyses. There was an increase of total cholesterol (p=0.00068), LDL-cholesterol (p=0.002), VLDL-cholesterol and triglycerides (p=0.0033) in B11nt group. There was an increase of total cholesterol (p=0.0007) and LDL-cholesterol (p=0.0000) in B70nt group, and no alterations were observed in the other groups. IgM decreased in B groups (p=0.0000) and no changes were observed in the splenic manipulation group. Number of Howell-Jolly bodies were lesser in Bt groups than in Bnt groups (p=0.03). Platelets were increased in B11t and B11nt groups (p=0.0000) and remained unchanged in the other groups. Autoimplants microscopic viability was better in Bt groups than in Bnt. The splenic autoimplants of rats treated with hyperbaric oxygen therapy showed a better functionality and viability than those subjected to other procedures.

  15. Blunt trauma induced splenic blushes are not created equal

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    Burlew Clay

    2012-03-01

    Full Text Available Abstract Background Currently, evidence of contrast extravasation on computed tomography (CT scan is regarded as an indication for intervention in splenic injuries. In our experience, patients transferred from other institutions for angioembolization have often resolved the blush upon repeat imaging at our hospital. We hypothesized that not all splenic blushes require intervention. Methods During a 10-year period, we reviewed all patients transferred with blunt splenic injuries and contrast extravasation on initial postinjury CT scan. Results During the study period, 241 patients were referred for splenic injuries, of whom 16 had a contrast blush on initial CT imaging (88% men, mean age 35 ± 5, mean ISS 26 ± 3. Eight (50% patients were managed without angioembolization or operation. Comparing patients with and without intervention, there was a significant difference in admission heart rate (106 ± 9 vs 83 ± 6 and decline in hematocrit following transfer (5.3 ± 2.0 vs 1.0 ± 0.3, but not in injury grade (3.9 ± 0.2 vs 3.5 ± 0.3, systolic blood pressure (125 ± 10 vs 115 ± 6, or age (38.5 ± 8.2 vs 30.9 ± 4.7. Of the 8 observed patients, 3 underwent repeat imaging immediately upon arrival with resolution of the blush. In the intervention group, 4 patients had ongoing extravasation on repeat imaging, 2 patients underwent empiric embolization, and 2 patients underwent splenectomy for physiologic indications. Conclusions For blunt splenic trauma, evidence of contrast extravasation on initial CT imaging is not an absolute indication for intervention. A period of observation with repeat imaging could avoid costly, invasive interventions and their associated sequelae.

  16. [Splenic late infarction after laparoscopic gastrectomy: a case report].

    Science.gov (United States)

    Soriano-Giménez, Víctor; Ruiz de Angulo-Martín, David; Munítiz-Ruiz, Vicente; Ortiz-Escandell, María de Los Ángeles; Martínez-de Haro, Luisa Fernanda; Parrilla-Paricio, Pascual

    2017-12-01

    Laparoscopic gastrectomy has emerged in recent years as an effective technique for the treatment of morbid obesity due to low mortality morbidity rates. Its complications include dehiscence suture line, and others such as splenic infarction. We discuss a case of splenic infarction after laparoscopic gastrectomy. 45 year old male with a BMI of 37.8 kg/m 2 , diabetes-II for 15 years, the last five in treatment with insulin, a fasting blood glucose around 140mg/dl, HbA1c of 7.3mg/dl and microangiopathy diabetic nephropathy. The patient underwent a laparoscopic sleeve gastrectomy and he was discharged from hospital 48hours later. 1 month later he presented at the hospital for epigastric pain and fever up to 40° C. An intra abdominal abscess was detected and there was no leakage. The spleen was normal. He was treated with radiological drainage. 9 months later the patient consulted again due to epigastric pain in upper left quadrant, associated with low-grade fever. Thoraco-abdominal CT images compatible with splenic infarction. Currently patient remains asymptomatic one year after surgery. Laparoscopic sleeve gastrectomy is one of the most popular procedures of bariatric surgery. Less common complications include abscess and the splenic infarction. Usually patients are asymptomatic, but sometimes cause fever and pain. Initial treatment should be conservative. Only in selected cases, would splenectomy be indicated. Splenic infarction is usually an early complication, but we should keep it in mind as a long term complication for patients with persistent fever and abdominal pain after laparoscopic gastrectomy. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  17. Reduction of CD19 autoimmunity marker on B cells of paediatric SLE patients through repressing PU.1/TNF-α/BAFF axis pathway by miR-155.

    Science.gov (United States)

    Aboelenein, H R; Hamza, M T; Marzouk, H; Youness, R A; Rahmoon, M; Salah, S; Abdelaziz, A I

    2017-06-01

    microRNA-155 (miR-155) is implicated in regulating B-cell activation and survival that is important in systemic lupus erythematosus (SLE) pathogenesis. PU.1, a target for miR-155, is a crucial regulator of B-cell development and enhances Tumour-Necrosis-factor-alpha (TNF-α) expression. TNF-α induces the expression of B-cell-activating-factor (BAFF). BAFF is reported to increase the expression of the autoimmunity marker; CD19. This study aimed to investigate the regulation of expression of PU.1 in pediatric-systemic-lupus-erythematosus (pSLE) patients by miR-155, and hence evaluate its impact on TNF-α/BAFF/CD19 signalling pathway. Screening revealed that PU.1 is upregulated in PBMCs and B-cells of pSLE patients. PU.1 expression directly correlated with systemic-lupus-erythematosus disease-activity-index-2 K SLEDAI-2K. Ectopic expression of miR-155 and knockdown of PU.1 suppressed PU.1, TNF-α and BAFF. Finally, miR-155 decreased the proportion of BAFF-expressing-B-cells and CD19 protein expression. These findings suggest that miR-155 suppresses autoimmunity through transcriptional repression of PU.1 and TNF-α, which in turn suppresses BAFF and CD19 protein expression.

  18. Interleukin 21 blockade modulates activated T- and B-cell homeostasis via B-cell activating factor pathway-mediated inhibition in a murine model of acute graft-versus-host disease.

    Science.gov (United States)

    Lim, Jung-Yeon; Park, Min-Jung; Im, Keon-Il; Kim, Nayoun; Park, Hyun-Sil; Lee, Sung-Hee; Kim, Eun-Kung; Nam, Young-Sun; Lee, Eun-Sol; Cho, Mi-La; Cho, Seok-Goo

    2015-01-01

    Interleukin (IL) 21 plays a key role in the development of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. Therapeutic manipulation of IL-21 activity may improve acute GVHD during the early-posttransplant period. We investigated the mechanisms regulating T- and B-cells during IL-21 blockade in acute GVHD. Interleukin 21 blockade enhanced regulatory T and T helper (Th) 2 cell differentiation and inhibited Th1- and Th17-derived transcription factors and cytokines as a modulator of activated T-cells. Interleukin 21(-/-) cell recipients showed increased mature B- and marginal-zone B-cells, but decreased memory B-cells, germinal center formation, and plasma cells that did not lead to immunoglobulin production. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in the induction and maintenance of T- and B-cell responses. We observed decreased levels of only BAFF during acute GVHD and confirmed that mammalian target of rapamycin complex 1 was reduced by the BAFF/BAFF-receptor pathway. Therefore, this study suggests that IL-21 blockade modulates activated T- and B-cell homeostasis via BAFF-pathway-mediated inhibition in acute GVHD following murine allogeneic bone marrow transplantation. Copyright © 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  19. BAFF, stimulatory DNA and IL-15 stimulates IgA(+) memory B cells and provides a novel approach for analysis of memory responses to mucosal vaccines.

    Science.gov (United States)

    Tengvall, Sara; Lundgren, Anna; Quiding-Järbrink, Marianne; Svennerholm, Ann-Mari

    2010-07-26

    Assessment of immune responses induced by mucosal vaccines is to a large extent based on measurement of IgA levels in mucosal secretions and detection of short-lived effector IgA-secreting cells circulating in peripheral blood. Since these immunological parameters poorly reflect long-term IgA-mediated responses, we sought to investigate novel approaches that would enable detection of vaccine specific IgA memory B cells. We demonstrate that stimulation of human peripheral blood mononuclear cells in vitro with immunostimulatory DNA in combination with B cell-activating factor (BAFF) and IL-15 promotes differentiation of IgA memory B cells to IgA-secreting cells. By using the inactivated oral cholera vaccine Dukoral we demonstrate that vaccine specific IgA memory B cells are induced by oral immunization and are circulating for at least 9 months after vaccination. We also show that stimulated IgA memory B cells do not secrete IgA unless they reencounter the specific antigen. Copyright 2010 Elsevier Ltd. All rights reserved.

  20. Splenic infarct as a diagnostic pitfall in radiology

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    Joshi Sanjeev

    2008-01-01

    Full Text Available Follow-up of colorectal carcinoma after therapy is based on symptoms, tumor markers, and imaging studies. Clinicians sometimes face diagnostic dilemmas because of unusual presentations on the imaging modalities coupled with rising serum markers. We report a case of colorectal carcinoma that presented with gastrointestinal symptoms 14 months after completion of treatment. Investigations showed rise in carcinoembryonic antigen (CEA. Suspecting disease recurrence, complete radioimaging workup was performed; the only abnormality detected was a smooth, hypodense area in the posterior third of the spleen on contrast-enhanced computed tomography abdomen. In view of the previous diagnosis of carcinoma colon, the symptoms reported by the patient, the elevated CEA, and the atypical CECT appearance, a diagnosis of splenic metastasis was made. The patient was subjected to splenectomy as a curative treatment. However, the histopathological report revealed it to be a splenic infarct. The present case reemphasizes the limitations of radiological studies in the follow-up of carcinoma colon.

  1. Howell--Jolly bodies: a clue to splenic infarction

    Energy Technology Data Exchange (ETDEWEB)

    Larrimer, J.H.; Mendelson, D.S.; Metz, E.N.

    1975-06-01

    Acute splenic infarction is characterized by left upper quadrant pain and occasionally by a friction rub. The differentiation from other intra-abdominal vascular diseases, such as ischemic bowel disease, renal infarction, and emboli to the mesenteric vessels can be difficult, and often the correct diagnosis has been made only at surgery or autopsy. In the past few years, radioisotope scanning of the spleen with technetium (/sup 99m/Tc) sulfur colloid has come into general use and appears to be a valuable aid in confirming the diagnosis. We describe the case of a patient with left upper quadrant abdominal pain of unknown origin in whom the appearance of Howell-Jolly bodies in her peripheral blood film proved to be an early sign of splenic infarction. (auth)

  2. Splenic imaging in a patient with functional asplenia

    Energy Technology Data Exchange (ETDEWEB)

    Wagman, P.G.; Dworkin, H.J.

    1989-04-01

    A 65-year-old woman presented with right upper extremity paralysis and left cerebrovascular accident. A routine complete blood count (CBC) demonstrated Howell-Jolly bodies on peripheral smear, and a liver-spleen scan showed absent splenic sulfur colloid uptake suggesting functional asplenia. A subsequent heat damaged red blood cell study demonstrated a normal sized spleen with preserved sequestering function, thereby excluding anatomic asplenia, vascular alterations, or congenital anomalies in the differential diagnosis of functional asplenia. This case illustrates the use of Tc-99m heat damaged red blood cells as a unique and useful diagnostic aid in identifying the presence and size of a spleen in patients with functional asplenia. It also demonstrates an apparent qualitative separation of splenic functions in processing sulfur colloid and heat damaged red blood cells.

  3. Partial splenic ablation in preparation for renal transplantation in children.

    Science.gov (United States)

    Guzzetta, P C; Stolar, C H; Potter, B M; Broadman, L; Ruley, E J

    1983-12-01

    Patients with end-stage renal disease who develop hypersplenism, patients with mild neutropenia, and those patients whose WBC fails to increase in response to cortisol administration will develop significant neutropenia following transplantation with routine doses of azathioprine. This "intolerance" of azathioprine mandates a reduction in the dose of azathioprine often resulting in allograft rejection. Splenectomy will prevent azathioprine-induced neutropenia, but the hazards of splenectomy in these immunosuppressed patients have led to attempts to salvage at least part of the spleen. Partial splenic ablation by embolization has been utilized in adults prior to transplantation to prevent azathioprine-induced neutropenia while preserving the spleen's protective mechanisms against infection. Eight children in our series of transplant candidates required a reduction of splenic function to prevent azathioprine induced neutropenia. One child had a functioning renal allograft but had recurrent neutropenia limiting the azathioprine dose. Partial splenic embolization was attempted in four children and was initially successful in two. Both patients later developed recurrent neutropenia and needed partial splenectomy. The two patients in whom partial splenic embolization was unsuccessful and five further patients in whom embolization was not attempted also underwent partial splenectomy. Approximately 75% to 80% of the spleen was resected. Six children have since undergone renal transplantation and one child had a transplant with chronic rejection at the time of partial splenectomy. Routine doses of azathioprine have been used in these children with no episodes of neutropenia or sepsis observed. We recommend partial splenectomy in those children requiring renal transplantation who are at risk for development of azathioprine induced neutropenia.

  4. Isolated metachronous splenic metastasis from synchronous colon cancer

    Directory of Open Access Journals (Sweden)

    Aker Fugen

    2006-07-01

    Full Text Available Abstract Background Isolated splenic metastases from colorectal cancer are very rare and there are only 13 cases reported in the English literature so far. Most cases are asymptomatic and the diagnosis is usually made by imaging studies during the evaluation of rising CEA level postoperatively. Case presentation A 76-year-old man underwent an extended left hemicolectomy for synchronous colon cancers located at the left flexure and the sigmoid colon. The tumors were staged as IIIC (T3N2M0 clinically and the patient received adjuvant chemotherapy. During the first year follow-up period, the patient remained asymptomatic with normal levels of laboratory tests including CEA measurement. However, a gradually rising CEA level after the 14th postoperative month necessitated further imaging studies including computed tomography of the abdomen which revealed a mass in the spleen that was subsequently confirmed by 18FDG- PET scanning to be an isolated metastasis. The patient underwent splenectomy 17 months after his previous cancer surgery. Histological diagnosis confirmed a metastatic adenocarcinoma with no capsule invasion. After an uneventful postoperative period, the patient has been symptom-free during the one-year of follow-up with normal blood CEA levels, although he did not accept to receive any further adjuvant therapy. To the best of our knowledge, this 14th case of isolated splenic metastasis from colorectal carcinoma is also the first reported case of splenic metastasis demonstrated preoperatively by 18FDG PET-CT fusion scanning which revealed its solitary nature as well. Conclusion Isolated splenic metastasis is a rare finding in the follow-up of colorectal cancer patients and long-term survival can be achieved with splenectomy.

  5. Splenic artery embolisation for portal hypertention in children

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    Meisheri Ila

    2010-01-01

    Full Text Available Background: Bleeding from esophageal varices is one of the most common causes of serious gastrointestinal haemorrhage in children. We analysed our experience with the use of splenic artery embolisation and variceal sclerotherapy for bleeding oesophageal varices. Patients and Methods: Records of all patients treated for bleeding oesophageal varices caused by portal hypertension from 1998 to 2004 were retrospectively analysed. Patients were followed up for five years. Results: Out of 25 patients treated, ten belonged to sclerotherapy (group A, eight to combined sclerotherapy and embolisation (group B, and seven to only embolisation (group C. The patients were selected randomly, only two patients who had active bleed recently were directly sclerosed. The splenic artery was embolised at the hilum using steel coils in 15 patients with portal hypertension and hypersplenism. Follow-up findings showed decrease in splenic mass, varices, and hyperdynamic flow. Conclusion: In spite of few patients and a short period of follow-up, our results pointed out that a serious consideration should be given to this procedure, as it slowed the sequel of portal hypertension and the complications associated with it. Patients who were embolised and followed up for five years had lesser rebleeds and complications than sclerotherapy patients.

  6. CT imaging of splenic sequestration in sickle cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Sheth, S.; Piomelli, S. [Columbia Univ., New York, NY (United States). Dept. of Pediatrics; Ruzal-Shapiro, C.; Berdon, W.E. [Columbia Univ., New York, NY (United States). Div. of Pediatric Radiology

    2000-12-01

    Pooling of blood in the spleen is a frequent occurrence in children with sickle cell diseases, particularly in the first few years of life, resulting in what is termed ''splenic sequestration crisis.'' The spectrum of severity in this syndrome is wide, ranging from mild splenomegaly to massive enlargement, circulatory collapse, and even death. The diagnosis is usually clinical, based on the enlargement of the spleen with a drop in hemoglobin level by >2 g/dl, and it is rare that imaging studies are ordered. However, in the patient who presents to the emergency department with non-specific findings of an acute abdomen, it is important to recognize the appearance of sequestration on imaging studies. We studied seven patients utilizing contrast-enhanced CT scans and found two distinct patterns - multiple, peripheral, non-enhancing low-density areas or large, diffuse areas of low density in the majority of the splenic tissue. Although radiological imaging is not always necessary to diagnose splenic sequestration, in those situations where this diagnosis is not immediately obvious, it makes an important clarifying contribution. (orig.)

  7. Pseudoaneurysm of the splenic artery mimicking a solid lesion

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    Raffaele Pezzilli

    2016-08-01

    Full Text Available A 64-year-old man presented to the hospital because of hematemesis; on admission, he had weakness and pale skin, tachycardia and hypotension. Laboratory tests revealed severe anemia (hemoglobin 7.8 g/dL; liver, renal and pancreatic function tests were normal. An upper digestive endoscopy revealed a gastric ulcer of the cardia, treated with metallic clips and adrenalin injection. The patient was treated with fluids and was transfused with three units of red blood cells. In the previous two months, due to the presence of bloating and diarrhea, associated with abdominal distension, a colon-computed tomography (CT revealed a large retroperitoneal hypodense mass, 53x37 mm in size, without contrast enhancement localized between the body and the tail of the pancreas and the stomach, near the splenic artery and without signs of infiltration. To better define the mass, endoscopic ultrasound and biopsy were performed; however histopathology of multiple biopsies was not diagnostic, because of the presence of necrotic tissue and inflammatory cells. Since hematemesis recurred, the patient underwent a second upper digestive endoscopic examination, but no source of bleeding was found. Then a new contrast enhanced CT was performed that showed a size reduction of the mass, the presence of blood in the stomach and a small pseudoaneurysm of the splenic artery. Because of these findings an angiograpghic study was carried out; angiography confirmed a splenic artery pseudoaneurysm that was successfully embolized with metal microcoils.

  8. CT imaging of splenic sequestration in sickle cell disease

    International Nuclear Information System (INIS)

    Sheth, S.; Piomelli, S.; Ruzal-Shapiro, C.; Berdon, W.E.

    2000-01-01

    Pooling of blood in the spleen is a frequent occurrence in children with sickle cell diseases, particularly in the first few years of life, resulting in what is termed ''splenic sequestration crisis.'' The spectrum of severity in this syndrome is wide, ranging from mild splenomegaly to massive enlargement, circulatory collapse, and even death. The diagnosis is usually clinical, based on the enlargement of the spleen with a drop in hemoglobin level by >2 g/dl, and it is rare that imaging studies are ordered. However, in the patient who presents to the emergency department with non-specific findings of an acute abdomen, it is important to recognize the appearance of sequestration on imaging studies. We studied seven patients utilizing contrast-enhanced CT scans and found two distinct patterns - multiple, peripheral, non-enhancing low-density areas or large, diffuse areas of low density in the majority of the splenic tissue. Although radiological imaging is not always necessary to diagnose splenic sequestration, in those situations where this diagnosis is not immediately obvious, it makes an important clarifying contribution. (orig.)

  9. Aiolos Overexpression in Systemic Lupus Erythematosus B Cell Subtypes and BAFF-Induced Memory B Cell Differentiation Are Reduced by CC-220 Modulation of Cereblon Activity.

    Science.gov (United States)

    Nakayama, Yumi; Kosek, Jolanta; Capone, Lori; Hur, Eun Mi; Schafer, Peter H; Ringheim, Garth E

    2017-10-01

    BAFF is a B cell survival and maturation factor implicated in the pathogenesis of systemic lupus erythematosus (SLE). In this in vitro study, we describe that soluble BAFF in combination with IL-2 and IL-21 is a T cell contact-independent inducer of human B cell proliferation, plasmablast differentiation, and IgG secretion from circulating CD27 + memory and memory-like CD27 - IgD - double-negative (DN) B cells, but not CD27 - IgD + naive B cells. In contrast, soluble CD40L in combination with IL-2 and IL-21 induces these activities in both memory and naive B cells. Blood from healthy donors and SLE patients have similar circulating levels of IL-2, whereas SLE patients exhibit elevated BAFF and DN B cells and reduced IL-21. B cell differentiation transcription factors in memory, DN, and naive B cells in SLE show elevated levels of Aiolos, whereas Ikaros levels are unchanged. Treatment with CC-220, a modulator of the cullin ring ligase 4-cereblon E3 ubiquitin ligase complex, reduces Aiolos and Ikaros protein levels and BAFF- and CD40L-induced proliferation, plasmablast differentiation, and IgG secretion. The observation that the soluble factors BAFF, IL-2, and IL-21 induce memory and DN B cell activation and differentiation has implications for extrafollicular plasmablast development within inflamed tissue. Inhibition of B cell plasmablast differentiation by reduction of Aiolos and Ikaros may have utility in the treatment of SLE, where elevated levels of BAFF and Aiolos may prime CD27 + memory and DN memory-like B cells to become Ab-producing plasmablasts in the presence of BAFF and proinflammatory cytokines. Copyright © 2017 by The American Association of Immunologists, Inc.

  10. Current and emerging treatment options for ANCA-associated vasculitis: potential role of belimumab and other BAFF/APRIL targeting agents

    Science.gov (United States)

    Lenert, Aleksander; Lenert, Petar

    2015-01-01

    Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises several clinical entities with diverse clinical presentations, outcomes, and nonunifying pathogenesis. AAV has a clear potential for relapses, and shows unpredictable response to treatment. Cyclophosphamide-based therapies have remained the hallmark of induction therapy protocols for more than four decades. Recently, B-cell depleting therapy with the anti-CD20 antibody rituximab has proved beneficial in AAV, leading to Food and Drug Administration approval of rituximab in combination with corticosteroids for the treatment of AAV in adults. Rituximab for ANCA-associated vasculitis and other clinical trials provided clear evidence that rituximab was not inferior to cyclophosphamide for remission induction, and rituximab appeared even more beneficial in patients with relapsing disease. This raised hopes that other B-cell-targeted therapies directed either against CD19, CD20, CD22, or B-cell survival factors, B-cell activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand could also be beneficial for the management of AAV. BAFF neutralization with the fully humanized monoclonal antibody belimumab has already shown success in human systemic lupus erythematosus and, along with another anti-BAFF reagent blisibimod, is currently undergoing Phase II and III clinical trials in AAV. Local production of BAFF in granulomatous lesions and elevated levels of serum BAFF in AAV provide a rationale for BAFF-targeted therapies not only in AAV but also in other forms of vasculitis such as Behcet’s disease, large-vessel vasculitis, or cryoglobulinemic vasculitis secondary to chronic hepatitis C infection. BAFF-targeted therapies have a very solid safety profile, and may have an additional benefit of preferentially targeting newly arising autoreactive B cells over non-self-reactive B cells. PMID:25609919

  11. Different IgM+B cell subpopulations residing within the peritoneal cavity of vaccinated rainbow trout are differently regulated by BAFF.

    Science.gov (United States)

    Granja, Aitor G; Tafalla, Carolina

    2017-10-05

    In teleost fish, IgM + B cells are one of the main responders against inflammatory stimuli in the peritoneal cavity, as IgM + B cells dominate the peritoneum after intraperitoneal stimulation, also increasing the levels of secreted IgM. BAFF, a cytokine known to play a major role in B cell biology, has been shown to be up-regulated along with its receptors in the peritoneum of rainbow trout upon antigenic exposure, however, the regulatory mechanisms underneath this response remain unclear. In this study, we have identified two different IgM + B cell types residing in the peritoneal cavity of previously vaccinated rainbow trout (Oncorhynchus mykiss): IgD + IgM hi MHCII hi cells, resembling naïve B cells, and IgD - IgM lo MHCII lo cells, resembling antibody-secreting cells. Based on their membrane IgM levels, these cell types were named IgM hi and IgM lo B cells, respectively. As each of these B cell populations showed a distinct expression pattern for the different BAFF receptors, we studied the effect of BAFF individually on each cell subset. Recombinant BAFF promoted the survival of IgM lo but not IgM hi B cells in vitro, resulting in increased levels of IgM-secreting cells. In contrast, BAFF increased the levels of membrane MHC II only on IgM hi B cells, suggesting different functions on these B cell subsets. Moreover, we also showed that peritoneal IgM hi B cells expressed BAFF at levels comparable to those seen on myeloid cells. These results point to BAFF as a main regulator of B cell homeostasis in the peritoneal cavity, suggesting that this cytokine can trigger different signals on different peritoneal B cell subsets in a specific manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Endovascular treatment of aneurysm of splenic artery arising from splenomesentric trunk using stent graft

    Energy Technology Data Exchange (ETDEWEB)

    Kulkami, Chinmay Bhimaji; Moorthy Srikanth; Pullara Sreekumar Karumathil; Kannan, Rajesh Ramaih [Department of Radiology, Amrita Institute of Medical Sciences, Amrita Lane (India)

    2013-12-15

    We report a rare case of aneurysm of splenic artery arising anomalously from the superior mesenteric artery (SMA). The aneurysm was treated successfully by coil embolization of the splenic artery distal to aneurysm and then deploying a stent graft in the SMA. A combination of stent graft and coil embolization for the treatment of aberrant splenic artery aneurysm has been reported only once. We describe the imaging findings and the endovascular procedure in this patient.

  13. A case of microgastria in association with splenic-gonadal fusion

    International Nuclear Information System (INIS)

    Mandell, G.A.; Alavi, A.; Heyman, S.; Ziegler, M.M.

    1983-01-01

    Microgastria is a rare congenital anomaly usually associated with asplenia. In this 2 1/2-year-old presenting with left hydrocele and inguinal hernia multiple accessory spleens were found in the inguinal-scrotal region compatible with splenic-gonadal fusion. sup(99m)Tc-sulfur colloid scanning is helpful in microgastria searching for the presence of splenic tissue and in splenic-gonadal fusion for the location of accessory heterotopic spleens. (orig.)

  14. Acute Brucellosis with Splenic Infarcts: A Case Report from a Tertiary Care Hospital in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Mishal Alyousef

    2015-01-01

    Full Text Available Splenic infarction is an extremely rare and unique presentation of brucellosis. Only few cases have been reported worldwide. We here report a case of a young man, presenting with acute onset of fever, left hypochondial pain, and vomiting. Further evaluation revealed multiple splenic infarcts and positive blood culture for brucellosis despite negative transesophageal echocardiography for endocarditis. Significant improvement in clinical symptoms and splenic lesions was achieved after six weeks of combination therapy against brucellosis.

  15. Detection of The TNFSF Members BAFF, APRIL, TWEAK and Their Receptors in Normal Kidney and Renal Cell Carcinomas

    Directory of Open Access Journals (Sweden)

    Vassiliki Pelekanou

    2011-01-01

    Full Text Available In advanced renal cell carcinoma (RCC, surgery combined with systemic chemotherapy and immunotherapy have had limited effectiveness. Therapeutic modalities targeting VEGF, PDGF, and c-kit using tyrosine kinase inhibitors and m-TOR using specific biologic factors are in development. Therapeutic approaches targeting TNF-alpha have shown limited efficacy, while anti-TRAIL (TNFSF10 antibodies have shown enhanced activity. The presence and potential significance of other members of the TNFSF has not been investigated. Here, we assayed the TNFSF members APRIL, BAFF, TWEAK and their receptors (BCMA, TACI, BAFFR, Fn14 in 86 conventional type clear cell RCC, using immunohistochemistry and correlated our findings with histological data and, in a limited series, follow-up of patients. We observed a differential expression of these TNFSF ligands and receptors in cancerous and non-cancerous structures. BAFF was found in all RCC; APRIL expression is associated with an aggressive phenotype, correlating negatively with patients' disease-free survival, while TWEAK and its receptor Fn14 are heterogeneously expressed, correlating negatively with the grade and survival of RCC patients. This is the first study, presenting together the TNFSF members APRIL, BAFF, TWEAK and their receptors in different areas of normal renal tissue and RCC, suggesting a potential role of these TNFSF members in renal tumor biology.

  16. Chemokine/cytokine profiling after rituximab: reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; Travelstead, Anna L; Verhulst, Steven J

    2011-03-01

    The aim of the study was to test the hypothesis that B-cell repopulation following rituximab (anti-CD20) therapy is orchestrated by chemokines and non-chemokine cytokines. Twenty-five children with opsoclonus-myoclonus syndrome (OMS) received rituximab with or without conventional agents. A comprehensive panel of 40 chemokines and other cytokines were measured in serum by ELISA and multiplexed fluorescent bead-based immunoassay. Serum BAFF concentration changed dramatically (even after first infusion) and inversely with B-cell depletion/repopulation and CXCL13 concentration at 1, 3, and 6 months. Negative correlations were found for BAFF concentration vs blood B cell percentage and serum CXCL13 concentration; positive correlations with serum rituximab concentrations. Six months after initiation of therapy, no significant difference in the levels of APRIL, CXCL10, IL-6, or 17 other cytokines/chemokines were detected. These data reveal a major role for BAFF in peripheral B cell repopulation following rituximab-induced B-cell depletion, and novel changes in CXCL13. ClinicalTrials.gov NCT0024436. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Tc-99m sulfur colloid spleen imaging following splenic artery and vein resection for pancreas organ donation

    International Nuclear Information System (INIS)

    Kuni, C.C.; Crass, J.R.; Du Cret, R.P.; Boudreau, R.J.; Loken, M.K.

    1987-01-01

    The authors retrospectively studied the records and Tc-99m sulfur colloid (TSC) splenic artery and vein resection for donation to HLA-compatible relatives. Of 37 patients with postoperative TSC studies, four had no postoperative splenic abnormalities. Nineteen of the abnormal TSC studies were followed with TSC studies 2 weeks to 14 months later; three showed no change, seven showed improvements,and ten became normal. One patient required splenectomy 2 days after pancreatectomy for splenic infarction; her TSC study showed no uptake. These data suggest that the spleen usually survives splenic artery and vein resection. Absent splenic TSC uptake raises the possibility of splenic infarction but usually improves

  18. Haematological and biochemical characteristics of the splenic effluent blood in schistosomal patients undergoing splenectomy

    Directory of Open Access Journals (Sweden)

    Andy Petroianu

    Full Text Available OBJECTIVE: To assess hematological and biochemical features of splenic effluent blood and their influence on the rise of hematological values after splenectomy. METHODS: we studied 20 patients undergoing surgical treatment for schistosomatic portal hypertension. We collected blood samples for CBC, coagulation, bilirubin and albumin in the splenic vein (perioperative and peripheral blood (immediately pre and postoperative periods. RESULTS: the splenic blood showed higher values of red blood cells, hemoglobin, hematocrit, platelet count, total leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils, as well as reduction of laboratory coagulation parameters in relation to peripheral blood collected preoperatively. In the postoperative peripheral blood there was an increase in the overall leukocytes and in their neutrophil component, and decreased levels of basophils, eosinophils and lymphocytes. The other postoperative variables of complete blood count and coagulation tests were not different compared with the splenic blood. The albumin values were lower postoperatively when compared to preoperative and splenic blood. There were higher values of direct bilirubin in the postoperative period when compared with the preoperative and splenic blood. Postoperative indirect bilirubin was lower compared to its value in the splenic blood. CONCLUSION: hematological and biochemical values of splenic effluent blood are higher than those found in peripheral blood in the presence of schistosomal splenomegaly. However, the splenic blood effluent is not sufficient to raise the blood levels found after splenectomy.

  19. Iatrogenic splenic injury: review of the literature and medico-legal issues

    Directory of Open Access Journals (Sweden)

    Feola Alessandro

    2016-01-01

    Full Text Available Iatrogenic splenic injury is a recognized complication in abdominal surgery. The aim of this paper is to understand the medico-legal issues of iatrogenic splenic injuries. We performed a literature review on PubMed and Scopus using iatrogenic splenic or spleen injury and iatrogenic splenic rupture as keywords. Iatrogenic splenic injury cases were identified. Most cases were related to colonoscopy, but we also identified cases related to upper gastrointestinal procedures, colonic surgery, ERCP, left nephrectomy and/or adrenalectomy, percutaneous nephrolithotomy, vascular operations involving the abdominal aorta, gynecological operation, left lung biopsy, chest drain, very rarely spinal surgery and even cardiopulmonary resuscitation. There are several surgical procedures that can lead to a splenic injury. However, from a medico-legal point of view, it is important to assess whether the cause can be attributed to a technical error of the operator rather than being an unpredictable and unpreventable complication. It is important for the medico-legal expert to have great knowledge on iatrogenic splenic injuries because it is important to evaluate every step of the first procedure performed, how a splenic injury is produced, and whether the correct treatment for the splenic injury was administered in a judgment.

  20. Iatrogenic splenic injury: review of the literature and medico-legal issues.

    Science.gov (United States)

    Feola, Alessandro; Niola, Massimo; Conti, Adelaide; Delbon, Paola; Graziano, Vincenzo; Paternoster, Mariano; Pietra, Bruno Della

    2016-01-01

    Iatrogenic splenic injury is a recognized complication in abdominal surgery. The aim of this paper is to understand the medico-legal issues of iatrogenic splenic injuries. We performed a literature review on PubMed and Scopus using iatrogenic splenic or spleen injury and iatrogenic splenic rupture as keywords. Iatrogenic splenic injury cases were identified. Most cases were related to colonoscopy, but we also identified cases related to upper gastrointestinal procedures, colonic surgery, ERCP, left nephrectomy and/or adrenalectomy, percutaneous nephrolithotomy, vascular operations involving the abdominal aorta, gynecological operation, left lung biopsy, chest drain, very rarely spinal surgery and even cardiopulmonary resuscitation. There are several surgical procedures that can lead to a splenic injury. However, from a medico-legal point of view, it is important to assess whether the cause can be attributed to a technical error of the operator rather than being an unpredictable and unpreventable complication. It is important for the medico-legal expert to have great knowledge on iatrogenic splenic injuries because it is important to evaluate every step of the first procedure performed, how a splenic injury is produced, and whether the correct treatment for the splenic injury was administered in a judgment.

  1. Haemorrhagic shock due to spontaneous splenic haemorrhage complicating antiplatelet therapy: endovascular management

    Directory of Open Access Journals (Sweden)

    Garge S Shaileshkumar

    2015-01-01

    Full Text Available Spontaneous splenic haemorrahge and rupture is a rare but life-threatening condition requiring urgent diagnosis and treatment. Splenic haemorrhage and rupture precipitated by thrombolytic or antiocoagulant therapy has been reported frequently in the literature, but only two cases due to ticlopidine and one case due to salicyclate have been reported. We report the case of a 54-year-old man with haemorrhagic shock due to spontaneous splenic haemorrhage and rupture following dual antiplatelet (aspirin and clopidogrel therapy. He was successfully treated with selective angioembolization of the bleeding branch of the splenic artery.

  2. Solitary splenic metastasis from nasopharyngeal carcinoma: a case report and systematic review of the literature.

    Science.gov (United States)

    Genova, Pietro; Brunetti, Francesco; Bequignon, Emilie; Landi, Filippo; Lizzi, Vincenzo; Esposito, Francesco; Charpy, Cecile; Calderaro, Julien; Azoulay, Daniel; de'Angelis, Nicola

    2016-07-15

    Solitary splenic metastases are a rare occurrence, and the nasopharyngeal carcinoma represents one of the most uncommon primary sources. The present study aimed to describe a rare case of a solitary single splenic metastasis from nasopharyngeal carcinoma and to assess the number of cases of isolated nasopharyngeal carcinoma metastases to the spleen reported in the literature. We describe the case of a 56-year-old man with a history of nasopharyngeal carcinoma and complete remission after chemo-radiotherapy. Three months after complete remission, positron emission tomography/computed tomography scan revealed a hypermetabolic splenic lesion without increased metabolic activity in other areas. After laparoscopic splenectomy, the pathology report confirmed a single splenic metastasis from undifferentiated carcinoma of the nasopharyngeal type. The postoperative period was uneventful. We also performed a systematic review of the literature using MEDLINE and Google Scholar databases. All articles reporting cases of splenic metastases from nasopharyngeal carcinoma, with or without histologic confirmation, were evaluated. The literature search yielded 15 relevant articles, which were very heterogeneous in their aims and methods and described only 25 cases of splenic metastases from nasopharyngeal carcinoma. The present review shows that solitary splenic metastases from nasopharyngeal carcinoma are a rare event, but it should be considered in patients presenting with splenic lesions at imaging and a history of primary or recurrent nasopharyngeal carcinoma. No evidence supports a negative impact of splenectomy in patients with solitary splenic metastasis from nasopharyngeal carcinoma.

  3. A Case of Multiple Splenic Lymph angiomas Diagnosed by Percutaneous Needle Biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Ki, Seung Seog; Jeong, Sook Hyang; Yoon, Chang Jin; Chang, Se Jung; Choi, Joon Hyuk; Ha, Ji Su; Kim, Soon Je [KEPCO Medical foundation Hanil General Hospital, Seoul (Korea, Republic of); Lee, Hye Seung [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2007-06-15

    Lymphangioma of the spleen is an extremely rare disease in adults, and performing splenectomy has been considered necessary for its diagnosis and treatment, but the diagnosis of an isolated splenic mass lesion without performing splenectomy is a challenging problem. Herein, we report on a case of multiple splenic lymphangiomas that were found incidentally in a 56-year-old female; these lesions were diagnosed by percutaneous splenic biopsy without splenectomy. We suggest that this approach is a reasonable option for benign looking-appearing splenic tumors because splenectomy and its postsplenectomy complications can be avoided

  4. A Case of Multiple Splenic Lymph angiomas Diagnosed by Percutaneous Needle Biopsy

    International Nuclear Information System (INIS)

    Ki, Seung Seog; Jeong, Sook Hyang; Yoon, Chang Jin; Chang, Se Jung; Choi, Joon Hyuk; Ha, Ji Su; Kim, Soon Je; Lee, Hye Seung

    2007-01-01

    Lymphangioma of the spleen is an extremely rare disease in adults, and performing splenectomy has been considered necessary for its diagnosis and treatment, but the diagnosis of an isolated splenic mass lesion without performing splenectomy is a challenging problem. Herein, we report on a case of multiple splenic lymphangiomas that were found incidentally in a 56-year-old female; these lesions were diagnosed by percutaneous splenic biopsy without splenectomy. We suggest that this approach is a reasonable option for benign looking-appearing splenic tumors because splenectomy and its postsplenectomy complications can be avoided

  5. Transjugular Endovascular Recanalization of Splenic Vein in Patients with Regional Portal Hypertension Complicated by Gastrointestinal Bleeding

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Xuefeng; Nie, Ling; Wang, Zhu; Tsauo, Jiaywei; Tang, Chengwei; Li, Xiao, E-mail: simonlixiao@126.com [West China Hospital, Sichuan University, Department of Gastroenterology (China)

    2013-05-02

    PurposeRegional portal hypertension (RPH) is an uncommon clinical syndrome resulting from splenic vein stenosis/occlusion, which may cause gastrointestinal (GI) bleeding from the esophagogastric varices. The present study evaluated the safety and efficacy of transjugular endovascular recanalization of splenic vein in patients with GI bleeding secondary to RPH.MethodsFrom December 2008 to May 2011, 11 patients who were diagnosed with RPH complicated by GI bleeding and had undergone transjugular endovascular recanalization of splenic vein were reviewed retrospectively. Contrast-enhanced computed tomography revealed splenic vein stenosis in six cases and splenic vein occlusion in five. Etiology of RPH was chronic pancreatitis (n = 7), acute pancreatitis with pancreatic pseudocyst (n = 2), pancreatic injury (n = 1), and isolated pancreatic tuberculosis (n = 1).ResultsTechnical success was achieved in 8 of 11 patients via the transjugular approach, including six patients with splenic vein stenosis and two patients with splenic vein occlusion. Two patients underwent splenic vein venoplasty only, whereas four patients underwent bare stents deployment and two covered stents. Splenic vein pressure gradient (SPG) was reduced from 21.5 ± 7.3 to 2.9 ± 1.4 mmHg after the procedure (P < 0.01). For the remaining three patients who had technical failures, splenic artery embolization and subsequent splenectomy was performed. During a median follow-up time of 17.5 (range, 3–34) months, no recurrence of GI bleeding was observed.ConclusionsTransjugular endovascular recanalization of splenic vein is a safe and effective therapeutic option in patients with RPH complicated by GI bleeding and is not associated with an increased risk of procedure-related complications.

  6. Clinical indications and biological mechanisms of splenic irradiation in autoimmune diseases

    International Nuclear Information System (INIS)

    Weinmann, M.; Becker, G.; Einsele, H.; Bamberg, M.

    2001-01-01

    Background: Splenic irradiation (SI) is a fairly unknown treatment modality in autoimmune disorders like autoimmune thrombocytopenia (AIT) or autoimmune hemolytic anemia (AIHA), which may provide an effective, low toxic and cost-effective treatment for selected patients. Patients, Materials and Methods: This article reviews the limited experiences on splenic irradiation in autoimmune thrombocytopenia by analyzing the current studies including 71 patients and some preliminary reports on splenic irradiation in autoimmune hemolytic anemia. Results: In autoimmune thrombocytopenia between 40 and 90% of all patients responded, but most of them relapsed within 4 to 6 months after splenic irradiation. Between 10 and 20% of all patients had a sustained response. The efficacy of splenic irradiation in HIV-associated cases of thrombocytopenia is probably lower than in other forms of autoimmune thrombocytopenia, but especially in this group immunosuppressive drug treatment of autoimmune thrombocytopenia exposes some problems. In autoimmune hemolytic anemia there are some case reports about efficacy of splenic irradiation. Toxicity of splenic irradiation in both diseases was very moderate. Conclusions: For HIV patients, for elderly patients or patients at high risk for complications following splenectomy splenic irradiation might be a treatment option. Splenic irradiation as preoperative treatment in patients not responding to or not suitable for immunosuppressive drugs prior to splenectomy may be a promising new application of splenic irradiation to reduce adverse effects of splenectomy in thrombocytopenic patients. A further analysis of the biological mechanisms underlying splenic irradiation may help to improve patient selection, to optimize dose concepts and treatment schedules and will improve understanding of radiotherapy as an immunomodulatory treatment modality. (orig.) [de

  7. Solitary splenic metastasis from ovarian carcinosarcoma: a case report

    Directory of Open Access Journals (Sweden)

    Gillespie Thomas

    2011-02-01

    Full Text Available Abstract Introduction Metastatic tumors to the spleen are rare but are usually found in conjunction with metastasis to other organs. The most common sources of splenic metastasis are breast, lung and colorectal cancers as well as melanoma and ovarian carcinoma. A solitary carcinosarcoma metastasis to the spleen of any origin is very rare. To the best of our knowledge, there are fewer than 30 reported cases of ovarian primary tumors with solitary metastasis to the spleen, and only three solitary primary carcinosarcomas to the spleen have been reported, of which one is female. We present what is, to the best of our knowledge, the first case of a solitary metastatic carcinosarcoma to the spleen arising from a primary ovarian carcinsarcoma. Case presentation A 72-year-old Hispanic woman status post-total abdominal hysterectomy for ovarian carcinosarcoma presented with complaints of early satiety and abdominal pain for the past two months with a 30-lb unintentional weight loss. An initial computed tomographic scan of her abdomen and pelvis revealed a 30 cm × 27 cm splenic mass with displacement of the left kidney, stomach and liver. The patient was found to have a solitary metastatic carcinosarcoma of the spleen with biphasic epithelial (carcinomatous and mesenchymal (sarcomatous elements consistent with carcinosarcoma. Conclusion Carcinosarcoma of the spleen is a rare tumor. Carcinosarcomas are a biphasic neoplasm comprising malignant epithelial and mesenchymal components arising from a stem cell capable of differentiation. They can arise anywhere in the female genital tract, most commonly from the endometrium. Even though it is rare, carcinosarcomas can metastasize to the spleen. This unique case of a solitary splenic metastasis from ovarian carcinosarcoma has particular interest in medicine, especially for the specialties of surgical oncology, pathology and hematology/oncology.

  8. Spontaneous Splenic Rupture in Vascular Ehlers-Danlos Syndrome.

    Science.gov (United States)

    Batagini, Nayara Cioffi; Gornik, Heather; Kirksey, Lee

    2015-01-01

    Vascular Ehlers-Danlos Syndrome (VEDS) is a rare autosomal dominant collagen vascular disorder. Different from other Ehler-Danlos Syndrome subtypes, VEDS has poor prognosis due to severe fragility of connective tissues and association with life-threatening vascular and gastrointestinal complications. Spontaneous splenic rupture is a rare but hazardous complication related to this syndrome. To date, only 2 cases have been reported in the literature. Here we present another case of this uncommon complication, occurring in a 54-year-old woman in clinical follow-up for VEDS who presented with sudden onset of abdominal pain and hypotension. © The Author(s) 2015.

  9. Emergency endovascular coiling of a ruptured giant splenic artery aneurysm

    Directory of Open Access Journals (Sweden)

    Erika Wernheden, MD

    2017-12-01

    Full Text Available Splenic artery aneurysms (SAAs are the third most common abdominal aneurysm. Endovascular treatment of SAAs is preferred, and coiling is the most commonly used technique. Ruptured giant (>5 cm SAAs are usually treated with open surgery including splenectomy. We present a rare case of a ruptured 15-cm giant SAA in an 84-year-old woman treated successfully with emergency endovascular coiling. To our knowledge, this is one of the few reports of emergency endovascular treatment for ruptured giant SAA.

  10. Occult splenic rupture in a case of chronic calcific pancreatitis with a brief review of literature

    Directory of Open Access Journals (Sweden)

    Sharada S.

    2015-01-01

    Conclusion: High clinical suspicion on the part of the treating physician and the emergency team is essential to the management of atraumatic splenic rupture. The increasing understanding of the pathophysiology and presentation of splenic complications in pancreatitis may alert the index physician to these fatal complications.

  11. http://www.bioline.org.br/js 95 Splenic Injuries in a Semi Urban ...

    African Journals Online (AJOL)

    jen

    Background: The management of splenic injury has changed dramatically over the last two decades. The objective of this study is to evaluate splenic ... incidence of systemic infection following splenectomy by encapsulated organisms: and soon ... battery 1 (1.4%), domestic injury 1(1.4%) and sport injury 1 (1.4%). Thirty four.

  12. Pancreatitis-Associated Splenic Artery Pseudoaneurysm: Endovascular Treatment with Self-Expandable Stent-Grafts

    International Nuclear Information System (INIS)

    Brountzos, Elias N.; Vagenas, Kostantinos; Apostolopoulou, Sotiria C.; Panagiotou, Irene; Lymberopoulou, Dimitra; Kelekis, Dimitrios A.

    2003-01-01

    We present a patient with a splenic arterypseudoaneurysm (SAPA) treated with placement of self-expandable stent-grafts. The procedure was complicated by stent-graft migration,but successful management resulted in lasting exclusion of the SAPA,while the patency of the splenic artery was preserved. This is the first report of self-expandable stent-graft treatment of SAPA

  13. Splenic rupture in a neonate – a rare complication | Lloyd | South ...

    African Journals Online (AJOL)

    Birth trauma is well described in the neonatal literature, but intra-abdominal injuries occur infrequently and are often forgotten in the differential diagnosis of a hypovolaemic shocked infant with an abdominal mass. The symptoms of splenic rupture are nonspecific, creating a diagnostic dilemma for the clinician. As splenic ...

  14. CT finding of ruptured splenic artery aneurysm after cesarean section : a case report

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Chang Woo; Kim, Hee Jin [CHA Medical College, Pundang CHA Gerneral Hospital Sungnam, (Korea, Republic of)

    2000-03-01

    Spontaneous rupture of a splenic artery aneurysm during puerperium is rare and is due to the non-specific clinical appearance, diagnosis is difficult. We describe a case of spontaneous rupture of splenic artery aneurysm after a Cesarean section. CT showed high-density ascites localized in the lesser sac and left retroperitoneum.

  15. CT finding of ruptured splenic artery aneurysm after cesarean section : a case report

    International Nuclear Information System (INIS)

    Ryu, Chang Woo; Kim, Hee Jin

    2000-01-01

    Spontaneous rupture of a splenic artery aneurysm during puerperium is rare and is due to the non-specific clinical appearance, diagnosis is difficult. We describe a case of spontaneous rupture of splenic artery aneurysm after a Cesarean section. CT showed high-density ascites localized in the lesser sac and left retroperitoneum

  16. Meningoencephalitis, pancytopenia, pulmonary insufficiency and splenic abscess in a patient with brucellosis

    International Nuclear Information System (INIS)

    Cokca, F.; Yilmaz-Bozkurt, G.; Azap, A.; Memikoglu, O.; Takeli, E.

    2006-01-01

    A complicated case of brucellosis with some rare features is reported. Brucellosis is a multisystematic disease. However, disseminated brucellosis with cerebral, pulmonary, hematopoietic and splenic involvement in an otherwise healthy patient is a rare event. In this article, we report a case of disseminated brucellosis who was initially diagnosed as myeldoplastic syndrome (MDS) and meningoencephalitis, pulmonary symptoms, and splenic abscess formation occurred thereafter. (author)

  17. A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs.

    Science.gov (United States)

    Grimes, Janet A; Prasad, Nripesh; Levy, Shawn; Cattley, Russell; Lindley, Stephanie; Boothe, Harry W; Henderson, Ralph A; Smith, Bruce F

    2016-12-03

    Splenic masses are common in older dogs; yet diagnosis preceding splenectomy and histopathology remains elusive. MicroRNAs (miRNAs) are short, non-coding RNAs that play a role in post-transcriptional regulation, and differential expression of miRNAs between normal and tumor tissue has been used to diagnose neoplastic diseases. The objective of this study was to determine differential expression of miRNAs by use of RNA-sequencing in canine spleens that were histologically confirmed as hemangiosarcoma, nodular hyperplasia, or normal. Twenty-two miRNAs were found to be differentially expressed in hemangiosarcoma samples (4 between hemangiosarcoma and both nodular hyperplasia and normal spleen and 18 between hemangiosarcoma and normal spleen only). In particular, mir-26a, mir-126, mir-139, mir-140, mir-150, mir-203, mir-424, mir-503, mir-505, mir-542, mir-30e, mir-33b, mir-365, mir-758, mir-22, and mir-452 are of interest in the pathogenesis of hemangiosarcoma. Findings of this study confirm the hypothesis that miRNA expression profiles are different between canine splenic hemangiosarcoma, nodular hyperplasia, and normal spleens. A large portion of the differentially expressed miRNAs have roles in angiogenesis, with an additional group of miRNAs being dysregulated in vascular disease processes. Two other miRNAs have been implicated in cancer pathways such as PTEN and cell cycle checkpoints. The finding of multiple miRNAs with roles in angiogenesis and vascular disease is important, as hemangiosarcoma is a tumor of endothelial cells, which are driven by angiogenic stimuli. This study shows that miRNA dysregulation is a potential player in the pathogenesis of canine splenic hemangiosarcoma.

  18. Predictors of splenic function preservation in children with sickle cell anemia treated with hydroxyurea.

    Science.gov (United States)

    Nottage, Kerri A; Ware, Russell E; Winter, Bryan; Smeltzer, Matthew; Wang, Winfred C; Hankins, Jane S; Dertinger, Stephen D; Shulkin, Barry; Aygun, Banu

    2014-11-01

    More than 90% of children with sickle cell anemia (SCA) lose splenic function by the age of 2 yrs. Splenic function may improve with hydroxyurea, but previous studies are conflicting. We prospectively evaluated the effect of hydroxyurea on splenic filtrative function. Children with SCA enrolled in the Hydroxyurea Study of Long-Term Effects (HUSTLE-NCT00305175) underwent clinical evaluations including Tc(99) m liver-spleen (LS) scans before hydroxyurea initiation and after 3 yrs of treatment to maximum tolerated dose (MTD). LS scans were classified as follows: no uptake, Hydroxyurea at MTD is associated with preserved or improved splenic filtrative function, with 33% demonstrating LS scan uptake after 3 yrs. Younger age, higher %HbF, and baseline splenic function are associated with a favorable outcome. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Common and uncommon features of focal splenic lesions on contrast-enhanced ultrasound: a pictorial review

    Energy Technology Data Exchange (ETDEWEB)

    Zavariz, Julia D., E-mail: julia.zavariz@hc.fm.usp.br [Universidade de São Paulo (HC/FMUSP), São Paulo, SP (Brazil). Faculdade de Medicina. Hospital das Clínicas; Konstantatou, Eleni; Deganello Annamaria; Bosanac, Diana; Huang, Dean Y.; Sellars, Maria E.; Sidhu, Paul S. [Department of Radiology, King’s College Hospital, Denmark Hill, London (United Kingdom)

    2017-11-15

    The characterization of focal splenic lesions by ultrasound can be quite challenging. The recent introduction of contrast-enhanced ultrasound (CEUS) has come to play a valuable role in the field of imaging splenic pathologies, offering the possibility of an ionizing radiation-free investigation. Because CEUS has been incorporated into everyday clinical practice, malignant diseases such as focal lymphomatous infiltration, metastatic deposits, benign cysts, traumatic fractures, and hemangiomas can now be accurately depicted and characterized without the need for further imaging. More specifically, splenic traumatic fractures do not require additional imaging by computed tomography (with ionizing radiation exposure) for follow-up, because splenic fractures and their complications are safely imaged with CEUS. In the new era of CEUS, more patients benefit from radiation-free investigation of splenic pathologies with high diagnostic accuracy. (author)

  20. Nonvisualization of an enlarged spleen on Ga-67 scintigraphy but demonstrated by CT after splenic irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Shih, W.J.; Domstad, P.A.; DeLand, F.H.; Maruyama, Y.

    1985-03-01

    The presence of an enlarged spleen using CT with the absence of splenic visualization in Ga-67 citrate images in a patient with chronic myelogenous leukemia and splenomegaly after splenic irradiation was observed. Since Howell-Jolly bodies had not been identified in the peripheral circulation, the finding of splenic nonvisualization was explained by disassociated splenic functions, which are not tightly coupled, and some activities that can be suppressed by irradiation without impairing others. The Ga-67 splenic localization mechanism is probably more sensitive and liable to disruption by irradiation, and was independent of spleen size. Ga-67 scintigraphy and Tc-99m sulfur colloid liver-spleen scintigraphy are two organ function-dependent imaging procedures, while CT provides anatomic information.

  1. Partial splenic embolization in patients with idiopathic portal hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Romano, Maurizio E-mail: maurizio.romano@ibb.cnr.it; Giojelli, Angela; Capuano, Gaetano; Pomponi, Domenico; Salvatore, Marco

    2004-03-01

    Purpose: To evaluate the effectiveness of partial splenic embolization (PSE) in patients with idiopathic portal hypertension (IPH) in reducing variceal bleeding episodes, splenomegaly and thrombocytopenia. Materials and methods: Six patients (2M, 4F, mean age 30.3 years) with IPH presenting with splenomegaly, thrombocytopenia and recurrent variceal bleeding were treated with PSE using gelatin sponge (four patients) or Contour particles (two patients) as embolization material. Results: PSE was performed successfully in all cases; 3F coaxial microcatheters were necessary in two patients due to extreme splenic artery tortuosity. The average amount of devascularized parenchyma at CT 1 week after PSE was 71%. Splenomegaly and thrombocytopenia improved in all cases, with a mean platelet count increase of 120000/mm{sup 3} and an average 68% reduction of spleen volume at follow up. Variceal bleeding did not recur after PSE. Esophageal or gastroesophageal varices disappeared (one patient) or significantly reduced (five patients) at endoscopic controls. No significant complications were noted. The follow up was of at least 18 months in all patients; mean follow up was 28.2 months. Conclusion: In patients with IPH PSE can be effective in preventing variceal bleedings, in reducing spleen volume and in significantly increasing platelet count; therapeutic results were durable in our population.

  2. Microwave coagulation therapy and drug injection to treat splenic injury.

    Science.gov (United States)

    Zhang, Guoming; Sun, Yuanyuan; Yu, Jie; Dong, Lei; Mu, Nannan; Liu, Xiaohong; Liu, Lanfen; Zhang, Yan; Wang, Xiaofei; Liang, Ping

    2014-01-01

    The present study compares the efficacy of 915- and 2450-MHz contrast-enhanced ultrasound (CEUS)-guided percutaneous microwave coagulation with that of CEUS-guided thrombin injection for the treatment of trauma-induced spleen hemorrhage. In a canine splenic artery hemorrhage model with two levels of arterial diameter (A, microwaves and drug injection. Therapy efficacy was measured by comparing bleeding rate, hemostatic time, bleeding index, bleeding volume, and pathology. The most efficient technique was CEUS-guided 915-MHz percutaneous microwave coagulation therapy in terms of action time and total blood loss. The success rate of the 915-MHz microwave group was higher than that of the 2450-MHz microwave and the drug injection groups (except A level, P microwave group than those in the 2450-MHz microwave and drug injection groups (P microwave group, but pathologic changes of light injury could be seen in the other groups. The present study provides evidence that microwave coagulation therapy is more efficient than thrombin injection for the treatment of splenic hemorrhage. Furthermore, treatment with 915-MHz microwaves stops bleeding more rapidly and generates a wider cauterization zone than does treatment with 2450-MHz microwaves. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Gallium arsenide exposure impairs splenic B cell accessory function.

    Science.gov (United States)

    Gondre-Lewis, Timothy A; Hartmann, Constance B; Caffrey, Rebecca E; McCoy, Kathleen L

    2003-03-01

    Gallium arsenide (GaAs) is utilized in industries for its semiconductor and optical properties. Chemical exposure of animals systemically suppresses several immune functions. The ability of splenic B cells to activate antigen-specific helper CD4(+) T cell hybridomas was assessed, and various aspects of antigen-presenting cell function were examined. GaAs-exposed murine B cells were impaired in processing intact soluble protein antigens, and the defect was antigen dependent. In contrast, B cells after exposure competently presented peptides to the T cells, which do not require processing. Cell surface expression of major histocompatibility complex (MHC) class II molecules and several costimulatory molecules on splenic B cells, which are critical for helper T cell activation, was not affected by chemical exposure. GaAs exposure also did not influence the stability of MHC class II heterodimers, suggesting that the defect may precede peptide exchange. GaAs-exposed B cells contained a normal level of aspartyl cathepsin activity; however, proteolytic activities of thiol cathepsins B and L were approximately half the control levels. Furthermore, two cleavage fragments of invariant chain, a molecular chaperone of MHC class II molecules, were increased in GaAs-exposed B cells, indicative of defective degradation. Thus, diminished thiol proteolytic activity in B cells may be responsible for their impaired antigen processing and invariant chain degradation, which may contribute to systemic immunosuppression caused by GaAs exposure.

  4. Computed tomographic findings of splenic injury and correlation with treatment

    International Nuclear Information System (INIS)

    Kim, Dong Jin; Koh, Joo Yaul; Kim, Myung Soon; Hong, In Soo; Cho, Whi Youl; Sung, Ki Joon

    1990-01-01

    According to recently reported classification, 46 patients with blunt splenic trauma were evaluate preoperatively with computed tomography(CT). Injures were graded I through IV and describe as capsular or subcapsular disruptions without parenchymal injury(3 patients); capsular and parenchymal injuries(23 patients); injuries involving hilum(3 patients); and fragmentation(17 patients). Nineteen patients were managed conservatively and 27 patients were managed surgically. Twelve patients(47%) out of those with Type I or Type II were managed surgically including five hemodynamically unstable patients and seven hemodynamically stable patients with associated injuries and unknown surgical criteria. On the other hand hemodynamically stable patients(25%) out of those with Type III or Type IV were managed surgically. The amount of hemoperitoneum was graded into small, moderate and large; small in three patients, moderate in 39 patients, and large in two patients. The amount of hemoperitoneum in patients with conservative treatment was moderate in 16 patients and large in one patient. And the amount of hemoperitoneum in patients with operative treatment was small in three patients, moderate in 23 patients and large in one patient. We concluded that CT was accurate method of determining the extent of splenic injury and evaluation of hemoperitoneum, but treatment choice should be based on the hemodynamic status of patients rather than the type of injury or the amount of hemoperitoneum by CT

  5. Walnut Polyphenol Extract Attenuates Immunotoxicity Induced by 4-Pentylphenol and 3-methyl-4-nitrophenol in Murine Splenic Lymphocyte.

    Science.gov (United States)

    Yang, Lubing; Ma, Sihui; Han, Yu; Wang, Yuhan; Guo, Yan; Weng, Qiang; Xu, Meiyu

    2016-05-12

    4-pentylphenol (PP) and 3-methyl-4-nitrophenol (PNMC), two important components of vehicle emissions, have been shown to confer toxicity in splenocytes. Certain natural products, such as those derived from walnuts, exhibit a range of antioxidative, antitumor, and anti-inflammatory properties. Here, we investigated the effects of walnut polyphenol extract (WPE) on immunotoxicity induced by PP and PNMC in murine splenic lymphocytes. Treatment with WPE was shown to significantly enhance proliferation of splenocytes exposed to PP or PNMC, characterized by increases in the percentages of splenic T lymphocytes (CD3+ T cells) and T cell subsets (CD4+ and CD8+ T cells), as well as the production of T cell-related cytokines and granzymes (interleukin-2, interleukin-4, and granzyme-B) in cells exposed to PP or PNMC. These effects were associated with a decrease in oxidative stress, as evidenced by changes in OH, SOD, GSH-Px, and MDA levels. The total phenolic content of WPE was 34,800 ± 200 mg gallic acid equivalents/100 g, consisting of at least 16 unique phenols, including ellagitannins, quercetin, valoneic acid dilactone, and gallic acid. Taken together, these results suggest that walnut polyphenols significantly attenuated PP and PNMC-mediated immunotoxicity and improved immune function by inhibiting oxidative stress.

  6. Walnut Polyphenol Extract Attenuates Immunotoxicity Induced by 4-Pentylphenol and 3-methyl-4-nitrophenol in Murine Splenic Lymphocyte

    Directory of Open Access Journals (Sweden)

    Lubing Yang

    2016-05-01

    Full Text Available 4-pentylphenol (PP and 3-methyl-4-nitrophenol (PNMC, two important components of vehicle emissions, have been shown to confer toxicity in splenocytes. Certain natural products, such as those derived from walnuts, exhibit a range of antioxidative, antitumor, and anti-inflammatory properties. Here, we investigated the effects of walnut polyphenol extract (WPE on immunotoxicity induced by PP and PNMC in murine splenic lymphocytes. Treatment with WPE was shown to significantly enhance proliferation of splenocytes exposed to PP or PNMC, characterized by increases in the percentages of splenic T lymphocytes (CD3+ T cells and T cell subsets (CD4+ and CD8+ T cells, as well as the production of T cell-related cytokines and granzymes (interleukin-2, interleukin-4, and granzyme-B in cells exposed to PP or PNMC. These effects were associated with a decrease in oxidative stress, as evidenced by changes in OH, SOD, GSH-Px, and MDA levels. The total phenolic content of WPE was 34,800 ± 200 mg gallic acid equivalents/100 g, consisting of at least 16 unique phenols, including ellagitannins, quercetin, valoneic acid dilactone, and gallic acid. Taken together, these results suggest that walnut polyphenols significantly attenuated PP and PNMC-mediated immunotoxicity and improved immune function by inhibiting oxidative stress.

  7. True and false splenic artery aneurysm on endoscopic ultrasonography: Two-case analysis.

    Science.gov (United States)

    Silina, T; Butkevich, Ð; Shpitonkov, A; Brovkin, A; Nalivaiskyi, A; Filatov, A; Kutuzov, T; Lukyanov, A; Mostovoy, I; Koshelev, M; Gordeev, S; Ostretsov, R

    2014-04-01

    The etiology of true and false splenic artery aneurysm is different, but the differential X-ray contrast diagnosis could be difficult. Purpose - to detect endoscopic ultrasonography (EUS) diagnostic capability for false and true splenic artery aneurysm by considering two clinical cases: With suspected stomach and pancreatic lesions. Patient, female, 50-year-old with suspected stomach lesion, complicated by gastric bleeding. Endoscopy - acute gastric ulcer. X-ray - submucosal gastric tumor. The patient was sent to the EUS with fine-needle aspiration. Patient, male, 73-year-old with suspected pancreatic neoplasm. Ultrasound - pancreatic cysts. Computed tomography (CT) - neoplasm of the pancreas body. Celiacography - splenic artery aneurysm. The patient was sent to the EUS to clarify the diagnosis. First patient EUS - anechoic rounded lesion with thick wall close to the stomach. Stomach wall layers were not differentiated above the lesion. Doppler - turbulent blood flow. EUS excluded submucosal lesion and proved the presence of aneurysm. CT confirmed the aneurysm. Post-operative histology - splenic artery pseudoaneurysm, destruction of the stomach wall and pancreatic parenchyma. Second patient EUS - ovoid solid-cystic lesion with thin hyperechoic "capsule." Doppler in cystic part - arterial blood flow. EUS suspected saccular splenic artery aneurysm with the neck and the residual lumen. Post-operative histology - true splenic artery aneurysm with thrombotic masses near the wall, pancreatic parenchyma was intact. EUS can reliably differentiate splenic artery aneurysm from gastric submucosal lesion and differentiate true and false aneurysm with high probability.

  8. The Straightened Splenic Vessels Method Improves Surgical Outcomes of Laparoscopic Distal Pancreatectomy.

    Science.gov (United States)

    Nagakawa, Yuichi; Sahara, Yatsuka; Hosokawa, Yuichi; Takishita, Chie; Kasuya, Kazuhiko; Tsuchida, Akihiko

    2017-01-01

    In laparoscopic distal pancreatectomy (LDP), isolating the splenic artery and vein requires advanced techniques. This study aimed to assess the efficacy of a novel method termed the 'straightened splenic vessels' (SSV) method for isolating the splenic vessels in LDP. In SSV, to adjust the instrument axis, the splenic artery was straightened by grasping 2 points of its nerve sheath. Then, the layer between the splenic artery's nerve sheath and the pancreatic parenchyma was dissected. Next, the pancreas was mobilized from body to tail, and the splenic vein was straightened by 3-point retraction before isolation. To evaluate this method's efficacy, we investigated 51 patients who underwent LDP. In 39 patients who underwent LDP with splenectomy, the mean operating time was significantly shorter in the SSV group than in the conventional group (p = 0.004). In 12 patients who underwent LDP with preserving the splenic vessels, the mean intraoperative blood loss in the SSV group was 27.6 ml, which was significantly lower than that in the conventional group (p = 0.012). This method may be applied as a standard procedure with little blood loss and short operation time for LDP. Larger prospective studies are needed to further evaluate the feasibility. © 2017 S. Karger AG, Basel.

  9. Etiologies and risks of splenic decapsulation after endoscopic retrograde cholangiopancreatography: case report and literature review.

    Science.gov (United States)

    Pamudurthy, Vijeta; Abraham, Raju Z; Betlej, Thomas; Shah, Ashish; Kim, Dong; Sasso, Brian; Chacko, Abraham

    2018-03-01

    Background and study aims  Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive diagnostic and interventional procedure used in conditions related to the pancreas and biliary tract. It has a complication rate ranging from 4 % to 10 %. Severe complications are few with the most common of them being post-ERCP pancreatitis, post-sphincterotomy bleeding, and perforation. A rare, but potentially life-threatening complication of ERCP is splenic injury. We report the case of a 60-year-old female with choledocholithiasis who sustained splenic decapsulation following ERCP. The exact causes of splenic injury are unknown, although several mechanisms are postulated. A literature review of splenic injuries post-ERCP shows that there are only 3 cases with post-ERCP splenic decapsulation. Our patient is the first one in whom splenic decapsulation occurred without any risk factors or technical difficulties during the procedure. A high index of suspicion for splenic injury is required in any patient who has severe pain, anemia, or hemorrhagic shock after ERCP.

  10. Tortuosity and calcification of the splenic artery. More than an additional finding

    International Nuclear Information System (INIS)

    Golder, W.A.

    2008-01-01

    Tortuosity of the splenic artery and calcification of the vessel wall are typical additional findings on plain abdominal x-ray. The combination of both anomalies is common in elderly persons presenting without symptoms of splenic ischemia. Its pathogenesis is thought to be multifactorial. In infancy and childhood, the splenic artery is stretched in its entire course. A growing difference between the length of the vessel and the distance between its origin and the splenic hilum gives rise to tortuosity. The artery's proximal segment is involved more frequently and more severely than the distal one. The tortuous route of the vessel is accentuated by the direction of its major branches, which is roughly perpendicular to the main trajectory. Neither tortuosity nor calcification should be taken to be risk factors for the comparatively common splenic artery aneurysm. Calcific deposits are not confined to the media but are also detected in the intima of the vascular wall. Critical narrowings of the lumen arising on the calcium deposits are not observed. Calcifying atherosclerosis of the splenic artery is comparable to medial sclerosis of the peripheral arteries frequently noticed in diabetics and dialysis patients. Only the less important calcification of the intima may be attributed to mechanisms of the hydrohemodynamic theory of atherosclerosis. The spleen's blood storage capacity may contribute to the characteristic age-dependent alterations of the shape and course of the splenic artery. (orig.) [de

  11. Pleural effusion following blunt splenic injury in the pediatric trauma population.

    Science.gov (United States)

    Kulaylat, Afif N; Engbrecht, Brett W; Pinzon-Guzman, Carolina; Albaugh, Vance L; Rzucidlo, Susan E; Schubart, Jane R; Cilley, Robert E

    2014-09-01

    Pleural effusion is a potential complication following blunt splenic injury. The incidence, risk factors, and clinical management are not well described in children. Ten-year retrospective review (January 2000-December 2010) of an institutional pediatric trauma registry identified 318 children with blunt splenic injury. Of 274 evaluable nonoperatively managed pediatric blunt splenic injures, 12 patients (4.4%) developed left-sided pleural effusions. Seven (58%) of 12 patients required left-sided tube thoracostomy for worsening pleural effusion and respiratory insufficiency. Median time from injury to diagnosis of pleural effusion was 1.5days. Median time from diagnosis to tube thoracostomy was 2days. Median length of stay was 4days for those without and 7.5days for those with pleural effusions (ppleural effusions managed medically or with tube thoracostomy (p=0.006), respectively. In multivariate analysis, high-grade splenic injury (IV-V) (OR 16.5, p=0.001) was associated with higher odds of developing a pleural effusion compared to low-grade splenic injury (I-III). Pleural effusion following pediatric blunt splenic injury has an incidence of 4.4% and is associated with high-grade splenic injuries and longer lengths of stay. While some symptomatic patients may be successfully managed medically, many require tube thoracostomy for progressive respiratory symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Extrahepatic portal venous obstruction: The effects of early ligation of splenic artery during splenectomy

    Directory of Open Access Journals (Sweden)

    Gazula Suhasini

    2009-01-01

    Full Text Available Aim: To objectively demonstrate the gain in blood volume and blood components following early ligation of splenic artery during splenectomy and splenorenal shunts in children with extra hepatic portal venous obstruction (EHPVO. Methods: Twenty-eight children (20 males and 8 females, mean age: 9.9 (±3.2 years with EHPVO and hypersplenism were recruited. We followed a protocol of systematically locating and ligating the splenic artery first, followed by a 30-minute waiting period to allow the massive spleen to decongest via the splenic vein and venous collaterals and then completing the splenectomy by standard procedure. No intravenous fluid was administered during this 30-minute period. Blood samples were drawn just prior to splenic artery ligation and soon after splenectomy for the estimation of hematological and biochemical parameters. Results: We noticed a highly significant increase in the hemoglobin, hematocrit, leukocyte, platelet, and RBC counts by early ligation of the splenic artery (p < 0.0004. The gain in hemoglobin and hematocrit was equivalent to a transfusion of atleast 100-150 ml of packed RBC. The increase in platelet count was equivalent to a platelet transfusion of atleast 4 units of platelet concentrates in an adult. There is a positive correlation between the splenic weight and the platelet gain (p= 0.0568 and the splenic volume on preoperative imaging and the platelet gain (p= 0.0251. Conclusion: Early ligation of the splenic artery during splenectomy results in passive splenic decongestion and thereby a significant gain in blood components. This protocol appears to be a feasible blood conservation method to avoid blood transfusions in this group of hypersplenic EHPVO patients.

  13. Increased Risk of Hemorrhagic and Ischemic Strokes in Patients With Splenic Injury and Splenectomy

    Science.gov (United States)

    Lin, Jiun-Nong; Lin, Cheng-Li; Lin, Ming-Chia; Lai, Chung-Hsu; Lin, Hsi-Hsun; Yang, Chih-Hui; Kao, Chia-Hung

    2015-01-01

    Abstract The spleen is a crucial organ in humans. Little is known about the association between stroke and splenic injury or splenectomy. The aim of this study was to determine the risk of stroke in patients with splenic injury and splenectomy. A nationwide cohort study was conducted by analyzing the National Health Insurance Research Database in Taiwan. For comparison, control patients were selected and matched with splenic injury patients in a ratio of 4:1 according to age, sex, and the year of hospitalization. We analyzed the risks of stroke using a Cox proportional-hazards regression analysis. A total of 11,273 splenic injury patients, including 5294 splenectomized and 5979 nonsplenectomized patients, and 45,092 control patients were included in this study. The incidence rates of stroke were 8.05, 6.53, and 4.25 per 1000 person-years in splenic injury patients with splenectomy, those without splenectomy, and the control cohort, respectively. Compared with the control cohort, splenic injury patients with splenectomy exhibited a 2.05-fold increased risk of stroke (95% confidence interval [CI] 1.8–2.34), whereas those without splenectomy exhibited a 1.74-fold increased risk (95% CI 1.51–2). Splenectomy entailed an additional 1.21-fold increased risk of stroke compared with nonsplenectomy in patients with splenic injury. This study revealed that splenic injury and splenectomy were significantly associated with an increased risk of hemorrhagic and ischemic strokes. The results of this study may alert physicians and patients to the complications of splenic injury and splenectomy. PMID:26334909

  14. Risk of venous thromboembolism in patients with splenic injury and splenectomy. A nationwide cohort study.

    Science.gov (United States)

    Lin, Jiun-Nong; Chen, Hsuan-Ju; Lin, Ming-Chia; Lai, Chung-Hsu; Lin, Hsi-Hsun; Yang, Chih-Hui; Kao, Chia-Hung

    2016-01-01

    The spleen is a crucial organ in humans. However, little is known about the association of venous thromboembolism (VTE) with splenic injury and splenectomy in trauma patients. The aim of this study was to determine the subsequent risk of VTE following splenic injury and splenectomy. A nationwide retrospective cohort study was conducted by analysing data from the National Health Insurance Research Database in Taiwan. We included 6,162 splenic injury patients (3,033 splenectomised and 3,129 nonsplenectomised patients) and 24,648 comparison patients who were selected by frequency match based on sex, age, and the index year during 2000-2006. All patients were followed until the occurrence of VTE, 31 December, 2011, death, or withdrawal from the insurance program. The age of patients with splenic injury was 41.93 ± 16.44 years. The incidence rates of VTE were 11.81, 8.46, and 5.21 per 10,000 person-years in the splenic injury patients with splenectomy, splenic injury patients without splenectomy, and comparison patients, respectively. Compared with the comparison cohort, splenic injury patients with splenectomy exhibited a 2.21-fold risk of VTE (95% confidence interval [CI], 1.43-3.43), whereas those without splenectomy exhibited a 1.71-fold risk of VTE (95% CI, 1.05-2.80). The overall incidence rate of VTE was 1.97-fold higher in the splenic injury cohort than the comparison cohort (95% CI, 1.38-2.81). Although splenectomy increased the risk of VTE 1.35-fold compared with no splenectomy, the difference was not statistically significant (95% CI, 0.74-2.45). These results may alert physicians and patients to the complications of splenic injury and splenectomy.

  15. Normal hepatic and splenic size in children: Scintigraphic determination

    International Nuclear Information System (INIS)

    Markisz, J.A.; New York Hospital - Cornell Medical Center, NY; Treves, S.T.; Davis, T.

    1987-01-01

    Measurements were made on sulfur colloid scintigrams of normal pediatric livers and spleens by analyzing 131 scans from 116 patients referred for liver or spleen trauma. Studies were used only if scans were normal, there was no history of malignancy or hepatic or splenic disease either prior to of after the study. Linear correlation was made with age, weight and both age and weight. All measured parameters correlated better with weight than with age, with vertical liver dimension exhibiting the best correlation (r=0.848). Multivariate analysis demonstrated uniformly better correlation of all measurements with both age and weight. Spleen and liver volumes were calculated assuming simple geometry, and showed excellent correlations. Graphical presentation of data will be useful in the clinical determination of hepatomegaly or splenomegaly in routine scintigraphy. (orig.)

  16. Rebleeding of a Splenic Artery Aneurysm after Coil Embolisation

    Directory of Open Access Journals (Sweden)

    Kyra D. Kingma

    2016-01-01

    Full Text Available Background. Splenic artery aneurysm (SAA is an uncommon and difficult diagnosis. SAA is more common in females. Only 20% of SAA is symptomatic and may present as a rupture. A ruptured SAA is associated with a 25% mortality rate. Case Presentation. We present a case of a male patient with a bleeding SAA that rapidly increased in size. Distal coiling was technically impossible and despite proximal coil embolisation the SAA continued to bleed. A laparotomy including splenectomy and partial pancreatectomy was performed with an uneventful patient recovery. Discussion. Endovascular management is currently considered the optimal treatment of SAA. However, careful monitoring and follow-up is needed after embolisation as rapid recanalization of the SAA may possibly occur, especially when distal coiling of the aneurysm is unsuccessful. Conclusion. Endovascular treatment of an SAA is not necessarily effective. Surgeons must be prepared to perform open procedures to further reduce mortality rates.

  17. Contrast analysis of the partial splenic artery embolization with splenectomy

    International Nuclear Information System (INIS)

    Lu Wusheng; He Qing; Zheng Zhiyong; Wu Shaoping; Xu Dawei

    2006-01-01

    Objective: To analyze the effects and the complications of partial splenic artery embolization (PSE) and splenectomy offering a feasible way to choose different therapeutic methods for hypersplenism. Methods: Forty-six patients treated with PSE and thirty-three undergone splenectomy were compared for their effectivenesses and complications in treating hypersplenism. Results: Thrombocyte and leucocyte counts increased markedly after the two kinds of treatment (P 0.05). The complication rate of the PSE was far more than that of the splenectomy (P<0.001). Conclusions Splenectomy is prior to PSE on patients with large mount of ascites, serious portal hypertension and splenomegaly. PSE is suitable for patients with poor liver function, blood coagulation disturbance, liver cancer complicated with hypersplenism and aging. (authors)

  18. The multidetector computed tomography angiography (MDCTA) in the diagnosis of splenic artery aneurysm and pseudoaneurysm

    Energy Technology Data Exchange (ETDEWEB)

    Saba, Luca; Mallarini, Giorgio (Dept. of Radiology, Azienda Ospedaliero Universitaria (AOU), Cagliari (Italy)), email: lucasaba@tiscali.it; Anzidei, Michele; Lucatelli, Pierleone (Dept. of Radiological Sciences, Univ. of Rome La Sapienza, Rome (Italy))

    2011-06-15

    Splenic artery aneurysm is the most frequent visceral artery aneurysm and rupture of the aneurysm is associated with a high mortality rate. It is important to discriminate between a true aneurysm and a pseudoaneurysm that may be caused by pancreatitis, iatrogenic and postoperative causes, trauma and peptic ulcer disease. Multidetector-row CT angiography (MDCTA) allows detailed visualization of the vascular anatomy and may allow identification of aneurysms and pseudoaneurysms that affect the splenic artery. The objective of this article is to provide a review of the general characteristics of splenic artery aneurysms and pseudoaneurysms and to describe the findings of MDCTA

  19. Multifocal splenic abscesses in immunocompetent adult due to cat-scratch disease.

    Science.gov (United States)

    Gkamprela, E; Papadimitropoulos, V; Papadopoulos, N; Deutsch, M

    2016-01-01

    Cat-scratch disease is caused by Bartonella henselae and transmitted to humans via the cats. Patients usually present with cutaneous lesions, regional lymphadenopathy and a brief period of fever. We report a rare case of an isolated splenic cat-scratch disease in an immunocompetent 27-year-old woman who presented with prolonged fever and multifocal splenic lesions. The patient was treated successfully with a long course of antibiotics. Isolated splenic lesions and fever is a rare manifestation of the cat-scratch disease. There is need of high suspicion index by the physicians to diagnose the disease promptly without invasive methods. Hippokratia 2016, 20(4): 306-308.

  20. Coil Migration after Transarterial Coil Embolization of a Splenic Artery Pseudoaneurysm

    Directory of Open Access Journals (Sweden)

    Bezawit D. Tekola

    2013-11-01

    Full Text Available A 48-year-old man with a history of splenic artery pseudoaneurysm requiring transarterial embolization 3 months earlier presented to the emergency department with abdominal pain and fever. Computed tomography showed evidence of embolization coil fragments within the gastrointestinal tract. Upper endoscopy showed a large gastric ulcer with numerous embolization coils extruding into the gastric lumen. The patient underwent partial gastrectomy, distal pancreatectomy and resection of the splenic artery pseudoaneurysm. This case illustrates a rare delayed complication of transarterial embolization of a splenic artery pseudoaneurysm.

  1. Subtotal resection and omentoplasty of the epidermoid splenic cyst: a case report

    Science.gov (United States)

    Spahija, Gazmend S; Hashani, Shemsedin I; Osmani, Eshref A; Hoxha, Sejdullah A; Hamza, Astrit H; Gashi-Luci, Lumturije H

    2009-01-01

    Introduction Nonparasitic splenic cysts are uncommon clinical entity and because of it, there is no information regarding their optimal surgical treatment. Case presentation A 41-years-old female with incidentally diagnosed nonparasitic splenic cyst which initially was asymptomatic. After two years of follow up, the patient underwent surgery; subtotal cystectomy and omentoplasty as an additional procedure. Postoperative course was uneventful. Conclusion Short and mid term results showed that near total cystectomy with omentoplasty was a safe successful procedure for treatment of epidermoid splenic cyst. PMID:19829799

  2. Splenic lesions observed in 71 splenectomized dogs: a retrospective study

    Directory of Open Access Journals (Sweden)

    Elisângela Olegário da Silva

    2016-10-01

    Full Text Available The spleen of dogs is frequently affected by disorders that vary from local and systemic origin. The difficulty in associating clinical and gross findings contributes for the choice of total splenectomy as the main treatment, leading to an impairment of the immune and hematopoietic functions. The aim of this study was to evaluate the pathological findings in the spleen of splenectomized dogs during 2008 to 2014 at a Veterinary Teaching Hospital. From the 71 cases analyzed, 97% (69/71 of the dogs were submitted to total splenectomy and 3% (2/71 to partial splenectomy. In 45 (63.4% of these cases, the histopathological diagnosis was non-neoplastic alterations; only 36.6% (26/71 had a splenic neoplasia. The main non-neoplastic lesions observed were nodular hyperplasia 24.4% (11/45, infarction 22.3% (10/45, and hematoma 20% (9/45. The most frequent tumors were hemangiosarcoma 50% (13/26, histiocytic sarcoma 23% (6/26, and lymphoma 11.5% (3/26. The clinical methods used to diagnose splenic lesions were ultrasonography 88% (63/71, radiography 2.8% (2/71 and exploratory laparotomy 4.2% (3/71. In 4.2% (3/71 the spleen changes were observed during the therapeutic ovariohysterectomy. The results of the present study showed a prevalence of benign disorders in the spleen of splenectomized dogs associated with a high incidence of total splenectomy performed, indicating a difficulty in recognizing the different lesions that can affect the spleen by the veterinarian medical.

  3. Splenic state in surviving patients with visceral heterotaxy.

    Science.gov (United States)

    Nagel, Bert H P; Williams, Helen; Stewart, Louise; Paul, Joanne; Stümper, Oliver

    2005-10-01

    To identify patients with visceral heterotaxy who are at risk from fulminant sepsis. We studied 38 patients, 37 having undergone abdominal ultrasound, all 38 having examination of blood films to establish presence of Howell-Jolly bodies, and all 38 documented to have had pneumococcal vaccination and prophylaxis with penicillin. We checked whether the parents were aware of the splenic state of their child, and when possible, we compared current results of blood films with those obtained postnatally. Two of the 17 patients with multiple spleens, all 11 without a detectable spleen, and 1 of 9 patients with a normal spleen, showed Howell-Jolly bodies in their blood films. In 5 of 23 patients with serial blood films, Howell-Jolly bodies had not been seen postnatally, but could now be detected in current blood films. Of these patients, 2 had multiple spleens, 1 did not have a spleen, and 1 had a solitary spleen of normal size. In the other patient, ultrasound could not be performed. Only one of these patients was receiving penicillin prophylactically, and had received pneumococcal vaccination. Of the 15 patients in whom Howell-Jolly bodies were present in the blood, only 8 parents knew about the potential risk for infection. Another 7 parents were sure that their child was taking penicillin regularly, and had received pneumococcal vaccination. Howell-Jolly bodies can be found in the blood of patients with visceral heterotaxy independent of the anatomical state of the spleen. As Howell-Jolly bodies can be encountered in the blood of such patients with increasing age, those with multiple and solitary spleens should be monitored regularly to identify those at risk. Parental knowledge of the splenic state, and compliance for prophylaxis using penicillin, and pneumococcal vaccination, were unsatisfactory in our cohort.

  4. BAFF, APRIL, TWEAK, BCMA, TACI and Fn14 proteins are related to human glioma tumor grade: immunohistochemistry and public microarray data meta-analysis.

    Directory of Open Access Journals (Sweden)

    Vassiliki Pelekanou

    Full Text Available Gliomas are common and lethal tumors of the central nervous system (CNS. Genetic alterations, inflammatory and angiogenic processes have been identified throughout tumor progression; however, treatment still remains palliative for most cases. Biological research on parameters influencing cell survival, invasion and tumor heterogeneity identified several cytokines interfering in CNS inflammation, oxidative stress and malignant transformation, including TNF-superfamily (TNFSF members. In this report we performed a meta-analysis of public gene-array data on the expression of a group of TNFSF ligands (BAFF, APRIL, TWEAK and their receptors (BAFF-R, TACI, BCMA, Fn14 in gliomas. In addition, we investigated by immunohistochemistry (IHC the tumor cells' expression of these ligands and receptors in a series of 56 gliomas of different grade. We show that in IHC, BAFF and APRIL as well as their cognate receptors (BCMA, TACI and Fn14 expression correlate with tumor grade. This result was not evidenced in micro-arrays meta-analysis. Finally, we detected for the first time Fn14, BAFF, BCMA and TACI in glioma-related vascular endothelium. Our data, combined with our previous report in glioma cell lines, suggest a role for these receptors and ligands in glioma biology and advance these molecules as potential markers for the classification of these tumors to the proliferative, angiogenic or stem-like molecular subtype.

  5. Expression of the B cell differentiation factor BAFF and chemokine CXCL13 in a murine model of Respiratory Syncytial Virus infection.

    Science.gov (United States)

    Alturaiki, Wael; McFarlane, Amanda J; Rose, Katie; Corkhill, Rachel; McNamara, Paul S; Schwarze, Jürgen; Flanagan, Brian F

    2018-01-26

    Innate immune responses are known to influence the subsequent development of adaptive immunity. We have previously shown that RSV infection of human airway epithelial cells results in production of the B cell growth factor, BAFF. To better understand how the airway responds to RSV infection by production of this and other factors to support or enhance local B cell responses to infection, we analysed the lung expression of BAFF and B cell homeostatic chemokines CXCL12, CXCL13, CCL19 and CCL21 in a murine model of RSV infection. Following infection with A2 strain RSV, the highest RSV N gene expression was observed at day 4 after challenge with virus. In contrast, two peaks of elevated BAFF expression at days 2 and 7 were observed. CXCL13 was significantly elevated at days 1, 2 and 7. CXCL12, CCL19 and CCL21 were expressed within lung tissue from control and RSV challenged animals but no significant difference in expression was found. Immunofluorescence showed BAFF to be present throughout the tissue however CXCL13 expression was localized to cell rich areas probably constituting lymphoid aggregates. Our results define the kinetics of B cell chemoattractant and growth factor expression during RSV infection and indicate an important role for these cytokines in the airway response to RSV infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Visualizing early splenic memory CD8+ T cells reactivation against intracellular bacteria in the mouse.

    Directory of Open Access Journals (Sweden)

    Marc Bajénoff

    Full Text Available Memory CD8(+ T cells represent an important effector arm of the immune response in maintaining long-lived protective immunity against viruses and some intracellular bacteria such as Listeria monocytogenes (L.m. Memory CD8(+ T cells are endowed with enhanced antimicrobial effector functions that perfectly tail them to rapidly eradicate invading pathogens. It is largely accepted that these functions are sufficient to explain how memory CD8(+ T cells can mediate rapid protection. However, it is important to point out that such improved functional features would be useless if memory cells were unable to rapidly find the pathogen loaded/infected cells within the infected organ. Growing evidences suggest that the anatomy of secondary lymphoid organs (SLOs fosters the cellular interactions required to initiate naive adaptive immune responses. However, very little is known on how the SLOs structures regulate memory immune responses. Using Listeria monocytogenes (L.m as a murine infection model and imaging techniques, we have investigated if and how the architecture of the spleen plays a role in the reactivation of memory CD8(+ T cells and the subsequent control of L.m growth. We observed that in the mouse, memory CD8(+ T cells start to control L.m burden 6 hours after the challenge infection. At this very early time point, L.m-specific and non-specific memory CD8(+ T cells localize in the splenic red pulp and form clusters around L.m infected cells while naïve CD8(+ T cells remain in the white pulp. Within these clusters that only last few hours, memory CD8(+ T produce inflammatory cytokines such as IFN-gamma and CCL3 nearby infected myeloid cells known to be crucial for L.m killing. Altogether, we describe how memory CD8(+ T cells trafficking properties and the splenic micro-anatomy conjugate to create a spatio-temporal window during which memory CD8(+ T cells provide a local response by secreting effector molecules around infected cells.

  7. Current and emerging treatment options for ANCA-associated vasculitis: potential role of belimumab and other BAFF/APRIL targeting agents

    Directory of Open Access Journals (Sweden)

    Lenert A

    2015-01-01

    Full Text Available Aleksander Lenert,1 Petar Lenert21Division of Rheumatology, University of Kentucky, Kentucky Clinic, Lexington, KY, USA; 2Division of Immunology, Department of Internal Medicine, The University of Iowa, Iowa City, IA, USAAbstract: Antineutrophil cytoplasmic antibody (ANCA-associated vasculitis (AAV comprises several clinical entities with diverse clinical presentations, outcomes, and nonunifying pathogenesis. AAV has a clear potential for relapses, and shows unpredictable response to treatment. Cyclophosphamide-based therapies have remained the hallmark of induction therapy protocols for more than four decades. Recently, B-cell depleting therapy with the anti-CD20 antibody rituximab has proved beneficial in AAV, leading to Food and Drug Administration approval of rituximab in combination with corticosteroids for the treatment of AAV in adults. Rituximab for ANCA-associated vasculitis and other clinical trials provided clear evidence that rituximab was not inferior to cyclophosphamide for remission induction, and rituximab appeared even more beneficial in patients with relapsing disease. This raised hopes that other B-cell-targeted therapies directed either against CD19, CD20, CD22, or B-cell survival factors, B-cell activating factor of the tumor necrosis factor family (BAFF and a proliferation-inducing ligand could also be beneficial for the management of AAV. BAFF neutralization with the fully humanized monoclonal antibody belimumab has already shown success in human systemic lupus erythematosus and, along with another anti-BAFF reagent blisibimod, is currently undergoing Phase II and III clinical trials in AAV. Local production of BAFF in granulomatous lesions and elevated levels of serum BAFF in AAV provide a rationale for BAFF-targeted therapies not only in AAV but also in other forms of vasculitis such as Behcet’s disease, large-vessel vasculitis, or cryoglobulinemic vasculitis secondary to chronic hepatitis C infection. BAFF

  8. Alteration of B cell subsets and the receptor for B cell activating factor (BAFF) in paediatric patients with type 1 diabetes.

    Science.gov (United States)

    Parackova, Zuzana; Klocperk, Adam; Rataj, Michal; Kayserova, Jana; Zentsova, Irena; Sumnik, Zdenek; Kolouskova, Stanislava; Sklenarova, Jana; Pruhova, Stepanka; Obermannova, Barbora; Petruzelkova, Lenka; Lebl, Jan; Kalina, Tomas; Sediva, Anna

    2017-09-01

    Lately, mounting evidence has shown that B cells play an important role in the pathogenesis of type 1 diabetes (T1D). Here, we present alterations in B cell subsets including BAFF receptor (BAFFR) expression in cohorts of patients with type 1 diabetes (T1D) and their relatives. B cells were studied in 438 patients with T1D (158 at disease onset and 280 with long-term disease), 136 first-degree relatives and 53 healthy controls. The B cell panel included transitional, naïve, MZ-like, switched memory B cells and plasmablasts. We also measured serum BAFF levels as well as BAFFR expression on both B and T cells. Moreover, the effect of BAFF on T and B lymphocytes was analysed in vitro. We observed a significant decrease in the proportion of transitional B cells in the patients with T1D, accompanied by an increased proportion of plasmablasts, especially in recent-onset patients and their relatives. While the BAFF serum levels did not differ in the patients with T1D, BAFFR-expressing B and especially T cell numbers were reduced in the T1D cohort, with the exception of patients with recent-onset disease who exhibited a significant increase in the number of BAFFR-expressing T cells. T cell activation and B cell proliferation were more pronounced after activation with BAFF in the T1D cohort compared to controls. The B cell panel in patients with T1D is characterized by significantly reduced populations of B cells in their early stages of development with a shift towards plasma cells. The dynamics of BAFFR-expressing B and T cells and the more pronounced responsiveness of the T1D T cells to BAFF point to the role of BAFF and T and B cell cooperation in the development of T1D. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  9. Isolated splenic metastasis of ovaric cancer. Case report and literature review.

    Science.gov (United States)

    Resta, G; Vedana, L; Marino, Silvia; Scagliarini, L; Bandi, M; Anania, G

    2014-01-01

    Splenic metastasis is extremely rare and are usually found in conjunction with metastasis of other organs. In addition, late recurrence even after 10 years of operation is very unusual. The most common sources of splenic metastasis are lung, colonrectal, melanoma, breast and ovarian carcinoma. We present a case of 67 year old woman who was admitted to our department with a solitary splenic metastases after hysterectomy with bilateral salpingo-oophorectomy for ovaric carcinoma 10 years ago. In conclusion, solitary splenic metastasis are very rare and the incidence of the reported cases in the medical literature is increasing. The treatment of choice is laparoscopic splenectomy that must be followed by chemotherapy in order to prevent the development of other possible micrometastases.

  10. Multiple Large Splenic Abscesses Managed with Computed Tomography-guided Percutaneous Catheter Drainage in Children

    Directory of Open Access Journals (Sweden)

    Jung Sook Yeom

    2013-12-01

    Full Text Available Splenic abscess is a rare finding in children. Splenectomy combined with broad-spectrum antibiotics has been the treatment of choice for multiple splenic abscesses. Herein, we report the case of a 14-year-old girl with multiple large splenic abscesses that were successfully managed after two image-guided percutaneous drainage procedures and administration of intravenous antibiotics. Initially, an abscess located at the periphery in the lower pole of the spleen was aspirated under ultrasound guidance. Finally, another abscess located near the hilum of the spleen was drained under computed tomography guidance. To the best of our knowledge, this is the first report of multiple large splenic abscesses treated with computed tomography-guided percutaneous drainage.

  11. Haemosuccus pancreaticus due to true splenic artery aneurysm: a rare cause of massive upper gastrointestinal bleeding

    Directory of Open Access Journals (Sweden)

    MK Roy

    2010-07-01

    Full Text Available “Haemosuccus pancreaticus” is an unusual cause of severe upper gastrointestinal bleeding and results from rupture of splenic artery aneurysm into the pancreatic duct. More commonly, it is a pseudoaneurysm of the splenic artery which develops as sequelae of pancreatitis. However, true aneurysm of the splenic artery without pancreatitis has rarely been incriminated as the etiologic factor of this condition. Owing to the paucity of cases and limited knowledge about the disease, diagnosis as well as treatment become challenging. Here we describe a 60-year-old male presenting with severe recurrent upper gastrointestinal bleeding and abdominal pain, which, after considerable delay, was diagnosed to be due to splenic artery aneurysm. Following an unsuccessful endovascular embolisation, the patient was cured by distal pancreatectomy and ligation of aneurysm.

  12. A colonic splenic flexure tumour presenting as an empyema thoracis: a case report.

    LENUS (Irish Health Repository)

    Murphy, K

    2009-01-01

    The case report describes the rare presentation of a 79-year-old patient with a locally perforated splenic flexure tumour of the colon presenting with an apparent empyema thoracis in the absence of abdominal signs or symptoms.

  13. A case of posttraumatic splenic translocation into the thorax; Przypadek pourazowego przemieszczenia sledziony do klatki piersiowej

    Energy Technology Data Exchange (ETDEWEB)

    Sosnowski, P.; Sikorski, L.; Ziemianski, A. [Akademia Medyczna, Poznan (Poland)

    1993-12-31

    A case of the left diaphragmatic hernia due to blunt thoracic and abdominal trauma is presented. Characteristic radiological signs of splenic translocation into the thorax contributed to quick diagnosis and immediate surgical intervention. (author). 5 refs, 2 figs.

  14. Splenic trauma: WSES classification and guidelines for adult and pediatric patients.

    Science.gov (United States)

    Coccolini, Federico; Montori, Giulia; Catena, Fausto; Kluger, Yoram; Biffl, Walter; Moore, Ernest E; Reva, Viktor; Bing, Camilla; Bala, Miklosh; Fugazzola, Paola; Bahouth, Hany; Marzi, Ingo; Velmahos, George; Ivatury, Rao; Soreide, Kjetil; Horer, Tal; Ten Broek, Richard; Pereira, Bruno M; Fraga, Gustavo P; Inaba, Kenji; Kashuk, Joseph; Parry, Neil; Masiakos, Peter T; Mylonas, Konstantinos S; Kirkpatrick, Andrew; Abu-Zidan, Fikri; Gomes, Carlos Augusto; Benatti, Simone Vasilij; Naidoo, Noel; Salvetti, Francesco; Maccatrozzo, Stefano; Agnoletti, Vanni; Gamberini, Emiliano; Solaini, Leonardo; Costanzo, Antonio; Celotti, Andrea; Tomasoni, Matteo; Khokha, Vladimir; Arvieux, Catherine; Napolitano, Lena; Handolin, Lauri; Pisano, Michele; Magnone, Stefano; Spain, David A; de Moya, Marc; Davis, Kimberly A; De Angelis, Nicola; Leppaniemi, Ari; Ferrada, Paula; Latifi, Rifat; Navarro, David Costa; Otomo, Yashuiro; Coimbra, Raul; Maier, Ronald V; Moore, Frederick; Rizoli, Sandro; Sakakushev, Boris; Galante, Joseph M; Chiara, Osvaldo; Cimbanassi, Stefania; Mefire, Alain Chichom; Weber, Dieter; Ceresoli, Marco; Peitzman, Andrew B; Wehlie, Liban; Sartelli, Massimo; Di Saverio, Salomone; Ansaloni, Luca

    2017-01-01

    Spleen injuries are among the most frequent trauma-related injuries. At present, they are classified according to the anatomy of the injury. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic derangement, and the associated injuries. The management of splenic trauma patients aims to restore the homeostasis and the normal physiopathology especially considering the modern tools for bleeding management. Thus, the management of splenic trauma should be ultimately multidisciplinary and based on the physiology of the patient, the anatomy of the injury, and the associated lesions. Lastly, as the management of adults and children must be different, children should always be treated in dedicated pediatric trauma centers. In fact, the vast majority of pediatric patients with blunt splenic trauma can be managed non-operatively. This paper presents the World Society of Emergency Surgery (WSES) classification of splenic trauma and the management guidelines.

  15. Radiation-induced splenic atrophy in patients with Hodgkin's disease and non-Hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Dailey, M.O.; Coleman, C.N.; Kaplan, H.S.

    1980-01-01

    Effective treatment of Hodgkin's disease requires the determination of the extent of the disease. This usually involves staging laparotomy, which includes splenectomy and biopsies of the para-aortic lymph nodes, liver, and bone marrow. Absence of the spleen predisposes a person to fulminant septicemia from encapsulated bacteria, a risk even greater in patients undergoing treatment for Hodgkin's disease. For this reason, some investigators have suggested that spleens not be removed for diagnosis but, rather, that they be included within the fields of radiation, which would preserve normal splenic function. We present a case of fatal spontaneous pneumococcal sepsis in a patient with splenic atrophy; the sepsis occurred 12 years after successful treatment of Hodgkin's disease by total nodal and splenic irradiation. A retrospective study of patients treated for Hodgkin's and non-Hodgkin's lymphomas indicated that atrophy and functional asplenia may be an important sequela of splenic irradiation

  16. Pneumococcal Sepsis Complicated by Splenic Abscesses and Purpura Fulminans in a 15-Month-Old Child

    Directory of Open Access Journals (Sweden)

    Scott Pangonis MD

    2016-02-01

    Full Text Available Streptococcus pneumoniae is an invasive organism that causes a wide range of common diseases, including sinusitis, acute otitis media, and pneumonia. Splenic abscesses and purpura fulminans (PF are rare complications of pneumococcal disease. Splenic abscesses caused by S pneumoniae have only been reported in the adult literature. PF has been described in the pediatric population as a rare complication in patients with invasive pneumococcal disease (IPD with and without underlying immunological disorders such as asplenia. Here, we report a patient with IPD complicated by splenic abscesses and PF. Our patient initially presented with bacteremia, septic shock, and disseminated intravascular coagulation. She subsequently developed PF and splenic abscesses. She survived her illness after receiving a total of 8 weeks of antibiotic therapy. This case highlights 2 rare complications of IPD and demonstrates the need to keep pneumococcal disease in the differential diagnosis even in children whose vaccination status is up to date.

  17. Subtotal splenectomy preserving the inferior splenic pole for the treatment of Hodgkin’s lymphoma

    Directory of Open Access Journals (Sweden)

    Andy Petroianu

    2017-01-01

    Conclusion: Subtotal splenectomy is efficacious to preserve the splenic functions and to prevent adverse effects of a large spleen on the treatment of Hodgkin’s lymphoma confined to superior pole and producing significant abdominal symptoms and hematological effects.

  18. Born-again spleen. Return of splenic function after splenectomy for trauma

    International Nuclear Information System (INIS)

    Pearson, H.A.; Johnston, D.; Smith, K.A.; Touloukian, R.J.

    1978-01-01

    We assessed splenic activity after splenectomy by interference phase microscopical examination of circulating red cells. Normal eusplenic children had a low number (<1%) of red cells with surface indentations or pits. About 20% of red cells of children who had electively been subjected to splenectomy for hematologic indications were pitted. Thirteen of 22 children who had had emergency splenectomy because of traumatic injury had a low percentage of pitted red cells, suggesting a return of splenic function. In five of these children a /sup 99m/Tc sulfur colloid scan demonstrated multiple nodules of recurrent splenic tissue. In contrast to the prevailing opinion that splenosis is rare, we have found it to be a frequent occurrence. Return of splenic function may, in part, account for the low frequency with which overwhelming bacterial sepsis and meningitis have been documented after splenectomy for traumatic indications

  19. Partial splenic embolization in a child with Gaucher disease, massive splenomegaly and severe thrombocytopenia

    Energy Technology Data Exchange (ETDEWEB)

    Pena, Andres H.; Clevac, Egor; Marie Cahill, Anne [Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Kaplan, Paige; Ganesh, Jaya [Children' s Hospital of Philadelphia, Division of Metabolic Diseases, Philadelphia, PA (United States)

    2009-09-15

    A 13-month-old boy with Gaucher disease presented with severe thrombocytopenia, anemia and massive splenomegaly. In addition he had significant respiratory compromise caused by abdominal compartment syndrome, requiring mechanical ventilation. Because of the degree of respiratory compromise and his existing bone marrow suppression, splenic artery embolization was chosen as an alternative to splenectomy. Splenic artery embolization was performed using 355-500-{mu}m polyvinyl alcohol particles, with 70% ablation achieved. Within 24 h of the procedure the platelet count had risen to greater than 70,000/mm{sup 3} and to more than 170,000/mm{sup 3} on postoperative day 4. At the 8-month follow-up the splenic size had decreased from 18 cm to 8 cm, with a platelet count of 578,000/mm{sup 3}. Partial splenic embolization provides a minimally invasive alternative to splenectomy in patients with Gaucher disease with massive splenomegaly and bone marrow suppression. (orig.)

  20. Blunt splenic trauma: splenectomy increases early infectious complications: a prospective multicenter study.

    Science.gov (United States)

    Demetriades, Demetrios; Scalea, Thomas M; Degiannis, Elias; Barmparas, Galinos; Konstantinidis, Agathoklis; Massahis, John; Inaba, Kenji

    2012-01-01

    The purpose of this study was to evaluate the effect of the method of splenic injury management on early infectious complications. Prospective observational, multicenter study which included all patients with blunt splenic injury surviving at least 72 hours. Epidemiologic and clinical data, grade of splenic injury, method of splenic management, and infectious complications during the initial hospitalization were collected according to a standardized collecting datasheet. Logistic regression analysis was used to identify independent risk factors for infectious complications. During a 22-month period, 269 eligible patients were enrolled in the study. Overall, 105 (39.0%) patients were observed; 48 (17.8%) underwent successful angioembolization, 19 (7.1%) underwent splenorrhaphy, and 97 (36.1%) underwent splenectomy. Multivariate analysis adjusting for age, hypotension on admission, Glasgow Coma Scale, Injury Severity Score, Abbreviated Injury Scale, laparotomy, grade of splenic injury, and associated solid and hollow viscus injuries, showed that splenectomy had a significantly higher incidence of infectious complications than splenic preservation (adjusted odds ratio [95% confidence interval], 9.62 [3.04-30.30]; p < 0.001). A regression model analysis identified splenectomy, hypotension on admission, associated hollow viscus injury, and high Injury Severity Score as independent risk factors for infectious complications. Forward logistic regression analysis, which included only the 176 patients with grades III to V splenic injuries, identified splenectomy as the most significant independent risk factors for infection (adjusted odds ratio [95% confidence interval], 16.67 [3.76-71.43]; p < 0.001). Splenectomy is an independent risk factor for early infectious complications. Splenic-preserving techniques should be considered more liberally.

  1. Treatment of splenic artery aneurysm with double overlapping bare stents: case report

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Hyo Sung; Han, Young Min; Jin, Gong Yong [School of Medicine, Chonbuk National Univ., Chonju (Korea, Republic of)

    2004-09-01

    The traditional treatment of splenic artery aneurysm (SAA) is generally surgery and/or transcatheter arterial embolization, but recently, the treatment of SAA using a stent graft has been reported. However, the acute angle of the celiac axis, as well as the tortuous path of the splenic artery makes the use of stent graft difficult for treatment of aneurysma. We report here a case of SAA treated with the technique of double overlapping metallic stents.

  2. Subtotal resection and omentoplasty of the epidermoid splenic cyst: a case report

    OpenAIRE

    Krasniqi, Avdyl S; Spahija, Gazmend S; Hashani, Shemsedin I; Osmani, Eshref A; Hoxha, Sejdullah A; Hamza, Astrit H; Gashi-Luci, Lumturije H

    2009-01-01

    Introduction Nonparasitic splenic cysts are uncommon clinical entity and because of it, there is no information regarding their optimal surgical treatment. Case presentation A 41-years-old female with incidentally diagnosed nonparasitic splenic cyst which initially was asymptomatic. After two years of follow up, the patient underwent surgery; subtotal cystectomy and omentoplasty as an additional procedure. Postoperative course was uneventful. Conclusion Short and mid term results showed that ...

  3. Portal, Splenic and Mesenteric Thrombosis in Hypereosinophilic Syndrome: A Case Report

    International Nuclear Information System (INIS)

    Hwang, Su Yeon; Jang, Kyung Mi; Kim, Min Jeong; Lee, Kwan Seop; Koh, Sung Hye; Jeon, Eui Yong; Lee, Hyun; Choi, Ju Hyun; Yie, Mi Yeon

    2009-01-01

    Idiopathic hypereosinophilic syndrome is a spectrum of diseases characterized by prominent peripheral eosinophilic leukocytosis without an identifiable cause. Several reports have described hepatic involvement as depicted on sonography and CT imaging in patients with hypereosinophilic syndrome. However, thrombosis of the portal, splenic and mesenteric veins in hypereosinophilic syndrome has been rarely reported. We present here a case of portal, splenic and mesenteric thrombosis in a 33-year-old man with hypereosinophilic syndrome

  4. Portal, Splenic and Mesenteric Thrombosis in Hypereosinophilic Syndrome: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Su Yeon; Jang, Kyung Mi; Kim, Min Jeong; Lee, Kwan Seop; Koh, Sung Hye; Jeon, Eui Yong; Lee, Hyun; Choi, Ju Hyun; Yie, Mi Yeon [Hallym University, Chuncheon (Korea, Republic of)

    2009-07-15

    Idiopathic hypereosinophilic syndrome is a spectrum of diseases characterized by prominent peripheral eosinophilic leukocytosis without an identifiable cause. Several reports have described hepatic involvement as depicted on sonography and CT imaging in patients with hypereosinophilic syndrome. However, thrombosis of the portal, splenic and mesenteric veins in hypereosinophilic syndrome has been rarely reported. We present here a case of portal, splenic and mesenteric thrombosis in a 33-year-old man with hypereosinophilic syndrome.

  5. Solitary splenic metastasis from nasopharyngeal carcinoma: a case report and systematic review of the literature

    OpenAIRE

    Genova, Pietro; Brunetti, Francesco; Bequignon, Emilie; Landi, Filippo; Lizzi, Vincenzo; Esposito, Francesco; Charpy, Cecile; Calderaro, Julien; Azoulay, Daniel; de?Angelis, Nicola

    2016-01-01

    Background Solitary splenic metastases are a rare occurrence, and the nasopharyngeal carcinoma represents one of the most uncommon primary sources. The present study aimed to describe a rare case of a solitary single splenic metastasis from nasopharyngeal carcinoma and to assess the number of cases of isolated nasopharyngeal carcinoma metastases to the spleen reported in the literature. Main body We describe the case of a 56-year-old man with a history of nasopharyngeal carcinoma and complete...

  6. IL-2, IL-4, IFN-γ or TNF-α enhances BAFF-stimulated cell viability and survival by activating Erk1/2 and S6K1 pathways in neoplastic B-lymphoid cells.

    Science.gov (United States)

    Gui, Lin; Zeng, Qingyu; Xu, Zhigang; Zhang, Hai; Qin, Shanshan; Liu, Chunxiao; Xu, Chong; Qian, Zhou; Zhang, Shuangquan; Huang, Shile; Chen, Long

    2016-08-01

    B-cell activating factor of the TNF family (BAFF) has been documented to act as a critical factor in the development of aggressive B lymphocytes and autoimmune diseases. However, the effect of various cytokines on BAFF-elicited neoplastic B-lymphoid cells is not known. In this study, we exhibited that administration of human soluble BAFF (hsBAFF), IL-2, IL-4, IFN-γ, or TNF-α alone increased cell viability and survival in Raji cells concentration-dependently, yet a more robust viability/survival was seen in the cells co-treatment of IL-2, IL-4, IFN-γ, or TNF-α with hsBAFF, respectively. Further research revealed that both Erk1/2 and S6K1 signaling pathways were essential for IL-2, IL-4, IFN-γ, or TNF-α enhancement of the viability/survival in the hsBAFF-stimulated cells, as inhibition of Erk1/2 with U0126 or down-regulation of Erk1/2, or blockage of S6K1 with rapamycin or silencing S6K1, or silencing S6K1/Erk1/2, respectively, reduced the cell viability/survival in the cells treated with/without hsBAFF±IL-2, IL-4, IFN-γ, or TNF-α. These findings indicate that IL-2, IL-4, IFN-γ or TNF-α enhances BAFF-stimulated cell viability/survival by activating Erk1/2 and S6K1 signaling in neoplastic B-lymphoid cells. Our data suggest that modulation of IL-2, IL-4, IFN-γ and/or TNF-α levels, or inhibitors of Erk1/2 or S6K1 may be a new approach to prevent BAFF-induced aggressive B-cell malignancies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Unusual case of pancreatic inflammatory myofibroblastic tumor associated with spontaneous splenic rupture

    Directory of Open Access Journals (Sweden)

    Hassan Fadi K

    2010-11-01

    Full Text Available Abstract Background Spontaneous splenic rupture considered a relatively rare but life threatening. The three commonest causes of spontaneous splenic rupture are malignant hematological diseases, viral infections and local inflammatory and neoplastic disorders. We describe a unique and unusual case of inflammatory myofibroblastic tumor of the tail of pancreas presented with massively enlarged spleen and spontaneous splenic rupture. Case presentation A 19 years old male patient with no significant past medical history presented to emergency room with abdominal pain and fatigue. Massively enlarged spleen was detected. Hypotension and rapid reduction of hemoglobin level necessitated urgent laparatomy. About 1.75 liters of blood were found in abdominal cavity. A large tumor arising from the tail of pancreas and local rupture of an enlarged spleen adjacent to the tumor were detected. Distal pancreatectomy and splenectomy were performed. To our knowledge, we report the first case of massively enlarged spleen that was complicated with spontaneous splenic rupture as a result of splenic congestion due to mechanical obstruction caused by an inflammatory myofibroblastic tumor of the tail of pancreas. A review of the literature is also presented. Conclusion Inflammatory myofibroblastic tumor of the tail of pancreas should be included in the differential diagnosis of the etiological causes of massively enlarged spleen and spontaneous splenic rupture.

  8. Laparoscopic resection of transverse colon cancer at splenic flexure: technical aspects and results.

    Science.gov (United States)

    Okuda, Junji; Yamamoto, Masashi; Tanaka, Keitaro; Masubuchi, Shinsuke; Uchiyama, Kazuhisa

    2016-03-01

    Laparoscopic resection of transverse colon cancer at splenic flexure is technical demanding and its efficacy remains controversial. The aim of this study was to investigate its technical aspects such as pitfalls and overcoming them, and to demonstrate the short-term and oncologic long-term outcomes. To overcome the difficulty in laparoscopic resection of transverse colon cancer at splenic flexure, we recognized the following technical tips as essential. First of all, we have to precisely identify major vessels variations feeding tumor. Secondary, anatomical dissection of mesocolon through medial approach is indispensible. Third, safe takedown of splenic flexure to fully mobilization of left hemicolon is mandatory. This cohort study analyzed 95 patients with stage II (43) and III (52) underwent resection of transverse colon cancer at splenic flexure. 61 laparoscopic surgeries (LAC) and 34 conventional open surgeries (OC) from December 1996 to December 2009 were evaluated. Short-term and oncologic long-term outcomes were recorded. Operative time was longer in LAC. However, blood loss was less, recovery of bowel function and hospital stay were shorter in LAC. There was no conversion in LAC and no significant difference in the postoperative complications. Regarding oncologic long-term outcomes, there were no significant differences between OC and LAC. Laparoscopic resection of transverse colon cancer at splenic flexure resulted in acceptable short-term and oncologic long-term outcomes. Once technical tips acquired, laparoscopic resection of transverse colon cancer at splenic flexure could be feasible as minimally invasive surgery.

  9. Splenic artery aneurysm: a diagnostic challenge in the setting of extensive portal venous collaterals

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, Grace S.; Vo, Nghia J.; Ishak, Gisele E.; Swanson, Jonathan O.; Otto, Randolph K. [University of Washington, Seattle Children' s Hospital, Department of Radiology, Seattle, WA (United States)

    2010-07-15

    We present a 16-year-old boy with autoimmune liver disease and longstanding portal hypertension in whom a CT arteriogram demonstrated a large aneurysm arising from the distal, extra-parenchymal portion of the splenic artery. Because of its location adjacent to multiple venous collaterals, the aneurysm was indistinguishable from splenic varices on initial imaging with Doppler sonography and on portal venous-phase CT. There is an increased risk of rupture of splenic artery aneurysms in the post-liver transplant period, with high associated mortality, and therefore diagnosis of splenic artery aneurysm prior to liver transplantation is clinically important. It is quite possible that the diagnosis of splenic artery aneurysm in this case would have been missed in the absence of dedicated arterial-phase imaging. As radiologists strive to reduce radiation exposure in children, this case highlights a potential diagnostic pitfall of both Doppler sonography and venous or single-acquisition arterial/venous-phase CT angiogram in children with venous collaterals and an undiagnosed splenic artery aneurysm. (orig.)

  10. Splenic artery aneurysm: a diagnostic challenge in the setting of extensive portal venous collaterals

    International Nuclear Information System (INIS)

    Phillips, Grace S.; Vo, Nghia J.; Ishak, Gisele E.; Swanson, Jonathan O.; Otto, Randolph K.

    2010-01-01

    We present a 16-year-old boy with autoimmune liver disease and longstanding portal hypertension in whom a CT arteriogram demonstrated a large aneurysm arising from the distal, extra-parenchymal portion of the splenic artery. Because of its location adjacent to multiple venous collaterals, the aneurysm was indistinguishable from splenic varices on initial imaging with Doppler sonography and on portal venous-phase CT. There is an increased risk of rupture of splenic artery aneurysms in the post-liver transplant period, with high associated mortality, and therefore diagnosis of splenic artery aneurysm prior to liver transplantation is clinically important. It is quite possible that the diagnosis of splenic artery aneurysm in this case would have been missed in the absence of dedicated arterial-phase imaging. As radiologists strive to reduce radiation exposure in children, this case highlights a potential diagnostic pitfall of both Doppler sonography and venous or single-acquisition arterial/venous-phase CT angiogram in children with venous collaterals and an undiagnosed splenic artery aneurysm. (orig.)

  11. Irreversible splenic atrophy following chronic LCMV infection is associated with compromised immunity in mice.

    Science.gov (United States)

    Mbanwi, Achire N; Wang, Chao; Geddes, Kaoru; Philpott, Dana J; Watts, Tania H

    2017-01-01

    Lymphocytic choriomeningitis virus clone 13 (LCMV13) infection of mice is a widely used model for investigating the mechanisms driving persistent viral infection in humans. LCMV13 disrupts splenic architecture early during infection, but this returns to normal within a few weeks. However, the long-term effects of LCMV13 infection on splenic structure have not been reported. Here, we report that persistent infection with LCMV13 results in sustained splenic atrophy that persists for at least 500 days following infection, whereas infection with the acutely infecting LCMV Armstrong is associated with a return to preinfection spleen weights. Splenic atrophy is associated with loss of T, B, and non-B non-T cells, with B cells most significantly affected. These effects were partly ameliorated by anti-NK1.1 or anti-CD8 antibody treatment. Antigen presentation was detectable at the time of contraction of the spleen, but no longer detected at late time points, suggesting that continued antigen presentation is not required to maintain splenic atrophy. Immunity to Salmonella infection and influenza vaccination were decreased after the virus was no longer detected. Thus splenic atrophy following LCMV13 infection is irreversible and may contribute to impaired immunity following clearance of LCMV13. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. DNA vaccine molecular adjuvants SP-D-BAFF and SP-D-APRIL enhance anti-gp120 immune response and increase HIV-1 neutralizing antibody titers.

    Science.gov (United States)

    Gupta, Sachin; Clark, Emily S; Termini, James M; Boucher, Justin; Kanagavelu, Saravana; LeBranche, Celia C; Abraham, Sakhi; Montefiori, David C; Khan, Wasif N; Stone, Geoffrey W

    2015-04-01

    Broadly neutralizing antibodies (bNAbs) specific for conserved epitopes on the HIV-1 envelope (Env) are believed to be essential for protection against multiple HIV-1 clades. However, vaccines capable of stimulating the production of bNAbs remain a major challenge. Given that polyreactivity and autoreactivity are considered important characteristics of anti-HIV bNAbs, we designed an HIV vaccine incorporating the molecular adjuvants BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand) with the potential to facilitate the maturation of polyreactive and autoreactive B cells as well as to enhance the affinity and/or avidity of Env-specific antibodies. We designed recombinant DNA plasmids encoding soluble multitrimers of BAFF and APRIL using surfactant protein D as a scaffold, and we vaccinated mice with these molecular adjuvants using DNA and DNA-protein vaccination strategies. We found that immunization of mice with a DNA vaccine encoding BAFF or APRIL multitrimers, together with interleukin 12 (IL-12) and membrane-bound HIV-1 Env gp140, induced neutralizing antibodies against tier 1 and tier 2 (vaccine strain) viruses. The APRIL-containing vaccine was particularly effective at generating tier 2 neutralizing antibodies following a protein boost. These BAFF and APRIL effects coincided with an enhanced germinal center (GC) reaction, increased anti-gp120 antibody-secreting cells, and increased anti-gp120 functional avidity. Notably, BAFF and APRIL did not cause indiscriminate B cell expansion or an increase in total IgG. We propose that BAFF and APRIL multitrimers are promising molecular adjuvants for vaccines designed to induce bNAbs against HIV-1. Recent identification of antibodies that neutralize most HIV-1 strains has revived hopes and efforts to create novel vaccines that can effectively stimulate HIV-1 neutralizing antibodies. However, the multiple immune evasion properties of HIV have hampered these efforts. These include the instability of

  13. Acquired A amyloidosis from injection drug use presenting with atraumatic splenic rupture in a hospitalized patient: a case report

    Directory of Open Access Journals (Sweden)

    Hanks Douglas K

    2011-01-01

    Full Text Available Abstract Introduction Little is known about splenic rupture in patients who develop systemic acquired A amyloidosis. This is the first report of a case of atraumatic splenic rupture in a patient with acquired A amyloidosis from chronic injection drug use. Case presentation A 58-year-old Caucasian man with a long history of injection drug use, hospitalized for infective endocarditis, experienced atraumatic splenic rupture and underwent splenectomy. Histopathological and microbiological analyses of the splenic tissue were consistent with systemic acquired A amyloidosis, most likely from injection drug use, that led to splenic rupture without any recognized trauma or evidence of bacterial embolization to the spleen. Conclusion In patients with chronic inflammatory conditions, including the use of injection drugs, who experience acute onset of left upper quadrant pain, the diagnosis of atraumatic splenic rupture must be considered.

  14. The clinical significance of T-cells, sIL-2R and TNF in evaluating patients with splenic autotransplantation

    International Nuclear Information System (INIS)

    Wang Haowei; Wu Haorong; Li Juncheng; Wu Jingchang

    2002-01-01

    To study the immunological effects of splenic autotransplantation, forty patients with splenic trauma were divided into two groups equally. One group underwent splenic autotransplantation and another underwent splenectomy. Control group included ten cases. Splenic autotransplantation and splenectomy group were compared with the control group. In the group of splenic autotransplantation, CD3 + , CD4 + , CD8 + , CD4 + /CD8 + dropped and sIL-2R, TNF rose after a week of operation. Then CD3 + , CD4 + , CD8 + , CD4 + /CD8 + rose and sIL-2R, TNF dropped three months later. In the group of splenectomy, CD 3+ , CD4 + , CD8 + and CD4 + /CD8 + dropped persistently, while sIL-2R and TNF rose postoperatively. Result showed splenic autotransplantation can help body to maintain T-cells level and improve the anti-infective ability

  15. Cystic angiomatosis with splenic involvement: unusual MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Vanhoenacker, F.M. [Dept. of Radiology, Univ. Hospital Antwerp, Edegem (Belgium); Dept. of Radiology, AZ St-Maarten, Campus Duffel, Duffel (Belgium); Schepper, A.M. [Dept. of Radiology, Univ. Hospital Antwerp, Edegem (Belgium); Raeve, H. [Dept. of Pathology, Univ. Hospital Antwerp, Edegem (Belgium); Berneman, Z. [Dept. of Hematology, Univ. Hospital Antwerp, Edegem (Belgium)

    2003-12-01

    Cystic angiomatosis is a rare disorder with a poor prognosis. We describe a case of a 33-year-old woman who presented with longstanding bone pain, hemolytic anemia, and an enlarged spleen. Radiologically, multiple osseous lesions with a mixed pattern of lytic and sclerotic areas were seen within the shoulders, spine, and pelvis. On CT and MRI of the abdomen, the spleen was markedly enlarged, with internal hyperdense foci on non-contrast CT scan, corresponding to low signal intensity areas on all MR pulse sequences. After administration of contrast, a mottled enhancement pattern throughout the entire spleen was seen both on CT and MRI. Cystic angiomatosis was proven by histological analysis of a biopsy specimen of an involved vertebra and histopathological examination of the spleen after subsequent splenectomy. This is the first report of a patient with disseminated cystic angiomatosis with splenic involvement in which the MRI features differ from the previous reports. Instead of the usual pattern consisting of multiple well-defined cystic lesions, a diffuse involvement replacing the entire spleen, with heterogeneous signal intensities on T2-weighted images and heterogeneous enhancement pattern, was seen in our patient. (orig.)

  16. Multiple foci of splenic tissue autotransplantation: Splenosis in diagnostic imaging

    International Nuclear Information System (INIS)

    Laskowska, K.; Burzynska-Makuch, M.; Drewa, S.; Lasek, W.; Pilecki, S.; Junik, R.

    2005-01-01

    Splenosis is usually defined as an autotransplantation of lienal tissue in the abdomen or cest following trauma to the spleen and/or splenectomy. The authors present the case of patient 15 years after a splenectomy performed because of extensive abdominal trauma. A new computed tomographic (CT) scan of the abdomen revealed multiple homogenous nodules, different in size, spread in the abdomen. Their density was characteristic of spleen. Ultrasound examination revealed only the largest tumors, located close to the liver and apparently isoechogenic to it. Static scintigraphy and SPECT were performed to prove the presence of splenosis. After treating the patient with colloid sulfide, multiple foci of increased radioisotope accumulation were identified in the abdomen, extrahepatic at the same locations as the masses visible on the CT scans, which were comparable to splenic tissue. Nodules revealed during CT or abdominal US in patients previously treated by splenectomy require further imaging with static scintigraphy of the liver and spleen in order to confirm or exclude splenosis. (author)

  17. Cystic angiomatosis with splenic involvement: unusual MRI findings

    International Nuclear Information System (INIS)

    Vanhoenacker, F.M.; Schepper, A.M.; Raeve, H.; Berneman, Z.

    2003-01-01

    Cystic angiomatosis is a rare disorder with a poor prognosis. We describe a case of a 33-year-old woman who presented with longstanding bone pain, hemolytic anemia, and an enlarged spleen. Radiologically, multiple osseous lesions with a mixed pattern of lytic and sclerotic areas were seen within the shoulders, spine, and pelvis. On CT and MRI of the abdomen, the spleen was markedly enlarged, with internal hyperdense foci on non-contrast CT scan, corresponding to low signal intensity areas on all MR pulse sequences. After administration of contrast, a mottled enhancement pattern throughout the entire spleen was seen both on CT and MRI. Cystic angiomatosis was proven by histological analysis of a biopsy specimen of an involved vertebra and histopathological examination of the spleen after subsequent splenectomy. This is the first report of a patient with disseminated cystic angiomatosis with splenic involvement in which the MRI features differ from the previous reports. Instead of the usual pattern consisting of multiple well-defined cystic lesions, a diffuse involvement replacing the entire spleen, with heterogeneous signal intensities on T2-weighted images and heterogeneous enhancement pattern, was seen in our patient. (orig.)

  18. Isolated splenic calcifications in two patients with portal hypertension; Calcificaciones esplenicas aisladas en dos pacientes con hipertension portal

    Energy Technology Data Exchange (ETDEWEB)

    Aleixandre, A.; Cugat, A. [Hospital de la Malvarrosa. Valencia (Spain); Ruiz, A.; Marti-Bonmati, L. [Hosptial Universitario Dr. Peset. Valencia (Spain); Tardaguila, F. [Clinica Provisa. Vigo (Spain)

    2002-07-01

    Calcification of the walls of the veins of the portal hypertension (PHT) (1-0), is uncommon. Calcification of the intra splenic vessels is exceptional. We report two cases of isolated calcification of intra splenic vessels, without calcification of the splenoportal venous axis, in patients with liver cirrhosis and PHT. The calcification was not clear. Computed tomography identified the calcification as linear tubular, branched structures located in the wall of intra splenic vessels. magnetic resonance imaging disclosed signs of cirrhosis and PHT but did not show the splenic classifications because of technical limitations. The cause of these calcifications was sustained PHT due to chronic liver disease. (Author) 15 refs.

  19. Computed tomography characteristics of hepatic and splenic abscesses associated with melioidosis: a 7- year study

    International Nuclear Information System (INIS)

    Apisarnthanarak, Piyaporn; Thairatananon, Atita; Muangsomboon, Kobkum

    2011-01-01

    Full text: This study aimed to characterise the CT findings associated with hepatic and splenic melioid abscesses. Patients with CT evidence of hepatic and/or splenic abscesses were retrospectively evaluated for clinical evidence of melioidosis over a 7-year period. After blinded review of the CT characteristics of intra-abdominal abscesses (IAA), we conducted a stratified analysis of patients with and without melioid IAA. Among 49 patients with CT evidence of hepatic and/or splenic IAA, the mean age was 50.2 years, 22 (44.9%) were women and eight (16.3%) had laboratory confirmation of melioidosis. For the 113 IAA, 33 were melioid abscesses (15 liver and 18 spleen) and 80 were non-melioid abscesses (69 liver and 11 spleen). Splenic IAA were more common in the melioid group (P = 0.001) and smaller in diameter than the hepatic IAA (P < 0.001). Melioid IAA were smaller than non-melioid IAA (P < 0.001) and the CT necklace sign was the strongest predictor for melioid IAA (odds ratio = 24.6, P = 0.006) with 100% specificity. Other significant predictors for melioidosis were concurrent hepatic and splenic involvement (P = 0.009), multiple abscesses (P = 0.015) and residence in an endemic area (P = 0.047). By multivariate analysis, concurrent hepatic and splenic involvement was the sole predictor of melioi dosis (adjusted odds ratio = 11.3, 95% confidence interval = 1.6-77.5, P = 0.014). The CT necklace sign, along with concurrent hepatic and splenic IAA, were highly suggestive of melioidosis in persons from Central Thailand.

  20. Incidental splenic nodules found on MR imaging done for assessment of iron overload in children

    Energy Technology Data Exchange (ETDEWEB)

    Ahyad, Rayan A.; Lam, Christopher Z.; Navarro, Oscar M. [University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada); Shearkhani, Omid [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada)

    2017-06-15

    MR imaging is used to assess iron overload in patients with hemoglobinopathies and in those who have undergone multiple blood transfusions. Sometimes splenic nodules are found incidentally on these examinations and this may cause diagnostic uncertainty. To determine the prevalence, imaging characteristics and evolution of splenic nodules found on MR imaging for iron overload evaluation. Retrospective review of all MR imaging examinations performed for iron overload assessment from 2005 to 2015 in a tertiary pediatric hospital. The presence of focal splenic nodules including number, size, signal characteristics and changes on follow-up MR imaging were recorded. Relevant patient clinical information including underlying hematological disease was also documented. A total of 318 patients had MR imaging for iron overload assessment. Of these, 25 (8%) had at least one incidental splenic nodule. Sickle cell disease was present in 22 patients (88%) and thalassemia in 3 (12%). On intermediate-weighted spin-echo images, the nodules had high signal intensity compared to the remainder of the spleen in 23 patients (92%) and low signal intensity in the remaining 2 (8%). In all patients (100%) the nodules showed progressive loss of signal intensity with increasing echo time values. Follow-up MR imaging was performed in 20 (80%) patients, which showed an increase in the size of the splenic nodules in 7 patients (35%) stability in 11 (55%) and a decrease in size in 2 (10%). It is not uncommon to find splenic nodules during MR evaluation of iron overload. In patients with sickle cell disease, most of these nodules are thought to represent preserved splenic tissue and appear hyperintense compared to the remainder of the spleen. They frequently remain stable on follow-up imaging, although about a third of them may show growth. Awareness of these nodules is important to avoid concern for potential malignancy and unnecessary investigations. (orig.)

  1. Incidental splenic nodules found on MR imaging done for assessment of iron overload in children

    International Nuclear Information System (INIS)

    Ahyad, Rayan A.; Lam, Christopher Z.; Navarro, Oscar M.; Shearkhani, Omid

    2017-01-01

    MR imaging is used to assess iron overload in patients with hemoglobinopathies and in those who have undergone multiple blood transfusions. Sometimes splenic nodules are found incidentally on these examinations and this may cause diagnostic uncertainty. To determine the prevalence, imaging characteristics and evolution of splenic nodules found on MR imaging for iron overload evaluation. Retrospective review of all MR imaging examinations performed for iron overload assessment from 2005 to 2015 in a tertiary pediatric hospital. The presence of focal splenic nodules including number, size, signal characteristics and changes on follow-up MR imaging were recorded. Relevant patient clinical information including underlying hematological disease was also documented. A total of 318 patients had MR imaging for iron overload assessment. Of these, 25 (8%) had at least one incidental splenic nodule. Sickle cell disease was present in 22 patients (88%) and thalassemia in 3 (12%). On intermediate-weighted spin-echo images, the nodules had high signal intensity compared to the remainder of the spleen in 23 patients (92%) and low signal intensity in the remaining 2 (8%). In all patients (100%) the nodules showed progressive loss of signal intensity with increasing echo time values. Follow-up MR imaging was performed in 20 (80%) patients, which showed an increase in the size of the splenic nodules in 7 patients (35%) stability in 11 (55%) and a decrease in size in 2 (10%). It is not uncommon to find splenic nodules during MR evaluation of iron overload. In patients with sickle cell disease, most of these nodules are thought to represent preserved splenic tissue and appear hyperintense compared to the remainder of the spleen. They frequently remain stable on follow-up imaging, although about a third of them may show growth. Awareness of these nodules is important to avoid concern for potential malignancy and unnecessary investigations. (orig.)

  2. Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling.

    Science.gov (United States)

    Arribas, Alberto J; Gómez-Abad, Cristina; Sánchez-Beato, Margarita; Martinez, Nerea; Dilisio, Lorena; Casado, Felipe; Cruz, Miguel A; Algara, Patrocinio; Piris, Miguel A; Mollejo, Manuela

    2013-07-01

    Splenic marginal zone lymphoma is a small B-cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B-cell lymphomas is hampered by the lack of specific markers. We have analyzed the gene expression and miRNA profiles of 31 splenic marginal zone lymphoma cases. For comparison, 7 spleens with reactive lymphoid hyperplasia, 10 spleens infiltrated by chronic lymphocytic leukemia, 12 spleens with follicular lymphoma, 6 spleens infiltrated by mantle cell lymphoma and 15 lymph nodes infiltrated by nodal marginal zone lymphoma were included. The results were validated by qRT-PCR in an independent series including 77 paraffin-embedded splenic marginal zone lymphomas. The splenic marginal zone lymphoma miRNA signature had deregulated expression of 51 miRNAs. The most highly overexpressed miRNAs were miR-155, miR-21, miR-34a, miR-193b and miR-100, while the most repressed miRNAs were miR-377, miR-27b, miR-145, miR-376a and miR-424. MiRNAs located in 14q32-31 were underexpressed in splenic marginal zone lymphoma compared with reactive lymphoid tissues and other B-cell lymphomas. Finally, the gene expression data were integrated with the miRNA profile to identify functional relationships between genes and deregulated miRNAs. Our study reveals miRNAs that are deregulated in splenic marginal zone lymphoma and identifies new candidate diagnostic molecules for splenic marginal zone lymphoma.

  3. Infarto esplénico secundario a pancreatitis aguda Splenic infarction secondary to acute pancreatitis

    Directory of Open Access Journals (Sweden)

    J. J. Arenal Vera

    2008-05-01

    Full Text Available Fundamento y objetivo: la estrecha relación anatómica del páncreas con los vasos esplénicos y el bazo es responsable de complicaciones esplénicas en el curso de la pancreatitis aguda. El objetivo es presentar dos casos clínicos de pancreatitis aguda grave que sufrieron infarto esplénico como complicación de la enfermedad pancreática. Pacientes, participantes: en un periodo de tres meses, dos pacientes fueron diagnosticados de infarto esplénico secundario a pancreatitis aguda. En ambos casos el diagnóstico y seguimiento evolutivo del infarto esplénico se hizo a través de tomografía axial computerizada. Resultados: en el primer paciente, las imágenes muestran de forma inequívoca la afectación de la arteria esplénica por el proceso inflamatorio pancreático. En el segundo, no se pudo demostrar afectación de los vasos esplénicos, por lo que la única posible explicación etiológica es un incremento de coagulabilidad intravascular. Conclusiones: sería recomendable añadir las complicaciones esplénicas al conjunto de complicaciones graves extrapancreáticas de la pancreatitis aguda. La tomografía axial computerizada es de gran utilidad para la detección y seguimiento de las complicaciones esplénicas de la pancreatitis aguda.Background and objective: the close anatomic relationship of the pancreas with the splenic vessels and the spleen is responsible for splenic complications in the course of acute pancreatitis. Our objective was to report two cases of severe acute pancreatitis complicated by splenic infarction. Patients: in a three-month period of time two patients were diagnosed with splenic infarction secondary to acute pancreatitis. In both cases splenic infarction diagnosis and follow-up were carried out using computed tomography. Results: in the first case images clearly showed a narrowing of the splenic artery due to the inflammatory pancreatic condition. In the second case no involvement of the splenic vessels could

  4. Factors Associated with Diffusely Increased Splenic F-18 FDG Uptake in Patients with Cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Keunyoung; Kim, Seongjang; Kim, Injoo; Kim, Dong Uk; Kim, Heeyoung; Kim, Sojung; Ahn, Sang Hyun [Pusan National Univ. Hospital, Busan (Korea, Republic of)

    2014-06-15

    Although diffuse splenic {sup 18}F-fluorodeoxyglucose (F-18 FDG) uptake exceeding hepatic activity, is considered abnormal, its clinical significance is rarely discussed in the literature. The aim of this study was to determine the contributing factors causing diffusely increased splenic FDG uptake in patients with cholangiocarcinoma. From January 2010 to March 2013, 140 patients (84 men, 56 women) were enrolled in this study. All patients had been diagnosed with cholangiocarcinoma and underwent F-18 FDG positron emission tomography/computed tomography (PET/CT) for the pretreatment staging work up. Clinical records were reviewed retrospectively. Various hematological parameters, C-reactive protein (CRP) level, CEA, CA19-9, pancreatic enzymes and liver function tests were conducted within 2 days after the F-18 FDG PET/CT study. Diffuse splenic uptake was observed in 23 patients (16.4%). Of those, 19 patients (82.6%) underwent endoscopic retrograde cholangiopancreastography (ERCP) 7 days before F-18 FDG PET/CT. The CRP level (p <0.001) and white blood cell count (p =0.023) were significantly higher in the group of patients with diffuse splenic FDG uptake. The hemoglobin (p <0.001) and the hematocrit (p <0.001) were significantly lower in patients with diffuse splenic FDG uptake. Pancreatic enzymes, liver function test results, and tumor markers were not significantly different between the patients who did or did not have diffusely increased splenic FDG uptake. The significant factors for diffuse splenic F-18 FDG uptake exceeding hepatic F-18 FDG uptake on multivariate analysis included: performing ERCP before F-18 FDG PET-CT (odds ratio [OR], 77.510; 95% CI, 7.624-132.105), and the presence of leukocytosis (OR, 12.436; 95% CI, 2.438-63.445) or anemia (OR, 1.211; 95% CI, 1.051-1.871). In conclusion, our study demonstrated that concurrent inflammation could be associated with diffusely increased splenic FDG uptake. We suggest that performing ERCP before F-18 FDG PET

  5. Effects of Al on the splenic immune function and NE in rats.

    Science.gov (United States)

    Hu, Chongwei; Li, Jing; Zhu, Yanzhu; Bai, Chongsheng; Zhang, Jihong; Xia, Shiliang; Li, Yanfei

    2013-12-01

    Norepinephrine (NE) regulates the splenic immune function and it may be related to the effects of Aluminum (Al) on the splenic immune function. Here, the aim of this study was to further explore the effects of aluminum trichloride (AlCl3) on the splenic immune function and its relationship with NE. Forty male Wistar rats were orally exposed to AlCl3 (0, 64.18, 128.36 and 256.72 mg/kg BW) through drinking water for 120 days. The CD3(+), CD4(+), CD8(+) T lymphocytes, the T and B lymphocytes proliferation rates and serum NE concentration were examined. The correlation analysis between splenic immune function and NE were done. The results showed that the CD3(+), CD4(+), CD8(+) T lymphocytes and the T and B lymphocytes proliferation rates decreased and NE concentration increased in AlCl3-treated rats. NE was negatively correlated with proportions of CD3(+), CD4(+) T lymphocytes and T and B lymphocytes proliferation rates, but not correlated with CD8(+) T lymphocytes. The results suggest that AlCl3 suppresses the splenic immune function and NE plays important role in this process. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. An unusual presentation of non pathological delayed splenic rupture: a case report.

    LENUS (Irish Health Repository)

    Khan, Suhail Aslam

    2009-01-01

    The diagnosis of Delayed Splenic Rupture poses a major challenge to even the most astute clinician, as it can mimic other medical emergencies. We present a case of an unusual presentation of delayed splenic rupture in a 23-year-old Caucasian man, who presented to the emergency department with a 2 day history of left upper quadrant pain. He initially denied any history of trauma. There were no signs of generalized peritonisim on examination but his haemoglobin level was low (8.9 gm\\/dl) for which there was no obvious cause identified. He was resuscitated and a computed tomography of the abdomen was performed. This revealed complete rupture of the splenic capsule with haemorrhagic fluid in the abdomen. With the computed tomography abdomen findings and further questioning of the patient, the only potential precipitating event that he could remember was a minor kick to the left upper quadrant more than 2 weeks ago while playing football. An urgent splenectomy was performed and histology confirmed complete rupture of the splenic capsule with a large adherent haematoma to the capsule. This case illustrates the difficulty in diagnosing delayed splenic rupture especially when accurate history is not available. A high index of suspicion is essential as delay in diagnosis can be fatal. Early diagnosis in suspected cases can be achieved by performing computed tomography of the abdomen.

  7. Splenic dynamics of indium-111 labeled platelets in idiopathic thrombocytopenic purpura

    Energy Technology Data Exchange (ETDEWEB)

    Syrjaelae, M.T.Sa.; Savolainen, S.; Nieminen, U.; Gripenberg, J.; Liewendahl, K.; Ikkala, E. (Helsinki Univ. Central Hospital (Finland))

    1989-09-01

    Splenic dynamics of {sup 111}In-labeled platelets and platelet-associated IgG in 33 patients with idiopathic thrombocytopenic purpura (ITP) were studied. Two half-lives were calculated for the biexponential splenic time-activity curve after i.v. injection of {sup 111}In-labeled platelets. There was no difference in the mean half-life of the rapid component of the splenic curve (ST1) when patients with negative or slightly positive platelet suspension immunofluorescence test (PSIFT) were compared to those with strongly positive PSIFT (3.0 {plus minus} 0.7 min vs. 3.6 {plus minus} 0.4, p greater than 0.05). Mean half-life of the slow component of the splenic curve (ST2) was found to be longer in patients with a strongly positive than a negative or weakly positive PSIFT (26 {plus minus} 5 min vs. 13.2 {plus minus} 1.0 min, p less than 0.01). It seems that determination of the two components of the splenic time-activity curve provides a useful method for studying platelet kinetics in ITP.

  8. Howell-Jolly body counting as a measure of splenic function. A reassessment.

    Science.gov (United States)

    Corazza, G R; Ginaldi, L; Zoli, G; Frisoni, M; Lalli, G; Gasbarrini, G; Quaglino, D

    1990-01-01

    Non-surgical and surgical asplenia predisposes to fatal infections; therefore, simple, non-invasive and repeatable tests for assessing splenic function are required, even in non-specialized medical institutions. Howell-Jolly bodies are the most characteristic peripheral blood abnormality after splenectomy, but their counting is not considered a reliable measure of splenic function. In this study, in a group of splenectomized subjects and of patients with non-surgical hyposplenism, we have compared counting of Howell-Jolly bodies, stained by both the May-Grünwald/Giemsa method and the Feulgen reaction, with pitted cell counting which is considered a reliable technique for the assessment of splenic hypofunction. A significant correlation has been found between Howell-Jolly body counts, stained by either technique, and pitted cell counts (P less than 0.0001). Through Howell-Jolly bodies were never detectable when pitted cell counts fell between 4 and 8%, values consistent with a very mild splenic hypofunction, for pitted cell counts above 8% their increase was always associated with increasing Howell-Jolly body counts. These data suggest that, although pitted cell counting represents a more sensitive method for evaluating splenic function, Howell-Jolly body counting may still be regarded as a simple and reliable technique for identifying and monitoring those cases associated with a real risk of overwhelming infections.

  9. Asymptomatic Partial Splenic Infarction In Laparoscopic Floppy Nissen Fundoplication And Brief Literature Review

    Science.gov (United States)

    Odabasi, Mehmet; Abuoglu, Haci Hasan; Arslan, Cem; Gunay, Emre; Yildiz, Mehmet Kamil; Eris, Cengiz; Ozkan, Erkan; Aktekin, Ali; Muftuoglu, Tolga

    2014-01-01

    Short gastric vessels are divided during the laparoscopic Nissen fundoplication resulting in splenic infarct in some cases. We report a case of laparoscopic floppy Nissen fundoplication with splenic infarct that was recognized during the procedure and provide a brief literature review. The patient underwent a laparoscopic floppy Nissen fundoplication. We observed a partial infarction of the spleen. She reported no pain. A follow-up computed tomography scan showed an infarct, and a 3-month abdominal ultrasound showed complete resolution. Peripheral splenic arterial branches have very little collateral circulation. When these vessels are occluded or injured, an area of infarction will occur immediately. Management strategies included a trial of conservative management and splenectomy for persistent symptoms or complications resulting from splenic infarct. In conclusion, we believe that the real incidence is probably much higher because many cases of SI may have gone undiagnosed during or following an operation, because some patients are asymptomatic. We propose to check spleen carefully for the possibility of splenic infarct. PMID:24833155

  10. Macrophages support splenic erythropoiesis in 4T1 tumor-bearing mice.

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    Min Liu

    Full Text Available Anemia is a common complication of cancer; a role of spleen in tumor-stress erythropoiesis has been suggested. However, the molecular mechanisms involved in the splenic erythropoiesis following tumor maintenance remain poorly understood. Here we show that tumor development blocks medullar erythropoiesis by granulocyte colony-stimulating factor (G-CSF and then causes anemia in murine 4T1 breast tumor-bearing mice. Meanwhile, tumor-stress promotes splenic erythropoiesis. Splenectomy worsened tumor-induced anemia, and reduced tumor volume and tumor weight, indicating the essential role of spleen in tumor-stress erythropoiesis and tumor growth. Tumor progression of these mice led to increased amounts of bone morphogenetic protein 4 (BMP4 in spleen. The in vivo role of macrophages in splenic erythropoiesis under tumor-stress conditions was investigated. Macrophage depletion by injecting liposomal clodronate decreased the expression of BMP4, inhibited splenic erythropoiesis, aggravated the tumor-induced anemia and suppressed tumor growth. Our results provide insight that macrophages and BMP4 are positive regulators of splenic erythropoiesis in tumor pathological situations. These findings reveal that during the tumor-stress period, the microenvironment of the spleen is undergoing changes, which contributes to adopt a stress erythropoietic fate and supports the expansion and differentiation of stress erythroid progenitors, thereby replenishing red blood cells and promoting tumor growth.

  11. Scintigraphic follow up of autologous splenic grafts: An experimental and clinical study

    International Nuclear Information System (INIS)

    Reilmann, H.; Creutzig, H.; Pabst, R.; Kamran, D.

    1984-01-01

    The risk of overwhelming sepsis in splenectomized patients is well known and autotransplantation of splenic tissue might be considered as a prophylactic approach. Little is known, however, of the success of grafting in man. In six patients with autologous grafts after emergency splenectomy the ''trapping function'' (TF) was measured by sequential scintigraphy with heat damaged red cells every third month. To correlate TF with blood flow and histology, different experiments were done in pigs: ligation of the splenic artery or partial splenectomy or total splenectomy with grafting of fragments either subfascially or in the greater momentum. TF, blood flow with Rb-86 and immune response was measured at different times after surgery. Remnants left at the main vessels did not grow, while splenic tissue left at smaller vessels increased in size. There were great differences in blood flow per gram splenic tissue, but a significant correlation between TF and blood flow. All experimental grafts showed a normal function both of the white and the red pulp. In patients there was a growth of grafts in four, while in two no TF could be measured. TF is an indicator of relative blood flow to splenic grafts and therefore useful in the follow up of grafted patients

  12. A case of splenic abscess diagnosed by computed tomography

    International Nuclear Information System (INIS)

    Yamasaku, Fusanosuke

    1983-01-01

    A 71-year-old man became febrile with transient pain of left upper quadrant for one or two days and admitted to prior hospital. He was treated with various antibiotics during about two months in prior hospital, but his fever continued and small amount of left pleural effusions were occasionally observed at his chest X-ray film. He was removed to Suibarago Hospital on July 17, 1980 introduced by prior hospital. On admission his temperature was 38.7 0 C, abdominal pain and jaundice were not present, liver, spleen and kidneys were not palpable. The WBC count was 19800/mm 3 with 76 % neutrophils and CRP reaction was 6+. No abnormality was found in his hepatic- and renal-function. Blood cultures were negative. A computed tomography (CT) of upper abdominal region showed irregular shaped multiple (maximum size: 2.5 x 3.5 cm in diameter) low density areas in enlarged spleen at the left upper side of left kidney. The diagnosis of multiple spleenic abscess was made and chemotherapy was instituted with clindamycin, dibekacin and cefotetan. Clinical symptomes were not changed and CT findings after three weeks were stationary. Splenectomy was performed on August 21. The spleen was covered with adherent surroundings organs namely stomach, diaphragm, colon and omentum. Abscesses were present in various sized yellowish granulomatous lesions. Aerobic and anaerobic culture of purulent materials yielded no growth. The patient recovered and discharged on November 9. CT is a non-invasive and valuable technique in diagnosis of splenic abscess. (author)

  13. [Routine screening of splenic or portal vein thrombosis after splenectomy].

    Science.gov (United States)

    Bouvier, A; Gout, M; Audia, S; Chalumeau, C; Rat, P; Deballon, O

    2017-01-01

    Portal and/or splenic vein thrombosis (PSVT) is common after splenectomy. It can be a life-threatening complication, with a risk of bowel ischemia and portal hypertension. An early diagnosis allows an effective medical treatment and prevents life-threatening complications. There is no consensus regarding the benefit of systematic screening of patients after splenectomy for PSVT. We started in January 2012 a routine screening of PSVT after elective splenectomy. The aim of this study was to assess this policy. Since January 2012, all patients undergoing an elective splenectomy had an abdominal CT-scan on postoperative-day 7. Demographic data, pathology, type of surgery, platelet counts before and after surgery, outcome, results of medical imaging, and management of PSVT and its results were recorded. Over 3 years, 52 patients underwent an elective splenectomy. All of them had a CT-scan at postoperative-day 7. A PSVT was found in 11 patients (21.2 %). They were all asymptomatic. Lymphoma and splenomegaly were the main factors associated with PSVT in the univariate analysis. All patients with PSVT were treated with anticoagulation and no complication of PSVT occurred. The follow-up CT confirmed the efficacy of anticoagulation therapy in all patients. Routine screening of PSVT after elective splenectomy is warranted because it allows to start anticoagulant therapy and avoid further life-threatening complications. The incidence of PSVT is particularly high among patients operated on for lymphoma or with splenomegaly. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  14. Active chronic sarcoidosis is characterized by increased transitional blood B cells, increased IL-10-producing regulatory B cells and high BAFF levels.

    Directory of Open Access Journals (Sweden)

    Anne Saussine

    Full Text Available BACKGROUND: Sarcoidosis is a multisystemic disease of unknown etiology characterized by a disproportionate Th1 granulomatous immune response in the organs involved. Plasmatic hypergammaglobulinemia and B cell accumulation in granulomatous lesions suggest the possible role of humoral immune responses in the pathogenesis of sarcoidosis. The purpose of this study is to describe B cell peripheral compartment in sarcoidosis. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed blood B cell subsets and BAFF levels in 33 patients with chronic sarcoidosis (active sarcoidosis n = 18; inactive sarcoidosis n = 15 and 18 healthy donors. Active chronic sarcoidosis patients had significantly less circulating memory B cells (p<0.01, more transitional (p<0.01 and increased numbers of IL-10-producing regulatory B cells (p<0.05 compared with healthy donors and patients with inactive sarcoidosis. BAFF serum levels were significantly higher in patients with active sarcoidosis (p<0.01 versus healthy donors and inactive sarcoidosis patients and strongly correlated with serum hypergammaglobulinemia (r = 0.53, p<0.01 and angiotensin converting enzyme levels (r = 0.61, p = <0.01. CONCLUSIONS/SIGNIFICANCE: These data show that there is an altered B cell homeostasis in active sarcoidosis and suggest BAFF antagonist drugs as potential new treatments of this disease.

  15. Vibration Induces BAFF Overexpression and Aberrant O-Glycosylation of IgA1 in Cultured Human Tonsillar Mononuclear Cells in IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Muyao Ye

    2016-01-01

    Full Text Available Objective. To investigate the influence of in vitro vibratory stimulation of human tonsillar mononuclear cells (TMCs. Methods. Fourteen IgA nephropathy (IgAN patients with chronic tonsillitis (CT and 12 CT patients with no renal pathology were enrolled. Group A TMCs were collected after 24 hours of culture and used to determine baseline levels. TMCs in groups B, C, D, E, and F were exposed to vibratory stimulation (60 Hz for 0 (as the control group, 1, 3, 5, and 10 minutes, respectively. Results. Baseline concentrations of B-cell-activation factor (BAFF and IgA1, BAFF mRNA expression, and aberrant O-glycosylation IgA1 level were higher in the IgAN group as compared to that in the CT group, and all increased after vibratory stimulation. Baseline mRNA expressions of core β1,3-galactosyltransferase (C1GALT1 and core β1,3GalT-specific molecular chaperone (Cosmc were lower in the IgAN group; the levels decreased further after vibratory stimulation. Conclusion. In patients with IgAN, vibratory stimulation of TMCs appears to induce IgA1 secretion through activation of BAFF release and to aberrant O-glycosylation IgA1 by suppressing C1GALT1 and Cosmc expression. In vitro vibratory stimulation of human TMCs mimics the vibratory simulation of palatine tonsils produced by vocal cords during phonation.

  16. SPLENIC INFARCTION: an intriguing and important cause of pain abdomen in high altitude

    Directory of Open Access Journals (Sweden)

    P. K. Hota

    2015-01-01

    Full Text Available Background: Patients with Sickle cell trait (SCT are usually asymptomatic. They are usually unaware of their condition unless they have a family history. There are specific situations, where these people suffer from the effects of sickle cell trait. Splenic syndrome at high altitude is one of the specific problems. It is usually seen after a patient with SCT has been inducted to high altitude like in case of mountaineers and military personnel deployed in high altitude warfare. Pain abdomen due to splenic infarction in individuals with SCT is one of the manifestations. These patients, if diagnosed in time, they can be spared from unnecessary surgical interventions. We present herewith our experience of splenic infarction due to SCT in high altitude and their management.

  17. Radionuclide evaluation of hemocatheretic function in a group of thalassemic patients after splenic embolization

    International Nuclear Information System (INIS)

    Bagni, B.; Feggi, L.M.; Prandini, N.; Soriani, S.

    1987-01-01

    Seven patients with thalassemia major underwent splenic embolization in order to assess splenic mass and function before and after treatment. Red blood cells, marked ''in vitro'' and chemically denatured with BMHP were also used to assess the blood parameters related to splenic function i.e. pretransfusional haemoglobin (Nb) and mean blood consumption (BC). The results show a statistically significant difference (p<0.01) for Hb and erythrocyte clearance before and after embolization. Before embolization no statistically significant correlations were found between the parameters examined, whereas after embolization there was a linear correlation at the limit of significance between BC and clearance halftime. The radionuclide method is proposed as safe and reproducible. Unlike blood chemical tests it also provides immediate information on the effects of embolization and a reliable parameter for follow-up

  18. Successful medical management of a neonate with spontaneous splenic rupture and severe hemophilia A.

    Science.gov (United States)

    Badawy, Sherif M; Rossoff, Jenna; Yallapragada, Sushmita; Liem, Robert I; Sharathkumar, Anjali A

    2017-03-01

    Splenic rupture in neonates is a rare event, usually occurring in the setting of underlying predisposing conditions. Here, we present the case of a term neonate who presented with worsening anemia in the setting of known hemolytic disease during the newborn period and was later found to have a spontaneous splenic rupture. He was subsequently diagnosed with severe hemophilia A, and was managed medically with recombinant factor VIII replacement therapy without any surgical intervention. This is the first reported case of a neonate who had spontaneous splenic rupture and severe hemophilia A, and underwent successful medical treatment without any surgical intervention. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

  19. Recanalization of Splenic Artery Aneurysm After Transcatheter Arterial Embolization Using N-Butyl Cyanoacrylate

    International Nuclear Information System (INIS)

    Matsumoto, Keiji; Ushijima, Yasuhiro; Tajima, Tsuyoshi; Nishie, Akihiro; Hirakawa, Masakazu; Ishigami, Kousei; Yamaji, Yukiko; Honda, Hiroshi

    2010-01-01

    A 65-year-old woman who had been diagnosed as having microscopic polyangiitis developed sudden abdominal pain and entered a state of shock. Abdominal CT showed massive hemoperitoneum, and emergent angiography revealed a ruptured splenic artery aneurysm. After direct catheterization attempts failed due to tortuous vessels and angiospasm, transcatheter arterial embolization using an n-butyl cyanoacrylate (NBCA)-lipiodol mixture was successfully performed. Fifty days later, the patient developed sudden abdominal pain again. Repeated angiography demonstrated recanalization of the splenic artery and splenic artery aneurysm. This time, the recanalized aneurysm was embolized using metallic coils with the isolation method. Physicians should keep in mind that recanalization can occur after transcatheter arterial embolization using N-butyl cyanoacrylate, which has been used as a permanent embolic agent.

  20. Functional asplenia and portal hypertension in a patient with primary splenic hemangiosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Yuecel, A.E.D.; Durak, H.; Bernay, I.; Bayraktar, Y.; Bekdik, C.; Telatar, H. (Hacettepe Univ., Ankara (Turkey))

    1990-05-01

    A 60-year-old man with primary splenic hemangiosarcoma (PSH) presented with weakness, weight loss, abdominal pain, and anemia. Physical examination revealed hepatomegaly, ascites, and firm, huge splenomegaly. Ultrasonography showed many nodular structures characterized by hypoechogenic and hyperechogenic areas. The patient also had portal hypertension, which was confirmed by physical findings and by measurement of portal vein pressure during operation. A liver-spleen scan using Tc-99m sulfur colloid and Tc-99m labeled heat denatured erythrocytes failed to demonstrate any splenic uptake, a reliable feature of functional asplenia. Although on a total body scan with Ga-67 citrate there was no splenic uptake, there was gallium uptake in the liver, where the presence of the metastatic lesion was histopathologically verified and confirmed by operation. There was also uptake in the middle zones of the lungs. Ga-67 citrate imaging appears to be helpful in the diagnosis of metastasis of PSH, and PSH can rarely cause portal hypertension.

  1. US and CT Findings of Splenic Hydatid Cyst: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Il Young; Kim, Sang Won; Shin, Hyeong Cheol; Han, Jong Kyu [Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of)

    2009-03-15

    Hydatid disease is a parasitic infection caused by the larvae of the cestode worms Echinococcus. In humans, the most commonly affected organ is the liver, the next second common organ is the lung. The third common affected organ is the spleen. In the case of splenic hydatid cyst, most cysts remain clinically silent and are diagnosed incidentally or when complications occur. We experienced a case of splenic hydatid cyst in a 28-year-old man. The patient complained of abdominal pain for 1 month. Abdominal ultrasound revealed a cystic lesion with daughter cysts in the spleen. The CT imaging also showed a cystic lesion with daughter cysts. We diagnosed it as a splenic hydatid cyst which was confirmed by pathology after surgery

  2. Splenic artery embolization using contour emboli before laparoscopic or laparoscopically assisted splenectomy.

    Science.gov (United States)

    Iwase, Kazuhiro; Higaki, Jun; Yoon, Hyung-Eun; Mikata, Shoki; Miyazaki, Minoru; Nishitani, Akiko; Hori, Shinichi; Kamiike, Wataru

    2002-10-01

    The present study assessed preoperative splenic artery embolization using spherical embolic material, super absorbent polymer microspheres (SAP-MS), before laparoscopic or laparoscopically assisted splenectomy. Distal splenic artery embolization using 250 to 400 microm SAP-MS was performed in nine cases with ITP and in seven cases with the other diseases with splenomegaly. Laparoscopic or laparoscopically assisted splenectomies, including a hand-assisted procedure and the procedure involving left upper minilaparotomy, were done 2 to 4 hours after embolization. Conversion to traditional laparotomy was not required in any of the 16 cases, while conversion to 12-cm laparotomy was required in one case with massive splenomegaly. Mean operating time was 161 minutes, and mean intraoperative blood loss was 290 mL. No major postoperative complications were identified, and only one patient reported postembolic pain before surgery. Preoperative splenic artery embolization using painless embolic material, SAP-MS, would be effective for easy and safe laparoscopic or laparoscopically assisted splenectomy.

  3. Isolated Splenic Metastasis from Renal Cell Carcinoma: Case Report and Review

    Directory of Open Access Journals (Sweden)

    J.A.G. Moir

    2011-04-01

    Full Text Available This report presents the case of a 70-year-old woman with a previous history of a left nephrectomy for renal cell carcinoma (RCC, who developed general malaise and fatigue. Abdominal computed tomography demonstrated an enhancing 6 × 7 cm necrotic lesion in the lower pole of the spleen suggestive of a metastasis. Given the highly suspicious nature of the lesion we proceeded to splenectomy. The tumour did not breach the splenic capsule, and there was no local diaphragmatic involvement. The mass was concluded to be a true metastasis of the original RCC rather than local recurrence of the disease. The causes of isolated solid splenic lesions are wide and varied, however a past or present history of malignancy should lead to a high index of suspicion for a splenic metastasis. We report an extremely unusual case of spread from a RCC.

  4. Effects of L-arginine and L-lysine mixtures on splenic sympathetic nerve activity and tumor proliferation.

    Science.gov (United States)

    Shen, Jiao; Horii, Yuko; Fujisaki, Yoshiyuki; Nagai, Katsuya

    2009-05-11

    Oral supplementations of L-arginine and L-lysine show tumor inhibition abilities. The splenic sympathetic nerve is involved in central modulation of cellular immunity and suppresses splenic natural killer cell activity in rats. An intravenous administration of a mixture of 10 mM L-arginine and L-lysine decreased splenic sympathetic nerve activity (splenic-SNA). We examined the effect of L-arginine and L-lysine mixtures on splenic-SNA in urethane-anesthetized rats by administration of 1 ml mixtures of 2 mM, 10 mM, and 50 mM L-arginine and L-lysine. We also studied the effect of the above mixtures on human colon cancer cell proliferation in athymic nude mice. An increase in splenic-SNA and tumor volume (2 mM), no effect (10 mM), and a decrease in both values (50 mM) were seen. Bivariate correlation analysis revealed a positive correlation between changes in splenic-SNA and tumor volume, indicating the tumor suppressing ability of weakened splenic-SNA.

  5. Dynamic contrast-enhanced MRI improves accuracy for detecting focal splenic involvement in children and adolescents with Hodgkin disease

    Energy Technology Data Exchange (ETDEWEB)

    Punwani, Shonit; Taylor, Stuart A.; Halligan, Steve [University College London, Centre for Medical Imaging, London (United Kingdom); University College London Hospital, Department of Radiology, London (United Kingdom); Cheung, King Kenneth; Skipper, Nicholas [University College London, Centre for Medical Imaging, London (United Kingdom); Bell, Nichola; Humphries, Paul D. [University College London Hospital, Department of Radiology, London (United Kingdom); Bainbridge, Alan [University College London, Department of Medical Physics and Bioengineering, London (United Kingdom); Groves, Ashley M.; Hain, Sharon F.; Ben-Haim, Simona [University College Hospital, Institute of Nuclear Medicine, London (United Kingdom); Shankar, Ananth; Daw, Stephen [University College London Hospital, Department of Paediatrics, London (United Kingdom)

    2013-08-15

    Accurate assessment of splenic disease is important for staging Hodgkin lymphoma. The purpose of this study was to assess T2-weighted imaging with and without dynamic contrast-enhanced (DCE) MRI for evaluation of splenic Hodgkin disease. Thirty-one children with Hodgkin lymphoma underwent whole-body T2-weighted MRI with supplementary DCE splenic imaging, and whole-body PET-CT before and following chemotherapy. Two experienced nuclear medicine physicians derived a PET-CT reference standard for splenic disease, augmented by follow-up imaging. Unaware of the PET-CT, two experienced radiologists independently evaluated MRI exercising a locked sequential read paradigm (T2-weighted then DCE review) and recorded the presence/absence of splenic disease at each stage. Performance of each radiologist was determined prior to and following review of DCE-MRI. Incorrect MRI findings were ascribed to reader (lesion present on MRI but missed by reader) or technical (lesion not present on MRI) error. Seven children had splenic disease. Sensitivity/specificity of both radiologists for the detection of splenic involvement using T2-weighted images alone was 57%/100% and increased to 100%/100% with DCE-MRI. There were three instances of technical error on T2-weighted imaging; all lesions were visible on DCE-MRI. T2-weighted imaging when complemented by DCE-MRI imaging may improve evaluation of Hodgkin disease splenic involvement. (orig.)

  6. Dynamic contrast-enhanced MRI improves accuracy for detecting focal splenic involvement in children and adolescents with Hodgkin disease

    International Nuclear Information System (INIS)

    Punwani, Shonit; Taylor, Stuart A.; Halligan, Steve; Cheung, King Kenneth; Skipper, Nicholas; Bell, Nichola; Humphries, Paul D.; Bainbridge, Alan; Groves, Ashley M.; Hain, Sharon F.; Ben-Haim, Simona; Shankar, Ananth; Daw, Stephen

    2013-01-01

    Accurate assessment of splenic disease is important for staging Hodgkin lymphoma. The purpose of this study was to assess T2-weighted imaging with and without dynamic contrast-enhanced (DCE) MRI for evaluation of splenic Hodgkin disease. Thirty-one children with Hodgkin lymphoma underwent whole-body T2-weighted MRI with supplementary DCE splenic imaging, and whole-body PET-CT before and following chemotherapy. Two experienced nuclear medicine physicians derived a PET-CT reference standard for splenic disease, augmented by follow-up imaging. Unaware of the PET-CT, two experienced radiologists independently evaluated MRI exercising a locked sequential read paradigm (T2-weighted then DCE review) and recorded the presence/absence of splenic disease at each stage. Performance of each radiologist was determined prior to and following review of DCE-MRI. Incorrect MRI findings were ascribed to reader (lesion present on MRI but missed by reader) or technical (lesion not present on MRI) error. Seven children had splenic disease. Sensitivity/specificity of both radiologists for the detection of splenic involvement using T2-weighted images alone was 57%/100% and increased to 100%/100% with DCE-MRI. There were three instances of technical error on T2-weighted imaging; all lesions were visible on DCE-MRI. T2-weighted imaging when complemented by DCE-MRI imaging may improve evaluation of Hodgkin disease splenic involvement. (orig.)

  7. Preserved function after angioembolisation of splenic injury in children and adolescents: a case control study.

    Science.gov (United States)

    Skattum, Jorunn; Loekke, Ruth Jeanette Vaaler; Titze, Thomas Larsen; Bechensteen, Anne Grete; Aaberge, Ingeborg S; Osnes, Liv Toril; Heier, Hans Erik; Gaarder, Christine; Naess, Paal Aksel

    2014-01-01

    Non-operative management for blunt splenic injuries was introduced to reduce the risk of overwhelming post splenectomy infection in children. To increase splenic preservation rates, splenic artery embolization (SAE) was added to our institutional treatment protocol in 2002. In the presence of clinical signs of ongoing bleeding, SAE was considered also in children. To our knowledge, the long term splenic function after SAE performed in the paediatric population has not been evaluated and constitutes the aim of the present study. A total of 11 SAE patients less than 17 years of age at the time of injury were included with 11 healthy volunteers serving as matched controls. Clinical examination, medical history, general blood counts, immunoglobulin quantifications and flowcytometric analysis of lymphocyte phenotypes were performed. Peripheral blood smears were examined for Howell-Jolly bodies (H-J bodies) and abdominal ultrasound was performed in order to assess the size and perfusion of the spleen. On average 4.6 years after SAE (range 1-8 years), no significant differences could be detected between the SAE patients and their controls. Total and Pneumococcus serospecific immunoglobulins and H-J bodies did not differ between the study groups, nor did general blood counts and lymphocyte numbers, including memory B cell proportions. The ultrasound examinations revealed normal sized and well perfused spleens in the SAE patients when compared to their controls. This case control study indicates preserved splenic function after SAE for splenic injury in children. Mandatory immunization to prevent severe infections does not seem warranted. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Endovascular Treatment of Active Splenic Bleeding After Colonoscopy: A Systematic Review of the Literature

    Energy Technology Data Exchange (ETDEWEB)

    Corcillo, Antonella, E-mail: antonella.corcillo@chuv.ch [Centre Hospitalier Universitaire Vaudois (CHUV), Departement de Medecine Interne (Switzerland); Aellen, Steve, E-mail: steve.aellen@hopitalvs.ch; Zingg, Tobias [Centre Hospitalier Universitaire Vaudois (CHUV), Service de Chirurgie Viscerale (Switzerland); Bize, Pierre [Centre Hospitalier Universitaire Vaudois (CHUV), Departement de Radiologie Interventionnelle (Switzerland); Demartines, Nicolas [Centre Hospitalier Universitaire Vaudois (CHUV), Service de Chirurgie Viscerale (Switzerland); Denys, Alban [Centre Hospitalier Universitaire Vaudois (CHUV), Departement de Radiologie Interventionnelle (Switzerland)

    2013-10-15

    Purpose: Colonoscopy is reported to be a safe procedure that is routinely performed for the diagnosis and treatment of colorectal diseases. Splenic rupture is considered to be a rare complication with high mortality and morbidity that requires immediate diagnosis and management. Nonoperative management (NOM), surgical treatment (ST), and, more recently, proximal splenic artery embolization (PSAE) have been proposed as treatment options. The goal of this study was to assess whether PSAE is safe even in high-grade ruptures. Methods: We report two rare cases of post colonoscopy splenic rupture. A systematic review of the literature from 2002 to 2010 (first reported case of PSAE) was performed and the three types of treatment compared. Results: All patients reviewed (77 of 77) presented with intraperitoneal hemorrhage due to isolated splenic trauma. Splenic rupture was high-grade in most patients when grading was possible. Six of 77 patients (7.8 %) were treated with PSAE, including the 2 cases reported herein. Fifty-seven patients (74 %) underwent ST. NOM was attempted first in 25 patients with a high failure rate (11 of 25 [44 %]) and requiring a salvage procedure, such as PSAE or ST. Previous surgery (31 of 59 patients), adhesions (10 of 13), diagnostic colonoscopies (49 of 71), previous biopsies or polypectomies (31 of 57) and female sex (56 of 77) were identified as risk factors. In contrast, splenomegaly (0 of 77 patients), medications that increase the risk of bleeding (13 of 30) and difficult colonoscopies (16 of 51) were not identified as risk factors. PSAE was safe and effective even in elderly patients with comorbidities and those taking medications that increase the risk of bleeding, and the length of the hospital stay was similar to that after ST. Conclusion: We propose a treatment algorithm based on clinical and radiological criteria. Because of the high failure rate after NOM, PSAE should be the treatment of choice to manage grade I through IV splenic

  9. Splenic Infarct and Pulmonary Embolism as a Rare Manifestation of Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Prashanth Rawla

    2017-01-01

    Full Text Available Cytomegalovirus (CMV is a type of herpes infection that has a characteristic feature of maintaining lifelong latency within the host cell. CMV manifestations can cover a broad spectrum from fever to as severe as pancytopenia, hepatitis, retinitis, meningoencephalitis, Guillain-Barre syndrome, pneumonia, and thrombosis. Multiple case reports of thrombosis associated with CMV have been reported. Deep vein thrombosis or pulmonary embolism is more common in immunocompetent patients while splenic infarct is more common in immunocompromised patients. However, here we report a female patient on low-dose methotrexate for rheumatoid arthritis who presented with both pulmonary embolism and splenic infarct.

  10. 613 cases of splenic rupture without risk factors or previously diagnosed disease: a systematic review

    Directory of Open Access Journals (Sweden)

    Aubrey-Bassler F

    2012-08-01

    Full Text Available Abstract Background Rupture of the spleen in the absence of trauma or previously diagnosed disease is largely ignored in the emergency literature and is often not documented as such in journals from other fields. We have conducted a systematic review of the literature to highlight the surprisingly frequent occurrence of this phenomenon and to document the diversity of diseases that can present in this fashion. Methods Systematic review of English and French language publications catalogued in Pubmed, Embase and CINAHL between 1950 and 2011. Results We found 613 cases of splenic rupture meeting the criteria above, 327 of which occurred as the presenting complaint of an underlying disease and 112 of which occurred following a medical procedure. Rupture appeared to occur spontaneously in histologically normal (but not necessarily normal size spleens in 35 cases and after minor trauma in 23 cases. Medications were implicated in 47 cases, a splenic or adjacent anatomical abnormality in 31 cases and pregnancy or its complications in 38 cases. The most common associated diseases were infectious (n = 143, haematologic (n = 84 and non-haematologic neoplasms (n = 48. Amyloidosis (n = 24, internal trauma such as cough or vomiting (n = 17 and rheumatologic diseases (n = 10 are less frequently reported. Colonoscopy (n = 87 was the procedure reported most frequently as a cause of rupture. The anatomic abnormalities associated with rupture include splenic cysts (n = 6, infarction (n = 6 and hamartomata (n = 5. Medications associated with rupture include anticoagulants (n = 21, thrombolytics (n = 13 and recombinant G-CSF (n = 10. Other causes or associations reported very infrequently include other endoscopy, pulmonary, cardiac or abdominal surgery, hysterectomy, peliosis, empyema, remote pancreato-renal transplant, thrombosed splenic vein, hemangiomata, pancreatic pseudocysts, splenic artery aneurysm

  11. The efficacy and benefits of transcatheter arterial embolization (TAE) in patients with blunt splenic injury

    International Nuclear Information System (INIS)

    Kwack, Kyu Sung; Kim, Young Ju; Lee, Myung Sub; Kim, Dong Jin; Hong, In Soo

    2000-01-01

    To evaluate the efficacy and benefits of transcatheter arterial embolization (TAE) in patients with blunt splenic injury after blunt abdominal trauma. We retrospectively analyzed the results of transcatheter arterial embolization in 23 patients who suffered splenic injury after blunt abdominal trauma. Fourteen of the patients were male, and 9 were female; 13 were adults, and 10 were children. Transcatheter arterial embolization was performed in patients with hypotension, tachycardia, evidence of hemodynamic instability due, for example, to low levels of Hgb and Hct, or those who needed fluid therapy or blood transfusion. After embolization the patients' progress was monitored by CT scanning, abdominal sonography, or 99m Tc-sulfur colloid scintigraphy. The degree of splenic injury was classified according to the system devised by Mirvis et al.; nine cases were CT grade III, and 14 were grade IV. After demonstrating angiographically the site of contrast leakage, embolization was performed; for this, a coil only was used in 16 cases, gelfoam only in four, and both coil and gelfoam in three. There were three sites of vascular embolization: 16 procedures were performed in the proximal part of the main trunk of the splenic artery, four in a superselected branch of this same artery, and three in both the splenic artery and one of its superselected branches. Of the 23 cases, 18 recovered without splenectomy after embolization, three adult patients died from coexisting conditions (spinal or cerebral injuries, liver cirrhosis, or pelvic bone fracture) or complications (acute renal failure or disseminated intravascular coagulation). Due to co-existing pancreatic and mesenteric vessel injury, two of the adult patients who underwent TAE also underwent delayed surgery; intraoperatively, there was no evidence of splenic rebleeding. In all patients who did not undergo surgery, follow-up observation revealed a decreased volume of hemoperitoneum, increased uptake of radionuclide in

  12. [Hepatic and splenic micro-abscess in cat scratch disease. Report of a case].

    Science.gov (United States)

    Luciano, A; Rossi, F; Bolognani, M; Trabucchi, C

    1999-01-01

    Cat-scratch disease (CSD) is an infection caused by a gram-negative bacillus known as Bartonella Henselae. Hepatosplenic disease occurs in only 0.3-0.7% of patients. In this report we describe a 7-year-old male presented with a 4-week history of fever, after diagnosis of CSD with regional lymphoadenitis. Ultrasonography and tomography identified hepatic and splenic abscesses. Antibiotic treatment for three months was associated with resolution of lesions. In Patients affected by CSD, ultrasonography and tomography permit to identify hepatic and/or splenic lesions, indicating systemic CSD.

  13. The effect of the cytoskeletal inhibitors on the splenic lymphocyte traffic and homing in rats

    International Nuclear Information System (INIS)

    Yang Huibin

    1989-01-01

    The rat splenic lymphocyte traffic and homing in vivo and the effect of cytoskeletal inhibitors on this process were investigated using the technique of γ-counting of 51 Cr-labelled lymphocytes. The results suggests that:(1) After 2 of intravenous injection, the 51 Cr-labelled lymphocytes from donor rat spleen mainly home to recipient rat spleen, liver, lungs, mesenteric lymph modes (MLN) and gut-associated lymphoid tissues. (2) A significant inhibiting effect on the ability of preferential homing of splenic lymphocytes treated with sodium azide, cytochalasin B or colchicine shows that microtubles and microfilaments play an important role in the lymphocyte traffic and homing

  14. Systemic Inflammation and Evidence of a Cardio-splenic Axis in Patients with Psoriasis

    DEFF Research Database (Denmark)

    Hjuler, Kasper F; Gormsen, Lars C; Vendelbo, Mikkel H

    2017-01-01

    The spleen is thought to play a role in atherosclerosis-associated immunity and cardiovascular research has indicated the existence of a cardio-splenic axis. The aim of this study was to assess splenic 18F-fluorodeoxyglucose uptake as a measure of systemic inflammation in patients with untreated...... inflammation. These results support the existence of systemic inflammation in patients with psoriasis, and provide the rationale for a mechanistic link between psoriasis-driven inflammation and cardiovascular comorbidity through a spleen-atherosclerotic axis....

  15. Contributions of scintigraphy and sonography to the diagnosis of traumatic splenic lesions in children

    International Nuclear Information System (INIS)

    Soucy, J.P.; Danais, S.; Filiatrault, D.; Lamoureux, J.; Lamoureux, F.

    1984-01-01

    20 children who were sent to the Nuclear Medicine and Sonography services for evaluation of the spleen in the context of a history of abdominal trauma were studied. All but one of the children were treated conservately, the exception having had on emergency renal procedure performed for renal rupture. The working diagnosis, based on the clinical that of splenic trauma in all cases. The result show a sensitivity of 90% (2 false negatives) for scintigraphy, and of 30% (14 false negatives) for sonography for the non-invasive diagnosis of splenic trauma in children [fr

  16. Successful emergency splenectomy during cardiac arrest due to cytomegalovirus-induced atraumatic splenic rupture

    DEFF Research Database (Denmark)

    Glesner, Matilde Kanstrup; Madsen, Kristian Rørbæk; Nielsen, Jesper Meng Rahn

    2015-01-01

    A 27-year-old woman was admitted to the emergency department with fever and a petechial rash on suspicion of meningitis. Shortly after arriving she developed cardiac arrest. Blood work up showed severe lactate acidosis, anaemia and thrombocytopenia. A focused assessment with sonography in trauma...... for 14 days with ganciclovir and meropenem and discharged on recovery. Atraumatic splenic rupture caused by viral infection is a rare condition although well described. In the case of our patient, thrombocytopenia added to the severity of the splenic rupture. A multidisciplinary team approach...

  17. The efficacy and benefits of transcatheter arterial embolization (TAE) in patients with blunt splenic injury

    Energy Technology Data Exchange (ETDEWEB)

    Kwack, Kyu Sung; Kim, Young Ju; Lee, Myung Sub; Kim, Dong Jin; Hong, In Soo [Wonju Christian Hospital, College of Medicine, Yonsei University, Wonju (Korea, Republic of)

    2000-07-01

    To evaluate the efficacy and benefits of transcatheter arterial embolization (TAE) in patients with blunt splenic injury after blunt abdominal trauma. We retrospectively analyzed the results of transcatheter arterial embolization in 23 patients who suffered splenic injury after blunt abdominal trauma. Fourteen of the patients were male, and 9 were female; 13 were adults, and 10 were children. Transcatheter arterial embolization was performed in patients with hypotension, tachycardia, evidence of hemodynamic instability due, for example, to low levels of Hgb and Hct, or those who needed fluid therapy or blood transfusion. After embolization the patients' progress was monitored by CT scanning, abdominal sonography, or {sup 99m}Tc-sulfur colloid scintigraphy. The degree of splenic injury was classified according to the system devised by Mirvis et al.; nine cases were CT grade III, and 14 were grade IV. After demonstrating angiographically the site of contrast leakage, embolization was performed; for this, a coil only was used in 16 cases, gelfoam only in four, and both coil and gelfoam in three. There were three sites of vascular embolization: 16 procedures were performed in the proximal part of the main trunk of the splenic artery, four in a superselected branch of this same artery, and three in both the splenic artery and one of its superselected branches. Of the 23 cases, 18 recovered without splenectomy after embolization, three adult patients died from coexisting conditions (spinal or cerebral injuries, liver cirrhosis, or pelvic bone fracture) or complications (acute renal failure or disseminated intravascular coagulation). Due to co-existing pancreatic and mesenteric vessel injury, two of the adult patients who underwent TAE also underwent delayed surgery; intraoperatively, there was no evidence of splenic rebleeding. In all patients who did not undergo surgery, follow-up observation revealed a decreased volume of hemoperitoneum, increased uptake of

  18. Clinical indications and biological mechanisms of splenic irradiation in autoimmune diseases

    Energy Technology Data Exchange (ETDEWEB)

    Weinmann, M.; Becker, G. [Tuebingen Univ. (Germany). Abt. fuer Strahlenonkologie; Einsele, H.; Bamberg, M. [Tuebingen Univ. (Germany). Abt. fuer Innere Medizin 2

    2001-02-01

    Background: Splenic irradiation (SI) is a fairly unknown treatment modality in autoimmune disorders like autoimmune thrombocytopenia (AIT) or autoimmune hemolytic anemia (AIHA), which may provide an effective, low toxic and cost-effective treatment for selected patients. Patients, Materials and Methods: This article reviews the limited experiences on splenic irradiation in autoimmune thrombocytopenia by analyzing the current studies including 71 patients and some preliminary reports on splenic irradiation in autoimmune hemolytic anemia. Results: In autoimmune thrombocytopenia between 40 and 90% of all patients responded, but most of them relapsed within 4 to 6 months after splenic irradiation. Between 10 and 20% of all patients had a sustained response. The efficacy of splenic irradiation in HIV-associated cases of thrombocytopenia is probably lower than in other forms of autoimmune thrombocytopenia, but especially in this group immunosuppressive drug treatment of autoimmune thrombocytopenia exposes some problems. In autoimmune hemolytic anemia there are some case reports about efficacy of splenic irradiation. Toxicity of splenic irradiation in both diseases was very moderate. Conclusions: For HIV patients, for elderly patients or patients at high risk for complications following splenectomy splenic irradiation might be a treatment option. Splenic irradiation as preoperative treatment in patients not responding to or not suitable for immunosuppressive drugs prior to splenectomy may be a promising new application of splenic irradiation to reduce adverse effects of splenectomy in thrombocytopenic patients. A further analysis of the biological mechanisms underlying splenic irradiation may help to improve patient selection, to optimize dose concepts and treatment schedules and will improve understanding of radiotherapy as an immunomodulatory treatment modality. (orig.) [German] Hintergrund: Die Bestrahlung der Milz zur Behandlung von haematologischen

  19. Temporal assessment of splenic function in patients who have undergone percutaneous image-guided splenic artery embolization in the setting of trauma.

    Science.gov (United States)

    Pirasteh, Ali; Snyder, Laura L; Lin, Roger; Rosenblum, David; Reed, Steven; Sattar, Abdus; Passalacqua, Matthew; Prologo, J David

    2012-01-01

    The role of transcatheter splenic arterial embolization (SAE) in the nonoperative management of splenic injury is evolving. The purpose of this study is to evaluate patients who have undergone SAE for laboratory markers of hyposplenism in the years after their procedure. Thirty-four subjects who had undergone SAE as part of nonoperative management of splenic trauma during a period of 10 years were included. A blood sample was collected from each patient for complete blood count and smear analysis for peripheral markers of hyposplenism (as indicated by Howell-Jolly bodies [HJBs]). Sample size and power analysis was performed, and likelihoods for various true prevalences were calculated. The average time interval from procedure to follow-up was 4.4 years. No participants had peripheral markers of hyposplenism or abnormalities in cell count on follow-up. Phagocytic function of the spleen in patients who have undergone SAE is preserved, as evidenced by the absence of HJBs on follow-up peripheral blood smears. Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

  20. Splenic dendritic cell involvement in FXR-mediated amelioration of DSS colitis

    NARCIS (Netherlands)

    Massafra, Vittoria; Ijssennagger, Noortje; Plantinga, Maud; Milona, Alexandra; Ramos Pittol, José M.; Boes, Marianne; van Mil, Saskia W C

    2016-01-01

    Inflammatory Bowel Disease (IBD) is a multifactorial disorder involving dysregulation of the immune response and bacterial translocation through the intestinal mucosal barrier. Previously, we have shown that activation of the bile acid sensor Farnesoid X Receptor (FXR), which belongs to the family

  1. Domestic violence as an unfortunate cause of splenic injury, fetal demise, and maternal morbidity

    Directory of Open Access Journals (Sweden)

    Shuchi M Jain

    2014-01-01

    Full Text Available Abuse of pregnant women is a serious health problem with the potential to cause life-threatening injuries to the mother and her baby. This is a case of domestic violence leading to splenic injury and massive intraperitoneal hemorrhage leading to fetal demise. Fortunately, timely interventions saved the mother′s life.

  2. Segmental resection with primary anastomosis is not always safe in splenic flexure perforation.

    Science.gov (United States)

    Weledji, Elroy P; Mokake, Martin D; Sinju, Motaze

    2016-01-16

    Familial adenomatous polyposis (FAP) is caused by a rare mutation of the adenomatous polyposis coli gene on Chromosome 5q. The risk of colorectal cancer in patients with FAP is nearly 100% and intensive endoscopic surveillance or prophylactic colectomy are mandatory. If extensive endoscopic surveillance is chosen, there is a cumulative risk of perforation and bleeding especially after polypectomy. We discussed the problems and options in the management of the late diagnosis of an iatrogenic perforation of the splenic flexure complicating endoscopic surveillance in FAP. We present a 35-year-old black African man with FAP who sustained a splenic flexure perforation following a colonoscopic polypectomy of a suspicious lesion. He underwent a splenic flexure resection and primary anastomosis that dehisced and the patient benefited from an emergency definitive colectomy and ileorectal anastomosis. Resection with primary anastomosis following iatrogenic perforation of the splenic flexure is not safe because of a high chance of anastomotic dehiscence. Following a late diagnosis in an unstable patient exteriorization of the perforation as a stoma is a better option prior to a definitive prophylactic colectomy.

  3. Intratracheal administration of fullerene nanoparticles activates splenic CD11b{sup +} cells

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Ning [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Kunugita, Naoki [Department of Environmental Health, National Institute of Public Health, 2-3-6, Minami, Wako 351-0197 (Japan); Ichinose, Takamichi [Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita 870-1201 (Japan); Song, Yuan [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Yokoyama, Mitsuru [Bio-information Research Center, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Arashidani, Keiichi [School of Health Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Yoshida, Yasuhiro, E-mail: freude@med.uoeh-u.ac.jp [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan)

    2011-10-30

    Highlights: {yields} Fullerene administration triggered splenic responses. {yields} Splenic responses occurred at different time-points than in the lung tissue. {yields} CD11b{sup +} cells were demonstrated to function as responder cells to fullerene. - Abstract: Fullerene nanoparticles ('Fullerenes'), which are now widely used materials in daily life, have been demonstrated to induce elevated pulmonary inflammation in several animal models; however, the effects of fullerenes on the immune system are not fully understood. In the present study, mice received fullerenes intratracheally and were sacrificed at days 1, 6 and 42. Mice that received fullerenes exhibited increased proliferation of splenocytes and increased splenic production of IL-2 and TNF-{alpha}. Changes in the spleen in response to fullerene treatment occurred at different time-points than in the lung tissue. Furthermore, fullerenes induced CDK2 expression and activated NF-{kappa}B and NFAT in splenocytes at 6 days post-administration. Finally, CD11b{sup +} cells were demonstrated to function as responder cells to fullerene administration in the splenic inflammatory process. Taken together, in addition to the effects on pulmonary responses, fullerenes also modulate the immune system.

  4. Splenic vein thrombosis and pancreatic fistula after minimally invasive distal pancreatectomy.

    Science.gov (United States)

    Kang, C M; Chung, Y E; Jung, M J; Hwang, H K; Choi, S H; Lee, W J

    2014-01-01

    This study aimed to investigate the clinical relevance of splenic vein thrombosis (SVT) in the splenic vein remnant following minimally invasive distal pancreatosplenectomy (DPS). Medical records of patients who underwent laparoscopic or robotic distal pancreatectomy (DP) with or without splenectomy between January 2006 and August 2012 were reviewed. Rates of SVT and clinically relevant postoperative pancreatic fistula (POPF) were compared in a group of patients undergoing DPS and a group having spleen-preserving DP. Seventy-nine patients had minimally invasive DP, of whom 38 (48 per cent) developed SVT in the splenic vein remnant. DPS was associated with POPF (P = 0.001) and SVT (P SVT length was closely related to the amount of peripancreatic fluid collection (P = 0.025) and POPF (P = 0.045). In a comparison of splenic vessel-sacrificing, spleen-preserving DP and DPS, postoperative platelet count was significantly higher in the DPS group (P SVT (P = 0.092) and POPF (P = 0.065) tended to be associated with DPS, suggesting that SVT may be related to both splenectomy and POPF. Minimally invasive DPS is associated with SVT and POPF. Preservation of the spleen should be considered when treating patients with benign and borderline malignant tumours of the distal pancreas. © 2013 BJS Society Ltd. Published by John Wiley & Sons Ltd.

  5. Splenic artery aneurysms: Two cases of varied etiology, clinical presentation and treatment outcome

    Directory of Open Access Journals (Sweden)

    Pejkić Siniša

    2015-01-01

    Full Text Available Introduction. Splenic artery aneurysms are potentially lethal lesions. We report two illustrative cases and discuss etiology, diagnosis and treatment of these aneurysms. Outline of Cases. Both patients, age 31 and 80 years, were biparous women. The younger woman, otherwise healthy, was referred from a local hospital 3 weeks after she underwent a left subcostal laparotomy and exploration for symptomatic abdominal mass diagnosed by CT. Angiography established the diagnosis of a large, non-ruptured splenic artery aneurysm. Elective aneurysmectomy with splenectomy was performed using the approach through the upper median laparotomy and bursa omentalis. Postoperative course was uneventful. Histopathology demonstrated cystic medial necrosis with chronic dissection. The other patient, elderly woman, presented urgently with acute abdominal pain and syncope and was diagnosed by computed tomography with a huge, ruptured splenic artery aneurysm. She underwent immediate aneurysmectomy with splenectomy using the same, above-mentioned approach. External pancreatic fistula and pancreatic pseudocyst complicated the postoperative course, requiring open pseudocyst drainage and cystojejunostomy. After a protracted hospitalization patient eventually recovered. The pathological diagnosis was atherosclerotic aneurysm. Conclusion. Splenic artery aneurysms are infrequent lesions, with varied etiology and clinical presentation. Timely diagnosis and adequate treatment prevent life-threatening rupture and lessen the risk of operative morbidity and mortality. [Projekat Ministarstva nauke Republike Srbije, br. 175008

  6. The role of splenic irradiation in treating HIV-associated immune thrombocytopenia

    International Nuclear Information System (INIS)

    Blauth, Jeanette; Fisher, Scot; Henry, David; Nichini, Franco

    1999-01-01

    Purpose: To evaluate our experience in treating patients with HIV-associated thrombocytopenia using splenic irradiation. Methods and Materials: From 1993 to 1998, 10 patients with HIV-related immune thrombocytopenia (ITP) were treated in our department with low-dose splenic irradiation. All patients had either failed more conventional treatment modalities or possessed some contraindication to them. Results: Nine of 10 patients had at least a small, transient rise in their platelet counts, but only two received a substantial therapeutic benefit. Of these two, one died shortly after completing his course of radiation therapy while the other maintained near normal platelet counts up to approximately 3((1)/(2)) years following treatment. There were no treatment-related morbidities and one patient was treated twice. Conclusion: While most patients with HIV-associated ITP may initially respond favorably to splenic irradiation with small rises in platelet count, few responses are likely to be sustained or provide clinically significant outcomes. Our results support those previously reported by others treating this same condition. What remains to be investigated is whether there are any prognostic indicators to help identify those patients most likely to respond to this treatment, thus enabling us to reserve splenic irradiation for those who might derive a substantial benefit from it

  7. Etiology and management of splenic injuries: The experience at Federal Teaching Hospital, Gombe, Northeast Nigeria

    Directory of Open Access Journals (Sweden)

    A A Adejumo

    2017-01-01

    Full Text Available Objective: To appraise the current management of splenic trauma with the available resources in our environment and re-emphasizing the role of a sound clinical judgment and early intervention. Methodology: This is a prospective cross-sectional study in which patients that sustained splenic injuries were resuscitated and optimized for laparotomy. Broad spectrum antibiotics and generous analgesia were given. Laparotomy was carried out in all patients and treatment was given according to the grade of injury sustained. Other systemic injuries were co-managed with other subspecialties. Results: Patients in the study were aged 7–52 years (male: female = 3.4:1. The modal age group was 11–20 years. All patients were managed operatively. The majority (51.5% of splenic trauma in our study were due to vehicular accidents. There was no statistical association between sonographic and intraoperative findings (P = 0.218. Splenectomy was the most common procedure carried out. Complications encountered include surgical site infection (9, 27.3%, respiratory tract infection (6, 18.2%, and deep vein thrombosis (1, 3.0%. The duration of hospital stay for patients was 9–26 days (mean = 12.69 ± 6.30 days. Conclusion: The management of splenic injuries has evolved over the years. The role of a sound clinical judgment is crucial to a successful management outcome, especially in the third world countries.

  8. Splenic arteriovenous malformation manifested by thrombocytopenia in hereditary hemorrhagic telangiectasia: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hee Jin; Choi, Jong Cheol; Oh, Jong Yeong; Cho, Jin Han; Kang, Myong Jin; Lee, Jin Hwa; Yoon, Seong Kuk; Nam, Kyeong Jin [College of Medicine, Dong-A University, Busan (Korea, Republic of)

    2008-09-15

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterized by epistaxis, telangiectases and visceral arteriovenous malformations (AVMs). The involvement of the gastrointestinal tract, liver, lung and cerebrum for HHT has been described, whereas little is known about AVMs of the spleen. We report here the radiological findings of a case of a splenic AVM manifested by thrombocytopenia in HHT.

  9. Splenic arteriovenous malformation manifested by thrombocytopenia in hereditary hemorrhagic telangiectasia: a case report

    International Nuclear Information System (INIS)

    Kwon, Hee Jin; Choi, Jong Cheol; Oh, Jong Yeong; Cho, Jin Han; Kang, Myong Jin; Lee, Jin Hwa; Yoon, Seong Kuk; Nam, Kyeong Jin

    2008-01-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterized by epistaxis, telangiectases and visceral arteriovenous malformations (AVMs). The involvement of the gastrointestinal tract, liver, lung and cerebrum for HHT has been described, whereas little is known about AVMs of the spleen. We report here the radiological findings of a case of a splenic AVM manifested by thrombocytopenia in HHT

  10. Intratracheal administration of fullerene nanoparticles activates splenic CD11b+ cells

    International Nuclear Information System (INIS)

    Ding, Ning; Kunugita, Naoki; Ichinose, Takamichi; Song, Yuan; Yokoyama, Mitsuru; Arashidani, Keiichi; Yoshida, Yasuhiro

    2011-01-01

    Highlights: → Fullerene administration triggered splenic responses. → Splenic responses occurred at different time-points than in the lung tissue. → CD11b + cells were demonstrated to function as responder cells to fullerene. - Abstract: Fullerene nanoparticles ('Fullerenes'), which are now widely used materials in daily life, have been demonstrated to induce elevated pulmonary inflammation in several animal models; however, the effects of fullerenes on the immune system are not fully understood. In the present study, mice received fullerenes intratracheally and were sacrificed at days 1, 6 and 42. Mice that received fullerenes exhibited increased proliferation of splenocytes and increased splenic production of IL-2 and TNF-α. Changes in the spleen in response to fullerene treatment occurred at different time-points than in the lung tissue. Furthermore, fullerenes induced CDK2 expression and activated NF-κB and NFAT in splenocytes at 6 days post-administration. Finally, CD11b + cells were demonstrated to function as responder cells to fullerene administration in the splenic inflammatory process. Taken together, in addition to the effects on pulmonary responses, fullerenes also modulate the immune system.

  11. Spleen and splenic vessel preserving distal pancreatectomy for bifocal PNET in a young patient with MEN1.

    Science.gov (United States)

    Conrad, Claudius; Schwarz, Lilian; Perrier, Nancy; Fleming, Jason B; Katz, Matthew H G; Aloia, Thomas A; Vauthey, Jean-Nicolas; Lee, Jeffrey E

    2016-10-01

    MEN1 patients requiring resection of neuroendocrine tumors (pNET) are frequently young, active patients in whom a minimal access approach minimizes perioperative morbidity and splenic preservation decreases the risk of post-splenectomy sepsis. Laparoscopic spleen preserving distal pancreatectomy can be performed with removal (Warshaw's technique) or preservation of the splenic vessels, the later having a higher rate of successful splenic preservation. This is an active, 16-year-old Jehovah's Witness with trifocal nonfunctioning neuroendocrine tumor in the proximal body and tail of the pancreas as part of MEN1 syndrome. A spleen preserving distal pancreatectomy was performed with the final pathology showing three pNET with low mitotic count and three lymph nodes free of cancer (final stage pT2pN0). This video demonstrates patient and trocar positioning as well as operative tactics for a laparoscopic distal pancreatectomy with preservation of splenic vessels. Intraoperative ultrasound is crucial in assessing pNETs' relation to critical vessels, pancreatic duct, and to exclude synchronous lesions. The video focuses on safe laparoscopic creation of the retropancreatic tunnel and dissecting the pancreas off the splenic vessels using novel energy devises to control direct splenic venous branches into the pancreas. Improvements in laparoscopic techniques and technology have enabled surgeons to preserve the major splenic vessels to avoid splenic infarcts, abscesses and re-operations, and minimize the risk of left-sided portal hypertension. Splenic preservation is particularly important in young MEN1 patients undergoing laparoscopic pancreatectomy for pNET due to the increased risk of overwhelming post-splenectomy sepsis.

  12. Increased Risk of Hemorrhagic and Ischemic Strokes in Patients With Splenic Injury and Splenectomy: A Nationwide Cohort Study.

    Science.gov (United States)

    Lin, Jiun-Nong; Lin, Cheng-Li; Lin, Ming-Chia; Lai, Chung-Hsu; Lin, Hsi-Hsun; Yang, Chih-Hui; Kao, Chia-Hung

    2015-09-01

    The spleen is a crucial organ in humans. Little is known about the association between stroke and splenic injury or splenectomy. The aim of this study was to determine the risk of stroke in patients with splenic injury and splenectomy.A nationwide cohort study was conducted by analyzing the National Health Insurance Research Database in Taiwan. For comparison, control patients were selected and matched with splenic injury patients in a ratio of 4:1 according to age, sex, and the year of hospitalization. We analyzed the risks of stroke using a Cox proportional-hazards regression analysis.A total of 11,273 splenic injury patients, including 5294 splenectomized and 5979 nonsplenectomized patients, and 45,092 control patients were included in this study. The incidence rates of stroke were 8.05, 6.53, and 4.25 per 1000 person-years in splenic injury patients with splenectomy, those without splenectomy, and the control cohort, respectively. Compared with the control cohort, splenic injury patients with splenectomy exhibited a 2.05-fold increased risk of stroke (95% confidence interval [CI] 1.8-2.34), whereas those without splenectomy exhibited a 1.74-fold increased risk (95% CI 1.51-2). Splenectomy entailed an additional 1.21-fold increased risk of stroke compared with nonsplenectomy in patients with splenic injury.This study revealed that splenic injury and splenectomy were significantly associated with an increased risk of hemorrhagic and ischemic strokes. The results of this study may alert physicians and patients to the complications of splenic injury and splenectomy.

  13. Ectopic expression of CXCL13, BAFF, APRIL and LT-β is associated with artery tertiary lymphoid organs in giant cell arteritis.

    Science.gov (United States)

    Ciccia, Francesco; Rizzo, Aroldo; Maugeri, Rosario; Alessandro, Riccardo; Croci, Stefania; Guggino, Giuliana; Cavazza, Alberto; Raimondo, Stefania; Cannizzaro, Alessandra; Iacopino, Domenico Gerardo; Salvarani, Carlo; Triolo, Giovanni

    2017-01-01

    To investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines. Reverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. Finally, expression of CXCL13, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and CCL21 by isolated myofibroblasts was evaluated before and after stimulation with Toll-like receptors (TLRs) agonists and cytokines. ATLOs were observed in the media layer of 60% of patients with GCA in close proximity to high endothelial venules and independently by the age of patients and the presence of atherosclerosis. ATLO formation was also accompanied by the expression of CXCL13, BAFF, a proliferation-inducing ligand (APRIL), lymphotoxin (LT)-β, interleukin (IL)-17 and IL-7, the presence of FDC precursors and of lymphoid conduits. Stimulation of myofibroblasts with TLR agonists and cytokines resulted in the upregulation of BAFF and CXCL13. ATLOs occur in the inflamed arteries of patients with GCA possibly representing the immune sites where immune responses towards unknown arterial wall-derived antigens may be organised. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. Outcome and Prognostic Factors for Canine Splenic Lymphoma Treated by Splenectomy (1995-2011) : A VSSO Retrospective Study

    NARCIS (Netherlands)

    van Stee, Lucinda L; Boston, Sarah E; Singh, Ameet; Romanelli, Giorgio; Rubio-Guzman, Alejandro; Scase, Tim J

    2015-01-01

    OBJECTIVE: To assess the outcome of canine splenic lymphoma treated with splenectomy and to evaluate prognostic factors, including involvement of other sites, adjuvant chemotherapy, and the effect of World Health Organization (WHO) histological classification of canine malignant lymphoma. DESIGN:

  15. Primary splenic angiosarcoma with liver metastasis: A rare neoplasm diagnosed on fine-needle aspiration cytology and cell block immunocytochemistry

    Directory of Open Access Journals (Sweden)

    Saniya Sharma

    2018-01-01

    Full Text Available Primary splenic angiosarcoma is a rare malignant vascular neoplasm of mesenchymal origin. The tumor is highly aggressive and has a high metastatic potential. It is usually diagnosed on histopathological examination of splenectomy specimen. Only few cases of angiosarcoma diagnosed by fine-needle aspiration (FNA cytology alone have been reported in the literature. The cytologic features of angiosarcoma are heterogeneous, however, diagnosis can be suggested by FNA when vasoformative features are present. A 55-year-old female presented with abdominal pain and hepatosplenomegaly. Computed tomography scan revealed a heterogeneous splenic lesion with liver metastases. FNA from the splenic and liver lesions showed moderately pleomorphic tumor cells closely associated with anastomosing vascular channels. Cell block immunocytochemistry (ICC showed tumor cells positive for CD31, CD34, CD68 as well as for CD99. FNA supplemented by cell block ICC can render a definite diagnosis of primary splenic angiosarcoma with liver metastasis.

  16. Splenic torsion and ureteropelvic junction obstruction - a case report; Torcao esplenica e estenose da juncao ureteropielica - relato de um caso

    Energy Technology Data Exchange (ETDEWEB)

    Barroso, Vivian Alvim; Bauab Junior, Tufik [Instituto de Radiodiagnostico Rio Preto, Sao Jose do Rio Preto, SP (Brazil); Barroso Junior, Ubirajara [Universidade Federal de Sao Paulo (UNIFESP), SP (Brazil). Escola Paulista de Medicina. Div. de Urologia

    2000-04-01

    We report a case of a 13-year-old boy with a pedicle splenic torsion associated with ureteropelvic junction obstruction. The symptoms, clinical outcome and the imaging findings are presented. (author)

  17. Blunt hepatic and splenic trauma in children: correlation of a CT injury severity scale with clinical outcome

    International Nuclear Information System (INIS)

    Ruess, L.; Sivit, C.J.; Eichelberger, M.R.; Taylor, G.A.; Bond, S.J.

    1995-01-01

    The purpose of this report is to compare a computed tomography (CT) injury severity scale for hepatic and splenic injury with the following outcome measures: requirement for surgical hemostasis, requirement for blood transfusion and late complications. Sixty-nine children with isolated hepatic injury and 53 with isolated splenic injury were prospectively classified at CT according to extent of parenchymal involvement. Clinical records were reviewed to determine clinical outcome. Ninety-seven children (80%) were managed non-operatively without transfusion. One child with hepatic injury required surgical hemostasis, and 17 (25%) required transfusion of blood. Increasing severity of hepatic injury at CT was associated with progressively greater frequency of transfusion (P = 0.002 by χ 2 -test). One child with splenic injury underwent surgery and eight (15%) required transfusion of blood. Splenic injury grade at CT did not correlate with frequency (P = 0.41 by χ 2 -test) or amount (P = 0.35 by factorial analysis of variance) of transfusion. There was one late complication in the nonsurgical group. A majority of children with hepatic and splenic injury were managed non-operatively without requiring blood transfusion. The severity of injury by CT scan did not correlate with need for surgery. Increasing grade of hepatic injury at CT was associated with increasing frequency of blood transfusion. CT staging was not discriminatory in predicting transfusion requirement in splenic injury. (orig.)

  18. Action of crude Radix Aconiti Lateralis (Fuzi) and its processed products on splenic lymphocytes growth investigated by microcalorimetry

    International Nuclear Information System (INIS)

    Liu, Tiantian; Zhao, Yanling; Wang, Jiabo; Zhou,