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Sample records for anti-human leukocyte antigen

  1. Influences of Pre-formed Donor-Specific Anti-Human Leukocyte Antigen Antibodies in Living-Donor Renal Transplantation: Results With Graft Immunocomplex Capture Fluorescence Analysis.

    Science.gov (United States)

    Nakamura, T; Ushigome, H; Watabe, K; Imanishi, Y; Masuda, K; Matsuyama, T; Harada, S; Koshino, K; Iida, T; Nobori, S; Yoshimura, N

    2017-06-01

    Advances in immunosuppressants enable organ transplantation for sensitized patients. However, influences of pre-formed donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have not been fully understood in renal transplantation (RT). On the other hand, immunocomplex capture fluorescence analysis (ICFA) is a reliable method to detect donor-specific anti-HLA antibodies and HLA antigen complexes. Graft ICFA can detect DSA in an allograft (g-DSA). To elucidate the consequences of pre-formed DSA, 198 patients who underwent living-donor RT were enrolled for this study (observation period: 57.8 ± 34.9 months); 187 patients in the DSA- group (excluding ABO-incompatible cases) and 11 patients in the DSA+ group. Before RT, all DSA+ patients had undergone rituximab administration and plasmapheresis. For a graft ICFA, the biopsy specimen (1 × 10 5 cells) was dissolved, and HLA antigens were captured by anti-HLA beads. Finally, DSA-HLA complexes were detected by means of PE-conjugated anti-human IgG antibodies and analyzed by use of a Luminex system. A ratio (sample/blank beads, mean of fluorescence intensity) was calculated: ≥1.0 was determined as positive g-DSA. There were no significant differences in 5-year graft survival (87.9%/100% in the DSA-/DSA+ groups, respectively). In terms of antibody-mediated rejection (AMR), within 1 month after RT, pathologically determined AMR occurred 3.2% and 63.4% in the DSA- and DSA+ groups, respectively (P < .0001). However, interestingly, more than half of them (57.1%) indicated only subclinical AMR, that is, no fluctuation of S-Cr. As representative of 2 cases of subclinical AMR, g-DSA deposition could be confirmed (1.15 ± 0.04) at 1 hour after reperfusion by graft ICFA. Furthermore, g-DSA shifted to 2.20 ± 0.98 at 3 weeks after transplantation, along with a decline in s-DSA mean of fluorescence intensity (1718-506.5). Although pathologically determined AMR occurred more frequently in pre-formed DSA+ recipients, it

  2. Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets.

    Science.gov (United States)

    Chang, Ying-Jun; Zhao, Xiang-Yu; Xu, Lan-Ping; Zhang, Xiao-Hui; Wang, Yu; Han, Wei; Chen, Huan; Wang, Feng-Rong; Mo, Xiao-Dong; Zhang, Yuan-Yuan; Huo, Ming-Rui; Zhao, Xiao-Su; Y, Kong; Liu, Kai-Yan; Huang, Xiao-Jun

    2015-07-10

    Small studies suggest an association of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) with primary graft failure (GF) following haploidentical stem cell transplantation, but primary graft rejection (GR) was not discriminated from primary poor graft function (PGF). In this study, we aimed to determine the association of DSAs with primary GF, including GR and PGF, in patients who underwent unmanipulated haploidentical blood and marrow transplantation. A total of 345 subjects were prospectively recruited and randomly selected as training group (n = 173) and validation group (n = 172). Patient plasma/serum was screened. For HLA antibody positive samples with a median fluorescent intensity (MFI) >500, DSAs were further tested using a LABScreen Single Antigen Kit (One Lambda). A total of 342 patients (99.1%) achieved sustained myeloid engraftment. The median times to neutrophil engraftment and platelet engraftment were 13 days (range, 8-28 days) and 18 days (range, 6-330 days), respectively. The cumulative incidence of primary GF was 6.4 ± 1.3% and included GR (0.9 ± 0.5%) and PGF (5.5 ± .2%). Of the 345 cases tested, 39 (11.3%) were DSA positive. Multivariate models showed that DSAs (MFI ≥ 10,000) were correlated to primary GR (P < 0.001) and that DSAs (MFI ≥ 2000) were strongly associated with primary PGF (P = 0.005). All patients were classified into three groups for analysis. Group A included cases that were DSA negative and those with a DSA MFI <2000 (n = 316), group B included cases with a 2000 ≤ MFI < 10,000 (n = 19), and group C included cases with a MFI ≥ 10,000 (n = 10). The DSAs were associated with an increased incidence of the primary GF (3.2 vs. 31.6 vs. 60%, for groups A, B, and C, respectively, P < 0.001), transplant-related mortality (TRM) rate (17.2 vs. 14.7 vs. 33.3%, for groups A, B, and C, respectively, P = 0.022), and inferior overall survival (OS, 77.3 vs. 85.3 vs. 44.4%, for groups A, B, and C

  3. Subclinical antibody-mediated rejection due to anti-human-leukocyte-antigen-DR53 antibody accompanied by plasma cell-rich acute rejection in a patient with cadaveric kidney transplantation.

    Science.gov (United States)

    Katsuma, Ai; Yamamoto, Izumi; Komatsuzaki, Yo; Niikura, Takahito; Kawabe, Mayuko; Okabayashi, Yusuke; Yamakawa, Takafumi; Katsumata, Haruki; Nakada, Yasuyuki; Kobayashi, Akimitsu; Tanno, Yudo; Miki, Jun; Yamada, Hiroki; Ohkido, Ichiro; Tsuboi, Nobuo; Yamamoto, Hiroyasu; Yokoo, Takashi

    2016-07-01

    A 56-year-old man who had undergone cadaveric kidney transplantation 21 months earlier was admitted to our hospital for a protocol biopsy; he had a serum creatinine level of 1.2 mg/dL and no proteinuria. Histological features showed two distinct entities: (i) inflammatory cell infiltration, in the glomerular and peritubular capillaries and (ii) focal, aggressive tubulointerstitial inflammatory cell infiltration, predominantly plasma cells, with mild tubulitis (Banff 13 classification: i2, t1, g2, ptc2, v0, ci1, ct1, cg0, cv0). Immunohistological studies showed mildly positive C4d immunoreactivity in the peritubular capillaries. The patient had donor specific antibody to human-leucocyte-antigen-DR53. We diagnosed him with subclinical antibody-mediated rejection accompanied by plasma cell-rich acute rejection. Both antibody-mediated rejection due to anti- human-leucocyte-antigen -DR53 antibodies and plasma cell-rich acute rejection are known to be refractory and have a poor prognosis. Thus, we started plasma exchange with intravenous immunoglobulin and rituximab for the former and 3 days of consecutive steroid pulse therapy for the latter. Three months after treatment, a follow-up allograft biopsy showed excellent responses to treatment for both histological features. This case report considers the importance of an early diagnosis and appropriate intervention for subclinical antibody-mediated rejection due to donor specific antibody to human-leucocyte-antigen-DR53 and plasma cell-rich acute rejection. © 2016 Asian Pacific Society of Nephrology.

  4. Monoclonal antibodies against rat leukocyte surface antigens

    NARCIS (Netherlands)

    van den Berg, T. K.; Puklavec, M. J.; Barclay, A. N.; Dijkstra, C. D.

    2001-01-01

    Monoclonal antibodies have proven to be powerful tools for studying the properties of leukocyte surface antigens and the cells that express them. In the past decades many monoclonal antibodies (mAb) for identifying the different rat leukocyte surface antigens have been described. A list of mAb is

  5. Classification of human leukocyte antigen (HLA) supertypes

    DEFF Research Database (Denmark)

    Wang, Mingjun; Claesson, Mogens H

    2014-01-01

    Identification of new antigenic peptides, derived from infectious agents or cancer cells, which bind to human leukocyte antigen (HLA) class I and II molecules, is of importance for the development of new effective vaccines capable of activating the cellular arm of the immune response. However......, the barrier to the development of peptide-based vaccines with maximum population coverage is that the restricting HLA genes are extremely polymorphic resulting in a vast diversity of peptide-binding HLA specificities and a low population coverage for any given peptide-HLA specificity. One way to reduce...... this complexity is to group thousands of different HLA molecules into several so-called HLA supertypes: a classification that refers to a group of HLA alleles with largely overlapping peptide binding specificities. In this chapter, we focus on the state-of-the-art classification of HLA supertypes including HLA...

  6. Human leukocyte antigen (HLA) polymorphism and type 1 diabetes ...

    African Journals Online (AJOL)

    Insulin-dependent diabetes mellitus or type 1 diabetes is an autoimmune multifactorial disease which has a great socio-economic impact. In Morocco, less is known about the contribution of Human leukocyte antigen (HLA) alleles to type 1 diabetes susceptibility. Our study focused on evaluating the distribution of class II ...

  7. Human leukocyte antigen-A genotype as a predictor of ...

    African Journals Online (AJOL)

    Aim of the study: To screen for CMV infection among solid organ transplantation patients using monitoring of CMV phosphoprotein 65 (CMVpp65) antigenemia and to detect if CMV infection and disease were associated with certain human leukocyte antigen (HLA)-A locus genotypes among the studied group. Subjects and ...

  8. Human leukocyte antigen-E alleles and expression in patients with serous ovarian cancer

    OpenAIRE

    Zheng, Hui; Lu, Renquan; Xie, Suhong; Wen, Xuemei; Wang, Hongling; Gao, Xiang; Guo, Lin

    2015-01-01

    Human leukocyte antigen-E (HLA-E) is one of the most extensively studied non-classical MHC class I molecules that is almost non-polymorphic. Only two alleles (HLA-E*0101 and HLA-E*0103) are found in worldwide populations, and suggested to be functional differences between these variants. The HLA-E molecule can contribute to the escape of cancer cells from host immune surveillance. However, it is still unknown whether HLA-E gene polymorphisms might play a role in cancer immune escape. To explo...

  9. Human leukocyte antigen-G within the male reproductive system

    DEFF Research Database (Denmark)

    Hviid, Thomas Vauvert F

    2015-01-01

    In sexual reproduction in humans, a man has a clear interest in ensuring that the immune system of his female partner accepts the semi-allogenic fetus. Increasing attention has been given to soluble immunomodulatory molecules in the seminal fluid as one mechanism of ensuring this, possibly by “pr...... plasma may even be associated with the chance of pregnancy in couples, where the male partner has reduced semen quality. More studies are needed to verify these preliminary findings....... by “priming” the woman’s immune system before conception and at conception. Recent studies have demonstrated the presence of the immunoregulatory and tolerance-inducible human leukocyte antigen (HLA)-G in the male reproductive organs. The expression of HLA-G in the blastocyst and by extravillous trophoblast...

  10. Human leukocyte antigen (HLA)-G during pregnancy part II

    DEFF Research Database (Denmark)

    Dahl, Mette; Klitkou, Louise; Christiansen, Ole B

    2015-01-01

    Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurrent...... miscarriage. Levels of soluble HLA-G (sHLA-G) in blood plasma from non-pregnant donors seem to be associated with these polymorphisms. In the current study, we have genotyped 246 mothers and their offspring for HLA-G polymorphisms in the 3'-untranslated region (3'UTR) and measured sHLA-G in maternal blood...... plasma samples from gestational week 20 and at term, as well as in fetal umbilical cord blood samples. This is the first large study simultaneously performing HLA-G genotyping of mother and offspring and measuring sHLA-G in both maternal and umbilical cord blood. The results showed that increasing...

  11. Evaluation of ascitic soluble human leukocyte antigen-G for distinguishing malignant ascites from benign ascites.

    Science.gov (United States)

    Sun, Juan; Chang, Yan-Xiang; Niu, Chun-Yan

    2017-11-01

    The overexpression of soluble human leukocyte antigen-G is associated with malignant tumours. The purpose of our study was to detect soluble human leukocyte antigen-G concentrations in ascites and to evaluate the value of ascitic soluble human leukocyte antigen-G for the diagnosis of malignant ascites. Enzyme-linked immunosorbent assay was used to detect soluble human leukocyte antigen-G levels in 64 patients with malignant ascites and 30 patients with benign ascites. Receiver operating characteristic curves were used to evaluate the diagnostic efficacy of ascitic soluble human leukocyte antigen-G for the detection of malignant ascites. Ascitic soluble human leukocyte antigen-G levels were significantly higher in the malignant ascites group than in the benign ascites group (20.718 ± 3.215 versus 12.467 ± 3.678 µg/L, t = 7.425, p G was 0.957 (95% confidence interval, 0.872-0.992). At a cut-off value of 19.60 µg/L, the sensitivity and specificity of ascitic soluble human leukocyte antigen-G were 87.5% (95% confidence interval, 71.0%-96.5%) and 100% (95% confidence interval, 88.4%-100%), respectively. With respect to area under the receiver operating characteristic curve, sensitivity and specificity, ascitic carcinoembryonic antigen (0.810, 68.75% and 83.33%, respectively) and carbohydrate antigen 19-9 (0.710, 65.63% and 70%, respectively) significantly differed (all p G was 75%, which was higher than the corresponding rates for ascitic carcinoembryonic antigen (31.25%) and carbohydrate antigen 19-9 (6.25%; both p G exhibited good performance for diagnosing malignant ascites, and particularly those that were cytology-negative and biopsy-positive.

  12. Swine Leukocyte Antigen Class II Is a Xenoantigen.

    Science.gov (United States)

    Ladowski, Joseph M; Reyes, Luz M; Martens, Gregory R; Butler, James R; Wang, Zheng-Yu; Eckhoff, Devin E; Tector, Matthew; Tector, A Joseph

    2018-02-01

    Over 130 000 patients in the United States alone need a lifesaving organ transplant. Genetically modified porcine organs could resolve the donor organ shortage, but human xenoreactive antibodies destroy pig cells and are the major barrier to clinical application of xenotransplantation. The objective of this study was to determine whether waitlisted patients possess preformed antibodies to swine leukocyte antigen (SLA) class II, homologs of the class II HLA. Sera from people currently awaiting solid organ transplant were tested for IgG binding to class II SLA proteins when expressed on mammalian cells. Pig fibroblasts were made positive by transfection with the class II transactivator. As a second expression system, transgenes encoding the alpha and beta chains of class II SLA were transfected into human embryonic kidney cells. Human sera containing IgG specific for class II HLA molecules exhibited greater binding to class II SLA positive cells than to SLA negative cells. Sera lacking antibodies against class II HLA showed no change in binding regardless of the presence of class II SLA. These antibodies could recognize either SLA-DR or SLA-DQ complexes. Class II SLA proteins may behave as xenoantigens for people with humoral immunity toward class II HLA molecules.

  13. CD Nomenclature 2015: Human Leukocyte Differentiation Antigen Workshops as a Driving Force in Immunology

    Czech Academy of Sciences Publication Activity Database

    Engel, P.; Boumsell, L.; Balderas, R.; Gattei, V.; Hořejší, Václav; Jin, B.Q.; Malavasi, F.; Mortari, F.; Schwartz-Albiez, R.; Stockinger, H.; van Zelm, M.C.; Zola, H.; Clark, G.

    2015-01-01

    Roč. 165, č. 10 (2015), s. 4555-4563 ISSN 0022-1767 Institutional support: RVO:68378050 Keywords : CD nomenclature, , * leukocyte antigens * HLDA workshop Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.985, year: 2015

  14. Human Leukocyte Antigen Mismatch and Steroid Maintenance in Kidney Transplantation.

    Science.gov (United States)

    Chopra, B; Sureshkumar, K K

    2015-12-01

    This study aimed to analyze the impact of chronic steroid maintenance (CSM) vs early steroid withdrawal (ESW) in kidney transplant recipients (KTRs) stratified by the level of human leukocyte antigen (HLA) mismatch. Adult KTRs between 2001 and 2011 who received antibody induction followed by calcineurin inhibitor (CNI)/mycophenolate mofetil (MMF) maintenance with or without steroid were identified from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database. Using multivariate analysis, graft and patient outcomes were compared for CSM vs ESW in KTRs stratified by HLA mismatch levels separately for depleting and nondepleting antibody-induced patients. Among 43,096 study patients, 26,582 received depleting induction (zero HLA mismatch = 5324 [CSM = 3416; ESW = 1908]; 5-6 HLA mismatch = 21,258 [CSM = 13,739; ESW = 7519]) and 16,514 patients received nondepleting induction (zero HLA mismatch = 4109 [CSM = 3453; ESW = 656]; 5-6 HLA mismatch = 12,405 [CSM = 10,890; ESW = 1515]). Adjusted graft failure risks for CSM vs ESW groups for zero HLA mismatch patients were as follows: HR 1.13, P = .07 (depleting induction); HR 1.30, P = .01 (nondepleting induction). Graft outcomes were similar for CSM vs ESW in 5-6 HLA mismatch groups for both induction types. Adjusted patient death risks were significantly higher for CSM vs ESW with depleting (HR 1.3, P = .003) and nondepleting (HR 1.45, P = .006) induction in zero HLA mismatch patients and only with depleting induction in 5-6 HLA mismatch groups (HR 1.16, P mismatch in KTRs selected for antibody induction and CNI/MMF maintenance. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Imputing amino acid polymorphisms in human leukocyte antigens.

    Directory of Open Access Journals (Sweden)

    Xiaoming Jia

    Full Text Available DNA sequence variation within human leukocyte antigen (HLA genes mediate susceptibility to a wide range of human diseases. The complex genetic structure of the major histocompatibility complex (MHC makes it difficult, however, to collect genotyping data in large cohorts. Long-range linkage disequilibrium between HLA loci and SNP markers across the major histocompatibility complex (MHC region offers an alternative approach through imputation to interrogate HLA variation in existing GWAS data sets. Here we describe a computational strategy, SNP2HLA, to impute classical alleles and amino acid polymorphisms at class I (HLA-A, -B, -C and class II (-DPA1, -DPB1, -DQA1, -DQB1, and -DRB1 loci. To characterize performance of SNP2HLA, we constructed two European ancestry reference panels, one based on data collected in HapMap-CEPH pedigrees (90 individuals and another based on data collected by the Type 1 Diabetes Genetics Consortium (T1DGC, 5,225 individuals. We imputed HLA alleles in an independent data set from the British 1958 Birth Cohort (N = 918 with gold standard four-digit HLA types and SNPs genotyped using the Affymetrix GeneChip 500 K and Illumina Immunochip microarrays. We demonstrate that the sample size of the reference panel, rather than SNP density of the genotyping platform, is critical to achieve high imputation accuracy. Using the larger T1DGC reference panel, the average accuracy at four-digit resolution is 94.7% using the low-density Affymetrix GeneChip 500 K, and 96.7% using the high-density Illumina Immunochip. For amino acid polymorphisms within HLA genes, we achieve 98.6% and 99.3% accuracy using the Affymetrix GeneChip 500 K and Illumina Immunochip, respectively. Finally, we demonstrate how imputation and association testing at amino acid resolution can facilitate fine-mapping of primary MHC association signals, giving a specific example from type 1 diabetes.

  16. Epidemiology of human leukocyte antigens among omani population.

    Science.gov (United States)

    Al Salmi, Issa; Metry, Abdul Massiah; Al Ismaili, Faisal; Hola, Alan; Shaheen, Faissal; Fakhoury, Hana; Hannawi, Suad

    2017-01-01

    Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA) typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH) from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation) years for the cohort were 33.2 (13.0). Males constituted 56.3% (490) while females constituted 43.7% (380). Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%), followed by HLA A11 (9.4%), and A32 (8.1%). Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%), followed by HLA-B-35 (13.6%), and HLA-B8 (7.9%). Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%). This was followed by HLA-DRB1*03 (14.57%) and HLA-DRB1*11 (9.48%). While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%). This was followed by allele HLA-DQB1*02 (26.48%) and HLA-DQB1*03 (17.18%). This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

  17. Epidemiology of human leukocyte antigens among omani population

    Directory of Open Access Journals (Sweden)

    Issa Al Salmi

    2017-01-01

    Full Text Available Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation years for the cohort were 33.2 (13.0. Males constituted 56.3% (490 while females constituted 43.7% (380. Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%, followed by HLA A11 (9.4%, and A32 (8.1%. Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%, followed by HLA-B-35 (13.6%, and HLA-B8 (7.9%. Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%. This was followed by HLA-DRB1*03 (14.57% and HLA-DRB1*11 (9.48%. While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%. This was followed by allele HLA-DQB1*02 (26.48% and HLA-DQB1*03 (17.18%. This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

  18. De nonklassiske humant leukocyt-antigen (HLA)-vaevstyper--fra implantation til transplantation

    DEFF Research Database (Denmark)

    Hviid, Thomas Vauvert F

    2006-01-01

    The classical and extremely polymorphic human leukocyte antigens (HLA) classes Ia and II have been studied in great detail and have significant importance in organ transplantation, autoimmune diseases and presentation of antigen peptides. However, in the human major histocompatibility complex (MHC...... of rejection episodes in heart and kidney/liver transplants....

  19. Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition

    Energy Technology Data Exchange (ETDEWEB)

    Archbold, Julia K.; Macdonald, Whitney A.; Gras, Stephanie; Ely, Lauren K.; Miles, John J.; Bell, Melissa J.; Brennan, Rebekah M.; Beddoe, Travis; Wilce, Matthew C.J.; Clements, Craig S.; Purcell, Anthony W.; McCluskey, James; Burrows, Scott R.; Rossjohn, Jamie; (Monash); (Queensland Inst. of Med. Rsrch.); (Melbourne)

    2009-07-10

    Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell-mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR-HLA-B*4405EENLLDFVRF complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes.

  20. A melanoma immune response signature including Human Leukocyte Antigen-E.

    Science.gov (United States)

    Tremante, Elisa; Ginebri, Agnese; Lo Monaco, Elisa; Benassi, Barbara; Frascione, Pasquale; Grammatico, Paola; Cappellacci, Sandra; Catricalà, Caterina; Arcelli, Diego; Natali, Pier Giorgio; Di Filippo, Franco; Mottolese, Marcella; Visca, Paolo; Benevolo, Maria; Giacomini, Patrizio

    2014-01-01

    Paired cultures of early-passage melanoma cells and melanocytes were established from metastatic lesions and the uninvolved skin of five patients. In this stringent autologous setting, cDNA profiling was used to analyze a subset of 1477 genes selected by the Gene Ontology term 'immune response'. Human Leukocyte Antigen E (HLA-E) was ranked 19th among melanoma-overexpressed genes and was embedded in a transformation signature including its preferred peptide ligand donors HLA-A, HLA-B, HLA-C, and HLA-G. Mostly undetectable in normal skin and 39 nevi (including rare and atypical lesions), HLA-E was detected by immunohistochemistry in 17/30 (57%) and 32/48 (67%) primary and metastatic lesions, respectively. Accordingly, surface HLA-E was higher on melanoma cells than on melanocytes and protected the former (6/6 cell lines) from lysis by natural killer (NK) cells, functionally counteracting co-expressed triggering ligands. Although lacking HLA-E, melanocytes (4/4 cultures) were nevertheless (and surprisingly) fully protected from NK cell lysis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Serum carcinoembryonic antigen is positively associated with leukocyte count in Korean adults.

    Science.gov (United States)

    Kwon, Yu-Jin; Lee, Hye-Sun; Shim, Jae-Yong; Lee, Yong-Jae

    2017-06-27

    Emerging evidence shows that serum carcinoembryonic antigen (CEA) levels may modestly be increased in non-neoplastic conditions such as cardiometabolic diseases, which are increasingly being seen as inflammatory diseases. Leukocyte count is widely evaluated marker of inflammation in clinical practice and a useful predictor of cardiometabolic disease. In this study, we aimed to determine the relationship between serum CEA levels and leukocyte counts in Korean adults. This cross-sectional study included a total of 19 834 individuals enrolled from a health promotion center between November 2006 and July 2010. Multiple linear regression analysis was performed to investigate the association between serum CEA levels and leukocyte counts after adjusting for confounding variables. According to both stepwise-method and enter-method multiple linear regression analyses, serum CEA levels were positively and independently associated with leukocyte counts (Pleukocyte counts in Korean adults. Our results suggested that an elevated serum CEA level may reflect chronic inflammation state. © 2017 Wiley Periodicals, Inc.

  2. Familial occurrence of subacute thyroiditis associated with human leukocyte antigen-B35

    NARCIS (Netherlands)

    Kramer, AB; Roozendaal, C; Dullaart, RPF

    Subacute thyroiditis (SAT) is a spontaneously remitting inflammatory disorder of the thyroid, associated with human leukocyte antigen (HLA)-B35, and may be virally induced in genetically predisposed individuals. A 57-year-old Caucasian man presented with symptoms of hyperthyroidism as well as

  3. Phylogenetic analysis of the swine leukocyte antigen - 2 gene for Korean native pigs

    Science.gov (United States)

    The objective of this study was to investigate genetic distances of the SLA-2 gene, to characterize SLA-2 alleles, and to provide basic genetic information of Korean pigs. The swine leukocyte antigen - 2 (SLA-2) gene in the MHC classical region was cloned with spleen tissues from Korean native pigs ...

  4. Association of human leukocyte antigen class I antigens in Iranian patients with pemphigus vulgaris.

    Science.gov (United States)

    Mortazavi, Hossein; Amirzargar, Ali Akbar; Esmaili, Nafiseh; Toofan, Hesam; Ehsani, Amir Hooshang; Hosseini, Seyed Hamed; Rezaei, Nima

    2013-04-01

    There are a limited number of reports indicating the role of human leukocyte antigen (HLA) class I alleles in pemphigus vulgaris. This study was designed to highlight the association of HLA class I alleles with pemphigus vulgaris in Iran. Fifty patients with pemphigus vulgaris, diagnosed based on clinical, histological and direct immunofluorescence findings were enrolled into this study. The control group consisted of 50 healthy, age- and sex-matched individuals. HLA typing of class I (A, B and C alleles) was carried out using polymerase chain reaction based on the sequence-specific primer method. This study showed the higher frequency of HLA-B*44:02 (P = 0.007), -C*04:01 (P pemphigus vulgaris was significantly lower than the controls. Regarding the linkage disequilibrium between HLA class I alleles, the HLA-A*03:01, -B*51:01, -C*16:02 haplotype (4% vs 0%, P = 0.04) is suggested to be a predisposing factor, whereas HLA-A*26:01, -B*38, -C*12:03 haplotype (0% vs 6%, P = 0.01) is suggested to be a protective factor. In conclusion, it is suggested that HLA-B*44:02, -C*04:01, -C*15:02 alleles and HLA-A*03:01, -B*51:01, -C*16:02 haplotype are susceptibility factors for development of pemphigus vulgaris in the Iranian population, while HLA-C*06:02, -C*18:01 alleles and HLA-A*26:01, -B*38, -C*12:03 haplotype may be considered as protective alleles. © 2013 Japanese Dermatological Association.

  5. The Many Faces of Human Leukocyte Antigen-G

    DEFF Research Database (Denmark)

    Dahl, Mette; Djurisic, Snezana; Hviid, Thomas Vauvert F

    2014-01-01

    . Its immunomodulatory functions involve interactions with different immune cells and possibly regulation of cell migration during placental development. Recent findings include HLA-G contributions from the father and the fetus itself. Much effort has been put into clarifying the role of HLA-G during......Pregnancy is an immunological paradox, where fetal antigens encoded by polymorphic genes inherited from the father do not provoke a maternal immune response. The fetus is not rejected as it would be theorized according to principles of tissue transplantation. A major contribution to fetal tolerance...

  6. Human leukocyte antigen class II genes and Helicobacter pylori infection: does genotype overwhelm environmental exposure?

    Science.gov (United States)

    Russo, Antonio; Maconi, Giovanni; Lombardo, Claudia; Settesoldi, Daniela; Ferrari, Daniela; Ravagnani, Fernando; Andreola, Salvatore; Pizzetti, Paolo; Spinelli, Pasquale; Bertario, Lucio

    2003-09-01

    We investigated associations between human leukocyte antigen class II genes, environmental exposures, and Helicobacter pylori infection. Sixty-eight subjects with histologically confirmed H. pylori and intestinal metaplasia (cases) and 70 healthy subjects without H. pylori (controls) matched for age, sex, and year of birth were included in this study. All patients answered a detailed questionnaire designed to collect sociodemographic characteristics, smoking, alcohol drinking, and dietary habits. Human leukocyte antigen class II genes were typed with genomic DNA. The cytotoxins CagA and VacA were investigated with serology. Odds ratios and corresponding 95% confidence intervals were estimated from multivariate conditional logistic regression. Multiple correspondence analysis was used to represent the interrelationships of a multiple contingency table. Human leukocyte antigen DRB1, DQA1, and DQB1 genotypes were not significantly associated with H. pylori infection and intestinal metaplasia. No significant association with blood group or Lewis antigen system was found. However, multiple correspondence analysis clearly associated H. pylori with environmental exposure: the control group largely consumed olive oil, fresh fruits, and vegetables and histories of never or formerly smoking and the case group (those positive for H. pylori and metaplasia) largely consumed eggs, meat and butter and had histories of smoking cigarettes. These findings suggested that H. pylori infection is not influenced by a genetic compound and confirmed the relevance of environmental exposure.

  7. Human leukocyte antigen-G polymorphism in relation to expression, function, and disease

    DEFF Research Database (Denmark)

    Larsen, Margit Hørup; Hviid, Thomas

    2009-01-01

    Human leukocyte antigen-G (HLA-G) is a nonclassical class Ib molecule belonging to the major histocompatibility complex. HLA-G appears to play a role in the suppression of immune responses and contribute to long-term immune escape or tolerance. The focus of this review is polymorphism in the HLA......-G gene and protein and its possible importance in expression, function, and disease associations....

  8. A computational method for identification of vaccine targets from protein regions of conserved human leukocyte antigen binding

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Simon, Christian; Kudahl, Ulrich J.

    2015-01-01

    Background: Computational methods for T cell-based vaccine target discovery focus on selection of highly conserved peptides identified across pathogen variants, followed by prediction of their binding of human leukocyte antigen molecules. However, experimental studies have shown that T cells ofte...... or proteome using human leukocyte antigen binding predictions and made a web-accessible software implementation freely available at http://met-hilab.cbs.dtu.dk/blockcons/....

  9. Current trends in platelet transfusions practice: The role of ABO-RhD and human leukocyte antigen incompatibility

    Directory of Open Access Journals (Sweden)

    Serena Valsami

    2015-01-01

    Full Text Available Platelet transfusions have contributed to the revolutionary modern treatment of hypoproliferative thrombocytopenia. Despite the long-term application of platelet transfusion in therapeutics, all aspects of their optimal use (i.e., in cases of ABO and/or Rh (D incompatibility have not been definitively determined yet. We reviewed the available data on transfusion practices and outcome in ABO and RhD incompatibility and platelet refractoriness due to anti-human leukocyte antigen (HLA antibodies. Transfusion of platelets with major ABO-incompatibility is related to reduced posttransfusion platelet (PLT count increments, compared to ABO-identical and minor, but still are equally effective in preventing clinical bleeding. ABO-minor incompatible transfusions pose the risk of an acute hemolytic reaction of the recipient that is not always related to high anti-A, B donor titers. ABO-identical PLT transfusion seems to be the most effective and safest therapeutic strategy. Exclusive ABO-identical platelet transfusion policy could be feasible, but alternative approaches could facilitate platelet inventory management. Transfusion of platelets from RhD positive donors to RhD negative patients is considered to be effective and safe though is associated with low rate of anti-D alloimmunization due to contaminating red blood cells. The prevention of D alloimmunization is recommended only for women of childbearing age. HLA alloimmunization is a major cause of platelet refractoriness. Managing patients with refractoriness with cross-matched or HLA-matched platelets is the current practice although data are still lacking for the efficacy of this practice in terms of clinical outcome. Leukoreduction contributes to the reduction of both HLA and anti-D alloimmunization.

  10. Severe neonatal neutropenia due to anti-human leucocyte antigen B49 alloimmunization only: a case report.

    Science.gov (United States)

    Tomicić, M; Starcević, M; Bux, J; Zach, V; Hundrić-Haspl, Z; Drazić, V; Grahovac, B

    2003-08-01

    Alloimmune neonatal neutropenia (ANN) is a rare but potentially life-threatening disorder of neonates. Demonstration of alloantibodies against granulocyte-specific antigens shared by neonatal and paternal granulocytes in the maternal serum is essential in the diagnosis of ANN. In contrast to granulocyte-specific alloantibodies, the significance of human leucocyte antigen (HLA) class I antibodies for ANN is still a matter of debate. We report on a case of severe isolated and prolonged neutropenia due to anti-HLA B49 alloimmunization only. Immediately after birth, severe, isolated neutropenia was observed and lasted for up to 2 months. Results of serologic testing showed only anti-HLA B49 antibodies in the maternal and neonate's sera. HLA typing showed HLA class I (B49) incompatibility between the mother and the child. Granulocyte-specific antibodies were not detected. Adsorption of the maternal serum with HLA B49-bearing platelets removed serum reactivity with paternal neutrophils. Our results support the idea that certain HLA class I antibodies can induce ANN.

  11. Modulation of the major histocompatibility complex class II-associated peptide repertoire by human histocompatibility leukocyte antigen (HLA)-DO

    NARCIS (Netherlands)

    van Ham, M.; van Lith, M.; Lillemeier, B.; Tjin, E.; Grüneberg, U.; Rahman, D.; Pastoors, L.; van Meijgaarden, K.; Roucard, C.; Trowsdale, J.; Ottenhoff, T.; Pappin, D.; Neefjes, J.

    2000-01-01

    Antigen presentation by major histocompatibility complex class II molecules is essential for antibody production and T cell activation. For most class II alleles, peptide binding depends on the catalytic action of human histocompatibility leukocyte antigens (HLA)-DM. HLA-DO is selectively expressed

  12. Human histocompatibility leukocyte antigen (HLA)-DM edits peptides presented by HLA-DR according to their ligand binding motifs

    NARCIS (Netherlands)

    van Ham, S. M.; Grüneberg, U.; Malcherek, G.; Bröker, I.; Melms, A.; Trowsdale, J.

    1996-01-01

    Human histocompatibility leukocyte antigen (HLA)-DM is a facilitator of antigen presentation via major histocompatibility complex (MHC) class II molecules. In the absence of HLA-DM, MHC class II molecules do not present natural peptides, but tend to remain associated with class II-associated

  13. Anti-Human Platelet Antigen-1a Immunoglobulin G Preparation Intended to Prevent Fetal and Neonatal Alloimmune Thrombocytopenia.

    Directory of Open Access Journals (Sweden)

    Ying-Jan Weng

    Full Text Available Fetal and neonatal alloimmune thrombocytopenia (FNAIT is a severe disease that is caused by maternal alloantibodies generated during pregnancy or at delivery as a result of incompatibility between maternal and fetal human platelet antigens (HPAs inherited from the father. Antibody-mediated immune suppression using anti-HPA-1a immunoglobulins is thought to be able to prevent FNAIT caused by HPA-1a. A fractionation process to prepare anti-HPA-1a immunoglobulin (Ig G (IgG from human plasma was therefore developed. Anti-HPA-1a plasma was obtained from volunteer mothers who underwent alloimmunization against HPA-1a during a previous pregnancy. Plasma was cryoprecipitated and the supernatant treated with caprylic acid and solvent/detergent (S/D, purified by chromatography, nanofiltered, concentrated, and sterile-filtered. The anti-HPA-1a immunoglobulin fraction was characterized for purity and safety. PAK12 and quantitative monoclonal antibody immobilization of platelet antigen (MAIPA assays were used to detect anti-HPA-1a IgG. Hepatitis C virus (HCV removal during nanofiltration was assessed by spiking experiments, using cell culture-derived reporter HCV and luciferase analysis. The caprylic acid treatment precipitated non-Ig proteins yielding a 90% pure Ig supernatant. S-HyperCel chromatography of the S/D-treated supernatant followed by HyperCel STAR AX provided high IgG recovery (>80% and purity (>99.5%, and efficient IgA and IgM removal. Concentrations of complement factors C3 and C4 were < 0.5 and < 0.4 mg/dL, respectively. The final IgG could be nanofiltered on Planova 20N under conditions removing more than 3 log HCV infectivity to baseline mock infection level, and concentrated to ca. 30 g/L. Proteolytic activity and thrombin generation were low in the final fraction. The Pak12 and MAIPA assays showed good recovery of anti-HPA-1a throughout the process. Clinical-grade HPA-1a IgG can be prepared using a process compliant with current quality

  14. Anti-Human Platelet Antigen-1a Immunoglobulin G Preparation Intended to Prevent Fetal and Neonatal Alloimmune Thrombocytopenia.

    Science.gov (United States)

    Weng, Ying-Jan; Husebekk, Anne; Skogen, Björn; Kjaer, Mette; Lin, Liang-Tzung; Burnouf, Thierry

    2016-01-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a severe disease that is caused by maternal alloantibodies generated during pregnancy or at delivery as a result of incompatibility between maternal and fetal human platelet antigens (HPAs) inherited from the father. Antibody-mediated immune suppression using anti-HPA-1a immunoglobulins is thought to be able to prevent FNAIT caused by HPA-1a. A fractionation process to prepare anti-HPA-1a immunoglobulin (Ig) G (IgG) from human plasma was therefore developed. Anti-HPA-1a plasma was obtained from volunteer mothers who underwent alloimmunization against HPA-1a during a previous pregnancy. Plasma was cryoprecipitated and the supernatant treated with caprylic acid and solvent/detergent (S/D), purified by chromatography, nanofiltered, concentrated, and sterile-filtered. The anti-HPA-1a immunoglobulin fraction was characterized for purity and safety. PAK12 and quantitative monoclonal antibody immobilization of platelet antigen (MAIPA) assays were used to detect anti-HPA-1a IgG. Hepatitis C virus (HCV) removal during nanofiltration was assessed by spiking experiments, using cell culture-derived reporter HCV and luciferase analysis. The caprylic acid treatment precipitated non-Ig proteins yielding a 90% pure Ig supernatant. S-HyperCel chromatography of the S/D-treated supernatant followed by HyperCel STAR AX provided high IgG recovery (>80%) and purity (>99.5%), and efficient IgA and IgM removal. Concentrations of complement factors C3 and C4 were < 0.5 and < 0.4 mg/dL, respectively. The final IgG could be nanofiltered on Planova 20N under conditions removing more than 3 log HCV infectivity to baseline mock infection level, and concentrated to ca. 30 g/L. Proteolytic activity and thrombin generation were low in the final fraction. The Pak12 and MAIPA assays showed good recovery of anti-HPA-1a throughout the process. Clinical-grade HPA-1a IgG can be prepared using a process compliant with current quality requirements

  15. Analysis of human leukocyte antigen genotypes in pemphigus with antidesmoglein antibody profile shift

    Directory of Open Access Journals (Sweden)

    Seiko Mitsui

    2016-12-01

    Full Text Available In particular pemphigus cases, the phenotypic transition between pemphigus vulgaris and pemphigus foliaceus is observed with the change of antibody profile between anti-desmoglein (Dsg 3 antibodies and anti-Dsg1 antibodies. In this study, we examined human leukocyte antigen (HLA genotypes of four pemphigus patients who presented with the phenotypic transition and/or antibody profile shift. Two out of four patients possessed a DRB1*0405-DQB1*0401, and two out of four patients possessed a DRB1*1405-DQB1*0503. These alleles might be associated with the development of phenotypic transition and antibody profile shift.

  16. Human Leukocyte Antigen-G (HLA-G) Polymorphism and Expression in Breast Cancer Patients

    OpenAIRE

    Jeong, Seri; Park, Seho; Park, Byeong-Woo; Park, Younhee; Kwon, Oh-Joong; Kim, Hyon-Suk

    2014-01-01

    Human leukocyte antigen-G (HLA-G) is known to be implicated in a tumor-driven immune escape mechanism in malignancies. The purpose of this study was to investigate HLA-G polymorphism and expression in breast cancer. HLA-G alleles were determined by direct DNA sequencing procedures from blood samples of 80 breast cancer patients and 80 healthy controls. Soluble HLA-G (sHLA-G) was measured by enzyme-linked immunosorbent assay (ELISA) from serum specimens. HLA-G expression in breast cancer lesio...

  17. Development of Anti-Human Mesothelin-Targeted Chimeric Antigen Receptor Messenger RNA-transfected Peripheral Blood Lymphocytes for Ovarian Cancer Therapy.

    Science.gov (United States)

    Hung, Chien-Fu; Xu, Xuequn; Li, Linhong; Ma, Ying; Jin, Qiu; Viley, Angelia; Allen, Cornell; Natarajan, Pachai; Shivakumar, Rama; Peshwa, Madhusudan V; Emens, Leisha A

    2018-04-02

    CD19-targeted chimeric antigen receptor (CAR) engineered T/natural killer (NK)-cell therapies can result in durable clinical responses in B-cell malignancies. However, CAR-based immunotherapies have been much less successful in solid cancers, in part due to "on-target off-tumor" toxicity related to expression of target tumor antigens on normal tissue. Based on preliminary observations of safety and clinical activity in proof-of-concept clinical trials, tumor antigen-specific messenger RNA (mRNA) CAR transfection into selected, activated, and expanded T/NK cells may permit prospective control of "on-target off-tumor" toxicity. To develop a commercial product for solid tumors, mesothelin was selected as an antigen target based on its association with poor prognosis and overexpression in multiple solid cancers. It was hypothesized that selecting, activating, and expanding cells ex vivo prior to mRNA CAR transfection would not be necessary, thus simplifying the complexity and cost of manufacturing. Now, the development of anti-human mesothelin mRNA CAR transfected peripheral blood lymphocytes (CARMA-hMeso) is reported, demonstrating the manufacture and cryopreservation of multiple cell aliquots for repeat administrations from a single human leukapheresis. A rapid, automated, closed system for cGMP-compliant transfection of mRNA CAR in up to 20 × 10 9 peripheral blood lymphocytes was developed. Here we show that CARMA-hMeso cells recognize and lyse tumor cells in a mesothelin-specific manner. Expression of CAR was detectable over approximately 7 days in vitro, with a progressive decline of CAR expression that appears to correlate with in vitro cell expansion. In a murine ovarian cancer model, a single intraperitoneal injection of CARMA-hMeso resulted in the dose-dependent inhibition of tumor growth and improved survival of mice. Furthermore, repeat weekly intraperitoneal administrations of the optimal CARMA-hMeso dose further prolonged disease control and survival

  18. Human leukocyte antigen class II susceptibility conferring alleles among non-insulin dependent diabetes mellitus patients

    International Nuclear Information System (INIS)

    Tipu, H.N.; Ahmed, T.A.; Bashir, M.M.

    2010-01-01

    To determine the frequency of Human Leukocyte Antigen (HLA) class II susceptibility conferring alleles among type 2 Diabetes mellitus patients, in comparison with healthy controls. Cross-sectional comparative study. Patients with non-insulin dependent Diabetes mellitus meeting World Health Organization criteria were studied. These were compared with age and gender matched healthy control subjects. For each subject (patients as well as controls), DNA was extracted from ethylene diamine tetra-acetate sample and HLA class II DRB1 typing was carried out at allele group level (DRB1*01-DRB1*16) by sequence specific primers. Human leukocyte antigen DRB1 type was determined by agarose gel electrophoresis and results were recorded. Frequencies were determined as number of an allele divided by total number of alleles per group; p-value was computed using Pearson's chi-square test. Among the 100 patients, there were 63 males and 37 females with 68 controls. A total of 13 different HLA DRB1 alleles were detected, with DRB1*15 being the commonest in both the groups. The allele DRB1*13 had statistically significant higher frequency in patient group as compared to controls (p 0.005). HLA DRB1*13 was found with a significantly increased frequency in non-insulin dependent Diabetes mellitus. (author)

  19. Human leukocyte antigens in indigenous (mapuche) people in a regional renal transplantation program in chile.

    Science.gov (United States)

    Droguett, M A; Oyarzún, M J; Alruiz, P; Jerez, V; Mezzano, S; Ardiles, L

    2005-10-01

    An active regional transplantation program established in the southern region of Chile has allowed the incorporation of ethnic minorities particularly Mapuche living in this geographic area in the development of a histocompatibility database. To identify possible differences in the human leukocyte (HLA) antigen distribution in Chilean Mapuche compared with non-Mapuche, we reviewed 442 HLA tissue-typing studies. Seventy-eight of 309 recipients (25%) and 18 of 133 donors (13%) were Mapuche. Among recipients, Mapuche people showed a significantly higher frequency of the HLA antigens, A28, B16, DR4, and DR8, and a lower one for A19, B15, and DR1 (P Mapuche individuals. A particularly higher frequency of the haplotype A28, -B16, -DR4 was also evidenced in Mapuche. Besides, these recipients showed a higher frequency of the allele -DR4 when compared with Mapuche donors. A greater frequency of some histocompatibility antigens in patients with chronic renal disease might be attributed to allelic concentration due to a high index of endogamy, but a possible association with the development of progressive renal disease cannot be ignored, especially when a higher prevalence of DR4 was observed among Mapuche recipients.

  20. Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors.

    Science.gov (United States)

    Dulberger, Charles L; McMurtrey, Curtis P; Hölzemer, Angelique; Neu, Karlynn E; Liu, Victor; Steinbach, Adriana M; Garcia-Beltran, Wilfredo F; Sulak, Michael; Jabri, Bana; Lynch, Vincent J; Altfeld, Marcus; Hildebrand, William H; Adams, Erin J

    2017-06-20

    Evidence is mounting that the major histocompatibility complex (MHC) molecule HLA-F (human leukocyte antigen F) regulates the immune system in pregnancy, infection, and autoimmunity by signaling through NK cell receptors (NKRs). We present structural, biochemical, and evolutionary analyses demonstrating that HLA-F presents peptides of unconventional length dictated by a newly arisen mutation (R62W) that has produced an open-ended groove accommodating particularly long peptides. Compared to empty HLA-F open conformers (OCs), HLA-F tetramers bound with human-derived peptides differentially stained leukocytes, suggesting peptide-dependent engagement. Our in vitro studies confirm that NKRs differentiate between peptide-bound and peptide-free HLA-F. The complex structure of peptide-loaded β 2 m-HLA-F bound to the inhibitory LIR1 revealed similarities to high-affinity recognition of the viral MHC-I mimic UL18 and a docking strategy that relies on contacts with HLA-F as well as β 2 m, thus precluding binding to HLA-F OCs. These findings provide a biochemical framework to understand how HLA-F could regulate immunity via interactions with NKRs. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Appropriate clinical use of human leukocyte antigen typing for coeliac disease: an Australasian perspective

    Science.gov (United States)

    Tye-Din, J A; Cameron, D J S; Daveson, A J; Day, A S; Dellsperger, P; Hogan, C; Newnham, E D; Shepherd, S J; Steele, R H; Wienholt, L; Varney, M D

    2015-01-01

    The past decade has seen human leukocyte antigen (HLA) typing emerge as a remarkably popular test for the diagnostic work-up of coeliac disease with high patient acceptance. Although limited in its positive predictive value for coeliac disease, the strong disease association with specific HLA genes imparts exceptional negative predictive value to HLA typing, enabling a negative result to exclude coeliac disease confidently. In response to mounting evidence that the clinical use and interpretation of HLA typing often deviates from best practice, this article outlines an evidence-based approach to guide clinically appropriate use of HLA typing, and establishes a reporting template for pathology providers to improve communication of results. PMID:25827511

  2. Human leukocyte antigen-G in the male reproductive system and in seminal plasma

    DEFF Research Database (Denmark)

    Larsen, Margit Hørup; Bzorek, Michael; Pass, Malene B

    2011-01-01

    One of the non-classical human leukocyte antigen (HLA) class Ib proteins, HLA-G, is believed to exert important immunoregulatory functions, especially during pregnancy. The presence of HLA protein in paternal seminal fluid has been suggested to have an influence on the risk of developing pre......-eclampsia. We have investigated whether HLA-G protein is present in human seminal plasma and in different tissue samples of the male reproductive system. Western blot technique and a soluble HLA-G (sHLA-G) assay were used to detect sHLA-G in human seminal plasma samples. Immunohistochemical staining...... was performed on paraffin-embedded tissue samples. We detected sHLA-G protein in seminal plasma, and HLA-G expression in normal testis and in epididymal tissue of the male reproductive system but not in the seminal vesicle. Furthermore, the results indicated a weak expression of HLA-G in hyperplastic prostatic...

  3. Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?

    NARCIS (Netherlands)

    Smit, L.A.M.; Strachan, D.P.; Vermeulen, R.; Bakker, P.I.W. de; Demenais, F.; Dumas, O.; Carsin, A.E.; Cullinan, P.; Curjuric, I.; Ghosh, R.E.; Heederik, D.; Imboden, M.; Jarvis, D.; Lathrop, M.; Moual, N. le; Mehta, A.; Miedinger, D.; Sigsgaard, T.; Siroux, V.; Vernez, D.; Zock, J.P.; Kauffmann, F.; Probst-Hensch, N.; Kogevinas, M.; Bouzigon, E.

    2014-01-01

    Recently, a locus centred on rs9273349 in the HLA-DQ region emerged from genome-wide association studies of adult-onset asthma. We aimed to further investigate the role of human leukocyte antigen (HLA) class II in adult-onset asthma and a possible interaction with occupational exposures. We imputed

  4. Human leukocyte antigen class II variants and adult-onset asthma : does occupational allergen exposure play a role?

    NARCIS (Netherlands)

    Smit, Lidwien A M; Strachan, David P; Vermeulen, Roel; de Bakker, Paul I W; Demenais, Florence; Dumas, Orianne; Carsin, Anne-Elie; Cullinan, Paul; Curjuric, Ivan; Ghosh, Rebecca E; Heederik, Dick; Imboden, Medea; Jarvis, Deborah; Lathrop, Mark; Le Moual, Nicole; Mehta, Amar; Miedinger, David; Sigsgaard, Torben; Siroux, Valérie; Vernez, David; Zock, Jan Paul; Kauffmann, Francine; Probst-Hensch, Nicole; Kogevinas, Manolis; Bouzigon, Emmanuelle

    2014-01-01

    Recently, a locus centred on rs9273349 in the HLA-DQ region emerged from genome-wide association studies of adult-onset asthma. We aimed to further investigate the role of human leukocyte antigen (HLA) class II in adult-onset asthma and a possible interaction with occupational exposures. We imputed

  5. Tapasin discriminates peptide-human leukocyte antigen-A*02:01 complexes formed with natural ligands

    DEFF Research Database (Denmark)

    Røder, Gustav Andreas; Geironson, Linda; Rasmussen, Michael

    2011-01-01

    A plethora of peptides are generated intracellularly, and most peptide-human leukocyte antigen (HLA)-I interactions are of a transient, unproductive nature. Without a quality control mechanism, the HLA-I system would be stressed by futile attempts to present peptides not sufficient for the stable...

  6. Epithelial human leukocyte antigen-DR expression predicts reduced recurrence rates and prolonged survival in rectal cancer patients.

    NARCIS (Netherlands)

    Bruin, EC de; Velde, CJ van de; Krieken, J.H.J.M. van; Marijnen, C.A.; Medema, J.P.

    2008-01-01

    PURPOSE: The development of local and distant recurrences is a major problem in the treatment of rectal cancer patients. In this study, we investigated whether epithelial human leukocyte antigen-DR (HLA-DR) expression allowed discrimination between high and low tumor recurrence rates, and analyzed

  7. Epithelial human leukocyte antigen-DR expression predicts reduced recurrence rates and prolonged survival in rectal cancer patients

    NARCIS (Netherlands)

    de Bruin, Elza C.; van de Velde, Cornelis J. H.; van Krieken, J. Han J. M.; Marijnen, Corrie A. M.; Medema, Jan Paul

    2008-01-01

    PURPOSE: The development of local and distant recurrences is a major problem in the treatment of rectal cancer patients. In this study, we investigated whether epithelial human leukocyte antigen-DR (HLA-DR) expression allowed discrimination between high and low tumor recurrence rates, and analyzed

  8. Arginine (Di)methylated Human Leukocyte Antigen Class I Peptides Are Favorably Presented by HLA-B*07

    NARCIS (Netherlands)

    Marino, Fabio; Mommen, Geert P M; Jeko, Anita; Meiring, Hugo D; van Gaans-van den Brink, Jacqueline A M; Scheltema, Richard A; van Els, Cécile A C M; Heck, Albert J R

    Alterations in protein post-translational modification (PTM) are recognized hallmarks of diseases. These modifications potentially provide a unique source of disease-related human leukocyte antigen (HLA) class I-presented peptides that can elicit specific immune responses. While phosphorylated HLA

  9. Human Leukocyte Antigen (HLA) Class I Restricted Epitope Discovery in Yellow Fewer and Dengue Viruses: Importance of HLA Binding Strength

    DEFF Research Database (Denmark)

    Lund, Ole; Nascimento, Eduardo J. M.; Maciel, Milton, Jr

    2011-01-01

    Epitopes from all available full-length sequences of yellow fever virus (YFV) and dengue fever virus (DENV) restricted by Human Leukocyte Antigen class I (HLA-I) alleles covering 12 HLA-I supertypes were predicted using the NetCTL algorithm. A subset of 179 predicted YFV and 158 predicted DENV...

  10. The potential usefulness of human leukocyte antigen typing for celiac disease screening: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Alicia Díaz-Redondo

    2015-07-01

    Full Text Available Background and aim: The presence of specific human leukocyte antigen-DQ2 and DQ8 seems to be necessary for celiac disease development, but the real contribution of its typing for screening is still uncertain. We aim to conduct a systematic review and meta-analysis of the diagnostic performance of human leukocyte antigen typing tests for celiac disease screening. Methods: Systematic review of published studies assessing accuracy of human leukocyte antigen DQ2 and DQ8 typing for the detection of celiac disease were selected. MEDLINE and EMBASE were searched from 1st January 2004 until 31st December 2013. Two independent researchers carried out selection and classification of studies, data extraction and analysis. Meta-analysis combining sensitivities, specificities and likelihood ratios of HLA-DQ2 and DQ8 for the diagnosis of celiac disease were carried out. Results: 6 studies including 1303 individuals were finally evaluated. Pooled sensitivity was 98% (95% confidence interval: 97-99. Overall specificity was 45% (95% confidence interval: 41-48. Regarding specificity, studies were heterogeneous and a subgroup analysis was done according to the type of population included. Overall negative likelihood ratio was 0.05 (0.03-0.09. Conclusions: Due to its great sensitivity and low negative likelihood ratio, human leukocyte antigen-DQ2/DQ8 typing would be an appropriate test for ruling out celiac disease in the general population suffering related symptoms, and even more in at risk population.

  11. The antigen processing machinery of class I human leukocyte antigens: linked patterns of gene expression in neoplastic cells.

    Science.gov (United States)

    Giorda, Ezio; Sibilio, Leonardo; Martayan, Aline; Moretti, Sara; Venturo, Irene; Mottolese, Marcella; Ferrara, Giovan Battista; Cappellacci, Sandra; Eibenschutz, Laura; Catricalà, Caterina; Grammatico, Paola; Giacomini, Patrizio

    2003-07-15

    The ultimate outcome of an immune response (escape or surveillance) depends on a delicate balance of opposing signals delivered by activating and inhibitory immune receptors expressed by cytotoxic T lymphocytes and natural killer cells. In this light, loss and down-regulation of human leukocyte antigens (HLA) class I molecules, while important for keeping tumors below the T-cell detection levels, may incite recognition of missing self. Conversely, the maintenance of normal levels of expression (or even up-regulation) may be favorable to tumors, at least in certain cases. In this study, we took advantage of a previously characterized panel of 15 early passage tumor cell lines (mainly from melanoma and lung carcinoma lesions) enriched with class I-low phenotypes. These cells were systematically characterized by Northern and/or Western blotting (e.g., mini-transcriptome/mini-proteome analysis) for the expression of HLA-A, -B, -C, beta(2)-microglobulin, and the members of the "antigen processing machinery" of class I molecules (LMP2, LMP7, TAP1, TAP2, tapasin, calreticulin, calnexin, and ERp57). In addition, we established four pairs of cultures, each comprising melanoma cells and normal melanocytes from the same patient. We found that approximately 97% of the 185 tested gene products are expressed (although often weakly), and in many cases coordinately regulated in 18 of 19 tumor cell lines. Linked expression patterns could be hierarchically arranged by statistical methods and graphically described as a class I HLA "coordinome." Deviations (both down- and up-regulation) from the coordinome expression pattern inherited from the normal, paired melanocyte counterpart, were allowed but limited in magnitude, as if melanoma cells were trying to keep a "low profile" HLA phenotype. We conclude that irreversible HLA loss is a rare event, and class I expression in tumor cells almost invariably results from reversible gene regulatory (rather than gene disruption) events.

  12. Increased soluble human leukocyte antigen-G levels in peripheral blood from climbers on Mount Everest.

    Science.gov (United States)

    Bourguignon, Michel; Yaghi, Layale; Flajollet, Sébastien; Radanne-Krawice, Irène; Rouas-Freiss, Nathalie; Lugrin, Didier; Richalet, Jean-Paul; Carosella, Edgardo D; Moreau, Philippe

    2010-11-01

    Soluble human leukocyte antigen-G (HLA-G) is involved in maternal-fetal tolerance, transplant acceptance, and tumor escape from immunosurveillance, operating by inhibiting activity of T, antigen presenting cells (APC), and natural killer (NK) cells. HLA-G gene expression is modulated in vitro after hypoxic conditions, a situation evidenced during pregnancy and tumor progression. In extreme altitude, mountaineers are in hypoxic conditions that generate physiologic adaptative responses, some of them giving rise to pathologic signs. We performed measurements of plasma soluble HLA-G in six climbers before departure of the expedition and during their ascent to and descent from summit of Mount Everest, and in 3 Sherpas at 5300-6400 m. We found that HLA-G levels are upregulated during the ascent with a unique pattern in comparison with angiogenic/lymphangiogenic factors. Our data suggest that HLA-G has to be taken into account in the mechanisms participating in adaptation to high altitudes and reinforce hypoxia as an important factor in the regulation of HLA-G expression. Copyright © 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  13. Clinical-pathological implication of human leukocyte antigen-F-positive gastric adenocarcinoma.

    Science.gov (United States)

    Ishigami, Sumiya; Arigami, Takaaki; Setoyama, Testuro; Okumura, Hiroshi; Sasaki, Ken; Uchikado, Yasuto; Kurahara, Hiroshi; Kijima, Yuko; Nishizono, Yuka; Nakajo, Akihiro; Natsugoe, Shoji

    2013-10-01

    Human leukocyte antigen (HLA)-F is a nonclassical HLA class I molecule that shows aberrant expression in cancer cells. Although the clinical implications of HLA-F expression in cancer patients have been described, the specific significance of this antigen in gastrointestinal cancer remains unclear. The present study examined the expression pattern and clinical implications of HLA-F in gastric adenocarcinoma. HLA-F expression was assessed in 179 patients by immunohistochemistry, and its association with clinical parameters including patient survival was analyzed. HLA-F expression was positive in 30.7% (55/179) of patients and in 50.0% (90/179) of peritumoral infiltrating lymphocytes. HLA-F expression in gastric adenocarcinoma was significantly correlated with the depth of invasion, nodal involvement, and lymphatic and venous invasions (P HLA-F positivity of infiltrating cells near the tumor showed no correlation with clinicopathological features. HLA-F-positive patients had a significantly worse prognosis than HLA-F-negative patients (P = 0.012). However, HLA-F expression was not an independent prognostic factor in multivariate analysis. The present study provides the first evidence that neo-HLA-F expression is of clinical significance in gastric adenocarcinoma. HLA-F expression in gastric adenocarcinoma may promote the aggressive behavior of tumors by suppressing the activity of antitumor immune effector cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Human leukocyte antigen (HLA)-E and HLA-F expression in gastric cancer.

    Science.gov (United States)

    Ishigami, Sumiya; Arigami, Takaaki; Okumura, Hiroshi; Uchikado, Yasuto; Kita, Yoshiaki; Kurahara, Hiroshi; Maemura, Kosei; Kijima, Yuko; Ishihara, Yuka; Sasaki, Ken; Uenosono, Yoshikazu; Natsugoe, Shoji

    2015-04-01

    Human leukocyte antigen (HLA)-E and HLA-F are classified as non-classical HLA class Ib antigens. Ectopic HLA-E and HLA-F expression was recently detected in cancer cells; however, the clinical implication of their expression remains unknown. A total of 209 patients with gastric cancer were enrolled in this study. Immunohistochemistry was used to evaluate the expression of HLA-E and HLA-F in gastric cancer specimens. HLA-E and HLA-F expression were seen in the cell membrane. HLA-E and HLA-F expression significantly correlated with depth of invasion, nodal involvement, lymphatic invasion, and venous invasion. No significant correlation between HLA-E and HLA-F expression was found (pHLA-E-positive group and HLA-F-positive group were significantly poorer than that of their respective negative groups. Combination of HLA-E and HLA-F made the p-value smaller than single analysis (pHLA-E and HLA-F expression simultaneously in gastric cancer. We identified that the HLA-E and HLA-F in gastric cancer independently affected clinical factors, including postoperative outcome. For HLA-E- or HLA-F-positive gastric cancer, we should settle on a treatment strategy that reinforces the host immune response. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  15. Evaluation of the humoral immune response to human leukocyte antigens in Brazilian renal transplant candidates.

    Directory of Open Access Journals (Sweden)

    Patricia Keiko Saito

    Full Text Available Pre-transplant sensitization to human leukocyte antigens (HLA is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA. The percentages of panel-reactive antibodies (PRA and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.. The PRA-positive group consisted of 182 (67.7% patients, and the PRA-negative group of 87 (32.3% patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1% were positive for class I and negative for class II, 39 (21.4% were negative for class I and positive for class II, and 81 (44.5% were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples.

  16. Dendritic cells take up and present antigens from viable and apoptotic polymorphonuclear leukocytes.

    Directory of Open Access Journals (Sweden)

    Carlos Alfaro

    Full Text Available Dendritic cells (DC are endowed with the ability to cross-present antigens from other cell types to cognate T cells. DC are poised to meet polymorphonuclear leukocytes (PMNs as a result of being co-attracted by interleukin-8 (IL-8, for instance as produced by tumor cells or infected tissue. Human monocyte-derived and mouse bone marrow-derived DC can readily internalize viable or UV-irradiated PMNs. Such internalization was abrogated at 4°C and partly inhibited by anti-CD18 mAb. In mice, DC which had internalized PMNs containing electroporated ovalbumin (OVA protein, were able to cross-present the antigen to CD8 (OT-1 and CD4 (OT-2 TCR-transgenic T cells. Moreover, in humans, tumor cell debris is internalized by PMNs and the tumor-cell material can be subsequently taken up from the immunomagnetically re-isolated PMNs by DC. Importantly, if human neutrophils had endocytosed bacteria, they were able to trigger the maturation program of the DC. Moreover, when mouse PMNs with E. coli in their interior are co-injected in the foot pad with DC, many DC loaded with fluorescent material from the PMNs reach draining lymph nodes. Using CT26 (H-2(d mouse tumor cells, it was observed that if tumor cells are intracellularly loaded with OVA protein and UV-irradiated, they become phagocytic prey of H-2(d PMNs. If such PMNs, that cannot present antigens to OT-1 T cells, are immunomagnetically re-isolated and phagocytosed by H-2(b DC, such DC productively cross-present OVA antigen determinants to OT-1 T cells. Cross-presentation to adoptively transferred OT-1 lymphocytes at draining lymph nodes also take place when OVA-loaded PMNs (H-2(d are coinjected in the footpad of mice with autologous DC (H-2(b. In summary, our results indicate that antigens phagocytosed by short-lived PMNs can be in turn internalized and productively cross-presented by DC.

  17. Human Leukocyte Antigen-DR Expression is Significantly Related to an Increased Disease-Free and Disease-Specific Survival in Patients With Cervical Adenocarcinoma

    NARCIS (Netherlands)

    Samuels, Sanne; Spaans, Vivian M.; Osse, Michelle; Peters, Lex A. W.; Kenter, Gemma G.; Fleuren, Gertjan J.; Jordanova, Ekaterina S.

    2016-01-01

    Human leukocyte antigen (HLA) class II antigens are expressed on antigen-presenting cells, that is, macrophages, dendritic cells, and B lymphocytes. Under the influence of IFN-γ, HLA class II molecules can also be expressed on T lymphocytes, epithelial and endothelial cells. In addition, HLA class

  18. Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients.

    Science.gov (United States)

    Tsamadou, Chrysanthi; Fürst, Daniel; Vucinic, Vladan; Bunjes, Donald; Neuchel, Christine; Mytilineos, Daphne; Gramatzki, Martin; Arnold, Renate; Wagner, Eva Maria; Einsele, Hermann; Müller, Carlheinz; Schrezenmeier, Hubert; Mytilineos, Joannis

    2017-11-01

    The immunomodulatory role of human leukocyte antigen (HLA)-E in hematopoietic stem cell transplantation (HSCT) has not been extensively investigated. To this end, we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E , in order to study the effect of HLA-E as a natural killer (NK)-alloreactivity mediator on HSCT outcome in an acute leukemia (AL) setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both univariate (53% vs 38%, P =0.002, 5-year OS) and multivariate (hazard ratio (HR)=0.63, confidence interval (CI) 95%=0.48-0.83, P =0.001) analyses. Further subgroup analysis demonstrated that the positive effect of HLA-E mismatch was significant and pronounced in advanced disease patients (n=120) (5-year OS: 50% vs 18%, P =0.005; HR=0.40, CI 95%=0.22-0.72, P =0.002; results from univariate and multivariate analyses, respectively). The study herein is the first to report an association between HLA-E incompatibility and improved post-transplant prognosis in AL patients who have undergone matched unrelated HSCT. Combined NK and T cell HLA-E-mediated mechanisms may account for the better outcomes observed. Notwithstanding the necessity for in vitro and confirmational studies, our findings highlight the clinical relevance of HLA-E matching and strongly support prospective HLA-E screening upon donor selection for matched AL unrelated HSCTs. Copyright© Ferrata Storti Foundation.

  19. Human leukocyte antigen in the allocation of kidneys from cadaveric donors in the United States.

    Science.gov (United States)

    Ting, Alan; Edwards, Leah Bennett

    2004-02-27

    Minorities wait longer for a cadaveric donor kidney transplant than whites. For example, the median waiting time to transplant for candidates listed from 1997 to 1998 was 874 days for whites, 1,493 days for blacks, 1,281 days for Hispanics, 1,491 days for Asians, and 1,466 days for others. The current allocation algorithm has been criticized as contributing to decreased access to transplants for racial minorities. There are two levels in the current algorithm: The first is mandatory national sharing between donors and patients with zero human leukocyte antigen (HLA)-A, B, and DR mismatches. The second occurs if there are no candidates and local placement is accomplished based on an algorithm with an HLA component that assigns seven, five, and two points to zero, one, and two HLA-B and DR mismatches, respectively. An analysis of the data shows that a higher percentage of white recipients (21%) received zero antigen mismatched kidneys compared with other races: blacks (7%), Hispanics (14%), and Asians (7%). Whites also received the highest percentage of kidneys with zero B and DR mismatches and one B and DR mismatch compared with the other races. These data indicate that the current algorithm favors whites over minorities, and it is most likely that giving points for HLA-B matching is a strong contributory factor. To address this inequity, the Organ Procurement and Transplantation Network and United Network for Organ Sharing Board of Directors approved a recommendation in November 2002 to change the HLA points to award two points for zero DR mismatches and one point for one DR mismatch. Obviously it will take some time to gather sufficient data to allow meaningful analysis of the effect of the policy change.

  20. Human leukocyte antigen-G (HLA-G) polymorphism and expression in breast cancer patients.

    Science.gov (United States)

    Jeong, Seri; Park, Seho; Park, Byeong-Woo; Park, Younhee; Kwon, Oh-Joong; Kim, Hyon-Suk

    2014-01-01

    Human leukocyte antigen-G (HLA-G) is known to be implicated in a tumor-driven immune escape mechanism in malignancies. The purpose of this study was to investigate HLA-G polymorphism and expression in breast cancer. HLA-G alleles were determined by direct DNA sequencing procedures from blood samples of 80 breast cancer patients and 80 healthy controls. Soluble HLA-G (sHLA-G) was measured by enzyme-linked immunosorbent assay (ELISA) from serum specimens. HLA-G expression in breast cancer lesions was also analyzed by immunohistochemistry staining. The presence of HLA-G 3' untranslated region (UTR) 14-bp sequence was analyzed and found to be associated with reduced risk of breast cancer susceptibility based on HLA-G expression in tissues (P = 0.0407). Levels of sHLA-G were higher in the breast cancer group (median 117.2 U/mL) compared to the control group (median 10.1 U/mL, Pcancer from normal controls and for detecting metastasis from other stages of breast cancer were 0.89 and 0.79, respectively. HLA-G polymorphism and expression may be involved in breast carcinogenesis and sHLA-G concentrations could be used as a diagnostic marker for detecting breast cancer.

  1. Plasma human leukocyte antigen-G (HLA-G) in patients with thyroid cancer

    Science.gov (United States)

    Akın, Murat; Aral, Latife Arzu; Yavuz, Aydın; Karabacak, Harun; Dikmen, Kürşat; Bostancı, Hasan

    2017-08-23

    Background/aim: A number of tumor markers detected in the serum or pathological specimens using immunohistochemical methods are used for early detection of malignancies and postoperative follow-up. Human leukocyte antigen-G (HLA-G) is a nonclassic HLA class I molecule. Recent studies suggested a relationship between HLA-G positivity and the stage or the phenotype of the malignancy. In this study, the relationship between serum HLA-G positivity and thyroid cancer was investigated. Materials and methods: Fifty patients with thyroid cancer and 45 healthy volunteers were included in this study. Serum HLA-G levels were measured using ELISA. Results: HLA-G was positive in only 3 out of 50 patients with thyroid cancer (2 papillary, 1 follicular type). On the other hand, HLA-G was positive in 20 out of 45 healthy subjects (P HLA-G was independent of sex and age in the whole study population. No correlation was found between serum HLA-G value and thyroid hormone profile, neither in papillary thyroid cancer nor follicular thyroid cancer patients. Conclusion: In this study, serum HLA-G was significantly less common in patients with thyroid cancer than in healthy controls.

  2. Cutaneous squamous cell cancer (cSCC) risk and the human leukocyte antigen (HLA) system.

    Science.gov (United States)

    Yesantharao, Pooja; Wang, Wei; Ioannidis, Nilah M; Demehri, Shadmehr; Whittemore, Alice S; Asgari, Maryam M

    2017-04-01

    Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer among Caucasians in the United States, with rising incidence over the past decade. Treatment for non-melanoma skin cancer, including cSCC, in the United States was estimated to cost $4.8 billion in 2014. Thus, an understanding of cSCC pathogenesis could have important public health implications. Immune function impacts cSCC risk, given that cSCC incidence rates are substantially higher in patients with compromised immune systems. We report a systematic review of published associations between cSCC risk and the human leukocyte antigen (HLA) system. This review includes studies that analyze germline class I and class II HLA allelic variation as well as HLA cell-surface protein expression levels associated with cSCC risk. We propose biological mechanisms for these HLA-cSCC associations based on known mechanisms of HLA involvement in other diseases. The review suggests that immunity regulates the development of cSCC and that HLA-cSCC associations differ between immunocompetent and immunosuppressed patients. This difference may reflect the presence of viral co-factors that affect tumorigenesis in immunosuppressed patients. Finally, we highlight limitations in the literature on HLA-cSCC associations, and suggest directions for future research aimed at understanding, preventing and treating cSCC. Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  3. Human leukocyte antigen-G (HLA-G polymorphism and expression in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Seri Jeong

    Full Text Available Human leukocyte antigen-G (HLA-G is known to be implicated in a tumor-driven immune escape mechanism in malignancies. The purpose of this study was to investigate HLA-G polymorphism and expression in breast cancer. HLA-G alleles were determined by direct DNA sequencing procedures from blood samples of 80 breast cancer patients and 80 healthy controls. Soluble HLA-G (sHLA-G was measured by enzyme-linked immunosorbent assay (ELISA from serum specimens. HLA-G expression in breast cancer lesions was also analyzed by immunohistochemistry staining. The presence of HLA-G 3' untranslated region (UTR 14-bp sequence was analyzed and found to be associated with reduced risk of breast cancer susceptibility based on HLA-G expression in tissues (P = 0.0407. Levels of sHLA-G were higher in the breast cancer group (median 117.2 U/mL compared to the control group (median 10.1 U/mL, P<0.001. The area under the receiver operating characteristic curve (AU-ROC values of sHLA-G for differentiating breast cancer from normal controls and for detecting metastasis from other stages of breast cancer were 0.89 and 0.79, respectively. HLA-G polymorphism and expression may be involved in breast carcinogenesis and sHLA-G concentrations could be used as a diagnostic marker for detecting breast cancer.

  4. The future (r)evolution of preimplantation genetic diagnosis/human leukocyte antigen testing: ethical reflections.

    Science.gov (United States)

    de Wert, Guido; Liebaers, Inge; Van de Velde, Hilde

    2007-09-01

    There has been increasing support for combining preimplantation genetic diagnosis (PGD) for specific diseases with a test for human leukocyte antigens (HLA) because the generation of HLA-matched umbilical cord blood cells may save the life of a diseased sibling. To date, this procedure has taken place in the context of conceiving another child--PGD/HLA testing type 1. However, it may well become possible to perform PGD/HLA testing outside this context, that is, to select matched embryos from which embryonic stem cells could be derived and used in cell therapy--PGD/HLA testing type 2. A proactive ethical analysis is needed and is presented in this article. Although PGD/HLA testing type 1 can be morally justified, the risks, pitfalls, and practical limitations of this procedure make it necessary to develop alternative strategies. PGD/HLA testing type 2 may provide an alternative strategy. From an ethical point of view, the controversial issue is that this procedure creates embryos purely for instrumental use. However, given the dominant view that the preimplantation embryo has only limited moral value, this alternative may be as morally justified as PGD/HLA testing type 1.

  5. Human Leukocyte Antigen Class I and Class II Polymorphisms and Serum Cytokine Profiles in Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Larissa Bahls

    2017-08-01

    Full Text Available Only a small proportion of women who are exposed to infection with high-risk human papillomavirus (HR-HPV progress to persistent infection and develop cervical cancer (CC. The immune response and genetic background of the host may affect the risk of progression from a HR-HPV infection to lesions and cancer. However, to our knowledge, no studies has been conducted to evaluate the relationship between variability of human leukocyte antigens (HLA genes and serum cytokine expression in this pathology. In the current study, we examined the associations of HLA alleles and haplotypes including Class I (HLA-A, -B and -C and II (HLA-DRB1, -DQA1 and -DQB1 with serum levels of cytokines interleukin (IL-6, tumor necrosis factor-α (TNF-α, IL-10 and IL-17 as well as risks of HPV infections, lesions and CC among admixed Brazilian women. HLA polymorphisms were associated with an increased risk or protection from HPV, lesions and CC. Additionally, we demonstrated a potential association of a HLA class I haplotype (HLA-B*14-C*08 with higher IL-10 cytokine serum levels in cervical disease, suggesting an association between HLA class I and specific cytokines in cervical carcinogenesis. However, larger studies with detailed HPV types coupled with genetic data are needed to further evaluate the effects of HLA and CC by HPV genotype.

  6. Inhibition of host immune response in colorectal cancer: Human leukocyte antigen-G and beyond

    Science.gov (United States)

    Garziera, Marica; Toffoli, Giuseppe

    2014-01-01

    Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their type, density and location are summarized in the Immune Score that has been shown to improve prognostic prediction of CRC patients. The non-classical MHC class I human leukocyte antigen-G (HLA-G), is a crucial tumor-driven immune escape molecule involved in immune tolerance. HLA-G and soluble counterparts are able to exert inhibitory functions by direct interactions with inhibitory receptors present on both innate cells such as natural killer cells, and adaptive immune cells as cytotoxic T and B lymphocytes. HLA-G may play a prominent role in CRC strategies to avoid host immunosurveillance. This review highlights the current knowledge on HLA-G contribution in CRC, in related inflammatory diseases and in other type of cancers and disorders. HLA-G genetic setting (specific haplotypes, genotypes and alleles frequencies) and association with circulating/soluble profiles was highlighted. HLA G prognostic and predictive value in CRC was investigated in order to define a novel prognostic immune biomarker in CRC. PMID:24744572

  7. Reduced third-trimester levels of soluble human leukocyte antigen G protein in severe preeclampsia.

    Science.gov (United States)

    Hackmon, Rinat; Koifman, Arie; Hyodo, Hironobu; Hyobo, Hirohito; Glickman, Hagit; Sheiner, Eyal; Geraghty, Daniel E

    2007-09-01

    Recently, lower maternal plasma human leukocyte antigen (HLA)-G protein levels in preeclampsia (PE) in the first and second trimester was reported. Thus, we sought to evaluate the levels of HLA-G protein in patients with severe PE during the third trimester. In this prospective case control study, amniotic fluid and maternal and cord blood samples were aspirated from 50 pregnant women during the third trimester. The study group included 26 pregnant women diagnosed with severe PE and 24 women without PE serving as controls. A soluble HLA-G-specific enzyme-linked immunosorbent assay was used to measure protein levels. Statistical analysis included the Student t test and simple regression analysis. Maternal serum HLA-G levels in PE pregnancies were found to be significantly lower as compared with normal pregnancies (10.97 +/- 6.55 vs 36.05 +/- 34.53 microg/mL; P = .003). A reduced level of maternal HLA-G protein was associated with severe PE during the third trimester. This finding may suggest an essential role for HLA-G in normal and preeclamptic pregnancies.

  8. Human leukocyte antigen (HLA-F) polymorphism is associated with chronic HBV infection.

    Science.gov (United States)

    Laaribi, Ahmed Baligh; Hannachi, Naila; Ben Yahia, Hamza; Marzouk, Manal; Mehri, Asma; Belhadj, Manel; Yacoub, Salwa; Letaief, Amel; Ouzari, Hadda-Imene; Boudabous, Abdellatif; Boukadida, Jalel; Rizzo, Roberta; Zidi, Inès

    2018-01-01

    Human leukocyte antigen (HLA)-F has been involved in immune regulation of infectious diseases. However, the role of HLA-F polymorphisms in hepatitis B infection outcomes remains unclear. Here, we aimed to determine HLA-F polymorphism implication in chronic HBV. Genotype analysis was performed for three single nucleotide polymorphisms (SNPs) of HLA-F and one SNP of HLA-E using PCR-SSP, in 252 Tunisian patients with chronic HBV infection stratified according to their HBV DNA levels (140 patients with low HBV DNA levels HLA-F SNPs (HLA-F*01:02, -F*01:03 and -F*01:04) have the same allelic and genotypic frequencies in patients and in CTRL. We reported a low HLA-F*01:02 and F*01:04 allelic frequencies in the Tunisian population; however, high HLA-F*01:03 allele frequencies were observed (17%). A significant association was found between the HLA-F*01:03 allele and decreased level of HBV DNA ( P  = 0.02 OR 0.56, 95% CI 0.35-0.92). No significant differences were observed in haplotype distribution between patients and CTRL. A significant association of HLA-F*01:03 with the level of HBV DNA suggests an important role of HLA-F in HBV replication control.

  9. Clinical implication of human leukocyte antigen (HLA)-F expression in breast cancer.

    Science.gov (United States)

    Harada, Aya; Ishigami, Sumiya; Kijima, Yuko; Nakajo, Akihiro; Arigami, Takaaki; Kurahara, Hiroshi; Kita, Yoshiaki; Yoshinaka, Heiji; Natsugoe, Shoji

    2015-11-01

    Human leukocyte antigen (HLA)-F is one of the non-classical HLA class I molecules that protects the fetus in pregnancy. HLA-F expression was immunohistochemically examined and the association between clinical parameters and HLA-F expression was analyzed. Cancerous HLA-F and stromal HLA-F-positive infiltrating cells were detected in 91 (40.0%) and 186 (81.6%) cases, respectively. HLA-F positivity in cancer cells was significantly associated with tumor size (P HLA-F positivity of cancer cells and HLA-F positive infiltrative cells (P HLA-F positivity did not affect patients' survival in 209 breast cancer. However, confined to stage II breast cancer, the HLA-F positive group showed significantly poorer outcomes than the HLA-F negative group (P HLA-F positivity in breast carcinoma affects clinicopathological factors and could be selected as a prognostic marker for limited clinical stage. © 2015 The Authors. Pathology International published by Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  10. Soluble human leukocyte antigen-G isoforms in maternal plasma in early and late pregnancy

    DEFF Research Database (Denmark)

    Rizzo, Roberta; Andersen, Anita Sylvest; Lassen, Michael Rud

    2009-01-01

    PROBLEM: Human Leukocyte Antigen (HLA)-G is a class Ib gene located in the human major histocompatibility complex (MHC). Several lines of investigation indicate that the HLA-G molecule is involved in the maternal acceptance of the semi-allogenic fetus during pregnancy and in the development...... of tolerance. Expression of soluble HLA-G (sHLA-G) is positively correlated with successful in vitro fertilization (IVF) treatments, and aberrant expression of HLA-G in certain complications of pregnancy, such as pre-eclampsia and spontaneous abortion, has been reported. The main purpose of this study...... was to investigate the levels of different soluble HLA-G isoforms in maternal plasma in early and late pregnancy. METHOD OF STUDY: Soluble HLA-G (sHLA-G) can be detected in maternal blood, and in this study, two different isoforms of sHLA-G, namely sHLA-G1 generated by shedding of membrane-bound HLA-G1 and HLA...

  11. Human leukocyte antigen-B27 alleles in Xinjiang Uygur patients with ankylosing spondylitis.

    Science.gov (United States)

    Zou, H-Y; Yu, W-Z; Wang, Z; He, J; Jiao, M

    2015-05-25

    We investigated the distribution of human leukocyte antigen (HLA)-B27 subtypes in Uygur ankylosing spondylitis patients in Xinjiang. B27-positive patients with ankylosing spondylitis were subtyped by using polymerase chain reaction-sequence-based typing. The HLA-B27 subtype frequencies of Uygur patients were compared with those in Han patients in Xinjiang and the other areas of China. B*2705 was the predominant subtype in Uygur patients with a frequency of 58.95%, which was much higher than that in Han patients in Xinjiang (31.58%, P ankylosing spondylitis patients; B*2704 was the main (61.18%) subtype in Han patients in Xinjiang, followed by B*2705 (31.58%) and was similar to the characteristics of Han patients in the other areas of China. B*2724 in Han ankylosing spondylitis patients has not been previously reported. Additionally, the B*2702/B*2705 homozygote was identified in Uygur patients. B*2702/B*2704, B*2704/B*2705, and B*2705/B*2705 homozygotes were identified in 3 Han patients. The distribution of HLAB27 subtypes in Uygur ankylosing spondylitis patients in Xinjiang significantly differed from that in Han patients. Understanding the distribution of HLAB27 subtypes in ethnic minority populations of Xinjiang is important for anthropological genetic studies and for analyzing the impact of genetic background on ankylosing spondylitis susceptibility.

  12. Persistence of hepatitis C virus in a white population: associations with human leukocyte antigen class 1.

    LENUS (Irish Health Repository)

    Fanning, Liam J

    2012-02-03

    The aim of this study was to define novel associations between human leukocyte antigen (HLA) class 1 alleles and persistence or clearance of the hepatitis C virus (HCV) in a white population. All individuals in the study were seropositive for anti-HCV antibodies. Viral status was determined by the Roche HCV Amplicor test. HLA-A, -B, -C allelic group profile was molecularly defined by reverse line probe hybridization. The strongest individual allelic group associations with persistent HCV infection were HLA A*11 (p = 0.044) and Cw*04 (p = 0.006). However, only the HLA C*04 association survived correction for multiple comparisons. Further analysis of alleles in linkage with HLA Cw*04 revealed that the haplotype HLA A*11, Cw*04 was present in 11 individuals, 10 of whom were viremic (p = 0.05). No gene dosage effect was observed. No association between HLA class 1 allelic groups and aviremia and virus load was evident in this white population. HLA B*44 is associated with low virus load in human immunodeficiency virus disease, but this association was not evident in this HCV-infected population. Novel HLA class 1 alleles associated with persistence of HCV have been identified.

  13. Donor-recipient human leukocyte antigen matching practices in vascularized composite tissue allotransplantation: a survey of major transplantation centers.

    Science.gov (United States)

    Ashvetiya, Tamara; Mundinger, Gerhard S; Kukuruga, Debra; Bojovic, Branko; Christy, Michael R; Dorafshar, Amir H; Rodriguez, Eduardo D

    2014-07-01

    Vascularized composite tissue allotransplant recipients are often highly sensitized to human leukocyte antigens because of multiple prior blood transfusions and other reconstructive operations. The use of peripheral blood obtained from dead donors for crossmatching may be insufficient because of life support measures taken for the donor before donation. No study has been published investigating human leukocyte antigen matching practices in this field. A survey addressing human leukocyte antigen crossmatching methods was generated and sent to 22 vascularized composite tissue allotransplantation centers with active protocols worldwide. Results were compiled by center and compared using two-tailed t tests. Twenty of 22 centers (91 percent) responded to the survey. Peripheral blood was the most commonly reported donor sample for vascularized composite tissue allotransplant crossmatching [78 percent of centers (n=14)], with only 22 percent (n=4) using lymph nodes. However, 56 percent of the 18 centers (n=10) that had performed vascularized composite tissue allotransplantation reported that they harvested lymph nodes for crossmatching. Of responding individuals, 62.5 percent (10 of 16 individuals) felt that lymph nodes were the best donor sample for crossmatching. A slight majority of vascularized composite tissue allotransplant centers that have performed clinical transplants have used lymph nodes for human leukocyte antigen matching, and centers appear to be divided on the utility of lymph node harvest. The use of lymph nodes may offer a number of potential benefits. This study highlights the need for institutional review board-approved crossmatching protocols specific to vascularized composite tissue allotransplantation, and the need for global databases for sharing of vascularized composite tissue allotransplantation experiences.

  14. Human Leukocyte Antigen (HLA) Genotype as a Contributor to Racial/Ethnic Differences in Breast Cancer: A Population-Based, Molecular Epidemiologic Study

    National Research Council Canada - National Science Library

    Glaser, Sally L

    2005-01-01

    .... The human leukocyte antigen (HLA) component of the immune system, coded by highly polymorphic genes whose distribution varies by race/ethnicity, may be a biologically based risk factor for breast cancer and thus may explain...

  15. Human Leukocyte Antigen (HLA) Genotype as a Contributor to Racial/Ethnic Differences in Breast Cancer: A Population-Based, Molecular Epidemiologic Study

    National Research Council Canada - National Science Library

    Glaser, Sally

    2004-01-01

    ... variation. The human leukocyte antigen (HLA) component of the immune system, encoded by highly polymorphic genes that vary across racial/ethnic groups, has been suggested to be a biologically based risk factor for breast cancer and thus...

  16. Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia.

    Science.gov (United States)

    Kuniholm, Mark H; Kovacs, Andrea; Gao, Xiaojiang; Xue, Xiaonan; Marti, Darlene; Thio, Chloe L; Peters, Marion G; Terrault, Norah A; Greenblatt, Ruth M; Goedert, James J; Cohen, Mardge H; Minkoff, Howard; Gange, Stephen J; Anastos, Kathryn; Fazzari, Melissa; Harris, Tiffany G; Young, Mary A; Strickler, Howard D; Carrington, Mary

    2010-05-01

    Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high-resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multiracial cohort of U.S. women with a high prevalence of HCV and HIV. Our primary analyses evaluated associations between 12 HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB1*0101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1-2.6), B*5701 (PR=2.0; 95% CI = 1.0-3.1), B*5703 (PR = 1.7; 95% CI = 1.0-2.5), and Cw*0102 (PR = 1.9; 95% CI = 1.0-3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), whereas DRB1*0301 (PR = 0.4; 95% CI = 0.2-0.7) was associated with HCV RNA positivity. DQB1*0301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2-11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (N = 838), but no significant relationships were observed. HLA genotype influences the host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance because they were a priori hypothesized.

  17. Genetic epistasis between killer immunoglobulin-like receptors and human leukocyte antigens in Kawasaki disease susceptibility.

    Science.gov (United States)

    Bossi, G; Mannarino, S; Pietrogrande, M C; Salice, P; Dellepiane, R M; Cremaschi, A L; Corana, G; Tozzo, A; Capittini, C; De Silvestri, A; Tinelli, C; Pasi, A; Martinetti, M

    2015-10-01

    Kawasaki disease (KD) is a pediatric acute multisystemic vasculitis complicated by development of coronary artery lesions. The breakthrough theory on KD etiopathogenesis points to pathogens/environmental factors triggered by northeastern wind coming from China. Natural Killer cells and T lymphocytes express the inhibitory/activating Killer Immunoglobulin-like Receptors (KIR) to elicit an immune response against pathogens by binding to human leukocyte antigens (HLA) class I epitopes. We first report on the role of KIR/HLA genetic epistasis in a sample of 100 Italian KD children. We genotyped KIR, HLA-A, HLA-B and HLA-C polymorphisms, and compared KD data with those from 270 Italian healthy donors. The HLA-A*11 ligand for KIR2DS2/2DS4/3DL2 was a KD susceptibility marker by itself (odds ratio (OR)=3.85, confidence interval (CI)=1.55-9.53, P=0.004). Although no epistasis between HLA-A*11 and KIR2DS2/S4 emerged, HLA-A*11 also engages KIR3DL2, a framework gene encoding for a pathogen sensor of CpG-oligodeoxynucleotides (CpG-ODN), and KD blood mononuclear cells are actually prone to pathogen CpG-ODN activation in the acute phase. Moreover, carriers of KIR2DS2/HLA-C1 and KIR2DL2/HLA-C1 were more frequent among KD, in keeping with data demonstrating the involvement of these HLA/KIR couples in autoimmune endothelial damage. The highest KD risk factor was observed among carriers of KIR2DL2 and two or more HLA ligands (OR=10.24, CI=1.87-56.28; P=0.007).

  18. Association of human leukocyte antigen donor-recipient matching and pediatric heart transplant graft survival.

    Science.gov (United States)

    Butts, Ryan J; Scheurer, Mark A; Atz, Andrew M; Moussa, Omar; Burnette, Ali L; Hulsey, Thomas C; Savage, Andrew J

    2014-07-01

    The effect of donor-recipient human leukocyte antigen (HLA) matching on outcomes remains relatively unexplored in pediatric patients. The objective of this study was to investigate the effects of donor-recipient HLA matching on graft survival in pediatric heart transplantation. The UNOS (United Network for Organ Sharing) database was queried for heart transplants occurring between October 31, 1987, and December 31, 2012, in a recipient aged ≤17 years with ≥1 postoperative follow-up visit. Retransplants were excluded. Transplants were divided into 3 donor-recipient matching groups: no HLA matches (HLA-no), 1 or 2 HLA matches (HLA-low), and 3 to 6 HLA matches (HLA-high). Primary outcome was graft loss. Four thousand four hundred seventy-one heart transplants met the study inclusion criteria. High degree of donor-recipient HLA matching occurred infrequently: HLA-high (n=269; 6%) versus HLA-low (n=2683; 60%) versus HLA-no (n=1495; 34%). There were no differences between HLA matching groups in the frequency of coronary vasculopathy (P=0.19) or rejection in the first post-transplant year (P=0.76). Improved graft survival was associated with a greater degree of HLA donor-recipient matching: HLA-high median survival, 17.1 (95% confidence interval, 14.0-20.2) years; HLA-low median survival, 14.2 (13.1-15.4) years; and HLA-no median survival, 12.1 (10.9-13.3 years) years; Pheart transplantation was associated with a higher degree of donor-recipient HLA matching, although a difference in the frequency of early rejection or development of coronary artery vasculopathy was not seen. © 2014 American Heart Association, Inc.

  19. KIR and Human Leukocyte Antigen Genotype Associated Risk of Cytomegalovirus Disease in Renal Transplant Patients.

    Science.gov (United States)

    Michelo, Clive M; van der Meer, Arnold; Tijssen, Henk J; Zomer, Ramona; Stelma, Foekje; Hilbrands, Luuk B; Joosten, Irma

    2015-07-01

    Cytomegalovirus(CMV) infections have a significant effect on morbidity and mortality in kidney transplants. We conducted a study to ascertain the association of natural killer cell killer immunoglobulin-like receptors and human leukocyte antigen (HLA) genotype with risk of CMV disease. The 90 CMV-negative patients receiving a first renal transplantation from a CMV-positive donor in this study received triple immunosuppressive therapy and prophylactic CMV treatment for up to 3 months after transplantation. We observed a 43.3% incidence rate of CMV disease within the first year after transplantation. Twenty-seven recipients experienced a rejection episode, 14 of which had CMV disease, mostly after rejection, suggesting that in this group, CMV disease is not a risk factor for rejection. KIR gene or genotype distribution were similar between the CMV diseased and CMV disease-free group. Twenty-seven recipients (30%) carried KIR-AA genotype, of which nine (33%) had CMV disease. Of the remaining 63 (70%) recipients with KIR-BX genotype, 30 (48%) had CMV disease. There was no significant difference between the two genotype groups with regard to occurrence of CMV disease, although there was a trend toward a lower incidence of CMV disease in recipients carrying the KIR-AA genotype. For CMV disease, we found no significant risk associated with the number of activating or inhibitory KIRs. Neither was missing KIR ligands for the inhibitory KIRs (HLA-C1/C2/Bw4) in recipients associated with lower rates of CMV disease. In CMV-negative recipients, genotypic analysis of KIR repertoire and HLA ligands does not provide risk factors for primary CMV disease after renal transplantation.

  20. EVALUATION OF HUMAN LEUKOCYTE ANTIGEN CLASS I AND II ANTIGENS IN HELICOBACTER PYLORI-POSITIVE PEDIATRIC PATIENTS WITH ACTIVE GASTRITIS AND DUODENAL ULCER.

    Science.gov (United States)

    Gönen, Sevim; Sari, Sinan; Kandur, Yaşar; Dalgiç, Buket; Söylemezoğlu, Oğuz

    2017-12-01

    As being the first bacteria determined to be carcinogenic, Helicobacter pylori (H. pylori) is a pathogen localized in the stomach in more than half of the world population. Some earlier studies have found a relation between tissue histocompatibility antigens and gastric cancers depending on the regions. The present study aimed to determine the distribution of human leukocyte antigen (HLA) class I and class II antigens in H. pylori-positive pediatric patients with active gastritis and duodenal ulcer, excluding cancer cases, in our center. The study included 40 patients diagnosed with H. pylori-positive active gastritis and duodenal ulcer and 100 controls consisting of healthy donor candidates. The HLA class I and class II antigens were studied in the isolated DNA samples using the polymerase chain reaction sequence-specific oligonucleotide probes. The frequency of HLA-B*51 antigen was significantly higher in the patient group than in the control group (40% vs 17%; P=0.003). There was no difference between the two groups in terms of the frequencies of HLA-A, HLA-C, HLA-DR, and HLA-DQ antigens. It was determined that HLA-B*51 plays a critical role in H. pylori infection.

  1. EVALUATION OF HUMAN LEUKOCYTE ANTIGEN CLASS I AND II ANTIGENS IN HELICOBACTER PYLORI-POSITIVE PEDIATRIC PATIENTS WITH ACTIVE GASTRITIS AND DUODENAL ULCER

    Directory of Open Access Journals (Sweden)

    Sevim GÖNEN

    2017-10-01

    Full Text Available ABSTRACT BACKGROUND: As being the first bacteria determined to be carcinogenic, Helicobacter pylori (H. pylori is a pathogen localized in the stomach in more than half of the world population. Some earlier studies have found a relation between tissue histocompatibility antigens and gastric cancers depending on the regions. OBJECTIVE: The present study aimed to determine the distribution of human leukocyte antigen (HLA class I and class II antigens in H. pylori-positive pediatric patients with active gastritis and duodenal ulcer, excluding cancer cases, in our center. METHODS: The study included 40 patients diagnosed with H. pylori-positive active gastritis and duodenal ulcer and 100 controls consisting of healthy donor candidates. The HLA class I and class II antigens were studied in the isolated DNA samples using the polymerase chain reaction sequence-specific oligonucleotide probes. RESULTS: The frequency of HLA-B*51 antigen was significantly higher in the patient group than in the control group (40% vs 17%; P=0.003. There was no difference between the two groups in terms of the frequencies of HLA-A, HLA-C, HLA-DR, and HLA-DQ antigens. CONCLUSION: It was determined that HLA-B*51 plays a critical role in H. pylori infection.

  2. Prognostic impact of programmed death-ligand 1 expression in correlation with human leukocyte antigen class I expression status in stage I adenocarcinoma of the lung.

    Science.gov (United States)

    Hirai, Ayako; Yoneda, Kazue; Shimajiri, Shohei; Kuroda, Koji; Hanagiri, Takeshi; Fujino, Yoshihisa; Tanaka, Fumihiro

    2018-01-01

    The study objective was to investigate the prognostic impact of programmed death-ligand 1 expression in correlation with human leukocyte antigen class I expression on tumor cells in early-stage adenocarcinoma of the lung, because both programmed death-ligand 1 and human leukocyte antigen class I molecules play important roles in cancer immunity. Ninety-four patients with completely resected pathologic stage I lung adenocarcinoma were retrospectively reviewed. Programmed death-ligand 1 expression on tumor cells was evaluated with immunohistochemistry in correlation with several clinicopathologic and molecular features, including human leukocyte antigen class I expression on tumor cells. Fifteen patients (16.0%) had tumor with positive programmed death-ligand 1 expression (percentage of tumor cells expressing programmed death-ligand 1, ≥5%), and the incidence was significantly higher in poorly differentiated tumors. There was no significant correlation between human leukocyte antigen class I expression and programmed death-ligand 1 expression. Programmed death-ligand 1 positivity was a significant factor to predict a poor survival (5-year survival, 66.7% vs 85.9%; P = .049), which was enhanced in tumors with normal human leukocyte antigen class I expression (P = .029) but was not evident in tumors with reduced human leukocyte antigen class I expression (P = .552). The prognostic impact of programmed death-ligand 1 expression on tumor cells in early-stage lung adenocarcinoma may be distinct according to concurrent human leukocyte antigen class I expression. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  3. Association between human leukocyte antigen-G genotype and success of in vitro fertilization and pregnancy outcome

    DEFF Research Database (Denmark)

    Hviid, T V F; Hylenius, S; Lindhard, A

    2004-01-01

    To determine if a 14-bp deletion/insertion polymorphism in the 3'-untranslated region of exon 8 of the gene encoding human leukocyte antigen (HLA)-G in a homozygous form is associated with repeated, unsuccessful in vitro fertilization (IVF) treatments, and with increased risk of recurrent...... spontaneous abortions (RSA), 29 white women undergoing IVF treatments, 61 RSA women and 93 fertile controls were HLA-G genotype. The HLA-G genotype, homozygous for the presence of the 14 bp sequence in exon 8, was significantly associated with reduced fertility with respect to unsuccessful IVF treatments...

  4. Modulation of Human Leukocyte Antigen-C by Human Cytomegalovirus Stimulates KIR2DS1 Recognition by Natural Killer Cells

    OpenAIRE

    van der Ploeg, Kattria; Chang, Chiwen; Ivarsson, Martin A.; Moffett, Ashley; Wills, Mark R.; Trowsdale, John

    2017-01-01

    The interaction of inhibitory killer cell Ig-like receptors (KIRs) with human leukocyte antigen (HLA) class I molecules has been characterized in detail. By contrast, activating members of the KIR family, although closely related to inhibitory KIRs, appear to interact weakly, if at all, with HLA class I. KIR2DS1 is the best studied activating KIR and it interacts with C2 group HLA-C (C2-HLA-C) in some assays, but not as strongly as KIR2DL1. We used a mouse 2B4 cell reporter system, which carr...

  5. Factors associated with anti-human leukocyte antigen antibodies in patients supported with continuous-flow devices and effect on probability of transplant and post-transplant outcomes

    DEFF Research Database (Denmark)

    Alba, Ana C; Tinckam, Kathryn; Foroutan, Farid

    2015-01-01

    and outcomes. METHODS: We included 143 consecutive heart failure patients who received a CF-VAD as a bridge-to-transplant at 3 institutions. Factors associated with post-VAD peak panel reactive antibodies (PRA) among several measurements were identified using multivariable linear regression. A parametric...... survival model was used to assess transplant waiting time and probability, risk of rejection, and a composite outcome of rejection, graft failure, and death. RESULTS: Thirty-six patients (25%) were female; mean age was 47 ± 13 years. Eighty-one patients (57%) had a pre-VAD PRA of 0%, and 16 were highly...... sensitized (PRA > 80%). Age, female sex, and pre-VAD PRA were independently associated with post-VAD PRA. A 10-year increase in age was associated with a 5% decrease in post-VAD PRA (p = 0.03). Post-VAD PRA was 19% higher in women vs men (p PRA was associated with a 4...

  6. Cutaneous Adverse Drug Reactions to Lamotrigine and Human Leukocyte Antigen Typing in North Indian Patients: A Case Series.

    Science.gov (United States)

    Srivastava, Shivani; Ramanujam, Bhargavi; Ihtisham, Kavish; Tripathi, Manjari

    2017-01-01

    Cutaneous adverse drug reaction (cADR) has limited epidemiological data in India. The older antiepileptic drugs, i.e., carbamazepine, phenytoin, valproic acid, phenobarbitone, etc., induce severe cADRs that have a strong associated with human leukocyte antigen (HLA)-related genetic risk factors. There is also evidence of association of certain HLA alleles with lamotrigine (LTG)-induced cADRs, but this has not been reported in the Indian population. Here, we report case series of three patients with LTG-induced "Stevens-Johnson syndrome (SJS)." Their HLA-B typing was also performed which showed the presence of HLA-B*15:02 in one case with SJS.

  7. Human leukocyte antigen genetics and clinical features of self-treated patients on a gluten-free diet.

    Science.gov (United States)

    Coburn, John A; Vande Voort, Jennifer L; Lahr, Brian D; Van Dyke, Carol T; Kroning, Cynthia M; Wu, Tsung-Teh; Gandhi, Manish J; Murray, Joseph A

    2013-01-01

    Increasingly, people start a gluten-free diet (GFD) without a clear celiac disease (CD) diagnosis. Human leukocyte antigen (HLA) genotyping is useful in ruling out CD in patients with equivocal results of serologic testing or small-bowel biopsy (SBB), but its utility and the clinical features of patients on self-treated GFD (ST-GFD) are largely unknown. Retrospective study of single tertiary care center cohort compared 137 patients on ST-GFD and 443 patients with well-defined CD. We compared HLA genotype, symptoms, serologic and SBB results, and response to GFD between the 2 groups. Analysis used univariate logistic regression modeling, adjusted for age and sex. Patients with ST-GFD presented more often with diarrhea (Pgluten sensitivity may play a role.

  8. Mechanisms and effects of loss of human leukocyte antigen class II expression in immune-privileged site-associated B-cell lymphoma

    NARCIS (Netherlands)

    Booman, M; Douwes, J; Glas, AM; Riemersma, SA; Jordanova, ES; Kok, K; Rosenwald, A; de Jong, D; Schuuring, E; Kluin, PM

    2006-01-01

    Purpose and Experimental Design: Loss of human leukocyte antigen (HLA) expression on tumor cells is frequent in diffuse large B-cell lymphoma (DLBCL) arising in immune-privileged sites, such as the testis and central nervous system, and is associated with small homozygous deletions of HLA-DQ/HLA-DR

  9. Anti-human platelet antigen (HPA)-1a antibodies may affect trophoblast functions crucial for placental development: a laboratory study using an in vitro model.

    Science.gov (United States)

    Eksteen, Mariana; Heide, Gøril; Tiller, Heidi; Zhou, Yan; Nedberg, Nora Hersoug; Martinez-Zubiaurre, Inigo; Husebekk, Anne; Skogen, Bjørn R; Stuge, Tor B; Kjær, Mette

    2017-04-21

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by maternal antibodies against paternal human platelet antigens (HPAs) on fetal platelets. Antibodies against HPA-1a are accountable for the majority of FNAIT cases. We have previously shown that high levels of maternal anti-HPA-1a antibodies are associated with clinically significant reduced birth weight in newborn boys. Chronic inflammatory placental lesions are associated with increased risk of reduced birth weight and have previously been reported in connection with FNAIT pregnancies. The HPA-1a epitope is located on integrin β3 that is associated with integrin αIIb (the fibrinogen receptor) on platelets and megakaryocytes. Integrin β3 is also associated with integrin αV forming the αVβ3 integrin heterodimer, the vitronectin receptor, which is expressed on various cell types, including trophoblast cells. It is therefore thinkable that maternal anti-HPA-1a antibodies present during early pregnancy may affect placenta function through binding to the HPA-1a antigen epitope on invasive throphoblasts. The aim of the study was to examine whether interaction of a human anti-HPA-1a monoclonal antibody (mAb) with HPA-1a on trophoblast cells affect adhesion, migration and invasion of extravillous trophoblast cells. An in vitro model with human anti-HPA-1a mAb, clone 26.4, and the first trimester extravillous trophoblast cell line HTR8/SVneo was employed. The xCELLigence system was utilized to assess the possible effect of anti-HPA-1a mAb on adhesion and migration of HTR8/SVneo cells. Specially designed chambers precoated with Matrigel were used to assess the effect on the invasive capacity of cells. We found that human anti-HPA-1a mAb 26.4 partially inhibits adhesion and migratory capacity of HTR8/SVneo cells. Our findings suggest that anti-HPA-1a antibodies may affect trophoblast functions crucial for normal placental development. Future studies including primary throphoblast

  10. Suppression of class I human histocompatibility leukocyte antigen by c-myc is locus specific

    NARCIS (Netherlands)

    Versteeg, R.; Krüse-Wolters, K. M.; Plomp, A. C.; van Leeuwen, A.; Stam, N. J.; Ploegh, H. L.; Ruiter, D. J.; Schrier, P. I.

    1989-01-01

    The c-myc oncogene downregulates class I HLA expression in human melanoma. The major class I HLA antigens are encoded by three loci, A, B, and C, and we investigated whether these loci are suppressed equally by c-myc. In three melanoma cell lines with high c-myc expression, we analyzed mRNA,

  11. Therapeutic application of human leukocyte antigen-G1 improves atopic dermatitis-like skin lesions in mice.

    Science.gov (United States)

    Maeda, Naoyoshi; Yamada, Chisato; Takahashi, Ami; Kuroki, Kimiko; Maenaka, Katsumi

    2017-09-01

    Human leukocyte antigen (HLA)-G is an immune checkpoint molecule that plays critical roles in immune response and in triggering inhibitory signaling to immune cells such as T cells, natural killer cells, and antigen-presenting cells. Thus, the application of HLA-G can be considered for treating immune response-related inflammatory disorders. We have previously reported that treatment with HLA-G1 and HLA-G2 ameliorates the joint swelling associated with collagen-induced arthritis of DBA/1 mice, an animal model for rheumatoid arthritis. In this study, we further investigated the effects of HLA-G1 on atopic dermatitis (AD), the most common inflammatory skin disorder. AD-like lesions were induced with the extract of the house dust mite Dermatophagoides farinae in NC/Nga mice. Continuous administration of HLA-G1 ameliorated the AD-like skin lesions in the mice. Furthermore, production of immunoglobulin E, interleukin (IL)-13, and IL-17A was significantly reduced in HLA-G1-treated mice, suggesting a Th2/Th17-mediated immune-inhibitory function of HLA-G1 in vivo. Our studies shed light on novel therapeutic strategies with recombinant HLA-G proteins for immune reaction-mediated chronic inflammatory disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The prognostic impact of human leukocyte antigen (HLA) class I antigen abnormalities in salivary gland cancer. A clinicopathological study of 288 cases.

    Science.gov (United States)

    Müller, Maximilian; Agaimy, Abbas; Zenk, Johannes; Ettl, Tobias; Iro, Heinrich; Hartmann, Arndt; Seliger, Barbara; Schwarz, Stephan

    2013-05-01

    To study abnormalities of proteins of the major histocompatibility complex class I in a series of 288 salivary gland carcinomas, and to correlate findings with patients' overall survival (OS). Protein expression of human leukocyte antigen (HLA)-A, heavy chain (HC)-10, β2 -microglobulin, low molecular weight polypeptides (LMP) 2 and 7, transporters associated with antigen processing (TAP) 1 and 2, calnexin, calreticulin, endoplasmic reticulum (ER) p57 and tapasin was evaluated by immunohistochemistry and semiquantitatively analyzed. As compared with normal salivary gland tissue, HLA-A, LMP7, TAP2 and HLA class I were significantly down-regulated in salivary gland carcinomas, whereas β2 -microglobulin, calnexin, LMP2, and TAP1 were upregulated. Expression of calreticulin, ERp57 and tapasin was unaltered. In univariate Kaplan-Meier analyses, low expression of LMP7 (P = 0.005) and high expression of β2 -microglobulin (P = 0.028), HLA-A (P < 0.001), TAP1 (P = 0.01), and tapasin (P < 0.001) were significantly associated with shorter OS. In multivariate analysis incorporating tumour stage, nodal/distant metastasis, and grade, HLA-A (P = 0.014), LMP7 (P = 0.033), and tapasin (P = 0.024), as well as distant metastasis (P = 0.012) and high tumour grade (P < 0.001), remained statistically significant. The prognostic influence of up-regulated HLA-A and tapasin and down-regulated LMP7 may provide a rationale for targeting these specific components of the antigen processing and presentation pathway in salivary gland carcinomas. © 2012 Blackwell Publishing Ltd.

  13. Comprehensive Analysis of Cytomegalovirus pp65 Antigen-Specific CD8+ T Cell Responses According to Human Leukocyte Antigen Class I Allotypes and Intraindividual Dominance

    Directory of Open Access Journals (Sweden)

    Seung-Joo Hyun

    2017-11-01

    Full Text Available To define whether individual human leukocyte antigen (HLA class I allotypes are used preferentially in human cytomegalovirus (CMV-specific cytotoxic T lymphocyte responses, CD8+ T cell responses restricted by up to six HLA class I allotypes in an individual were measured in parallel using K562-based artificial antigen-presenting cells expressing both CMV pp65 antigen and one of 32 HLA class I allotypes (7 HLA-A, 14 HLA-B, and 11 HLA-C present in 50 healthy Korean donors. The CD8+ T cell responses to pp65 in the HLA-C allotypes were lower than responses to those in HLA-A and -B allotypes and there was no difference between the HLA-A and HLA-B loci. HLA-A*02:01, -B*07:02, and -C*08:01 showed the highest magnitude and frequency of immune responses to pp65 at each HLA class I locus. However, HLA-A*02:07, -B*59:01, -B*58:01, -B*15:11, -C*03:02, and -C*02:02 did not show any immune responses. Although each individual has up to six different HLA allotypes, 46% of the donors showed one allotype, 24% showed two allotypes, and 2% showed three allotypes that responded to pp65. Interestingly, the frequencies of HLA-A alleles were significantly correlated with the positivity of specific allotypes. Our results demonstrate that specific HLA class I allotypes are preferentially used in the CD8+ T cell immune response to pp65 and that a hierarchy among HLA class I allotypes is present in an individual.

  14. Immunochip analysis identifies novel susceptibility loci in the human leukocyte antigen region for acquired thrombotic thrombocytopenic purpura.

    Science.gov (United States)

    Mancini, I; Ricaño-Ponce, I; Pappalardo, E; Cairo, A; Gorski, M M; Casoli, G; Ferrari, B; Alberti, M; Mikovic, D; Noris, M; Wijmenga, C; Peyvandi, F

    2016-12-01

    Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura SUMMARY: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. Similarly to what has been found for other autoimmune disorders, there is evidence of a genetic contribution, including the association of the human leukocyte antigen (HLA) class II complex with disease risk. Objective To identify novel genetic risk factors in acquired TTP. Patients/Methods We undertook a case-control genetic association study in 190 European-origin TTP patients and 1255 Italian healthy controls by using the Illumina Immunochip. Replication analysis in 88 Italian cases and 456 controls was performed with single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We identified one common variant (rs6903608) located within the HLA class II locus that was independently associated with acquired TTP at genome-wide significance and conferred a 2.6-fold increased risk of developing a TTP episode (95% confidence interval [CI] 2.02-3.27, P = 1.64 × 10 -14 ). We also found five non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and rs1334768 (nominal P-values ranging from 1.59 × 10 -5 to 7.60 × 10 -5 ). Replication analysis confirmed the association of HLA variant rs6903608 with acquired TTP (pooled P = 3.95 × 10 -19 ). Imputation of classic

  15. Human Leukocyte Antigen Class II Alleles Are Associated with Hepatitis C Virus Natural Susceptibility in the Chinese Population

    Directory of Open Access Journals (Sweden)

    Ming Yue

    2015-07-01

    Full Text Available Human leukocyte antigen (HLA class II molecule influences host antigen presentation and anti-viral immune response. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs within HLA class II gene were associated with different clinical outcomes of hepatitis C virus (HCV infection. Three HLA class II SNPs (rs3077, rs2395309 and rs2856718 were genotyped by TaqMan assay among Chinese population, including 350 persistent HCV infection patients, 194 spontaneous viral clearance subjects and 973 HCV-uninfected control subjects. After logistic regression analysis, the results indicated that the rs2856718 TC genotype was significantly associated with the protective effect of the HCV natural susceptibility (adjusted OR: 0.712, 95% CI: 0.554–0.914 when compared with reference TT genotype, and this remained significant after false discovery rate (FDR correction (p = 0.024. Moreover, the protective effect of rs2856718 was observed in dominant genetic models (adjusted OR: 0.726, 95% CI: 0.574–0.920, and this remained significant after FDR correction (p = 0.024. In stratified analysis, a significant decreased risk was found in rs2856718C allele in the male subgroup (adjusted OR: 0.778, 95% CI: 0.627–0.966 and hemodialysis subgroup (adjusted OR: 0.713, 95% CI: 0.552–0.921. Our results indicated that the genetic variations of rs2856718 within the HLA-DQ gene are associated with the natural susceptibility to HCV infection among the Chinese population.

  16. Crystallographic Structure of the Human Leukocyte Antigen DRA, DRB3*0101: Models of a Directional Alloimmune Respone and Autoimmunity

    Energy Technology Data Exchange (ETDEWEB)

    Parry,C.; Gorski, J.; Stern, L.

    2007-01-01

    We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin {alpha}II{sub B}{beta}III glycoprotein peptide which contains a Leu/Pro dimorphism. The 33:Leu dimorphism is the epitope for the T cell directed response in neonatal alloimmune thrombocytopenia and post-transfusion purpura in individuals with the {alpha}II{sub B}{beta}III 33:Pro allele, and defines the unidirectional alloimmune response. This condition is always associated with DR52a. The crystallographic structure has been refined to 2.25 {angstrom}. There are two {alpha}{beta} heterodimers to the asymmetric unit in space group P4{sub 1}2{sub 1}2. The molecule is characterized by two prominent hydrophobic pockets at either end of the peptide binding cleft and a deep, narrower and highly charged P4 opening underneath the beta 1 chain. Further, the peptide in the second molecule displays a sharp upward turn after pocket P9. The structure reveals the role of pockets and the distinctive basic P4 pocket, shared by DR52a and DR3, in selecting their respective binding peptide repertoire. We observe an interesting switch in a residue from the canonically assigned pocket 6 seen in prior class II structures to pocket 4. This occludes the P6 pocket helping to explain the distinctive '1-4-9' peptide binding motif. A {beta}57 Asp {yields} Val substitution abrogates the salt-bridge to {alpha}76 Arg and along with a hydrophobic {beta}37 is important in shaping the P9 pocket. DRB3*0101 and DRB1*0301 belong to an ancestral haplotype and are associated with many autoimmune diseases linked to antigen presentation, but whereas DR3 is susceptible to type 1 diabetes DR52a is not. This dichotomy is explored for clues to the disease.

  17. Fine-mapping the human leukocyte antigen locus in rheumatoid arthritis and other rheumatic diseases: identifying causal amino acid variants?

    Science.gov (United States)

    van Heemst, Jurgen; Huizinga, Tom J W; van der Woude, Diane; Toes, René E M

    2015-05-01

    To provide an update on and the context of the recent findings obtained with novel statistical methods on the association of the human leukocyte antigen (HLA) locus with rheumatic diseases. Novel single nucleotide polymorphism fine-mapping data obtained for the HLA locus have indicated the strongest association with amino acid positions 11 and 13 of HLA-DRB1 molecule for several rheumatic diseases. On the basis of these data, a dominant role for position 11/13 in driving the association with these diseases is proposed and the identification of causal variants in the HLA region in relation to disease susceptibility implicated. The HLA class II locus is the most important risk factor for several rheumatic diseases. Recently, new statistical approaches have identified previously unrecognized amino acid positions in the HLA-DR molecule that associate with anticitrullinated protein antibody-negative and anticitrullinated protein antibody-positive rheumatoid arthritis. Likewise, similar findings have been made for other rheumatic conditions such as giant-cell arteritis and systemic lupus erythematosus. Interestingly, all these studies point toward an association with the same amino acid positions: amino acid positions 11 and 13 of the HLA-DR β chain. As both these positions influence peptide binding by HLA-DR and have been implicated in antigen presentation, the novel fine-mapping approach is proposed to map causal variants in the HLA region relevant to rheumatoid arthritis and several rheumatic diseases. If these interpretations are correct, they would direct the biological research aiming to address the explanation for the HLA-disease association. Here, we provide an overview of the recent findings and evidence from literature that, although relevant new insights have been obtained on HLA-disease associations, the interpretation of the biological role of these amino acids as causal variants explaining that such associations should be taken with caution.

  18. Ionizing radiation modulates the surface expression of human leukocyte antigen-G in a human melanoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Michelin, S.; Gallegos, C.E.; Dubner, D. [Radiopathology Laboratory, Nuclear Regulatory Authority, Buenos Aires (Argentina); Favier, B.; Carosella, E.D. [CEA, I2BM, Hopital Saint-Louis, IUH, Service de Recherches en Hemato-Immunologie, Paris (France)

    2009-07-01

    Human leukocyte antigen G (HLA-G) is a nonclassical HLA class I molecule involved in fetus protection from the maternal immune system, transplant tolerance, and viral and tumoral immune escape. Tumor-specific HLA-G expression has been described for a wide variety of malignancies, including melanomas. The aim of this study was to evaluate whether ionizing radiation (IR) could modulate the surface expression of HLA-G1 in a human melanoma cell line that expresses endogenously membrane-bound HLA-G1. For this purpose, cells were exposed to increasing doses of {gamma}-irradiation (0-20 Gy) and HLA-G1 levels at the plasma membrane were analyzed at different times postirradiation by flow cytometry. HLA-G total expression and the presence of the soluble form of HLA-G1 (sHLA-G1) in the culture medium of irradiated cells were also evaluated. IR was capable of down regulating cell surface and total HLA-G levels, with a concomitant increase of sHLA-G1 in the medium. These results could indicate that {gamma}-irradiation decreases HLA-G1 surface levels by enhancing the proteolytic cleavage of this molecule. (authors)

  19. Construction and application of a Korean reference panel for imputing classical alleles and amino acids of human leukocyte antigen genes.

    Science.gov (United States)

    Kim, Kwangwoo; Bang, So-Young; Lee, Hye-Soon; Bae, Sang-Cheol

    2014-01-01

    Genetic variations of human leukocyte antigen (HLA) genes within the major histocompatibility complex (MHC) locus are strongly associated with disease susceptibility and prognosis for many diseases, including many autoimmune diseases. In this study, we developed a Korean HLA reference panel for imputing classical alleles and amino acid residues of several HLA genes. An HLA reference panel has potential for use in identifying and fine-mapping disease associations with the MHC locus in East Asian populations, including Koreans. A total of 413 unrelated Korean subjects were analyzed for single nucleotide polymorphisms (SNPs) at the MHC locus and six HLA genes, including HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1. The HLA reference panel was constructed by phasing the 5,858 MHC SNPs, 233 classical HLA alleles, and 1,387 amino acid residue markers from 1,025 amino acid positions as binary variables. The imputation accuracy of the HLA reference panel was assessed by measuring concordance rates between imputed and genotyped alleles of the HLA genes from a subset of the study subjects and East Asian HapMap individuals. Average concordance rates were 95.6% and 91.1% at 2-digit and 4-digit allele resolutions, respectively. The imputation accuracy was minimally affected by SNP density of a test dataset for imputation. In conclusion, the Korean HLA reference panel we developed was highly suitable for imputing HLA alleles and amino acids from MHC SNPs in East Asians, including Koreans.

  20. Construction and application of a Korean reference panel for imputing classical alleles and amino acids of human leukocyte antigen genes.

    Directory of Open Access Journals (Sweden)

    Kwangwoo Kim

    Full Text Available Genetic variations of human leukocyte antigen (HLA genes within the major histocompatibility complex (MHC locus are strongly associated with disease susceptibility and prognosis for many diseases, including many autoimmune diseases. In this study, we developed a Korean HLA reference panel for imputing classical alleles and amino acid residues of several HLA genes. An HLA reference panel has potential for use in identifying and fine-mapping disease associations with the MHC locus in East Asian populations, including Koreans. A total of 413 unrelated Korean subjects were analyzed for single nucleotide polymorphisms (SNPs at the MHC locus and six HLA genes, including HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1. The HLA reference panel was constructed by phasing the 5,858 MHC SNPs, 233 classical HLA alleles, and 1,387 amino acid residue markers from 1,025 amino acid positions as binary variables. The imputation accuracy of the HLA reference panel was assessed by measuring concordance rates between imputed and genotyped alleles of the HLA genes from a subset of the study subjects and East Asian HapMap individuals. Average concordance rates were 95.6% and 91.1% at 2-digit and 4-digit allele resolutions, respectively. The imputation accuracy was minimally affected by SNP density of a test dataset for imputation. In conclusion, the Korean HLA reference panel we developed was highly suitable for imputing HLA alleles and amino acids from MHC SNPs in East Asians, including Koreans.

  1. Human leukocyte antigen (HLA)-G and cervical cancer immunoediting: a candidate molecule for therapeutic intervention and prognostic biomarker?

    Science.gov (United States)

    Gimenes, Fabrícia; Teixeira, Jorge Juarez Vieira; de Abreu, André Luelsdorf Pimenta; Souza, Raquel Pantarotto; Pereira, Monalisa Wolski; da Silva, Vânia Ramos Sela; Bôer, Cinthia Gandolfi; Maria-Engler, Silvya Stuchi; Bonini, Marcelo Gialluisi; Borelli, Sueli Donizete; Consolaro, Márcia Edilaine Lopes

    2014-12-01

    While persistent infection with oncogenic types of human Papillomavirus (HPV) is required for cervical epithelial cell transformation and cervical carcinogenesis, HPV infection alone is not sufficient to induce tumorigenesis. Only a minor fraction of HPV infections produce high-grade lesions and cervical cancer, suggesting complex host-virus interactions. Based on its pronounced immunoinhibitory properties, human leukocyte antigen (HLA)-G has been proposed as a possible prognostic biomarker and therapeutic target relevant in a wide variety of cancers and viral infections, but to date remains underexplored in cervical cancer. Given the possible influence of HLA-G on the clinical course of HPV infection, cervical lesions and cancer progression, a better understanding of HLA-G involvement in cervical carcinogenesis might contribute to two aspects of fundamental importance: 1. Characterization of a novel diagnostic/prognostic biomarker to identify cervical cancer and to monitor disease stage, critical for patient screening; 2. Identification of HLA-G-driven immune mechanisms involved in lesion development and cancer progression, leading to the development of strategies for modulating HLA-G expression for treatment purposes. Thus, this systematic review explores the potential involvement of HLA-G protein expression and polymorphisms in cervical carcinogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Human leukocyte antigen-G expression and polymorphisms promote cancer development and guide cancer diagnosis/treatment

    Science.gov (United States)

    Zhang, Yanwen; Yu, Shuwen; Han, Yali; Wang, Yunshan; Sun, Yuping

    2018-01-01

    Human leukocyte antigen-G (HLA-G) is a non-classical HLA molecule, predominantly expressed in cytotrophoblast cells to protect the fetus during pregnancy. Notably, a high frequency of HLA-G expression has been observed in a wide variety of cancer types in previous studies. Furthermore, HLA-G expression in cancer has been considered to be detrimental, since it can protect cancer cells from natural killer cell cytotoxic T lymphocyte-mediated destruction, promote tumor spreading and shorten the survival time of patients by facilitating tumor immune evasion. In addition, HLA-G polymorphisms have been investigated in numerous types of cancer and are considered as risk factors and predictive markers of cancer. This review focuses on HLA-G expression and its polymorphisms in cancer, analyzing the mechanisms of HLA-G in promoting cancer development, and evaluating the potential and value of its clinical application as a diagnostic and prognostic biomarker, or even as a prospective therapeutic target in certain types of tumors. PMID:29399142

  3. Human leukocyte antigen-G expression and polymorphisms promote cancer development and guide cancer diagnosis/treatment.

    Science.gov (United States)

    Zhang, Yanwen; Yu, Shuwen; Han, Yali; Wang, Yunshan; Sun, Yuping

    2018-01-01

    Human leukocyte antigen-G (HLA-G) is a non-classical HLA molecule, predominantly expressed in cytotrophoblast cells to protect the fetus during pregnancy. Notably, a high frequency of HLA-G expression has been observed in a wide variety of cancer types in previous studies. Furthermore, HLA-G expression in cancer has been considered to be detrimental, since it can protect cancer cells from natural killer cell cytotoxic T lymphocyte-mediated destruction, promote tumor spreading and shorten the survival time of patients by facilitating tumor immune evasion. In addition, HLA-G polymorphisms have been investigated in numerous types of cancer and are considered as risk factors and predictive markers of cancer. This review focuses on HLA-G expression and its polymorphisms in cancer, analyzing the mechanisms of HLA-G in promoting cancer development, and evaluating the potential and value of its clinical application as a diagnostic and prognostic biomarker, or even as a prospective therapeutic target in certain types of tumors.

  4. Human Leukocyte Antigen Typing Using a Knowledge Base Coupled with a High Throughput Oligonucleotide Probe Array Analysis

    Directory of Open Access Journals (Sweden)

    Vladimir eBrusic

    2014-11-01

    Full Text Available Human leukocyte antigens (HLA are important biomarkers since multiple diseases, drug toxicity, and vaccine responses reveal strong HLA associations. Current clinical HLA typing is an elimination process requiring serial testing. We present an alternative an in situ synthesized DNA-based microarray method that contains hundreds of thousands of probes representing a complete overlapping set covering 1,610 clinically relevant HLA class I alleles accompanied by computational tools for assigning HLA type to 4-digit resolution. Our proof-of-concept experiment included 21 blood samples, 18 cell lines, and multiple controls. The method is accurate, robust, and amenable to automation. Typing errors were restricted to homozygous samples or those with very closely related alleles from the same locus, but readily resolved by targeted DNA sequencing validation of flagged samples. High-throughput HLA typing technologies that are effective, yet inexpensive, can be used to analyze the world’s populations, benefiting both global public health and personalized health care.

  5. Role of human leukocyte antigen-G in the induction of adaptive type 1 regulatory T cells.

    Science.gov (United States)

    Gregori, Silvia; Magnani, Chiara Francesca; Roncarolo, Maria-Grazia

    2009-12-01

    Adaptive type 1 regulatory T (Tr1) cells are suppressor cells characterized by the production of interleukin (IL)-10 in the absence of IL-4. IL-10 is essential not only for suppression of effector cells by Tr1 cells, but also for their differentiation in vitro and in vivo. However, little is known on the molecular mechanisms underneath the IL-10-mediated induction of Tr1 cells. Human Leukocyte Antigen (HLA)-G, a non-classical HLA class I molecule, has both direct inhibitory effects on natural killer cells, dendritic cells (DC), and T cells and long-term tolerogenic indirect effects by inducing regulatory T (Tr) cells. In the present review, we discuss current findings on Tr-cell induction by the different isoforms of HLA-G, focusing on the relationship among HLA-G, its ligands, and IL-10. We recently described a subset of human DC, termed DC-10, that express high levels of HLA-G and ILT4, secrete high amounts of IL-10, and induce allospecific Tr1 cells in vitro via an IL-10-dependent ILT4/HLA-G pathway. IL-10, HLA-G, and ILT4 may also be involved in Tr1-cell induction in vivo. Overall, these data demonstrate that cross-regulation between IL-10 and HLA-G may be instrumental for Tr1-cell induction and tolerance.

  6. Natural Killer Cell Interactions with Classical and Non-Classical Human Leukocyte Antigen Class I in HIV-1 Infection

    Science.gov (United States)

    Hölzemer, Angelique; Garcia-Beltran, Wilfredo F.; Altfeld, Marcus

    2017-01-01

    Natural killer (NK) cells are effector lymphocytes of the innate immune system that are able to mount a multifaceted antiviral response within hours following infection. This is achieved through an array of cell surface receptors surveilling host cells for alterations in human leukocyte antigen class I (HLA-I) expression and other ligands as signs of viral infection, malignant transformation, and cellular stress. This interaction between HLA-I ligands and NK-cell receptor is not only important for recognition of diseased cells but also mediates tuning of NK-cell-effector functions. HIV-1 alters the expression of HLA-I ligands on infected cells, rendering them susceptible to NK cell-mediated killing. However, over the past years, various HIV-1 evasion strategies have been discovered to target NK-cell-receptor ligands and allow the virus to escape from NK cell-mediated immunity. While studies have been mainly focusing on the role of polymorphic HLA-A, -B, and -C molecules, less is known about how HIV-1 affects the more conserved, non-classical HLA-I molecules HLA-E, -G, and -F. In this review, we will focus on the recent progress in understanding the role of non-classical HLA-I ligands in NK cell-mediated recognition of HIV-1-infected cells. PMID:29184550

  7. Cytokine and human leukocyte antigen (HLA) profile for graft-versus-host disease (GVHD) after organ transplantation.

    Science.gov (United States)

    Chen, Xinhua; Meng, Xueqin; Xu, Yuning; Xie, Haiyang; Yin, Shengyong; Li, Hongchun; Wu, Liming; Zheng, Shusen

    2016-10-12

    Graft-versus-host disease (GVHD) after liver and kidney transplantation has high mortality and causes diagnostic challenges. This study aims to describe the cytokine and human leukocyte antigen (HLA) profile in the GVHD after liver and kidney transplantation. A high-throughput detection kit was applied and altogether 18 different cytokines were tested simultaneously. GVHD patients included 23 post-liver transplantation patients; 22 post-renal transplantation patients; The control patients include 22 hepatocellular carcinoma (HCC) patients without transplantation and 20 healthy controls. Their HLA characters were compared. The full spectrum of cytokines was present. The inflammatory markers were activated significantly in liver transplantation. The level of inflammatory markers in liver transplantation was higher than that in renal transplantation, HCC or healthy controls. GVHD was associated with the HLA characters; HLA characters are involved in liver GVHD occurrence and act as risk factors. Our findings confirmed that the inflammatory cytokines play a pathogenic role in GVHD and can be used as early diagnostic markers. The HLA mismatch acts as a risk factor in liver transplantation to predict GVHD occurrence.

  8. Swine Leukocyte Antigen- Gene Variation and Its Association with Piglet Diarrhea in Large White, Landrace and Duroc

    Directory of Open Access Journals (Sweden)

    Q. L. Yang

    2013-08-01

    Full Text Available The swine leukocyte antigen class II molecules are possibly associated with the induction of protective immunity. The study described here was to investigate the relationship between polymorphisms in exon 2 of the swine DQA gene and piglet diarrhea. This study was carried out on 425 suckling piglets from three purebred pig strains (Large White, Landrace and Duroc. The genetic diversity of exon 2 in swine DQA was detected by PCR-SSCP and sequencing analysis, eight unique SSCP patterns (AB, BB, BC, CC, CD, BD, BE and DD representing five specific allele (A to E sequences were detected. Sequence analysis revealed 21 nucleotide variable sites and resulting in 12 amino acid substitutions in the populations. A moderate level polymorphism and significant deviations from Hardy-Weinberg equilibrium of the genotypes distribution were observed in the populations (p<0.01. The association analysis indicated that there was a statistically significant difference in the score of piglet diarrhea between different genotypes, individuals with genotype CC showed a lower diarrhea score than genotypes AB (0.98±0.09, BB (0.85±0.77 and BC (1.25±0.23 (p<0.05, and significantly low than genotype BE (1.19±0.19 (p<0.01, CC genotype may be a most resistance genotype for piglet diarrhea.

  9. A crypto-Dravidian origin for the nontribal communities of South India based on human leukocyte antigen class I diversity.

    Science.gov (United States)

    Thomas, R; Nair, S B; Banerjee, M

    2006-09-01

    The Dravidian communities are considered to be the original inhabitants of India, now restricted to South India. The southern most state, Kerala, is socio-culturally stratified into Hindus, Muslims and Christians on the basis of religion. The origin of these religious communities in Kerala is considered to be unique in comparison with that in other parts of the country. These communities were later influenced by the hierarchical caste structure established by the Hindu Brahmins. In the present study, we compared six nontribal (Namboothiri, Nair, Ezhava, Pulaya, Malabar Muslim and Syrian Christian) communities belonging to the major religious groups in Kerala (Hindu, Muslim and Christian) based on the human leukocyte antigen (HLA)-A, -B and -C diversity. Our aim was to understand the genomic substructuring associated with the changing social scenario in various caste and religious groups and compare it with the Dravidian tribal and other world populations. The present study reveals that the HLA diversity of the Dravidian communities is very distinct from that in the other world populations. It is obvious that the nontribal communities of Kerala display a greater Dravidian influence, but traces of genetic admixture with the Mediterranean, western European, central Asian and East Asian populations can be observed. This characterizes the crypto-Dravidian features of the nontribal communities of Kerala. Demic diffusion of the local progressive communities with the migrant communities may have given rise to crypto-Dravidian features among the nontribal communities of Kerala.

  10. Whole blood transcriptional profiling reveals significant down-regulation of human leukocyte antigen class I and II genes in essential thrombocythemia, polycythemia vera and myelofibrosis

    DEFF Research Database (Denmark)

    Skov, Vibe; Riley, Caroline Hasselbalch; Thomassen, Mads

    2013-01-01

    be down-regulation of major histocompatibility (MHC) class I and II genes, which are used by tumor cells to escape antitumor T-cell-mediated immune responses. We have performed whole blood transcriptional profiling of genes encoding human leukocyte antigen (HLA) class I and II molecules, β2-microglobulin...... and members of the antigen processing machinery of HLA class I molecules (LMP2, LMP7, TAP1, TAP2 and tapasin). The findings of significant down-regulation of several of these genes may possibly be of major importance for defective tumor immune surveillance. Since up-regulation of HLA genes is recorded during...

  11. A modern approach for epitope prediction: identification of foot-and-mouth disease virus peptides binding bovine leukocyte antigen (BoLA) class I molecules

    DEFF Research Database (Denmark)

    Pandya, Mital; Rasmussen, Michael; Hansen, Andreas

    2015-01-01

    Major histocompatibility complex (MHC) class I molecules regulate adaptive immune responses through the presentation of antigenic peptides to CD8+ T cells. Polymorphisms in the peptide binding region of class I molecules determine peptide binding affinity and stability during antigen presentation......, and different antigen peptide motifs are associated with specific genetic sequences of class I molecules. Understanding bovine leukocyte antigen (BoLA), peptide-MHC class I binding specificities may facilitate development of vaccines or reagents for quantifying the adaptive immune response to intracellular...... pathogens, such as foot-and-mouth disease virus (FMDV). Six synthetic BoLA class I (BoLA-I) molecules were produced, and the peptide binding motif was generated for five of the six molecules using a combined approach of positional scanning combinatorial peptide libraries (PSCPLs) and neural network...

  12. Human leukocyte antigen HLADRB1 determinants susceptibility to gastroesophageal reflux disease

    Directory of Open Access Journals (Sweden)

    Batool Mutar MAHDI

    Full Text Available ABSTRACT BACKGROUND Gastroesophageal reflux disease (GERD is characterized by diverse symptoms. There is an evidence for a genetic component to GERD as supported by familial aggregation of this disease. OBJECTIVE To investigate whether certain human leucocyte antigen genes HLA-DRB1 are associated with GERD. METHODS Patients and controls were prospectively recruited from GIT center at Al-Kindy Teaching Hospital (Baghdad-Iraq between January 2014 and July 2016. Sixty Iraqi Arab Muslims patients with a history of heartburn and dyspepsia compared with 100 Iraqi Arab Muslims controls. All study patients and control groups underwent upper gastrointestinal endoscopic examinations and their serums were analyzed for CagA antibodies Immunoglobulin G (IgG for H. pylori. HLA-DRB1 genotyping were done to both groups. RESULTS A total of 60 patients with erosive gastritis; GERD (Grade II and III were evaluated, together with 100 controls. There is a significant increase of H. pylori infection (P=0.0001 in GERD patients than control group. HLA-DRB1* 15:01 was significantly increased in GERD patients in comparison with control group and an increased frequency of HLADRB1*11:01 in control group compared with patients group. CONCLUSION There is an association between HLA-DRB1 *15:01 in GERD patients with H. pylori positive patients.

  13. Genetic considerations in human sex-mate selection: partners share human leukocyte antigen but not short-tandem-repeat identity markers.

    Science.gov (United States)

    Israeli, Moshe; Kristt, Don; Nardi, Yuval; Klein, Tirza

    2014-05-01

    Previous studies support a role for MHC on mating preference, yet it remains unsettled as to whether mating occurs preferentially between individuals sharing human leukocyte antigen (HLA) determinants or not. Investigating sex-mate preferences in the contemporary Israeli population is of further curiosity being a population with distinct genetic characteristics, where multifaceted cultural considerations influence mate selection. Pairs of male-female sex partners were evaluated in three groups. Two groups represented unmarried (n = 1002) or married (n = 308) couples and a control group of fictitious male-female couples. HLA and short-tandem-repeat (STR) genetic identification markers were assessed for the frequency of shared antigens and alleles. Human leukocyte antigen results showed that Class I and/ or Class II single antigen as well as double antigen sharing was more common in sex partners than in control group couples (P < 0.001). Married versus unmarried pairs were not distinguishable. In contrast, STR-DNA markers failed to differentiate between sex-mates and controls (P = 0.78). Sex partnerships shared HLA determinants more frequently than randomly constituted male-female pairs. The observed phenomenon does not reflect a syngenetic background between sex-mates as STR markers were not selectively shared. Thus, sex-mate selection in man may contravene the evolutionary pressure for genetic diversity in regard to HLA. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Long-term in vitro reactivity for human leukocyte antigen antibodies and comparison of detection using serum versus plasma.

    Science.gov (United States)

    Norris, Philip J; Lee, Jar-How; Carrick, Danielle M; Gottschall, Jerome L; Lebedeva, Mila; de Castro, B R; Kleinman, Steven H; Busch, Michael P

    2009-02-01

    Human leukocyte antigen (HLA) antibodies are a possible cause of transfusion-related acute lung injury (TRALI), and fluorescent bead assays are often used for antibody detection. Serum is the manufacturer's recommended sample, but plasma may be easier to obtain for studies of HLA antibody prevalence and TRALI case investigations. Specimens were obtained from 44 multiparous females positive for the presence of HLA antibodies by lymphocytotoxicity testing at least 13 years prior and from 1000 contemporary blood donors. Screening tests were performed using a multiplex bead-based assay. In addition to comparing results obtained with paired plasma and serum samples, the effects of storage at 4 degrees C for 1 week and of multiple freeze-thaw cycles were evaluated. Of 42 evaluable subjects with HLA antibodies documented more than 13 years earlier, only 1 showed loss of detectable antibodies, with 39 (93%) positive in the screening assay for HLA Class I and 24 (57%) positive in the screening assay for HLA Class II antibodies. In 968 evaluable contemporary donors, 291 screened positive for the presence of HLA Class I and 206 for HLA Class II antibodies using a low assay cutoff. Screening test concordance using paired plasma and serum samples was high, particularly for subjects with higher-level antibodies. Refrigeration of samples for 1 week did not significantly affect assay results, while repeated freeze-thaw cycles caused a decrement in signal level. Serum and plasma samples gave concordant results in the majority of cases, particularly for specimens with higher-level antibodies. High-level HLA antibodies were present in most individuals for more than 13 years.

  15. The prognostic impact of programmed cell death ligand 1 and human leukocyte antigen class I in pancreatic cancer.

    Science.gov (United States)

    Imai, Daisuke; Yoshizumi, Tomoharu; Okano, Shinji; Uchiyama, Hideaki; Ikegami, Toru; Harimoto, Norifumi; Itoh, Shinji; Soejima, Yuji; Aishima, Shinichi; Oda, Yoshinao; Maehara, Yoshihiko

    2017-07-01

    Pancreatic ductal adenocarcinoma (PDA) is associated with an immunosuppressive tumor-microenvironment (TME) that supports the growth of tumors and mediates tumors enabling evasion of the immune system. Expression of programmed cell death ligand 1 (PD-L1) and loss of human leukocyte antigen (HLA) class I on tumor cells are methods by which tumors escape immunosurveillance. We examined immune cell infiltration, the expression of PD-L1 and HLA class I by PDA cells, and the correlation between these immunological factors and clinical prognosis. PDA samples from 36 patients were analyzed for HLA class I, HLA-DR, PD-L1, PD-1, CD4, CD8, CD56, CD68, and FoxP3 expression by immunohistochemistry. The correlations between the expression of HLA class I, HLA-DR, PD-L1 or PD-1 and the pattern of tumor infiltrating immune cells or the patients' prognosis were assessed. PD-L1 expression correlated with tumor infiltration by CD68 + and FoxP3 + cells. Low HLA class I expression was an only risk factor for poor survival. PD-L1 negative and HLA class I high-expressing PDA was significantly associated with higher numbers of infiltrating CD8 + T cells in the TME, and a better prognosis. Evaluation of both PD-L1 and HLA class I expression by PDA may be a good predictor of prognosis for patients. HLA class I expression by tumor cells should be evaluated when selecting PDA patients who may be eligible for treatment with PD-1/PD-L1 immune checkpoint blockade therapies. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  16. Lesion human leukocyte antigen-F expression is associated with a poor prognosis in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Xu, Yongfu; Han, Haixiong; Zhang, Fabiao; Lv, Shangdong; Li, Zhengyu; Fang, Zheping

    2015-01-01

    Human leukocyte antigen (HLA)-F, a non-classical HLA-class I molecule, has attracted attention as an important immunosuppressive molecule in recent years, although the clinical relevance of HLA-F expression in cancer patients remains unclear. In the present study, HLA-F expression in 90 primary hepatocellular carcinoma (HCC) lesions and 55 corresponding adjacent normal liver tissues was analyzed by immunohistochemistry, and the associations between HLA-F expression and clinicopathological parameters and patient survival times were analyzed. Positive HLA-F expression was observed in 47.8% (43/90) of the HCC lesions and in 10.9% (6/55) of the normal liver tissues. HLA-F expression in HCC lesions was significantly correlated with patient gender (P=0.02), and venous or lymphatic invasion (P=0.02). Patients who were HLA-F-positive had worse survival times than those who were HLA-F-negative (P=0.04). The mean overall survival times for HLA-F-negative and -positive patients were 44.2 months [95% confidence interval (CI), 37.7-50.7] and 33.0 months (95% CI, 25.1-40.8), respectively. Multivariate analysis revealed that HLA-F was an independent prognostic factor for HCC patients with a hazard ratio of 2.1 (95% CI, 1.0-4.4). In conclusion, the present study demonstrated that HLA-F expression was associated with poor survival in HCC patients, and is correlated with tumor cell invasion and metastasis.

  17. Nonclassical human leukocyte antigen (HLA-G, HLA-E, and HLA-F) in coronary artery disease.

    Science.gov (United States)

    Zidi, Ines; Kharrat, Najla; Abdelhedi, Rania; Hassine, Amna Ben; Laaribi, Ahmed Baligh; Yahia, Hamza Ben; Abdelmoula, Nouha Bouayed; Abid, Leila; Rebai, Ahmed; Rizzo, Roberta

    2016-04-01

    Several evidences suggest the association between the evolution of coronary artery disease (CAD) and the development of coronary syndrome that is often associated with disrupted plaque and partial or complete thrombosis of the related artery. Because of the inflammatory nature of CAD, we investigated the human leukocyte antigen (HLA)-G, HLA-E, and HLA-F genetic polymorphisms within CAD patients and evaluated their potential association with this disease in Tunisian population. Different polymorphisms in HLA-G (14-bp Insertion/Deletion, +3142C/G), HLA-E (HLA-E*01:01/01:03 A/G), HLA-F (HLA-F*01:02 T/C, 01:03 C/T, 01:04 A/C) genes were typed using different laboratory techniques in a cohort of 89 CAD patients and 84 controls. A significant association was reported between the HLA-G +3142 G allele (OR=1.64, 95% CI=1.05-2.56, p=0.02) and increased risk of CAD. No association was found for the other studied polymorphisms. When we considered the haplotypes, we found TDELCA and TDELGG haplotypes associated to CAD with p=0.008 and p=0.030, respectively, suggesting the potential interaction between HLA-G and HLA-E genes. Our findings indicated that the HLA-G +3142C/G polymorphism and TDELCA and TDELGG haplotypes can harbour a reliable diagnosis value for the risk of CAD development suggesting that HLA-G, -E and -F molecules might be involved in the pathogenesis of the disease. However, further studies are necessary to confirm our results. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  18. Modulation of Human Leukocyte Antigen-C by Human Cytomegalovirus Stimulates KIR2DS1 Recognition by Natural Killer Cells.

    Science.gov (United States)

    van der Ploeg, Kattria; Chang, Chiwen; Ivarsson, Martin A; Moffett, Ashley; Wills, Mark R; Trowsdale, John

    2017-01-01

    The interaction of inhibitory killer cell Ig-like receptors (KIRs) with human leukocyte antigen (HLA) class I molecules has been characterized in detail. By contrast, activating members of the KIR family, although closely related to inhibitory KIRs, appear to interact weakly, if at all, with HLA class I. KIR2DS1 is the best studied activating KIR and it interacts with C2 group HLA-C (C2-HLA-C) in some assays, but not as strongly as KIR2DL1. We used a mouse 2B4 cell reporter system, which carries NFAT-green fluorescent protein with KIR2DS1 and a modified DAP12 adaptor protein. KIR2DS1 reporter cells were not activated upon coculture with 721.221 cells transfected with different HLA-C molecules, or with interferon-γ stimulated primary dermal fibroblasts. However, KIR2DS1 reporter cells and KIR2DS1 + primary natural killer (NK) cells were activated by C2-HLA-C homozygous human fetal foreskin fibroblasts (HFFFs) but only after infection with specific clones of a clinical strain of human cytomegalovirus (HCMV). Active viral gene expression was required for activation of both cell types. Primary NKG2A - KIR2DS1 + NK cell subsets degranulated after coculture with HCMV-infected HFFFs. The W6/32 antibody to HLA class I blocked the KIR2DS1 reporter cell interaction with its ligand on HCMV-infected HFFFs but did not block interaction with KIR2DL1. This implies a differential recognition of HLA-C by KIR2DL1 and KIR2DS1. The data suggest that modulation of HLA-C by HCMV is required for a potent KIR2DS1-mediated NK cell activation.

  19. Association between Genetic Polymorphism in the Swine Leukocyte Antigen- Gene and Piglet Diarrhea in Three Chinese Pig Breeds

    Directory of Open Access Journals (Sweden)

    Q. L. Yang

    2014-09-01

    Full Text Available The swine leukocyte antigen (SLA-DRA locus is noteworthy among other SLA class II loci for its limited variation and has not been investigated in depth. This study was investigated to detect polymorphisms of four exons of SLA-DRA gene and its association with piglet diarrhea in Landrace, Large White and Duroc pigs. No polymorphisms were detected in exon 3, while 2 SNPs (c.178G>A and c.211T>C, 2 SNPs (c.3093A>C and c.3104C>T and 5 SNPs (c.4167A>G, c.4184A>G, c.4194A>G, c.4246A>G and c.4293G>A were detected in exon 1, exon 2 and exon 4 respectively, and 1 SNP (c.4081T>C in intron 3. Statistical results showed that genotype had significant effect on piglet diarrhea, individuals with genotype BC had a higher diarrhea score when compared with the genotypes AA, AB, AC and CC. Futhermore, genotype AC had a higher diarrhea score than the genotype CC in exon 1 (p<0.05; diarrhea scores of genotype AA and BB were higher than those of genotypes AC and CC in exon 2 (p<0.05; individuals with genotype AA had a higher diarrhea score than individuals with genotype AB and BB in exon 4 (p<0.05. Fourteen common haplotypes were founded by haplotype constructing of all SNPs in the three exons, its association with piglet diarrhea appeared that Hap2, 5, 8, 10, and 14 may be the susceptible haplotypes and Hap9 may be the resistant haplotype to piglet diarrhea. The genetic variations identified of the SLA-DRA gene may potentially be functional mutations related to piglet diarrhea.

  20. Comparative case control study of clinical features and human leukocyte antigen susceptibility between familial and nonfamilial vitiligo

    Directory of Open Access Journals (Sweden)

    Misri Rachita

    2009-01-01

    Full Text Available Background: Various studies worldwide suggest that human leukocyte antigen (HLA region may be involved in the genetic susceptibility of vitiligo but little information is available from India. Aim: To find the HLA associated susceptibility to develop vitiligo in Indian patients and to detect role of HLA in familial vitiligo. Methods: This was a case controlled study which included all patients suffering from vitiligo over a period of one and half years. Clinical details were noted and sera collected from these patients were screened for the presence of HLA class I antibodies. The clinical features and HLA antigens were assessed and comparison was made between patients with familial and nonfamilial vitiligo. Results: Out of 114 patients studied, 84 had family history and 30 had no family history. Patients with family history of vitiligo have higher chances of acquiring vitiligo if first degree relatives are affected compared to if second degree relatives are affected. Family history of vitiligo is associated with an early onset of vitiligo (< 20 years. There was no statistically significant difference in the type, stability, and severity of vitiligo in both the groups. HLA results in both the groups revealed increase in HLA A2, A11, A31, A33, B17, B35, B40, and B44 alleles while HLA A9, B13, and B53 alleles were decreased. Family history was associated with HLA A2, A28, A31, and B44 alleles. Early onset of vitiligo (< 20 years was significantly associated with HLA A2, A11, B17, B35, and B44 alleles. The patients with severe affection (> 10% area showed in significant association with HLA A10 and B8. Conclusion: Family history of vitiligo is associated with an early onset of vitiligo. There is no correlation of family history with the type of vitiligo, stability of lesions, and areas involved. Severity is not associated with family history. Apart from other alleles, alleles A2, and B44 play a significant role in vitiligo in the Indian patients.

  1. Human leukocyte antigen-G expression in differentiated human airway epithelial cells: lack of modulation by Th2-associated cytokines

    Directory of Open Access Journals (Sweden)

    White Steven R

    2013-01-01

    Full Text Available Abstract Background Human leukocyte antigen (HLA-G is a nonclassical class I antigen with immunomodulatory roles including up-regulation of suppressor T regulatory lymphocytes. HLA-G was recently identified as an asthma susceptibility gene, and expression of a soluble isoform, HLA-G5, has been demonstrated in human airway epithelium. Increased presence of HLA-G5 has been demonstrated in bronchoalveolar lavage fluid recovered from patients with mild asthma; this suggests a role for this isoform in modulating airway inflammation though the mechanisms by which this occurs is unclear. Airway inflammation associated with Th2 cytokines such as IL-4 and IL-13 is a principal feature of asthma, but whether these cytokines elicit expression of HLA-G is not known. Methods We examined gene and protein expression of both soluble (G5 and membrane-bound (G1 HLA-G isoforms in primary differentiated human airway epithelial cells collected from normal lungs and grown in air-liquid interface culture. Cells were treated with up to 10 ng/ml of either IL-4, IL-5, or IL-13, or 100 ng/ml of the immunomodulatory cytokine IL-10, or 10,000 U/ml of the Th1-associated cytokine interferon-beta, for 24 hr, after which RNA was isolated for evaluation by quantitative PCR and protein was collected for Western blot analysis. Results HLA-G5 but not G1 was present in dAEC as demonstrated by quantitative PCR, western blot and confocal microscopy. Neither G5 nor G1 expression was increased by the Th2-associated cytokines IL-4, IL-5 or IL-13 over 24 hr, nor after treatment with IL-10, but was increased 4.5 ± 1.4 fold after treatment with 10,000 U/ml interferon-beta. Conclusions These data demonstrate the constitutive expression of a T lymphocyte regulatory molecule in differentiated human airway epithelial cells that is not modulated by Th2-associated cytokines.

  2. Low expression of soluble human leukocyte antigen G in early gestation and subsequent placenta-mediated complications of pregnancy.

    Science.gov (United States)

    Marozio, Luca; Garofalo, Anna; Berchialla, Paola; Tavella, Anna Maria; Salton, Loredana; Cavallo, Franco; Benedetto, Chiara

    2017-09-01

    Abnormal placentation is a common pathogenic mechanism of many placenta-mediated complications of late pregnancy, including pre-eclampsia, fetal growth restriction, stillbirth, and placental abruption. During successful placentation, the trophoblast (which is a semi-allograft) is not rejected by decidual immune cells because of maternal immune tolerance, mainly induced by human leukocyte antigen G (HLA-G). Deficient HLA-G expression seems to be associated with the development of complications of pregnancy. The aim of this study was to determine whether low soluble HLA-G (sHLA-G) levels in maternal blood at the beginning of pregnancy may be associated with subsequent placenta-mediated complications. For this retrospective case-control study, 117 cases of placenta-mediated complications of pregnancy and 234 controls with uneventful pregnancy were selected. Plasma sHLA-G levels were measured at 11-13 weeks' gestation by the enzyme-linked immunosorbent assay method in blood samples previously obtained at first-trimester prenatal screening for chromosomal fetal abnormalities. Women who subsequently developed placenta-mediated complications had significantly lower sHLA-G levels at the beginning of pregnancy (median, 43.08 IU/mL) than controls (median, 49.10 IU/mL; P = 0.008). An sHLA-G level lower than 43.50 IU/mL at the end of the first trimester was associated with a twofold increased risk of developing a pregnancy complication (odds ratio, 1.82; 95% confidence interval, 1.22-2.73). The strongest association, although only moderately strong, was observed with severe pre-eclampsia (odds ratio, 2.66; 95% confidence interval, 1.08-6.56). Placenta-mediated complications of pregnancy may be associated with low sHLA-G levels in the first trimester, suggesting a potential role of sHLA-G in the early stages of placentation. © 2017 Japan Society of Obstetrics and Gynecology.

  3. Human leukocyte antigen class I and II alleles and cervical adenocarcinoma: a pooled analysis of two epidemiologic studies

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    Mahboobeh eSafaeian

    2014-06-01

    Full Text Available Associations between human leukocyte antigens (HLA alleles and cervical cancer are largely representative of squamous cell carcinoma (SCC, the major histologic subtype. We evaluated the association between HLA class I (A, B, and C and class II (DRB1 and DQB1 loci and risk of cervical adenocarcinoma (ADC, a less common but aggressive histologic subtype.We pooled data from the Eastern and Western US cervical cancer studies, and evaluated the association between individual alleles and allele combinations and ADC (n=630 ADC; n=775 controls. Risk estimates were calculated for 11 a priori (based on known associations with cervical cancer regardless of histologic type and 38 non a priori common alleles, as odds ratios (OR and 95% confidence intervals (CI, adjusted for age and study. In exploratory analysis, we compared the risk associations between subgroups with HPV16 or HPV18 DNA in ADC tumor tissues in the Western US study cases and controls. Three of the a priori alleles were significantly associated with decreased risk of ADC (DRB1*13:01 (OR=0.61; 95%CI:0.41-0.93, DRB1*13:02 (OR=0.49; 95%CI:0.31-0.77, and DQB1*06:03 (OR=0.64; 95%CI:0.42-0.95; one was associated with increased risk (B*07:02(OR=1.39; 95%CI:1.07-1.79. Among alleles not previously reported, DQB1*06:04 (OR=0.46; 95%CI: 0.27-0.78 was associated with decreased risk of ADC and C*07:02 (OR=1.41; 95%CI:1.09-1.81 was associated with increased risk. We did not observe a difference by histologic subtype. ADC was most strongly associated with increased risk with B*07:02/C*07:02 alleles (OR=1.33; 95%CI:1.01-1.76 and decreased risk with DRB1*13:02/DQB1*06:04 (OR=0.41; 95%CI:0.21-0.80. Results suggest that HLA allele associations with cervical ADC are similar to those for cervical SCC. An intriguing finding was the difference in risk associated with several alleles restricted to HPV16 or HPV18 related tumors, consistent with the hypothesis that HLA recognition is HPV type specific.

  4. Identification of Lck-derived peptides applicable to anti-cancer vaccine for patients with human leukocyte antigen-A3 supertype alleles

    OpenAIRE

    Naito, M; Komohara, Y; Ishihara, Y; Noguchi, M; Yamashita, Y; Shirakusa, T; Yamada, A; Itoh, K; Harada, M

    2007-01-01

    The identification of peptide vaccine candidates to date has been focused on human leukocyte antigen (HLA)-A2 and -A24 alleles. In this study, we attempted to identify cytotoxic T lymphocyte (CTL)-directed Lck-derived peptides applicable to HLA-A11+, -A31+, or -A33+ cancer patients, because these HLA-A alleles share binding motifs, designated HLA-A3 supertype alleles, and because the Lck is preferentially expressed in metastatic cancer. Twenty-one Lck-derived peptides were prepared based on t...

  5. The expression and functional activity of membrane-bound human leukocyte antigen-G1 are influenced by the 3'-untranslated region

    DEFF Research Database (Denmark)

    Svendsen, Signe Goul; Hantash, Basil M; Zhao, Longmei

    2013-01-01

    Human Leukocyte Antigen (HLA)-G is an immunosuppressive molecule acting on both the innate and adaptive immune system. A 14 bp insertion/deletion polymorphism (rs66554220) in the 3'-untranslated region (3'UTR) of the HLA-G gene has been associated with a number of diseases, pregnancy complications...... insertion were the most efficient in inhibiting NK cytotoxicity but showed a lower soluble HLA-G1 per mHLA-G1 ratio than the HLA-G1 K562 cells lacking the 14 bp insertion. Our data suggest 3'UTR polymorphism may play an important role in HLA-G regulation with implications on a range of diseases....

  6. Immunological recovery and dose evaluation in IFN-alpha treatment of hairy cell leukemia: analysis of leukocyte differentiation antigens, NK and 2',5'-oligoadenylate synthetase activity

    DEFF Research Database (Denmark)

    Nielsen, B; Hokland, M; Justesen, J

    1989-01-01

    , the number of NK cells normalized in 90 to 180 d, whereas normalization of B cell number was seen only after 180 to 360 d of treatment. Mean pretreatment 2-5A synthetase activity was normal or low, but upon treatment the levels rose immediately to higher than normal values and remained high throughout......A low-dose interferon (IFN)-alpha regimen for the treatment of hairy cell leukemia (HCL) was evaluated by following changes in leukocyte differentiation antigens (LDA), natural killer cell (NK) and 2',5'-oligoadenylate (2-5A) synthetase activities. Due to hairy cells' (HC) weak expression...... of several antigens positive for T cells, B cells, NK cells and monocytes, the use of a double marker specific for hairy cells was needed to distinguish the different subpopulations. Analysis of LDA in peripheral blood (PB) showed a total normalization of the T cell and monocyte numbers within 90 days...

  7. Nonstructural Protein 4 of Porcine Reproductive and Respiratory Syndrome Virus Modulates Cell Surface Swine Leukocyte Antigen Class I Expression by Downregulating β2-Microglobulin Transcription.

    Science.gov (United States)

    Qi, Pengfei; Liu, Ke; Wei, Jianchao; Li, Yuming; Li, Beibei; Shao, Donghua; Wu, Zhuanchang; Shi, Yuanyuan; Tong, Guangzhi; Qiu, Yafeng; Ma, Zhiyong

    2017-03-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of PRRS, which has important impacts on the pig industry. PRRSV infection results in disruption of the swine leukocyte antigen class I (SLA-I) antigen presentation pathway. In this study, highly pathogenic PRRSV (HP-PRRSV) infection inhibited transcription of the β2-microglobulin (β2M) gene ( B2M ) and reduced cellular levels of β2M, which forms a heterotrimeric complex with the SLA-I heavy chain and a variable peptide and plays a critical role in SLA-I antigen presentation. HP-PRRSV nonstructural protein 4 (Nsp4) was involved in the downregulation of β2M expression. Exogenous expression of Nsp4 downregulated β2M expression at both the mRNA and the protein level and reduced SLA-I expression on the cell surface. Nsp4 bound to the porcine B2M promoter and inhibited its transcriptional activity. Domain III of Nsp4 and the enhancer PAM element of the porcine B2M promoter were identified as essential for the interaction between Nsp4 and B2M These findings demonstrate a novel mechanism whereby HP-PRRSV may modulate the SLA-I antigen presentation pathway and provide new insights into the functions of HP-PRRSV Nsp4. IMPORTANCE PRRSV modulates the host response by disrupting the SLA-I antigen presentation pathway. We show that HP-PRRSV downregulates SLA-I expression on the cell surface via transcriptional inhibition of B2M expression by viral Nsp4. The interaction between domain III of Nsp4 and the enhancer PAM element of the porcine B2M promoter is essential for inhibiting B2M transcription. These observations reveal a novel mechanism whereby HP-PRRSV may modulate SLA-I antigen presentation and provide new insights into the functions of viral Nsp4. Copyright © 2017 American Society for Microbiology.

  8. Protective Effect of Human Leukocyte Antigen (HLA Allele DRB1*13:02 on Age-Related Brain Gray Matter Volume Reduction in Healthy Women

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    Lisa M. James

    2018-03-01

    Full Text Available Background: Reduction of brain volume (brain atrophy during healthy brain aging is well documented and dependent on genetic, lifestyle and environmental factors. Here we investigated the possible dependence of brain gray matter volume reduction in the absence of the Human Leukocyte Antigen (HLA allele DRB1*13:02 which prevents brain atrophy in Gulf War Illness (James et al., 2017. Methods: Seventy-one cognitively healthy women (32–69 years old underwent a structural Magnetic Resonance Imaging (sMRI scan to measure the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter. Participants were assigned to two groups, depending on whether they lacked the DRB1*13:02 allele (No DRB1*13:02 group, N = 60 or carried the DRB1*13:02 allele (N = 11. We assessed the change of brain gray matter volume with age in each group by performing a linear regression where the brain volume (adjusted for total intracranial volume was the dependent variable and age was the independent variable. Findings: In the No DRB1*13:02 group, the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter were reduced highly significantly. In contrast, none of these volumes showed a statistically significant reduction with age in the DRB1*13:02 group. Interpretation: These findings document the protective effect of DRB1*13:02 on age-dependent reduction of brain gray matter in healthy individuals. Since the role of this allele is to connect to matching epitopes of external antigens for the subsequent production of antibodies and elimination of the offending antigen, we hypothesize that its protective effect may be due to the successful elimination of such antigens to which we are exposed during the lifespan, antigens that otherwise would persist causing gradual brain atrophy. In addition, we consider a possible beneficial role of DRB1*13:02 attributed to its binding to cathepsin S, a known harmful substance in brain

  9. Regulation of T cell response to leishmania antigens by determinants of histocompatibility leukocyte class I and II molecules

    Directory of Open Access Journals (Sweden)

    Bacellar O.

    1998-01-01

    Full Text Available It has been shown that HLA class I molecules play a significant role in the regulation of the proliferation of T cells activated by mitogens and antigens. We evaluated the ability of mAb to a framework determinant of HLA class I molecules to regulate T cell proliferation and interferon gamma (IFN-g production against leishmania, PPD, C. albicans and tetanus toxoid antigens in patients with tegumentary leishmaniasis and healthy subjects. The anti-major histocompatibility complex (MHC mAb (W6/32 suppressed lymphocyte proliferation by 90% in cultures stimulated with aCD3, but the suppression was variable in cultures stimulated with leishmania antigen. This suppression ranged from 30-67% and was observed only in 5 of 11 patients. IFN-g production against leishmania antigen was also suppressed by anti-HLA class I mAb. In 3 patients IFN-g levels were suppressed by more than 60%, while in the other 2 cultures IFN-g levels were 36 and 10% lower than controls. The suppression by HLA class I mAb to the proliferative response in leishmaniasis patients and in healthy controls varied with the antigens and the patients or donors tested. To determine whether the suppression is directed at antigen presenting cells (APCs or at the responding T cells, experiments with antigen-primed non-adherent cells, separately incubated with W6/32, were performed. Suppression of proliferation was only observed when the W6/32 mAb was added in the presence of T cells. These data provide evidence that a mAb directed at HLA class I framework determinants can suppress proliferation and cytokine secretion in response to several antigens.

  10. Validation of celiac disease diagnoses recorded in the Danish National Patient Register using duodenal biopsies, celiac disease-specific antibodies, and human leukocyte-antigen genotypes

    DEFF Research Database (Denmark)

    Sander, Stine Dydensborg; Stordal, Ketil; Hansen, Tine Plato

    2016-01-01

    PURPOSE: The purpose of this study was to validate the celiac disease diagnoses recorded in the Danish National Patient Register. To validate the diagnoses, we used information on duodenal biopsies from a national register of pathology reports (the Patobank) and information on celiac disease......-specific antibodies and human leukocyte antigen (HLA) genotypes obtained from patient medical records. PATIENTS AND METHODS: We included all the children who were born from 1995 to 2012 and who were registered as having celiac disease in the Danish National Patient Register. We reviewed all the pathology reports...... on duodenal biopsies in the Patobank and the information in the medical records on celiac disease-specific antibodies (ie, anti-tissue transglutaminase 2 IgA and IgG, endomysial antibodies IgA, and anti-deamidated gliadin peptide IgG) and HLA genotypes. RESULTS: We identified 2,247 children who were...

  11. Linkage disequilibrium between human leukocyte antigen (HLA) class II and HLA-G--possible implications for human reproduction and autoimmune disease

    DEFF Research Database (Denmark)

    Hviid, Thomas Vauvert F; Christiansen, Ole B

    2005-01-01

    A line of investigation indicates that one or several genes in the human major histocompatibility complex (MHC) influences reproductive success. Studies have revealed associations between human leukocyte antigen (HLA) class II genes and risk of recurrent spontaneous abortion (RSA) and pre...... candidate gene for a possible influence on pregnancy outcome. HLA-G has immunomodulatory functions. We have studied linkage disequilibrium between HLA class II genes, primarily HLA-DRB1 alleles, and HLA-G alleles in women with RSA and their partners (n = 103) and in control women and their partners (n = 92......-eclampsia. However, these genes are not expressed at the feto-maternal interface. Furthermore, associations between polymorphisms in the nonclassical HLA class Ib gene, HLA-G, and reproductive outcome have been demonstrated. HLA-G is expressed by extravillous trophoblast during pregnancy, making it a more obvious...

  12. identification of heparin-binding sites in the fibronectin type III domains of the leukocyte common antigen (CD45)

    Czech Academy of Sciences Publication Activity Database

    Kavan, Daniel; Vančurová, M.; Ulbrichová, D.; Hladíková, I.; Pospíšil, Miloslav; Bezouška, Karel

    2004-01-01

    Roč. 3, č. 69 (2004), s. 645-658 ISSN 0010-0765 R&D Projects: GA AV ČR IAA7020006 Institutional research plan: CEZ:AV0Z5020903 Keywords : lectin-like receptors * lectins * antigens Subject RIV: EE - Microbiology, Virology Impact factor: 1.062, year: 2004

  13. Human leukocyte antigen (DR1)-DQB1*0501 and (DR15)-DQB1*0602 haplotypes are associated with humoral responses to early food allergens in children.

    Science.gov (United States)

    Savilahti, Emma M; Ilonen, Jorma; Kiviniemi, Minna; Saarinen, Kristiina M; Vaarala, Outi; Savilahti, Erkki

    2010-01-01

    Infants' immunological responses to cow's milk (CM) proteins, which in 2-3% result in allergy, may partially depend on genetic factors. We evaluated whether genes with immunological functions, i.e. human leukocyte antigen (HLA) II, the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) and filaggrin, modulate immune responses to dietary antigens. We analyzed 14 HLA class II haplotypes, the PTPN22 1858 SNP (R620W allele) and 5 known filaggrin null mutations from blood samples of 87 patients with CM allergy (CMA) and 76 control subjects (age 8.0-9.3 years). Serum levels of IgA, IgG, IgG1 and IgG4 antibodies to beta-lactoglobulin, alpha-casein and ovalbumin were measured with enzyme-linked immunosorbent assay, levels of IgE antibodies to CM, ovalbumin and birch with UniCap (Phadia, Uppsala, Sweden). In children with CMA, the HLA (DR15)-DQB1*0602 haplotype was associated with high levels of beta-lactoglobulin-specific total IgG (p food allergens, whereas none of these genes was associated with CMA. Copyright 2009 S. Karger AG, Basel.

  14. Electrostatic modifications of the human leukocyte antigen-DR P9 peptide-binding pocket and susceptibility to primary sclerosing cholangitis.

    Science.gov (United States)

    Hov, Johannes R; Kosmoliaptsis, Vasilis; Traherne, James A; Olsson, Marita; Boberg, Kirsten M; Bergquist, Annika; Schrumpf, Erik; Bradley, J Andrew; Taylor, Craig J; Lie, Benedicte A; Trowsdale, John; Karlsen, Tom H

    2011-06-01

    The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P = 1.2 × 10(-32) and P = 1.8 × 10(-22) in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket. The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DRβ chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. Copyright © 2011 American Association for the Study of Liver Diseases.

  15. Human Leukocyte Antigen (HLA) and Immune Regulation: How Do Classical and Non-Classical HLA Alleles Modulate Immune Response to Human Immunodeficiency Virus and Hepatitis C Virus Infections?

    Science.gov (United States)

    Crux, Nicole B.; Elahi, Shokrollah

    2017-01-01

    The genetic factors associated with susceptibility or resistance to viral infections are likely to involve a sophisticated array of immune response. These genetic elements may modulate other biological factors that account for significant influence on the gene expression and/or protein function in the host. Among them, the role of the major histocompatibility complex in viral pathogenesis in particular human immunodeficiency virus (HIV) and hepatitis C virus (HCV), is very well documented. We, recently, added a novel insight into the field by identifying the molecular mechanism associated with the protective role of human leukocyte antigen (HLA)-B27/B57 CD8+ T cells in the context of HIV-1 infection and why these alleles act as a double-edged sword protecting against viral infections but predisposing the host to autoimmune diseases. The focus of this review will be reexamining the role of classical and non-classical HLA alleles, including class Ia (HLA-A, -B, -C), class Ib (HLA-E, -F, -G, -H), and class II (HLA-DR, -DQ, -DM, and -DP) in immune regulation and viral pathogenesis (e.g., HIV and HCV). To our knowledge, this is the very first review of its kind to comprehensively analyze the role of these molecules in immune regulation associated with chronic viral infections. PMID:28769934

  16. Ekspresi Human Leukocyte Antigen-G (HLA-G dan Heat-Shock Protein-70 (Hsp-70 pada Pertumbuhan Janin Terhambat

    Directory of Open Access Journals (Sweden)

    Sri Sulistyowati

    2014-03-01

    Full Text Available Intra uterine growth retardation (IUGR is one of the leading causes of higher morbidity and mortality in perinatal. Immune maladaptation affects trophoblast invasion and spiralis arteria remodeling that will cause placental tissue hypoxia. This research aimed to analyze human leukocyte antigen-G (HLA-G and heat-shock protein-70 (Hsp-70 expression on the IUGR trophoblast and normal pregnancy, by applying analytical observational method and cross sectional approach. This research was conducted at the Obstetric and Gynecology Department of Dr. Moewardi Hospital Surakarta from November to December 2011. The total samples were 30, divided into two groups. There were 15 samples trophoblast on IUGR and 15 samples trophoblast from normal pregnancy. All samples were tested for HLA-G and Hsp-70 using immunohistochemistry. The data were analyzed by using t-test. The mean of HLA-G expression on the IUGR groups was 32.42±8.90 and on the normal pregnancy groups was 43.92±14.91 (p=0.016. Heat-shock protein70 expression on the IUGR groups was 2.4355+0.26647 and on the normal pregnancy groups was 1.5920+0.17142 with p=0.008. In conclusion, in IUGR, the HLA-G expression is lower and the Hsp-70 expression is higher than in normal pregnancy.

  17. Attitudes of Chinese couples in Hong Kong regarding using preimplantation genetic diagnosis (PGD) and human leukocyte antigens (HLA) typing to conceive a 'Saviour Child'.

    Science.gov (United States)

    Hui, Edwin C; Chan, Carina; Liu, Athena; Chow, Kathy

    2009-06-01

    To investigate Hong Kong couples' attitudes and concerns about using preimplantation genetic diagnosis (PGD) and human leukocyte antigens (HLA) typing to conceive a disease-free and tissue-compatible 'Saviour Child (SC)' to save an afflicted sibling. Two cohorts of Chinese couples, one with natural pregnancies and the other receiving in vitro fertilization (IVF) services, were studied using a structured questionnaire. Although most couples believed that embryos possess moral rights, they considered it acceptable to reproduce a donor child if it was safe for the child, and tissue transplantation was the only available treatment for the sick sibling. Most couples believed that the donor child would not suffer adverse physical or psychological effects but rather would gain positive psychological benefits, and opined that parents using PGD/HLA-typing suffer sacrificially for their children. In response to one specific question, one-third of the couples agreed to use the donor child as a lifetime organ donor and supported the use of PGD for non-medical gender selection. One-quarter were willing to reject PGD/HLA-typing because of its potential for non-medical genetic enhancement. Probably influenced by the Chinese tradition of strong familism, couples in Hong Kong generally show positive attitudes towards using PGD/HLA-typing to reproduce a 'SC' to save a sibling affected with life-threatening diseases amenable to treatment with genetically compatible tissue. (c) 2009 John Wiley & Sons, Ltd.

  18. A genomic study on distribution of human leukocyte antigen (HLA-A and HLA-B alleles in Lak population of Iran

    Directory of Open Access Journals (Sweden)

    Farhad Shahsavar

    2017-03-01

    Full Text Available Anthropological studies based on the highly polymorphic gene, human leukocyte antigen (HLA, provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as infertility treatment, designing peptide vaccines against tumors, and infectious or autoimmune diseases. The aim of this study was to determine HLA-A and HLA-B allele frequencies in 100 unrelated Lak/lᴂk/individuals from Lorestan province of Iran. Finally, we compared the results with that previously described in Iranian population. Commercial HLA-Type kits from BAG (Lich, Germany company were used for determination of the HLA-A and HLA-B allele frequencies in genomic DNA, based on polymerase chain reaction with sequence specific primer (PCR-SSP assay. The differences between the populations in distribution of HLA-A and HLA-B alleles were estimated by chi-squared test with Yate's correction. The most frequent HLA-A alleles were *24 (20%, *02 (18%, *03 (12% and *11 (10%, and the most frequent HLA-B alleles were *35 (24%, *51 (16%, *18 (6% and *38 (6% in Lak population. HLA-A*66 (1%, *74(1% and HLA-B*48 (1%, *55(1% were the least observed frequencies in Lak population. Our results based on HLA-A and HLA-B allele frequencies showed that Lak population possesses the previously reported general features of Iranians but still with unique.

  19. [Analysis of the association of human leukocyte antigen DQ gene polymorphisms with unexplained recurrent spontaneous abortion among ethnic Han Chinese from Wenzhou region].

    Science.gov (United States)

    Zheng, Jiayong; Zhang, Hongping; Xu, Xiaomin; Ma, Weide; Li, Jianxin; Xia, Shuqi; Wang, Hai; Shen, Xiaolu

    2016-02-01

    To assess the association of human leukocyte antigen DQ gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) among ethnic Han Chinese from Wenzhou region. Fifty couples with URSA (URSA group) and 66 couples with normal pregnancy history (control group) were recruited. The alleles of HLA-DQA1 and HLA-DQB1 were analyzed by polymerase chain reaction with specific sequence primers (PCR-SSP) in all subjects. The frequency distribution of HLA-DQ alleles, odds ratios (OR) between each group and sharing of HLA-DQ alleles were calculated. The frequency distribution of HLA-DQB1*03:03 allele in the females with URSA was significantly higher than that healthy females (21.00% vs. 9.85%, OR=2.433, 95%CI: 1.232-4.894, χ(2)=5.657, PHLA-DQA1 alleles in couples with URSA was increased compared with the control group (70.27% vs. 44.64%, OR=2.931, 95%CI: 1.216-7.067, PHLA-DQA1 alleles may contribute to the susceptibility of URSA among ethnic Han Chinese from Wenzhou region. The allele of HLA-DQB1*03:03 in the females may be predisposing factor for URSA. However, the HLA-DQB1*05:02 allele in both gender and HLA-DQB1*05:03 allele in females may confer a protective effect.

  20. Low expression of human histocompatibility soluble leukocyte antigen-G (HLA-G5) in invasive cervical cancer with and without metastasis, associated with papilloma virus (HPV).

    Science.gov (United States)

    Guimarães, Marcia C M; Soares, Christiane P; Donadi, Eduardo A; Derchain, Sophie F M; Andrade, Liliana A L A; Silva, Tarsia G A; Hassumi, Marcela K; Simões, Renata T; Miranda, Fabiana A; Lira, Régia C P; Crispim, Janaina; Soares, Edson G

    2010-05-01

    Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class Ib molecule that acts as a specific immunosuppressor. Some studies have demonstrated that human papillomavirus (HPV) seems to be involved in lower or absent HLA-G expression, particularly in cervical cancer. In this study, we performed a cross-sectional study, systematically comparing the qualitative expression of the HLA-G5 isoform in invasive cervical carcinoma (ICC), stratifying patients according to the presence [ICC with metastasis (ICC(W))] and absence [ICC without metastasis (ICC(WT))] of metastasis, correlating these findings with interference of HPV and demographic and clinical variables. Seventy-nine patients with a diagnosis of ICC were stratified into two groups: ICC(WT) (n=52 patients) and ICC(W) (n=27). Two biopsies were collected from each patient (one from the tumor lesion and one from a lymph node). Immunohistochemistry analyses were performed for the HLA-G5 isoform, for HPV detection, and virus typing. HLA-G5 isoform molecules were detected in 25 cases (31.6%), 17 (32.7%) without metastasis and 8 (29.6%) with metastasis. HPV was detected in the cervical lesions of 74 patients (93.7%), but low expression of the HLA-G5 isoform was observed in all HPV-related cases. These findings are important; however, additional studies are necessary to identify the influence of HPV with HLA-G5 isoform expression on invasive cervical malignancies.

  1. Histocompatibility leukocyte antigen-D related expression is specifically altered and predicts mortality in septic shock but not in other causes of shock.

    Science.gov (United States)

    Caille, Vincent; Chiche, Jean-Daniel; Nciri, Noureddine; Berton, Christine; Gibot, Sébastien; Boval, Bernadette; Payen, Didier; Mira, Jean-Paul; Mebazaa, Alexandre

    2004-12-01

    Although the expression of monocyte histocompatibility leukocyte antigen (HLA)-DR has been shown to be decreased during human sepsis, its level of expression in other nonseptic critical conditions is unclear. The aim of this study was to compare the level of HLA-DR expression on circulating monocytes among patients with septic, hemorrhagic, and cardiogenic shocks and severe sepsis without shock. At admission, HLA-DR expression was exclusively decreased in patients with septic shock (n = 30; P shock (n = 16), hemorrhagic shock (n = 11), severe sepsis without shock (n = 18), and healthy volunteers (n = 8). HLA-DR expression was not predictive for overall mortality, but at day 1, an HLA-DR expression of less than 14 of mean fluorescence intensity (that corresponds to 40% labeled monocytes) was predictive of mortality exclusively in patients with septic shock (odds ratio, 11.4 and 95% confidence interval, 1.7; 78.4; P culture, and number of units of blood or plasma transfused did not correlate with decreased HLA-DR expression. Thus, the decrease in HLA-DR expression is specific to septic shock and is associated, in septic shock patients, with increased mortality risk.

  2. Human Leukocyte Antigen (HLA and Immune Regulation: How Do Classical and Non-Classical HLA Alleles Modulate Immune Response to Human Immunodeficiency Virus and Hepatitis C Virus Infections?

    Directory of Open Access Journals (Sweden)

    Nicole B. Crux

    2017-07-01

    Full Text Available The genetic factors associated with susceptibility or resistance to viral infections are likely to involve a sophisticated array of immune response. These genetic elements may modulate other biological factors that account for significant influence on the gene expression and/or protein function in the host. Among them, the role of the major histocompatibility complex in viral pathogenesis in particular human immunodeficiency virus (HIV and hepatitis C virus (HCV, is very well documented. We, recently, added a novel insight into the field by identifying the molecular mechanism associated with the protective role of human leukocyte antigen (HLA-B27/B57 CD8+ T cells in the context of HIV-1 infection and why these alleles act as a double-edged sword protecting against viral infections but predisposing the host to autoimmune diseases. The focus of this review will be reexamining the role of classical and non-classical HLA alleles, including class Ia (HLA-A, -B, -C, class Ib (HLA-E, -F, -G, -H, and class II (HLA-DR, -DQ, -DM, and -DP in immune regulation and viral pathogenesis (e.g., HIV and HCV. To our knowledge, this is the very first review of its kind to comprehensively analyze the role of these molecules in immune regulation associated with chronic viral infections.

  3. Human Leukocyte Antigen-B27: The Genetic Predisposition Leading to Reactive Arthritis during Induction Phase Chemotherapy for Acute Myeloid Leukemia

    Science.gov (United States)

    Bartakke, Sandip P; Sampagar, Abhilasha Ashok; Bafna, Vibha Sanjay; Patel, Putun

    2017-01-01

    We report a case of reactive arthritis (ReA) during induction phase chemotherapy of a 15-year-old male patient with acute myeloid leukemia (AML) M4 with inv(16), most probably due to a genetic predisposition of being human leukocyte antigen b27 (HLA-B27) positive. The episode of ReA recurred during consolidation therapy; however, the patient was asymptomatic after the completion of treatment. The link between HLA-B27 and a large family of inflammatory rheumatic diseases is a well-established fact, but interestingly, there is also a molecular link between HLA-B27 and hematological malignancies. This case brings to our notice, the common immunological, molecular, and microbiological link between AML, HLA-B27, and ReA. It also emphasizes the fact that clinicians should have a high index of suspicion of HLA-B27 positivity, if a case of AML develops arthritis during chemotherapy, since early introduction of immunosuppressive medications for arthritis may reduce morbidity and prevent delay in the administration of further chemotherapy cycles. PMID:29200696

  4. Human Leukocyte Antigens and Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma: Old Associations Offer New Clues into the Role of Immunity in Infection-Associated Cancers

    Directory of Open Access Journals (Sweden)

    Wen-Hui eSu

    2013-12-01

    Full Text Available Nasopharyngeal carcinoma (NPC is an Epstein-Barr virus (EBV associated tumor. In addition to EBV, host genetic factors are believed to be important determinants of NPC risk. Of all genes studies to date, human leukocyte antigen (HLA genes have shown the most consistent evidence for association with NPC, both from candidate-gene studies and genome-wide association studies (GWAS. In this report we summarize results from recent studies that evaluated the association between HLA and NPC, and discuss whether findings reflect direct causal associations for HLA genes and/or indirect associations that mark causal associations with other genes in the gene-dense major histocompatibility (MHC region where HLA resides. We also compare GWAS results across cancer sites for which strong hits in the MHC region were observed to generate new hypotheses regarding the role of HLA genes in the development of EBV-associated cancers such as NPC. Of note, we report that MHC associations for EBV-associated cancers (NPC, EBV+ Hodgkin lymphoma are driven by HLA class I genes. In contrast, MHC associations for other viral-associated cancers (cervical cancer, hepatocellular carcinoma or other hematopoetic cancers (EBV- Hodgkin lymphoma, leukemia, non-Hodgkin lymphomas are driven by HLA class II genes, and those for other solid tumors with less clear links to infections (lung, testicular, prostate cancers are driven by non-HLA genes in the MHC region. Future studies should aim to better understand these patterns.

  5. Identification of peptides from foot‐and‐mouth disease virus structural proteins bound by class I swine leukocyte antigen (SLA) alleles, SLA‐1*0401 and SLA‐2*0401

    DEFF Research Database (Denmark)

    Pedersen, Lasse Eggers; Harndahl, M.; Nielsen, Morten

    2013-01-01

    Characterization of the peptide‐binding specificity of swine leukocyte antigen (SLA) class I and II molecules is critical to the understanding of adaptive immune responses of swine toward infectious pathogens. Here, we describe the complete binding motif of the SLA‐2*0401 molecule based on a posi......Characterization of the peptide‐binding specificity of swine leukocyte antigen (SLA) class I and II molecules is critical to the understanding of adaptive immune responses of swine toward infectious pathogens. Here, we describe the complete binding motif of the SLA‐2*0401 molecule based...... within the structural proteins of foot‐and‐mouth disease virus (FMDV), strain A24 were analyzed as candidate T‐cell epitopes. Peptides predicted by the NetMHCpan were tested in ELISA for binding to the SLA‐1*0401 and SLA‐2*0401 major histocompatibility complex class I proteins. Four of the 10 predicted...

  6. Human Leukocyte Antigen-G: A Promising Prognostic Marker of Disease Progression to Improve the Control of Human African Trypanosomiasis.

    Science.gov (United States)

    Gineau, Laure; Courtin, David; Camara, Mamadou; Ilboudo, Hamidou; Jamonneau, Vincent; Dias, Fabricio C; Tokplonou, Leonidas; Milet, Jacqueline; Mendonça, Priscila B; Castelli, Erick C; Camara, Oumou; Camara, Mariam; Favier, Benoit; Rouas-Freiss, Nathalie; Moreau, Philippe; Donadi, Eduardo A; Bucheton, Bruno; Sabbagh, Audrey; Garcia, André

    2016-11-01

     Human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense can be diagnosed in the early hemolymphatic stage (stage 1 [S1]) or meningoencephalitic stage (stage 2 [S2]). Importantly, individuals harbouring high and specific antibody responses to Tbg antigens but negative parasitology are also diagnosed in the field (seropositive [SERO]). Whereas some develop the disease in the months following their initial diagnosis (SERO/HAT), others remain parasitologically negative for long periods (SERO) and are apparently able to control infection. Human leucocyte antigen (HLA)-G, an immunosuppressive molecule, could play a critical role in this variability of progression between infection and disease.  Soluble HLA-G (sHLA-G) was measured in plasma for patients in the SERO (n = 65), SERO/HAT (n = 14), or HAT (n = 268) group and in cerebrospinal fluid for patients in S1 (n = 55), early S2 (n = 93), or late S2 (n = 110). Associations between these different statuses and the soluble level or genetic polymorphisms of HLA-G were explored.  Plasma sHLA-G levels were significantly higher in HAT (P = 6 × 10 -7 ) and SERO/HAT (P = .007) than SERO patients. No difference was observed between the SERO/HAT and HAT groups. Within the HAT group, specific haplotypes (HG010102 and HG0103) displayed increased frequencies in S1 (P = .013) and late S2 (P = .036), respectively.  These results strongly suggest the involvement of HLA-G in HAT disease progression. Importantly, high plasma sHLA-G levels in SERO patients could be predictive of subsequent disease development and could represent a serological marker to help guide therapeutic decision making. Further studies are necessary to assess the predictive nature of HLA-G and to estimate both sensitivity and specificity. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  7. A Novel Family of Human Leukocyte Antigen Class II Receptors May Have Its Origin in Archaic Human Species*

    Science.gov (United States)

    Temme, Sebastian; Zacharias, Martin; Neumann, Jürgen; Wohlfromm, Sebastian; König, Angelika; Temme, Nadine; Springer, Sebastian; Trowsdale, John; Koch, Norbert

    2014-01-01

    HLA class II α and β chains form receptors for antigen presentation to CD4+ T cells. Numerous pairings of class II α and β subunits from the wide range of haplotypes and isotypes may form, but most of these combinations, in particular those produced by isotype mixing, yielded mismatched dimers. It is unclear how selection of functional receptors is achieved. At the atomic level, it is not known which interactions of class II residues regulate selection of matched αβ heterodimers and the evolutionary origin of matched isotype mixed dimer formation. In this study we investigated assembly of isotype-mixed HLA class II α and β heterodimers. Assembly and carbohydrate maturation of various HLA-class II isotype-mixed α and β subunits was dependent on the groove binding section of the invariant chain (Ii). By mutation of polymorphic DPβ sequences, we identified two motifs, Lys-69 and GGPM-(84–87), that are engaged in Ii-dependent assembly of DPβ with DRα. We identified five members of a family of DPβ chains containing Lys-69 and GGPM 84–87, which assemble with DRα. The Lys/GGPM motif is present in the DPβ sequence of the Neanderthal genome, and this ancient sequence is related to the human allele DPB1*0401. By site-directed mutagenesis, we inspected Neanderthal amino acid residues that differ from the DPB1*0401 allele and aimed to determine whether matched heterodimers are formed by assembly of DPβ mutants with DRα. Because the *0401 allele is rare in the sub-Saharan population but frequent in the European population, it may have arisen in modern humans by admixture with Neanderthals in Europe. PMID:24214983

  8. A novel family of human leukocyte antigen class II receptors may have its origin in archaic human species.

    Science.gov (United States)

    Temme, Sebastian; Zacharias, Martin; Neumann, Jürgen; Wohlfromm, Sebastian; König, Angelika; Temme, Nadine; Springer, Sebastian; Trowsdale, John; Koch, Norbert

    2014-01-10

    HLA class II α and β chains form receptors for antigen presentation to CD4(+) T cells. Numerous pairings of class II α and β subunits from the wide range of haplotypes and isotypes may form, but most of these combinations, in particular those produced by isotype mixing, yielded mismatched dimers. It is unclear how selection of functional receptors is achieved. At the atomic level, it is not known which interactions of class II residues regulate selection of matched αβ heterodimers and the evolutionary origin of matched isotype mixed dimer formation. In this study we investigated assembly of isotype-mixed HLA class II α and β heterodimers. Assembly and carbohydrate maturation of various HLA-class II isotype-mixed α and β subunits was dependent on the groove binding section of the invariant chain (Ii). By mutation of polymorphic DPβ sequences, we identified two motifs, Lys-69 and GGPM-(84-87), that are engaged in Ii-dependent assembly of DPβ with DRα. We identified five members of a family of DPβ chains containing Lys-69 and GGPM 84-87, which assemble with DRα. The Lys/GGPM motif is present in the DPβ sequence of the Neanderthal genome, and this ancient sequence is related to the human allele DPB1*0401. By site-directed mutagenesis, we inspected Neanderthal amino acid residues that differ from the DPB1*0401 allele and aimed to determine whether matched heterodimers are formed by assembly of DPβ mutants with DRα. Because the *0401 allele is rare in the sub-Saharan population but frequent in the European population, it may have arisen in modern humans by admixture with Neanderthals in Europe.

  9. Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus

    DEFF Research Database (Denmark)

    Finsen, B.R.; Jørgensen, Martin Balslev; Diemer, Nils Henrik

    1993-01-01

    Leukocyte common antigen, macrophages, blood-brain barrier, neural degeneration, fascia dentata, neuropathology......Leukocyte common antigen, macrophages, blood-brain barrier, neural degeneration, fascia dentata, neuropathology...

  10. Human Leukocyte Antigen Class I Genes Associated With Stevens-Johnson Syndrome and Severe Ocular Complications Following Use of Cold Medicine in a Brazilian Population.

    Science.gov (United States)

    Wakamatsu, Tais H; Ueta, Mayumi; Tokunaga, Katsushi; Okada, Yukinori; Loureiro, Renata R; Costa, Karita A; Sallum, Juliana Maria F; Milhomens, José Arthur; Inoue, Chikara; Sotozono, Chie; Gomes, José Álvaro P; Kinoshita, Shigeru

    2017-04-01

    Describing the association with human leukocyte antigen (HLA) alleles could facilitate the understanding of increased risk factors for development of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients with severe ocular complications (SOCs). To investigate the association between HLA class I genes and cold medicine (CM)-associated SJS/TEN with SOCs. This case-control study was conducted between February 8, 2013, and August 29, 2014. Thirty-nine Brazilian patients with CM-SJS/TEN of 74 patients with SJS/TEN with SOCs and 133 healthy Brazilian volunteers were enrolled. Human leukocyte antigen class I genes (HLA-A, HLA-B, and HLA-C) were examined to determine whether there was a genetic predisposition for CM-SJS/TEN with SOC. Patients were interviewed to identify possible etiologic factors. Data analysis was performed from April 14, 2013, to August 29, 2014. Genetic predisposition for CM-SJS/TEN with SOCs by analysis of HLA class I genes. Of 74 patients included in the analysis, 32 (43%) were male; mean (SD) age was 36.01 [15.42] years. HLA-A*66:01 (odds ratio [OR], 24.0; 95% CI, 2.79-206.0; P < .001), HLA-B*44:03 (OR, 2.71; 95% CI, 1.11-6.65; P = .04), and HLA-C*12:03 (OR, 5.6; 95% CI, 1.67-18.80; P = .006) were associated with Brazilian CM-SJS/TEN with SOCs, and HLA-A*11:01 (OR, 0.074; 95% CI, 0.004-1.26; P = .008), HLA-B*08:01 (OR, 0.15; 95% CI, 0.02-1.15; P = .048), and HLA-B*51:01 (OR, 0.23; 95% CI, 0.05-1.03; P = .045) were inversely associated with Brazilian CM-SJS/TEN with SOCs (39 cases: 19 Pardo and 16 European ancestry; 14 males and 25 females; age, 35.2 [14.4] years; and 133 controls: 66 Pardo and 61 European ancestry; 55 males and 78 females; age, 41.2 [12.9] years). When multiple test correction within the HLA locus, HLA-A*66:01 and HLA-C*12:03 demonstrated associations. When participants were segregated into Pardo and locus is considered, HLA-A*66:01 was associated with CM-SJS/TEN with SOC among

  11. Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation

    Directory of Open Access Journals (Sweden)

    Tülay Kılıçaslan Ayna

    2013-03-01

    Full Text Available Objective: In this study, we aimed to investigate the incidence, dynamics and profiles of human leukocyte antigen (HLA-directed antibodies developed after transplantation and their impact on graft rejection and outcome in kidney recipients. Study Design: Prospective follow-up study. Material and Methods: A total of 56 kidney recipients were monitored at 1st, 6th and 12th months for the development of anti-HLA antibodies using bead based flow-cytometry assays (Flow PRA tests. Results: In 21 (37.5% patients, panel reactive antibodies (PRA was positive after transplantation, however, in 35 (62.5% patients PRA was found negative. Twelve (57.1% patients with post-transplantation HLA-reactive antibodies [PRA (+] and 8 (22.9% patients with no detectable alloantibodies [PRA (-] were developed allograft rejection (p=0.010. In the PRA positive patient group the rates of early period infection and delayed graft function (DGF were higher than the PRA negative patient group. Serum creatinine levels of PRA positive group at 6. and 12. months after transplantation were significantly higher than the PRA negative group (p=0.015 and p=0.048, respectively. The rejection rates of patients who had class I and II HLA antibodies were significantly higher than the patients who had either class I or II HLA antibodies (p=0.011. Acute rejection rates were significantly higher in patients who had class I and II HLA antibodies at the first month (p=0.007. Conclusion: Higher occurrence of rejection episodes in PRA positive group may show the importance of anti-HLA antibody monitoring using Flow-PRA after renal transplantation as a prognostic marker in terms of graft survival.

  12. Association of human leukocyte antigen (HLA)-DQ and HLA-DQA1/DQB1 alleles with Vogt–Koyanagi–Harada disease

    Science.gov (United States)

    Liu, Bing; Deng, Tuo; Zhu, Linxin; Zhong, Jingxiang

    2018-01-01

    Abstract Objective: The aim of this study was to evaluate the association of human leukocyte antigen (HLA)-DQ and HLA-DQA1/DQB1 alleles with Vogt–Koyanagi–Harada (VKH), providing further evidences on the genetic background of this disease. Methods: A comprehensive literature search was conducted on the relationship of HLA-DQ and/or HLA-DQA1/DQB1 alleles with VKH through PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP, and databases for grey literature. The last search was in October 2017. Pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated from extracted data to access the strength of the association between a genotype and VKH. Results: HLA-DQ4 was confirmed to increase the risk of VKH significantly (OR = 4.63, 95% CI: 1.74–12.31, P = .002), while HLA-DQ1 seemed to reduce VKH occurrence with OR = 0.32 (95% CI: 0.22–0.47, P HLA-DQA1∗0301-(OR = 4.52, 95% CI: 1.42–14.35, P = .01) and HLA-DQB1∗0401-(OR = 23.12, 95% CI: 11.54–46.31, P HLA-DQA1∗0103, 0401, 0501 and HLA-DQB1∗0301, 0402, 0601, 0603 were significant protective genetic factors. Conclusion: We concluded that HLA-DQ4 carriers had a higher risk of VKH and HLA-DQ1 seemed to be protective. People with positive HLA-DQA1∗0301 and HLA-DQB1∗0401 demonstrated to be more susceptible to VKH. HLA-DQA1∗0103, 0401, 0501 and HLA-DQB1∗0301, 0402, 0601, 0603 could be potential protectors. PMID:29443768

  13. Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin-Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT).

    Science.gov (United States)

    Karnes, Jason H; Shaffer, Christian M; Cronin, Robert; Bastarache, Lisa; Gaudieri, Silvana; James, Ian; Pavlos, Rebecca; Steiner, Heidi E; Mosley, Jonathan D; Mallal, Simon; Denny, Joshua C; Phillips, Elizabeth J; Roden, Dan M

    2017-09-01

    Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate qtypes were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary. © 2017 Pharmacotherapy Publications, Inc.

  14. Killer-cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) class I genetic diversity in four South African populations.

    Science.gov (United States)

    Gentle, Nikki L; Loubser, Shayne; Paximadis, Maria; Puren, Adrian; Tiemessen, Caroline T

    Killer-cell Immunoglobulin-like Receptor (KIR) and Human Leukocyte Antigen (HLA) genotypes vary considerably between individuals and populations due to KIR/HLA allelic variation and variable haplotype configurations of KIR. HLA mediate natural killer cell activity by serving as KIR ligands. KIR/HLA polymorphisms associate with both disease susceptibility and severity. We determined the frequencies of KIR, KIR genotypes and KIR-HLA combinations in 364 healthy individuals from four South African populations. Study participants included black African (n=167), Caucasian (n=97), Mixed ancestry (n=50) and Indian (n=50) individuals. We identified 48 KIR genotypes that included two genotypes not previously reported. Based on KIR gene content, Indian individuals represented the most distinct group, showing the highest frequencies of KIR2DL2, KIR2DL5, KIR2DS1, KIR2DS2, KIR2DS3 and KIR3DS1, the lowest frequencies of KIR2DL3, KIR2DS4 and KIR3DL1; and a KIR2DL4-negative individual. KIR2DS1 and KIR3DS1 were infrequent in black African populations. HLA-C2 was more common in black African individuals, while HLA-C1 predominated in the other populations. Indian individuals were more likely to possess KIR2DL2 paired with HLA-C1, while Caucasian individuals exhibited the highest frequencies of KIR2DL3 paired with HLA-C1. This report provides comprehensive reference data for further study of the roles of KIR/HLA in non-communicable and infectious diseases in South African populations. Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  15. Association of human leukocyte antigen variants and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: A meta-analysis.

    Science.gov (United States)

    Li, Xingang; Zhao, Zhigang; Sun, Shu-Sen

    2017-05-01

    The association between human leukocyte antigen (HLA) variants and allopurinol-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) was evaluated through a pooled analysis of published studies. A comprehensive search was performed in multiple databases, including PubMed, MEDLINE, ISI Web of Knowledge, EMBASE, Cochrane Register of Controlled Trials, and Science Direct. Studies investigating the association between HLA alleles with allopurinol-induced SJS or TEN were retrieved, and the data were independently extracted. The overall odds ratios (ORs) with corresponding 95% confidence intervals were calculated to determine the association between the presence of HLA variant in at least one allele and allopurinol-induced SJS or TEN. To test the robustness of the meta-analysis results, a sensitivity analysis was performed by removing each study one at a time and calculating the pooled ORs of the remaining studies. The fixed-effects and random-effects models were used to pool the collected data. A total of 4 studies with 81 allopurinol-induced SJS or TEN cases and matched controls (allopurinol-tolerant patients) or population controls (general population) were identified. SJS and TEN were found to be significantly associated with HLA-A*33:03 and HLA-C*03:02 alleles in both groups of studies with matched controls and population controls. All of the pooled ORs were not significantly affected by the remaining studies and different modeling methods, indicating robust results. A strong association was found between HLA-A*33:03 and HLA-C*03:02 alleles and allopurinol-induced SJS or TEN, especially in an Asian population. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  16. Correlation and agreement between eplet mismatches calculated using serological, low-intermediate and high resolution molecular human leukocyte antigen typing methods.

    Science.gov (United States)

    Fidler, Samantha; D'Orsogna, Lloyd; Irish, Ashley B; Lewis, Joshua R; Wong, Germaine; Lim, Wai H

    2018-03-02

    Structural human leukocyte antigen (HLA) matching at the eplet level can be identified by HLAMatchmaker, which requires the entry of four-digit alleles. The aim of this study was to evaluate the agreement between eplet mismatches calculated by serological and two-digit typing methods compared to high-resolution four-digit typing. In a cohort of 264 donor/recipient pairs, the evaluation of measurement error was assessed using intra-class correlation to confirm the absolute agreement between the number of eplet mismatches at class I (HLA-A, -B, C) and II loci (HLA-DQ and -DR) calculated using serological or two-digit molecular typing compared to four-digit molecular typing methods. The proportion of donor/recipient pairs with a difference of >5 eplet mismatches between the HLA typing methods was also determined. Intra-class correlation coefficients between serological and four-digit molecular typing methods were 0.969 (95% confidence intervals [95% CI] 0.960-0.975) and 0.926 (95% CI 0.899-0.944), respectively; and 0.995 (95% CI 0.994-0.996) and 0.993 (95% CI 0.991-0.995), respectively between two-digit and four-digit molecular typing methods. The proportion of donor/recipient pairs with a difference of >5 eplet mismatches at class I and II loci was 4% and 16% for serological versus four-digit molecular typing methods, and 0% and 2% for two-digit versus four-digit molecular typing methods, respectively. In this small predominantly Caucasian population, compared with serology, there is a high level of agreement in the number of eplet mismatches calculated using two-compared to four-digit molecular HLA-typing methods, suggesting that two-digit typing may be sufficient in determining eplet mismatch load in kidney transplantation.

  17. Analysis of killer cell immunoglobulin-like receptors and their human leukocyte antigen-ligands gene polymorphisms in Iranian patients with systemic lupus erythematosus.

    Science.gov (United States)

    Akhtari, M; Farazmand, A; Mahmoudi, M; Akbarian, M; Ahmadzadeh, N; Mirkazemi, Z; Mostafaei, S; Jamshidi, A R

    2016-10-01

    Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease. Natural killer (NK) cells play a critical role in the pathogenesis of autoimmune disorders that mainly express killer cell immunoglobulin-like receptors (KIRs). The present study was undertaken to determine the association of the KIR alleles, genotypes, and KIR-human leukocyte antigen (HLA) ligand gene combinations with the susceptibility to SLE. The genotyping of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method. The study population consisted of 230 SLE patients and 273 ethnical-, age-, and sex-matched healthy controls. The association of the polymorphisms with the prevalence of 11 clinical criteria in patients was analyzed. The carrier frequency of HLA-A-Bw4 was modestly decreased in the SLE patients. The prevalence of hematological and renal disorders was significantly increased in patients with combination of KIR3DL1(+); HLA-B-Bw4(Thr80+) and KIR2DS1(+); HLA-C2(+) genes, respectively. Female patients with combination of KIR2DL2(+); HLA-C1(-) genes were more likely to develop serositis. In addition the prevalence of renal disorders, oral ulcer and serositis was significantly increased in male patients with KIR3DP1(+), KIR2DS1(+), and KIR2DS3(+) genotypes respectively. Our results showed that the presence of activating KIR receptors alone or in combination with their HLA ligands and the absence of inhibitory KIRs in combination with their HLA ligands may activate NK cells and are significantly correlated with the prevalence of renal disease, hematologic disorders, serositis, and oral ulcer in SLE patients. © The Author(s) 2016.

  18. Impact of human leukocyte antigen-B*51-restricted cytotoxic T-lymphocyte pressure on mutation patterns of nonnucleoside reverse transcriptase inhibitor resistance.

    Science.gov (United States)

    Gatanaga, Hiroyuki; Ode, Hirotaka; Hachiya, Atsuko; Hayashida, Tsunefusa; Sato, Hironori; Takiguchi, Masafumi; Oka, Shinichi

    2010-03-13

    The objective of this study is to determine the impact of human leukocyte antigen (HLA)-B*51-restricted cytotoxic T-lymphocyte (CTL) pressure on the development of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance. The prevalence of HIV-1 harboring an escape mutation, I135X, in a major epitope of HLA-B*51-restricted CTL located in reverse transcriptase is increasing worldwide. We analyzed the effects of escape mutations on the emerging mutation patterns of NNRTI resistance. Monoclonal HIV-1 sequences harboring each of the escape mutations, including I135L (HIV-1I135L), I135V (HIV-1I135V), I135T (HIV-1I135T), and I135R (HIV-1I135R) in reverse transcriptase, and a wild-type monoclonal HIV-1 (HIV-1WT) were cultured in the presence of increasing concentrations of efavirenz. Induced mutations during culture passages of the culture were analyzed. E138K emerged during the cultural passages of HIV-1I135V, HIV-1I135T, and HIV-1I135R, but not during the passages of HIV-1WT. The combination of I135T, the most frequent escape mutation, and E138K (HIV-1I135T/E138K) conferred significant resistance to efavirenz, nevirapine, and etravirine. The HIV-1I135L/E138K and HIV-1I135R/E138K were significantly resistant to nevirapine and etravirine, respectively, though each solo of escape mutations and E138K did not confer significant resistance to NNRTI. Computational analysis indicated that I135T and E138K cooperatively extend the gap between the binding site of reverse transcriptase and NNRTI. HLA-B*51-restricted CTL can induce novel mutation patterns of NNRTI resistance by selecting escape mutations. The spread of CTL escape variants may alter the mutation patterns of drug resistance.

  19. Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients

    Directory of Open Access Journals (Sweden)

    H.M. Farouk

    2009-09-01

    Full Text Available Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%. RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3% and HLA-DRB1*04 alleles (83.3%. Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05. HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.

  20. Human leukocyte antigen and major histocompatibility complex class I-related chain A antibodies after kidney transplantation in Turkish renal transplant recipients.

    Science.gov (United States)

    Seyhun, Y; Ozdilli, K; Oguz, F; Karahan, G; Onal, E; Turkmen, A; Eldegez, U; Nane, I; Çalişkan, Y; Bakkaloglu, H; Carin, M

    2012-01-01

    This study was designed to determine whether human leukocyte antigen (HLA) and major histocompatibility complex class I chain-related A (MICA) antibody (Ab) production during the first 6 months posttransplantation correlated with long-term graft survival and rejection rate. The study group included 147 first transplantations from either living related (LRDs) or deceased donors (DDs) who were divided into two subgroups: rejection (RG, n = 28) and nonrejection (NRG, n = 119). Serum samples (n = 441) collected from each patient on posttransplant days 30, 90, and 180 were tested for HLA and MICA Ab using the Luminex technique. Among 82 Ab-positive patients (55.8%), 40 had both HLA and MICA, 33 only HLA, and 9 only MICA Ab in the posttransplant period. The rates of HLA class I, class II, or both Ab positivities were greater in the RG than the NRG (P = .011, .037, and .0275, respectively). At 180 days posttransplant, 64.3% of patients in the RG had Ab and 41.2% in the NRG (P = .0349). The data for the LRD (n = 116) group were similar to those for the entire group; whereas there was no significant difference in Ab positivity between RG and NRG patients who received organs from DDs. There was no significant difference with respect to HLA class II and/or MICA Ab positivity between RG and NRG among patients who lacked HLA class I Ab. We confirmed that HLA and MICA Ab may be harmful posttransplant, promoting rejection processes and representing an important cause of graft failure. HLA class II and MICA Ab positivities were only important predictors of graft failure when present together with HLA class I positivity. Patients who developed HLA alone or both HLA and MICA Ab rejected their grafts more frequently than Ab-negative recipients. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Cell surface expression level variation between two common Human Leukocyte Antigen alleles, HLA-A2 and HLA-B8, is dependent on the structure of the C terminal part of the alpha 2 and the alpha 3 domains

    DEFF Research Database (Denmark)

    Dellgren, Christoffer; Nehlin, Jan O; Barington, Torben

    2015-01-01

    Constitutive cell surface expression of Human Leukocyte Antigen (HLA) class I antigens vary extremely from tissue to tissue and individual antigens may differ widely in expression levels. Down-regulation of class I expression is a known immune evasive mechanism used by cancer cells and viruses....... Moreover, recent observations suggest that even minor differences in expression levels may influence the course of viral infections and the frequency of complications to stem cell transplantation. We have shown that some human multipotent stem cells have high expression of HLA-A while HLA-B is only weakly...... expressed, and demonstrate here that this is also the case for the human embryonic kidney cell line HEK293T. Using quantitative flow cytometry and quantitative polymerase chain reaction we found expression levels of endogenous HLA-A3 (median 71,204 molecules per cell) 9.2-fold higher than the expression of...

  2. Outcomes of Patients with Myeloid Malignancies Treated with Allogeneic Hematopoietic Stem Cell Transplantation from Matched Unrelated Donors Compared with One Human Leukocyte Antigen Mismatched Related Donors Using HLA Typing at 10 Loci

    Science.gov (United States)

    Ciurea, Stefan O.; Saliba, Rima M.; Rondon, Gabriela; Patah, Poliana A.; Aung, Fleur; Cano, Pedro; Andersson, Borje S.; Kebriaei, Partow; Popat, Uday; Fernandez-Vina, Marcelo; Champlin, Richard E.; de Lima, Marcos

    2014-01-01

    Most candidates for hematopoietic stem cell transplantation (HSCT) lack a human leukocyte antigen (HLA)-identical sibling donor. Some patients may have a related donor with whom they are mismatched at 1 antigen/allele. It is not known whether such a match is preferable to a matched unrelated donor (MUD). We evaluated the outcomes (survival, relapse, nonrelapse mortality [NRM]) of all 28 patients with a single HLA antigen/allele mismatch identified through high-resolution HLA typing at HLA-A, -B, -C, -DRB1, and -DQB1, and all 318 patients with myeloid malignancies who received transplants from a 10/10 MUD treated during the same period of time at a single institution. Overall, outcomes for patients treated from a 1-antigen/allele mismatch related donor were significantly worse than from a MUD, primarily because of increased NRM. Overall survival (OS) rates at 3 years for 1-antigen/allele mismatched related donor and MUD transplant recipients were 19% and 45% (P =.007), and NRM rates were 40% and 26% (P =.05), respectively. Patients with class I mismatches appeared to have poorer OS than did patients with class II mismatches. A higher incidence of graft rejection was identified in the mismatched related donor group (P =.02). These results indicate that transplant outcomes are better with a MUD than with a 1 antigen/allele-mismatched related donor. PMID:20969970

  3. Breed differences in development of anti-insulin antibodies in diabetic dogs and investigation of the role of dog leukocyte antigen (DLA) genes.

    Science.gov (United States)

    Holder, Angela L; Kennedy, Lorna J; Ollier, William E R; Catchpole, Brian

    2015-10-15

    Administration of insulin for treatment of diabetes mellitus in dogs can stimulate an immune response, with a proportion of animals developing anti-insulin antibodies (AIA). For an IgG antibody response to occur, this would require B cell presentation of insulin peptides by major histocompatibility complex (MHC) class II molecules, encoded by dog leukocyte antigen (DLA) genes, in order to receive T-cell help for class switching. DLA genes are highly polymorphic in the dog population and vary from breed to breed. The aim of the present study was to evaluate AIA reactivity in diabetic dogs of different breeds and to investigate whether DLA genes influence AIA status. Indirect ELISA was used to determine serological reactivity to insulin in diabetic dogs, treated with either a porcine or bovine insulin preparation. DLA haplotypes for diabetic dogs were determined by sequence-based typing of DLA-DRB1, -DQA1 and -DQB1 loci. Significantly greater insulin reactivity was seen in treated diabetic dogs (n=942) compared with non-diabetic dogs (n=100). Relatively few newly diagnosed diabetic dogs (3/109) were found to be AIA positive, although this provides evidence that insulin autoantibodies might be involved in the pathogenesis of the disease in some cases. Of the diabetic dogs treated with a bovine insulin preparation, 52.3% (182/348) were AIA positive, compared with 12.6% (75/594) of dogs treated with a porcine insulin preparation, suggesting that bovine insulin is more immunogenic. Breeds such as dachshund, Cairn terrier, miniature schnauzer and Tibetan terrier were more likely to develop AIA, whereas cocker spaniels were less likely to develop AIA, compared with crossbreed dogs. In diabetic dogs, DLA haplotype DRB1*0015--DQA1*006--DQB1*023 was associated with being AIA positive, whereas the haplotype DLA-DRB1*006--DQA1*005--DQB1*007 showed an association with being AIA negative. These research findings suggest that DLA genes influence AIA responses in treated diabetic

  4. Human leukocyte antigen class II (DRB1 and DQB1) alleles and haplotypes frequencies in patients with pemphigus vulgaris among the Serbian population.

    Science.gov (United States)

    Zivanovic, D; Bojic, S; Medenica, L; Andric, Z; Popadic, D

    2016-05-01

    The etiology of pemphigus vulgaris (PV) is multifactorial and includes genetic, environmental, hormonal, and immunological factors. Inheritance of certain Human class II leukocyte antigen (HLA) alleles is by far the best-established predisposing factor for the development of PV. Class II HLA alleles vary among racial/ethnic backgrounds. We have determined an association between HLA class II alleles and PV among the Serbian population. A total of 72 patients with confirmed diagnosis of PV were genotyped for HLA class II alleles. HLA frequencies were compared with unrelated healthy bone marrow donors. The statistical significance of differences between patients and controls was evaluated using Fisher's exact test. The DRB1*04 and DRB1*14 allelic groups were associated with PV (P adj = 4.45 × 10(-13) and 4.06 × 10(-19) respectively), while HLA-DRB1*11 was negatively associated with PV (P adj = 0.0067) suggesting a protective role. DRB1*04:02, DRB1*14:04, DQB1*03:02 and DQB1*05:03 alleles were shown to be strongly associated with PV (P adj = 1.63 × 10(-12), 5.20 × 10(-7), 1.28 × 10(-6), and 4.44 × 10(-5), respectively). The frequency of HLA DRB1*04-DQB1*03 and HLA DRB1*14-DQB1*05 haplotypes in PV patients was significantly higher than in controls (31.3% vs 8.8%, P adj =7.66 × 10(-8) and 30.6% vs 6.3%, P adj = 3.22 × 10(-10), respectively). At high-resolution level, statistical significance was observed in HLA-DRB1*04:02-DQB1*03:02 and HLA-DRB1*14:04-DQB1*05:03 haplotypes (P adj = 5.55 × 10(-12), and P adj = 3.91 × 10(-6), respectively). Our findings suggest that HLA-DRB1*04:02, DRB1*14:04, HLA-DQB1* 03:02 and DQB1*05:03 alleles and HLA-DRB1*04:02-DQB1*03:02 and HLA-DRB1*14:04-DQB1*05:03 haplotypes are genetic markers for susceptibility for PV, while DRB1*11 allelic group appears protective in Serbian population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. High-Resolution Analyses of Human Leukocyte Antigens Allele and Haplotype Frequencies Based on 169,995 Volunteers from the China Bone Marrow Donor Registry Program.

    Science.gov (United States)

    Zhou, Xiao-Yang; Zhu, Fa-Ming; Li, Jian-Ping; Mao, Wei; Zhang, De-Mei; Liu, Meng-Li; Hei, Ai-Lian; Dai, Da-Peng; Jiang, Ping; Shan, Xiao-Yan; Zhang, Bo-Wei; Zhu, Chuan-Fu; Shen, Jie; Deng, Zhi-Hui; Wang, Zheng-Lei; Yu, Wei-Jian; Chen, Qiang; Qiao, Yan-Hui; Zhu, Xiang-Ming; Lv, Rong; Li, Guo-Ying; Li, Guo-Liang; Li, Heng-Cong; Zhang, Xu; Pei, Bin; Jiao, Li-Xin; Shen, Gang; Liu, Ying; Feng, Zhi-Hui; Su, Yu-Ping; Xu, Zhao-Xia; Di, Wen-Ying; Jiang, Yao-Qin; Fu, Hong-Lei; Liu, Xiang-Jun; Liu, Xiang; Zhou, Mei-Zhen; Du, Dan; Liu, Qi; Han, Ying; Zhang, Zhi-Xin; Cai, Jian-Ping

    2015-01-01

    Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis

  6. The human leukocyte antigen G promotes trophoblast fusion and β-hCG production through the Erk1/2 pathway in human choriocarcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ji-meng [School of Medicine, Nankai University, Tianjin 300071 (China); State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Zhao, Hong-xi [Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038 (China); Wang, Li [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China); Gao, Zhi-ying, E-mail: gaozy301@yahoo.com.cn [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China); Yao, Yuan-qing, E-mail: yqyao@126.com [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China)

    2013-05-10

    Highlights: •HLA-G expression promotes BeWo cells fusion and fusogenic gene expression. •HLA-G is capable of inducing β-hCG production in human choriocarcinoma cell lines. •Up-regulation of β-hCG production by HLA-G is mediated via the Erk1/2 pathway. -- Abstract: The human leukocyte antigen G (HLA-G) is expressed on the fetal–maternal interface and plays a role in protecting fetal-derived trophoblasts from the maternal immune response, allowing trophoblasts to invade the uterus. However, HLA-G also possesses immune suppressing-independent functions. We found that HLA-G expressing BeWo choriocarcinoma cells increased cell–cell fusion compared to control BeWo cells under forskolin treatment. Regardless of forskolin treatment, the expression of fusogenic gene mRNAs, including syncytin-1, the transcription factor glial cell missing 1 (Gcm1), and beta human chorionic gonadotropin (β-hCG) were elevated. HLA-G up-regulates β-hCG production in human choriocarcinoma cells because HLA-G knockdown in JEG-3 cells induces a dramatic decrease in β-hCG compared with control cells. The defect in β-hCG production in HLA-G knocked-down cells could not be completely overcome by stimulating hCG production through increasing intracellular cAMP levels. HLA-G expressing cells have increased phosphorylation levels for extracellular signal-regulated kinase1/2 (Erk1/2) in BeWo cells. The Erk1/2 pathway is inactivated after the inhibition of HLA-G expression in JEG-3 cells. Finally, Erk1/2 inhibition was able to suppress the increased hCG production induced by HLA-G expression. Together, these data suggest novel roles for HLA-G in regulating β-hCG production via the modulation of the Erk1/2 pathway and by inducing trophoblast cell fusion.

  7. The human leukocyte antigen G promotes trophoblast fusion and β-hCG production through the Erk1/2 pathway in human choriocarcinoma cell lines

    International Nuclear Information System (INIS)

    Wang, Ji-meng; Zhao, Hong-xi; Wang, Li; Gao, Zhi-ying; Yao, Yuan-qing

    2013-01-01

    Highlights: •HLA-G expression promotes BeWo cells fusion and fusogenic gene expression. •HLA-G is capable of inducing β-hCG production in human choriocarcinoma cell lines. •Up-regulation of β-hCG production by HLA-G is mediated via the Erk1/2 pathway. -- Abstract: The human leukocyte antigen G (HLA-G) is expressed on the fetal–maternal interface and plays a role in protecting fetal-derived trophoblasts from the maternal immune response, allowing trophoblasts to invade the uterus. However, HLA-G also possesses immune suppressing-independent functions. We found that HLA-G expressing BeWo choriocarcinoma cells increased cell–cell fusion compared to control BeWo cells under forskolin treatment. Regardless of forskolin treatment, the expression of fusogenic gene mRNAs, including syncytin-1, the transcription factor glial cell missing 1 (Gcm1), and beta human chorionic gonadotropin (β-hCG) were elevated. HLA-G up-regulates β-hCG production in human choriocarcinoma cells because HLA-G knockdown in JEG-3 cells induces a dramatic decrease in β-hCG compared with control cells. The defect in β-hCG production in HLA-G knocked-down cells could not be completely overcome by stimulating hCG production through increasing intracellular cAMP levels. HLA-G expressing cells have increased phosphorylation levels for extracellular signal-regulated kinase1/2 (Erk1/2) in BeWo cells. The Erk1/2 pathway is inactivated after the inhibition of HLA-G expression in JEG-3 cells. Finally, Erk1/2 inhibition was able to suppress the increased hCG production induced by HLA-G expression. Together, these data suggest novel roles for HLA-G in regulating β-hCG production via the modulation of the Erk1/2 pathway and by inducing trophoblast cell fusion

  8. The association of human leukocyte antigen B27 with anterior uveitis in patients from the western region of Saudi Arabia: a retrospective study

    Directory of Open Access Journals (Sweden)

    Bawazeer AM

    2013-10-01

    Full Text Available Ahmed M Bawazeer,1,2 Heba Ismail Joharjy1 1Uveitis Services, Department of Ophthalmology, King Abdulaziz University, 2Magrabi Eye and Ear Hospital, Jeddah, Saudi Arabia Background: The association of human leukocyte antigen B27 (HLA-B27 with anterior uveitis is well known. The prevalence of HLA-B27 and its relation to anterior uveitis is related to race and geographic location. The association is strongest in Western countries and weakest in Eastern countries. Data regarding this association from Middle Eastern countries are limited. Thus, we undertook the study reported here to evaluate the association of HLA-B27 with anterior uveitis in patients in a tertiary center in the western region of the Saudi Arabia. Methods: The study involved a retrospective analysis of the records of patients with anterior uveitis, referred to the uveitis clinic in Magrabi Eye and Ear Hospital, Jeddah, Saudi Arabia, from 1999 to 2010. The cost-effectiveness of HLA-B27 testing was analyzed. Results: Among the 587 cases of uveitis, 335 (57.1%; mean age 37.56±12.82 years; 203 male and 132 female cases were of anterior uveitis. All patients with anterior uveitis were investigated for HLA-B27 positivity. Idiopathic anterior uveitis was the most common (80%, followed by Fuchs heterochromic cyclitis (7.45% and ankylosing spondylitis (3.8%. Only two patients were HLA-B27 positive. The cost-effectiveness of HLA-B27 testing was found to be 165,000 Saudi riyals (44,594 US dollars per positive case. Conclusion: HLA-B27-related uveitis appears to be very rare in our part of the world. Idiopathic uveitis is the most common type of anterior uveitis. The cost-effectiveness of HLA-B27 testing is low for patients with anterior uveitis in the western region of Saudi Arabia. Keywords: HLA-B27, Saudi population, cost-effectiveness, idiopathic anterior uveitis, Fuchs heterochromic cyclitis, ankylosing spondylitis

  9. High resolution human leukocyte antigen (HLA class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

    Directory of Open Access Journals (Sweden)

    Barquera Rodrigo

    2009-02-01

    Full Text Available Abstract Background The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA alleles play an important role in immunity (cellular immunity and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory. Methods We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls. Results HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; p = 0.031. HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947 – 294.670. DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027–0.223, p = 0.00001. Conclusion Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the

  10. High resolution human leukocyte antigen (HLA) class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

    International Nuclear Information System (INIS)

    Cantú de León, David; Yu, Neng; Yunis, Edmond J; Granados, Julio; Pérez-Montiel, Delia; Villavicencio, Verónica; Carranca, Alejandro García; Betancourt, Alejandro Mohar; Acuña-Alonzo, Victor; López-Tello, Alberto; Vargas-Alarcón, Gilberto; Barquera, Rodrigo

    2009-01-01

    The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA) alleles play an important role in immunity (cellular immunity) and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory. We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP) of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls. HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; p = 0.031). HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947 – 294.670). DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027–0.223, p = 0.00001). Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the first study in Mexican population where high resolutions HLA

  11. Anti-Thyroid Peroxidase Reactivity Is Heightened in Pemphigus Vulgaris and Is Driven by Human Leukocyte Antigen Status and the Absence of Desmoglein Reactivity

    Science.gov (United States)

    Seiffert-Sinha, Kristina; Khan, Shahzaib; Attwood, Kristopher; Gerlach, John A.; Sinha, Animesh A.

    2018-01-01

    Pemphigus vulgaris (PV) belongs to an autoimmune disease cluster that includes autoimmune thyroid disease (AITD), suggesting common mechanisms driving autoimmune susceptibility. Our group has shown that PV patients exhibit significant reactivity to AITD-related anti-thyroid peroxidase (anti-TPO), and anti-TPO antibodies affect signaling pathways in keratinocytes similar to anti-desmoglein (Dsg) 3 antibodies. To further assess the relevance of anti-TPO reactivity in PV, we analyzed anti-TPO levels in 280 PV and 167 healthy control serum samples across a comprehensive set of variable and static parameters of disease activity and etiopathogenesis. PV patients have significantly higher activity rates (A.R.s) for anti-TPO than healthy controls, but levels do not differ between phases of clinical activity and remission. Patients that carry both the PV-associated human leukocyte antigen (HLA) alleles DRB1*0402 and DQB1*0503, or DQB1*0503 alone show a low prevalence of anti-TPO (A.R. 9.5 and 4.8%, respectively), while patients that lack expression of these alleles or carry DRB1*0402 alone have a much higher prevalence of anti-TPO (A.R. 23.1 and 15.8%, respectively), suggesting that the absence of DQB1*0503 may predispose patients to the development of anti-TPO antibodies. Similarly, anti-Dsg1−/3− patients have a higher anti-TPO A.R. (26.9%) than anti-Dsg1−/3+ (18.8%), anti-Dsg1+/3− (14.3%), and anti-Dsg1+/3+ (3.9%) patients. Our data suggest that anti-TPO reactivity in PV is driven by genetic markers that may be in linkage disequilibrium with the established PV-susceptibility alleles and that this association drives the selection of a combination of anti-Dsg and anti-TPO antibodies, with anti-TPO filling the gap in active patients that do not carry the established PV-associated autoantibodies and/or are lacking the established PV-HLA-susceptibility alleles. PMID:29675021

  12. Anti-Thyroid Peroxidase Reactivity Is Heightened in Pemphigus Vulgaris and Is Driven by Human Leukocyte Antigen Status and the Absence of Desmoglein Reactivity

    Directory of Open Access Journals (Sweden)

    Kristina Seiffert-Sinha

    2018-04-01

    Full Text Available Pemphigus vulgaris (PV belongs to an autoimmune disease cluster that includes autoimmune thyroid disease (AITD, suggesting common mechanisms driving autoimmune susceptibility. Our group has shown that PV patients exhibit significant reactivity to AITD-related anti-thyroid peroxidase (anti-TPO, and anti-TPO antibodies affect signaling pathways in keratinocytes similar to anti-desmoglein (Dsg 3 antibodies. To further assess the relevance of anti-TPO reactivity in PV, we analyzed anti-TPO levels in 280 PV and 167 healthy control serum samples across a comprehensive set of variable and static parameters of disease activity and etiopathogenesis. PV patients have significantly higher activity rates (A.R.s for anti-TPO than healthy controls, but levels do not differ between phases of clinical activity and remission. Patients that carry both the PV-associated human leukocyte antigen (HLA alleles DRB1*0402 and DQB1*0503, or DQB1*0503 alone show a low prevalence of anti-TPO (A.R. 9.5 and 4.8%, respectively, while patients that lack expression of these alleles or carry DRB1*0402 alone have a much higher prevalence of anti-TPO (A.R. 23.1 and 15.8%, respectively, suggesting that the absence of DQB1*0503 may predispose patients to the development of anti-TPO antibodies. Similarly, anti-Dsg1−/3− patients have a higher anti-TPO A.R. (26.9% than anti-Dsg1−/3+ (18.8%, anti-Dsg1+/3− (14.3%, and anti-Dsg1+/3+ (3.9% patients. Our data suggest that anti-TPO reactivity in PV is driven by genetic markers that may be in linkage disequilibrium with the established PV-susceptibility alleles and that this association drives the selection of a combination of anti-Dsg and anti-TPO antibodies, with anti-TPO filling the gap in active patients that do not carry the established PV-associated autoantibodies and/or are lacking the established PV-HLA-susceptibility alleles.

  13. Association of selected human leukocyte antigen alleles (HLA-DQA1*0102, HLA-DQA1*0103 and HLA–DQB1*0301) with Helicobacter pylori infection among dyspeptic patients

    OpenAIRE

    Piyumali Sandareka Arachchi; Chinthika Prabhashinie Gunasekara; Manjula Manoji Weerasekera; Nushka Lahiri Ubhayawardana; Deepaka Weerasekera; Kamani Samarasinghe; Bimalka Seneviratne; Neluka Fernando

    2016-01-01

    Background: Helicobacter pylori has been identified as a group I carcinogenic bacteria that infect the gastric mucosa leading to gastritis, peptic ulcer disease, lymphoma and gastric cancer. Pathogenesis of H. pylori depends on the virulence of the strain, host immune response and modulating factors like smoking and diet. Objective: This study aimed to assess the association of selected HLA (Human Leukocyte Antigen) alleles; HLA-DQA1*0102, HLA-DQA1*0103 and HLA-DQB1*0301, with the pr...

  14. Cryopreservation of Human Mucosal Leukocytes.

    Directory of Open Access Journals (Sweden)

    Sean M Hughes

    Full Text Available Understanding how leukocytes in the cervicovaginal and colorectal mucosae respond to pathogens, and how medical interventions affect these responses, is important for developing better tools to prevent HIV and other sexually transmitted infections. An effective cryopreservation protocol for these cells following their isolation will make studying them more feasible.To find an optimal cryopreservation protocol for mucosal mononuclear leukocytes, we compared cryopreservation media and procedures using human vaginal leukocytes and confirmed our results with endocervical and colorectal leukocytes. Specifically, we measured the recovery of viable vaginal T cells and macrophages after cryopreservation with different cryopreservation media and handling procedures. We found several cryopreservation media that led to recoveries above 75%. Limiting the number and volume of washes increased the fraction of cells recovered by 10-15%, possibly due to the small cell numbers in mucosal samples. We confirmed that our cryopreservation protocol also works well for both endocervical and colorectal leukocytes. Cryopreserved leukocytes had slightly increased cytokine responses to antigenic stimulation relative to the same cells tested fresh. Additionally, we tested whether it is better to cryopreserve endocervical cells on the cytobrush or in suspension.Leukocytes from cervicovaginal and colorectal tissues can be cryopreserved with good recovery of functional, viable cells using several different cryopreservation media. The number and volume of washes has an experimentally meaningful effect on the percentage of cells recovered. We provide a detailed, step-by-step protocol with best practices for cryopreservation of mucosal leukocytes.

  15. Cryopreservation of Human Mucosal Leukocytes.

    Science.gov (United States)

    Hughes, Sean M; Shu, Zhiquan; Levy, Claire N; Ferre, April L; Hartig, Heather; Fang, Cifeng; Lentz, Gretchen; Fialkow, Michael; Kirby, Anna C; Adams Waldorf, Kristina M; Veazey, Ronald S; Germann, Anja; von Briesen, Hagen; McElrath, M Juliana; Dezzutti, Charlene S; Sinclair, Elizabeth; Baker, Chris A R; Shacklett, Barbara L; Gao, Dayong; Hladik, Florian

    2016-01-01

    Understanding how leukocytes in the cervicovaginal and colorectal mucosae respond to pathogens, and how medical interventions affect these responses, is important for developing better tools to prevent HIV and other sexually transmitted infections. An effective cryopreservation protocol for these cells following their isolation will make studying them more feasible. To find an optimal cryopreservation protocol for mucosal mononuclear leukocytes, we compared cryopreservation media and procedures using human vaginal leukocytes and confirmed our results with endocervical and colorectal leukocytes. Specifically, we measured the recovery of viable vaginal T cells and macrophages after cryopreservation with different cryopreservation media and handling procedures. We found several cryopreservation media that led to recoveries above 75%. Limiting the number and volume of washes increased the fraction of cells recovered by 10-15%, possibly due to the small cell numbers in mucosal samples. We confirmed that our cryopreservation protocol also works well for both endocervical and colorectal leukocytes. Cryopreserved leukocytes had slightly increased cytokine responses to antigenic stimulation relative to the same cells tested fresh. Additionally, we tested whether it is better to cryopreserve endocervical cells on the cytobrush or in suspension. Leukocytes from cervicovaginal and colorectal tissues can be cryopreserved with good recovery of functional, viable cells using several different cryopreservation media. The number and volume of washes has an experimentally meaningful effect on the percentage of cells recovered. We provide a detailed, step-by-step protocol with best practices for cryopreservation of mucosal leukocytes.

  16. Radiolabeled leukocytes

    International Nuclear Information System (INIS)

    Datz, F.L.; Taylor, A.T.

    1986-01-01

    Leukocytes are a heterogeneous group of nucleated cells that follow similar patterns of differentiation in the bone marrow. Although the various leukocyte cell types perform somewhat different functions, they act as a group to protect the host from hazards of the internal and external environment, such as infection and neoplasia, and they assist in the repair of damaged tissue. Leukocytes spend a small fraction of their life in the peripheral blood, using it only for transportation to sites where they are needed to perform their defensive functions. In adults, the mature types of leukocytes are neutrophils (59 percent of the leukocyte population), lymphocytes (34 percent), monocytes (four percent), eosinophils (three percent), and basophils (0.5 percent). Neutrophils, eosinophils, and basophils all contain nuclei with finitely granular, evenly distributed chromatin and are collectively called granulocytes. In addition to the main categories of leukocytes listed above, there are subsets of many of these classes of cells; for example, natural killer cells are a subset of lymphocytes

  17. Validation of celiac disease diagnoses recorded in the Danish National Patient Register using duodenal biopsies, celiac disease-specific antibodies, and human leukocyte-antigen genotypes

    Directory of Open Access Journals (Sweden)

    Dydensborg Sander S

    2016-12-01

    Full Text Available Stine Dydensborg Sander,1-3 Ketil Størdal,4,5 Tine Plato Hansen,6 Anne-Marie Nybo Andersen,7 Joseph A Murray,8 Søren Thue Lillevang,9 Steffen Husby1,2 1Hans Christian Andersen Children’s Hospital, Odense University Hospital, 2Institute of Clinical Research, University of Southern Denmark, 3Odense Patient Data Explorative Network (OPEN, Odense University Hospital, Odense, Denmark; 4Mental and Physical Health, Norwegian Institute of Public Health, Oslo, 5Department of Pediatrics, Ostfold Hospital Trust, Fredrikstad, Norway; 6Department of Pathology, Hvidovre Hospital, 7Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 8Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 9Department of Clinical Immunology, Odense University Hospital, Odense, Denmark Purpose: The purpose of this study was to validate the celiac disease diagnoses recorded in the Danish National Patient Register. To validate the diagnoses, we used information on duodenal biopsies from a national register of pathology reports (the Patobank and information on celiac disease-specific antibodies and human leukocyte antigen (HLA genotypes obtained from patient medical records.Patients and methods: We included all the children who were born from 1995 to 2012 and who were registered as having celiac disease in the Danish National Patient Register. We reviewed all the pathology reports on duodenal biopsies in the Patobank and the information in the medical records on celiac disease-specific antibodies (ie, anti-tissue transglutaminase 2 IgA and IgG, endomysial antibodies IgA, and anti-deamidated gliadin peptide IgG and HLA genotypes.Results: We identified 2,247 children who were registered in the Danish National Patient Register with celiac disease. Duodenal biopsies for 1,555 of the children (69% were registered in the Patobank; 1,127 (50% had a biopsy that was compatible with celiac disease (ie, Marsh 2–3. We accessed the medical

  18. Use of flow cytometry to identify monoclonal antibodies that recognize conserved epitopes on orthologous leukocyte differentiation antigens in goats, llamas, and rabbits

    Czech Academy of Sciences Publication Activity Database

    Davis, W. C.; Drbal, Karel; El-Aziz, A.; Mosaad, A.E.; Elbagory, A.R.M.; TIbary, A.; Barrington, G.M.; Park, Y.H.; Hamilton, M.J.

    2007-01-01

    Roč. 119, 1-2 (2007), s. 123-130 ISSN 0165-2427 Institutional research plan: CEZ:AV0Z50520514 Keywords : flow cytometry * monoclonal antibodies * leukocyte s Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.957, year: 2007

  19. A modern approach for epitope prediction: identification of foot-and-mouth disease virus peptides binding bovine leukocyte antigen (BoLA) class I molecules

    Science.gov (United States)

    Major histocompatibility complex (MHC) class I molecules regulate adaptive immune responses through the presentation of antigenic peptides to CD8positive T-cells. Polymorphisms in the peptide binding region of class I molecules determine peptide binding affinity and stability during antigen presenta...

  20. Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case-control study.

    Science.gov (United States)

    Steele, Natasha Z R; Carr, Jessie S; Bonham, Luke W; Geier, Ethan G; Damotte, Vincent; Miller, Zachary A; Desikan, Rahul S; Boehme, Kevin L; Mukherjee, Shubhabrata; Crane, Paul K; Kauwe, John S K; Kramer, Joel H; Miller, Bruce L; Coppola, Giovanni; Hollenbach, Jill A; Huang, Yadong; Yokoyama, Jennifer S

    2017-03-01

    Alzheimer disease (AD) is a progressive disorder that affects cognitive function. There is increasing support for the role of neuroinflammation and aberrant immune regulation in the pathophysiology of AD. The immunoregulatory human leukocyte antigen (HLA) complex has been linked to susceptibility for a number of neurodegenerative diseases, including AD; however, studies to date have failed to consistently identify a risk HLA haplotype for AD. Contributing to this difficulty are the complex genetic organization of the HLA region, differences in sequencing and allelic imputation methods, and diversity across ethnic populations. Building on prior work linking the HLA to AD, we used a robust imputation method on two separate case-control cohorts to examine the relationship between HLA haplotypes and AD risk in 309 individuals (191 AD, 118 cognitively normal [CN] controls) from the San Francisco-based University of California, San Francisco (UCSF) Memory and Aging Center (collected between 1999-2015) and 11,381 individuals (5,728 AD, 5,653 CN controls) from the Alzheimer's Disease Genetics Consortium (ADGC), a National Institute on Aging (NIA)-funded national data repository (reflecting samples collected between 1984-2012). We also examined cerebrospinal fluid (CSF) biomarker measures for patients seen between 2005-2007 and longitudinal cognitive data from the Alzheimer's Disease Neuroimaging Initiative (n = 346, mean follow-up 3.15 ± 2.04 y in AD individuals) to assess the clinical relevance of identified risk haplotypes. The strongest association with AD risk occurred with major histocompatibility complex (MHC) haplotype A*03:01~B*07:02~DRB1*15:01~DQA1*01:02~DQB1*06:02 (p = 9.6 x 10-4, odds ratio [OR] [95% confidence interval] = 1.21 [1.08-1.37]) in the combined UCSF + ADGC cohort. Secondary analysis suggested that this effect may be driven primarily by individuals who are negative for the established AD genetic risk factor, apolipoprotein E (APOE) ɛ4. Separate

  1. Optimisation of the CT h4S bioassay for detection of human interleukin-4 secreted by mononuclear cells stimulated by phytohaemaglutinin or by human leukocyte antigen mismatched mixed lymphocyte culture

    DEFF Research Database (Denmark)

    Petersen, Søren Lykke; Russell, Charlotte Astrid; Bendtzen, Klaus

    2002-01-01

    high anti-recipient IL-4 producing HTLp frequencies have been reported and associated with a decreased risk of GVHD. The aim of the present study was to define the optimal conditions for combined determination of IL-2 and IL-4 producing anti-recipient HTLp frequencies. We have optimised the CT.h4S......S bioassay detects 5 pg/ml of human recombinant IL-4 with no detection of IL-2 in concentrations below 500 pg/ml. We have found 72 h of culture optimal for detection of IL-2 and IL-4 produced by human mononuclear cells (MNC) in response to stimulation with phytohaemaglutinin and for detection of IL......-2 in human leukocyte antigen (HLA)-mismatched mixed leukocyte culture (MLC). An interindividual variation in cytokine accumulation was demonstrated for IL-4 but not for IL-2. With the use of 5x10(4) responder cells/well no IL-4 could be detected in HLA-mismatched MLC between days 1 and 16. The lack...

  2. The production and crystallization of the human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 complexed with deamidated gliadin peptides implicated in coeliac disease

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Kate N.; Reid, Hugh H.; Borg, Natalie A.; Broughton, Sophie E.; Huyton, Trevor [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia); Anderson, Robert P. [Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050 (Australia); Department of Gastroenterology, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050 (Australia); McCluskey, James [Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010 (Australia); Rossjohn, Jamie, E-mail: jamie.rossjohn@med.monash.edu.au [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia)

    2007-12-01

    The production and crystallization of human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 in complex with deamidated gliadin peptides is reported. Crystals of HLA-DQ2{sup PQPELPYPQ} diffracted to 3.9 Å, while the HLA-DQ8{sup EGSFQPSQE} crystals diffracted to 2.1 Å, allowing structure determination by molecular replacement. The major histocompatibility complex (MHC) class II molecules HLA-DQ2 and HLA-DQ8 are key risk factors in coeliac disease, as they bind deamidated gluten peptides that are subsequently recognized by CD4{sup +} T cells. Here, the production and crystallization of both HLA-DQ2 and HLA-DQ8 in complex with the deamidated gliadin peptides DQ2 α-I (PQPELPYPQ) and DQ8 α-I (EGSFQPSQE), respectively, are reported.

  3. Human Leukocyte Antigen-G Is Frequently Expressed in a Multicentric Study on Glioblastoma and May Be Induced in Vitro by Combined 5-aza-2'-deoxycytidine and Interferon-γ Treatments

    DEFF Research Database (Denmark)

    Wastowski, Isabela J; Simões, Renata T; Yaghi, Layale

    2012-01-01

    -G protein expression was associated with a better long-term survival rate. The mechanisms underlying HLA-G gene expression were investigated in glioma cell lines U251MG, D247MG, and U138MG. Induction of HLA-G transcriptional activity was dependent of 5-aza-2'-deoxycytidine treatment and enhanced......Human leukocyte antigen-G (HLA-G) is a nonclassical major histocompatibility complex (MHC) class I molecule involved in immune tolerance processes, playing an important role in the maintenance of the semi-allogeneic fetus. Although HLA-G expression is restricted in normal tissues, it is broadly...... expressed in malignant tumors and may favor tumor immune escape. We analyzed HLA-G protein and mRNA expression in tumor samples from patients with glioblastoma collected in France, Denmark, and Brazil. We found HLA-G protein expression in 65 of 108 samples and mRNA in 20 of 21 samples. The absence of HLA...

  4. Presence or absence of a known diabetic ketoacidosis precipitant defines distinct syndromes of "A-β+" ketosis-prone diabetes based on long-term β-cell function, human leukocyte antigen class II alleles, and sex predilection.

    Science.gov (United States)

    Nalini, Ramaswami; Ozer, Kerem; Maldonado, Mario; Patel, Sanjeet G; Hampe, Christiane S; Guthikonda, Anu; Villanueva, Jesus; O'Brian Smith, E; Gaur, Lakshmi K; Balasubramanyam, Ashok

    2010-10-01

    Ketosis-prone diabetes (KPD) is heterogeneous. Longitudinal follow-up revealed that patients with "A-β+" KPD (absent autoantibodies and preserved β-cell function) segregated into 2 subgroups with distinct evolution of β-cell function and glycemic control. Generalized linear analysis demonstrated that the variable that most significantly differentiated them was presence of a clinically evident precipitating event for the index diabetic ketoacidosis (DKA). Hence, we performed a comprehensive analysis of A-β+ KPD patients presenting with "provoked" compared with "unprovoked" DKA. Clinical, biochemical, and β-cell functional characteristics were compared between provoked and unprovoked A-β+ KPD patients followed prospectively for 1 to 8 years. Human leukocyte antigen class II allele frequencies were compared between these 2 groups and population controls. Unprovoked A-β+ KPD patients (n = 83) had greater body mass index, male preponderance, higher frequency of women with oligo-/anovulation, more frequent African American ethnicity, and less frequent family history of diabetes than provoked A-β+ KPD patients (n = 64). The provoked group had higher frequencies of the human leukocyte antigen class II type 1 diabetes mellitus susceptibility alleles DQB1*0302 (than the unprovoked group or population controls) and DRB1*04 (than the unprovoked group), whereas the unprovoked group had a higher frequency of the protective allele DQB1*0602. β-Cell secretory reserve and glycemic control improved progressively in the unprovoked group but declined in the provoked group. The differences persisted in comparisons restricted to patients with new-onset diabetes. "Unprovoked" A-β+ KPD is a distinct syndrome characterized by reversible β-cell dysfunction with male predominance and increased frequency of DQB1*0602, whereas "provoked" A-β+ KPD is characterized by progressive loss of β-cell reserve and increased frequency of DQB1*0302 and DRB1*04. Unprovoked DKA predicts long

  5. De novo expression of human leukocyte antigen-DR (HLA-DR) and loss of beta-catenin expression in tubular epithelial cells: a possible event in epithelial-mesenchymal transition in canine renal diseases.

    Science.gov (United States)

    Benali, S L; Lees, G E; Nabity, M B; Mantovani, R; Bonsembiante, F; Aresu, L

    2013-10-01

    Tubulointerstitial fibrosis (TIF) plays a central role in the progression to end-stage renal disease. Tubular epithelial cells (TECs) undergo epithelial-mesenchymal transition (EMT) and may contribute to the progression of TIF. Using immunohistochemistry, the primary aim of this study was to assess the expression of β-catenin, human leukocyte antigen-DR (HLA-DR) and vimentin in renal biopsies from dogs with spontaneous kidney diseases of varying severities. Morphological diagnosis, severity of inflammation, TIF, HLA-DR expression and clinicopathological variables were compared in dogs with renal injury to identify any potential relationship between the different factors; β-catenin down-regulation was used as a marker of EMT. Fibrosis, HLA-DR expression, serum creatinine concentration (SCr), and urine protein-to-creatinine ratio (UPC) were all increased and β-catenin expression decreased in dogs with primary glomerular disease compared with dogs with acute tubular necrosis. HLA-DR expression by TECs was positively correlated to fibrosis, inflammation, UPC, and SCr. β-catenin expression was negatively correlated to fibrosis, inflammation and HLA-DR expression. The progression of renal failure correlated closely with tubulointerstitial damage. De novo HLA-DR expression associated with β-catenin down-regulation by TECs may represent a possible step in the progression of TIF and EMT. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B, and HLA-G-DRB1 haplotypes in families with recurrent miscarriage

    DEFF Research Database (Denmark)

    Kolte, Astrid M; Steffensen, Rudi; Nielsen, Henriette S

    2010-01-01

    A 14-base pair (bp) long insertion (ins)/deletion (del) polymorphism in exon 8 in the 3'-untranslated region of the human leukocyte antigen (HLA)-G gene is suggested to affect transcription of the gene. Carriage of the G14bp ins is associated with low levels of soluble HLA-G and increases the risk...... of recurrent miscarriage (RM). Due to existence of strong linkage disequilibrium (LD) in the HLA region, the primary susceptibility genes for RM in the HLA-G region have not yet been identified. HLA-A, -B, -DRB1, and -G14bp polymorphisms were investigated in 29 Caucasian families with two or more siblings...... suffering unexplained RM. Strong positive LD was detected between the G14bp ins and HLA-A*01, -A*11, -A*31, -B*08, and DRB1*03, whereas strong negative LD was found between G14bp ins and HLA-A*02, -A*03, and -A*24. The frequency of haplotypes with HLA-G14bp ins inherited from the mother was significantly...

  7. A case report of fulminant type 1 diabetes mellitus associated with drug-induced hypersensitivity syndrome in an elderly patient with coxsackie B4 virus infection and human leukocyte antigen-A24 haplotype.

    Science.gov (United States)

    Takeno, Ayumu; Kanazawa, Ippei; Morita, Miwa; Takedani, Kai; Miyake, Hitomi; Yamamoto, Masahiro; Nogami, Kyoko; Kaneko, Sakae; Sugimoto, Toshitsugu

    2018-01-30

    Drug-induced hypersensitivity syndrome (DIHS) is a severe systemic adverse drug reaction. Previous studies showed that DIHS is associated with the onset of fulminant type 1 diabetes mellitus (FT1D). Although genetic background and abnormalities in immune response or viral infection are considered to be associated with pathogenesis of FT1D, it remains unclear whether virus infection and specific human leukocyte antigen (HLA) typing are involved in DIHS-associated FT1D. Here, we report a case of a 78-year-old female patient with FT1D after DIHS treatment. She was diagnosed as DIHS caused by carbamazepine, and treatment with predonisolone was initiated. After 46 days from the occurrence of DIHS, she was admitted to our hospital because of type 1 diabetes mellitus and diabetic ketoacidosis. Although her Hemoglobin A1c (HbA1c) was elevated by predonisolone treatment (HbA1c: 9.2%), we diagnosed her as fulminant type 1 diabetes mellitus considering the abrupt onset of the ketoacidosis. Her general condition was improved by treatment with fluid infusion and insulin administration. During her clinical course, the infection of coxsackie B4 virus was observed. In addition, the examination of HLA typing showed HLA-A24 haplotype. These findings suggest that the coxsackie B4 virus infection may be involved in the pathogenesis of DIHS-induced FT1D, and that HLA-A24 haplotype might relate to DIHS-associated FT1D.

  8. Ubiquitination of human leukocyte antigen (HLA)-DM by different membrane-associated RING-CH (MARCH) protein family E3 ligases targets different endocytic pathways.

    Science.gov (United States)

    Jahnke, Martin; Trowsdale, John; Kelly, Adrian P

    2012-03-02

    HLA-DM plays an essential role in the peptide loading of classical class II molecules and is present both at the cell surface and in late endosomal peptide-loading compartments. Trafficking of DM within antigen-presenting cells is complex and is, in part, controlled by a tyrosine-based targeting signal present in the cytoplasmic tail of DMβ. Here, we show that DM also undergoes post-translational modification through ubiquitination of a single lysine residue present in the cytoplasmic tail of the α chain, DMα. Ubiquitination of DM by MARCH1 and MARCH9 induced loss of DM molecules from the cell surface by a mechanism that cumulatively involved both direct attachment of ubiquitin chains to DMα and a functional tyrosine-based signal on DMβ. In contrast, MARCH8-induced loss of surface DM was entirely dependent upon the tyrosine signal on DMβ. In the absence of this tyrosine residue, levels of DM remained unchanged irrespective of whether DMα was ubiquitinated by MARCH8. The influence of MARCH8 was indirect and may have resulted from modification of components of the endocytic machinery by ubiquitination.

  9. Ubiquitination of Human Leukocyte Antigen (HLA)-DM by Different Membrane-associated RING-CH (MARCH) Protein Family E3 Ligases Targets Different Endocytic Pathways*

    Science.gov (United States)

    Jahnke, Martin; Trowsdale, John; Kelly, Adrian P.

    2012-01-01

    HLA-DM plays an essential role in the peptide loading of classical class II molecules and is present both at the cell surface and in late endosomal peptide-loading compartments. Trafficking of DM within antigen-presenting cells is complex and is, in part, controlled by a tyrosine-based targeting signal present in the cytoplasmic tail of DMβ. Here, we show that DM also undergoes post-translational modification through ubiquitination of a single lysine residue present in the cytoplasmic tail of the α chain, DMα. Ubiquitination of DM by MARCH1 and MARCH9 induced loss of DM molecules from the cell surface by a mechanism that cumulatively involved both direct attachment of ubiquitin chains to DMα and a functional tyrosine-based signal on DMβ. In contrast, MARCH8-induced loss of surface DM was entirely dependent upon the tyrosine signal on DMβ. In the absence of this tyrosine residue, levels of DM remained unchanged irrespective of whether DMα was ubiquitinated by MARCH8. The influence of MARCH8 was indirect and may have resulted from modification of components of the endocytic machinery by ubiquitination. PMID:22247549

  10. HLA-DQA1 and HLA-DQB1 genes in Tsachilas Indians from Ecuador: new insights in population analysis by Human Leukocyte Antigens.

    Science.gov (United States)

    Iorio, A; De Angelis, F; Garzoli, A; Battistini, A; De Stefano, G F

    2014-06-01

    Human Leucocyte Antigen (HLA) loci are widely known for their role in the generation of immune responses and are often considered to be effective in reconstructing human relationships. This is due to the high degree of polymorphism and the rarity of recombination observed at HLA loci. In this study, we have made an attempt to support the potential of HLA class II loci by analysing DQA1 and DQB1 in 52 Ecuadorians with ties to the Tsachilas community. Little is known about this populations either ethnologically or historically: they are considered retaining much of the ancient Chibchan culture in spite of the lack of significant genetic characterization. A total of 21 alleles were observed, with very low heterozygosity. The obtained data were then assessed for relationship reconstruction. The compiled database of 63 populations was segregated and resolved in clusters corresponding to the ethnogeographic distribution of the populations. This analysis of Central and Southern Amerindians allowed us to support a historical hypothesis related to the origin and migration of Ecuadorian people. Indeed, the relationships with neighbour human groups, especially Cayapas and Colombians, could shed light on the genetic similarity within ancient Chibchan culture that was dispersed by tribes coming up the Barbacoas. This indicates that if an appropriate analysis was to be carried out on a set of populations representative of different geographic locations, and that analysis was properly interpreted, then there would be a high possibility that HLA class II loci could infer accurate assessments, as revealed by uniparental markers. © 2014 John Wiley & Sons Ltd.

  11. A single Alal 39-to-Glu substitution in the Renibacterium salmoninarum virulence-associated protein p57 results in antigenic variation and is associated with enhanced p57 binding to Chinook salmon leukocytes

    Science.gov (United States)

    Wiens, Gregory D.; Pascho, Ron; Winton, James R.

    2002-01-01

    The gram-positive bacterium Renibacterium salmoninarum produces relatively large amounts of a 57-kDa protein (p57) implicated in the pathogenesis of salmonid bacterial kidney disease. Antigenic variation in p57 was identified by using monoclonal antibody 4C11, which exhibited severely decreased binding to R. salmoninarum strain 684 p57 and bound robustly to the p57 proteins of seven other R. salmoninarum strains. This difference in binding was not due to alterations in p57 synthesis, secretion, or bacterial cell association. The molecular basis of the 4C11 epitope loss was determined by amplifying and sequencing the two identical genes encoding p57, msa1 and msa2. The 5′ and coding sequences of the 684 msa1 and msa2 genes were identical to those of the ATCC 33209 msa1and msa2 genes except for a single C-to-A nucleotide mutation. This mutation was identified in both the msa1 and msa2 genes of strain 684 and resulted in an Ala139-to-Glu substitution in the amino-terminal region of p57. We examined whether this mutation in p57 altered salmonid leukocyte and rabbit erythrocyte binding activities. R. salmoninarum strain 684 extracellular protein exhibited a twofold increase in agglutinating activity for chinook salmon leukocytes and rabbit erythrocytes compared to the activity of the ATCC 33209 extracellular protein. A specific and quantitative p57 binding assay confirmed the increased binding activity of 684 p57. Monoclonal antibody 4C11 blocked the agglutinating activity of the ATCC 33209 extracellular protein but not the agglutinating activity of the 684 extracellular protein. These results indicate that the Ala139-to-Glu substitution altered immune recognition and was associated with enhanced biological activity of R. salmoninarum 684 p57.

  12. Association of de novo human leukocyte antigen and major histocompatibility complex class I chain-related gene-A antibodies and proteinuria with graft survival 5 years after renal transplantation.

    Science.gov (United States)

    Zhang, L-W; Peng, Z-G; Xian, W-H; Cui, X-Q; Sun, H-B; Li, E-G; Geng, L-N; Zhao, P; Tian, J

    2013-11-01

    Association of de novo human leukocyte antigen (HLA) and major histocompatibility complex class I chain-related gene-A (MICA) antibodies and proteinuria with graft survival 5 years after renal transplantation. De novo presence of HLA and MICA antibodies after renal transplantation is associated with poor graft survival. Proteinuria after transplantation is also considered a risk factor for premature graft loss. In this study, we investigated the association of de novo HLA and MICA antibodies on proteinuria after renal transplantation and the association of proteinuria and de novo antibodies with graft survival. We enrolled 275 patients without preexisting HLA and MICA antibodies followed for >5 years after renal transplantation. All donor organs were from living-related donors or from an organ donation program. HLA and MICA antibodies were detected by the Luminex method. Patients with proteinuria (>150 mg/d) underwent intermittent 24-hour proteinuria examination. The frequencies of de novo HLA and MICA antibody 5 years after transplantation were 25.8% and 12%, respectively. In total, 26.5% of patients had proteinuria at the 5-year follow-up. De novo HLA antibody was associated with increased proteinuria after transplantation (relative risk, 3.12). HLA antibody and proteinuria were both associated with poor 5-year graft survival (P = .027 and P = .006, respectively). De novo HLA and MICA antibodies and proteinuria after renal transplantation are all associated with poor graft survival. De novo HLA antibody is independent risk factor for posttransplant proteinuria, and proteinuria affects the association of de novo antibodies with decreased graft survival after transplantation. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Association of human leukocyte antigen (HLA)-DQ and HLA-DQA1/DQB1 alleles with Vogt-Koyanagi-Harada disease: A systematic review and meta-analysis.

    Science.gov (United States)

    Liu, Bing; Deng, Tuo; Zhu, Linxin; Zhong, Jingxiang

    2018-02-01

    The aim of this study was to evaluate the association of human leukocyte antigen (HLA)-DQ and HLA-DQA1/DQB1 alleles with Vogt-Koyanagi-Harada (VKH), providing further evidences on the genetic background of this disease. A comprehensive literature search was conducted on the relationship of HLA-DQ and/or HLA-DQA1/DQB1 alleles with VKH through PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP, and databases for grey literature. The last search was in October 2017. Pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated from extracted data to access the strength of the association between a genotype and VKH. HLA-DQ4 was confirmed to increase the risk of VKH significantly (OR = 4.63, 95% CI: 1.74-12.31, P = .002), while HLA-DQ1 seemed to reduce VKH occurrence with OR = 0.32 (95% CI: 0.22-0.47, P HLA-DQA1*0301-(OR = 4.52, 95% CI: 1.42-14.35, P = .01) and HLA-DQB1*0401-(OR = 23.12, 95% CI: 11.54-46.31, P HLA-DQA1*0103, 0401, 0501 and HLA-DQB1*0301, 0402, 0601, 0603 were significant protective genetic factors. We concluded that HLA-DQ4 carriers had a higher risk of VKH and HLA-DQ1 seemed to be protective. People with positive HLA-DQA1*0301 and HLA-DQB1*0401 demonstrated to be more susceptible to VKH. HLA-DQA1*0103, 0401, 0501 and HLA-DQB1*0301, 0402, 0601, 0603 could be potential protectors.

  14. Effect of Eucommia ulmoides Oliv., Gynostemma pentaphyllum (Thunb.) Makino, and Curcuma longa L. on Th1- and Th2-cytokine responses and human leukocyte antigen-DR expression in peripheral blood mononuclear cells of septic patients.

    Science.gov (United States)

    Wu, Huang-Pin; Lin, Yin-Ku

    2018-05-10

    Many traditional Chinese medicines (TCM), such as Eucommia ulmoides Oliv., Gynostemma pentaphyllum (Thunb.) Makino, and Curcuma longa L., have been reported to have various immune-modulatory effects. To determine the effects of extracts from these three TCM on type 1 T help (Th1)- and Th2-cytokine responses and human leukocyte antigen (HLA)-DR expression in peripheral blood mononuclear cells (PBMCs) obtained from septic patients. Lipopolysaccharide (LPS)-stimulated PBMCs of healthy controls and septic patients were cultured for 48 hs with or without 0.05/0.1 mg/ml of TCM extract. HLA-DR expression in monocytes was detected using flow cytofluorimetry. The interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin (IL)- 2, IL-5, IL-10, and IL-13 levels in supernatants were measured with a human enzyme-linked immunosorbent assay. Treatment with either 0.05 or 0.1 mg/ml of C. longa L. extract significantly restored the percentage of HLA-DR-positive monocytes, which was decreased by LPS in control and patient groups. Treatment with 0.05 or 0.1 mg/ml E. ulmoides Oliv. and C.longa L. extract decreased IL-10 production from LPS-stimulated PBMCs of controls and patients. In patients with sepsis, C. longa L. extract decreased IL-10 production to a greater degree than did E. ulmoides Oliv extract. Although IFN-γ, TNF-α, or IL-13 productions from LPS-stimulated PBMCs were influenced by E. ulmoides Oliv., G. pentaphyllum (Thunb.) Makino, or C. longa L. in control or sepsis groups in this study, only the influence of IL-10 was consistent in both control and sepsis groups. By enhancing monocyte HLA-DR expression and decreasing IL-10 production, C. longa L. might help restore inflammatory responses in septic patients to eradicate pathogens. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. HLA-B27 antigen

    Science.gov (United States)

    Human leukocyte antigen B27; Ankylosing spondylitis-HLA; Psoriatic arthritis-HLA; Reactive arthritis-HLA ... Erythrocyte sedimentation rate ( ESR ) Rheumatoid factor X-rays HLA testing is also used to match donated tissue ...

  16. File list: ALL.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.Polymorphonuclear_leukocytes hg19 All antigens Blood Polymorphonuclear... leukocytes SRX1016682,SRX1016679,SRX1016680,SRX1016681 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.20.AllAg.Polymorphonuclear_leukocytes.bed ...

  17. File list: ALL.Bld.10.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.10.AllAg.Polymorphonuclear_leukocytes hg19 All antigens Blood Polymorphonuclear... leukocytes SRX1016682,SRX1016679,SRX1016681,SRX1016680 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.10.AllAg.Polymorphonuclear_leukocytes.bed ...

  18. File list: ALL.Bld.50.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.Polymorphonuclear_leukocytes hg19 All antigens Blood Polymorphonuclear... leukocytes SRX1016682,SRX1016679,SRX1016680,SRX1016681 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.50.AllAg.Polymorphonuclear_leukocytes.bed ...

  19. File list: ALL.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Polymorphonuclear_leukocytes hg19 All antigens Blood Polymorphonuclear... leukocytes SRX1016679,SRX1016682,SRX1016681,SRX1016680 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.05.AllAg.Polymorphonuclear_leukocytes.bed ...

  20. Leukocyte esterase urine test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003584.htm Leukocyte esterase urine test To use the sharing features on this page, please enable JavaScript. Leukocyte esterase is a urine test to look for ...

  1. Dynamic Detection of Anti-Human Leukocyte Antigen (HLA) Antibodies but not HLA-DP Loci Mismatches Can Predict Acute Graft-versus-Host Disease and Overall Survival in HLA 12/12-Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies.

    Science.gov (United States)

    Pan, Zhijuan; Yuan, Xiaoni; Li, Yang; Wu, Xiaojin; Zhu, Wenjuan; Bao, Xiaojin; Zhao, Qinqin; He, Jun

    2016-01-01

    The National Marrow Donor Program and Center for International Blood and Marrow Transplant Research provided guidelines for the use of anti-HLA antibodies and HLA-DP-mismatched loci in unrelated donor hematopoietic stem cell transplantation (HSCT). However, a deeper understanding of other potentially useful biomarkers for predicting clinical outcomes in HLA-A, -B, -C, -DRB1, -DQB1, and -DQA1 (12/12)-matched unrelated donor HSCT is needed to further improve clinical outcomes. We tested HLA genotyping for 123 pairs of patients and donors. Anti-HLA antibodies using the Luminex method was applied to 123, 117, and 106 serum samples collected before and 1 month and 3 months after transplantation. The presences of anti-HLA antibodies at the 3 time points were 37.4% (46 of 123), 40.2% (47 of 117), and 22.6% (24 of 106). Mismatch of HLA-DPB1 and/or DPA1 allele between patient-donor pairs was 83.6% (92 of 110). Patients with anti-HLA antibodies had delayed platelet recovery. The presence of anti-HLA antibodies and their dynamic changes after transplantation were associated with increased occurrence of grades II to IV acute and chronic graft-versus-host disease (GVHD), higher treatment-related mortality, and reduced overall survival (OS) and disease-free survival, especially in acute myeloid leukemia and myelodysplastic syndrome patients. Multivariate analysis showed that presence of anti-HLA antibodies before transplantation was a risk factor for GVHD and OS. Furthermore, HLA-DP loci-matched subgroup showed a trend towards a lower rate of acute GVHD and a higher OS in the anti-HLA Abs-negative group. Our results suggest that dynamic changes of anti-HLA antibodies independently predict for a negative outcome of HSCT, independent of HLA-DP loci mismatches. Routine monitoring for anti-HLA antibody dynamics should be conducted before and after HSCT. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  2. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 103, č. 4 (2001), s. 401-406 ISSN 0019-2805 R&D Projects: GA ČR GA310/99/0349 Institutional research plan: CEZ:AV0Z5052915 Keywords : antigen * CD * leukocyte Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.656, year: 2001

  3. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 19, č. 6 (2001), s. 556-562 ISSN 1066-5099 R&D Projects: GA AV ČR IAA7052904 Institutional research plan: CEZ:AV0Z5052915 Keywords : CD * leukocyte antigens Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.689, year: 2001

  4. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 31, č. 10 (2001), s. 2841-2847 ISSN 0014-2980 R&D Projects: GA AV ČR IAA7052904 Keywords : CD * leukocyte antigens Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.990, year: 2001

  5. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 211, č. 2 (2001), s. 81-85 ISSN 0008-8749 R&D Projects: GA ČR GA310/99/0349 Institutional research plan: CEZ:AV0Z5052915 Keywords : antigen * CD * leukocyte Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.604, year: 2001

  6. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 70, č. 5 (2001), s. 685-690 ISSN 0741-5400 R&D Projects: GA AV ČR IAA7052904 Institutional research plan: CEZ:AV0Z5052915 Keywords : CD * leukocyte antigens Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.516, year: 2001

  7. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 13, č. 9 (2001), s. 1095-1098 ISSN 0953-8178 R&D Projects: GA ČR GA310/99/0349 Institutional research plan: CEZ:AV0Z5052915 Keywords : antigen * CD * leukocyte Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.611, year: 2001

  8. Human leukocyte antigen-e alleles are associated with hepatitis c virus, torque teno virus, and toxoplasma co-infections but are not associated with hepatitis b virus, hepatitis d virus, and GB virus c co-infections in human immunodeficiency virus patients

    Directory of Open Access Journals (Sweden)

    Afiono Agung Prasetyo

    2016-01-01

    Full Text Available Context: Data regarding the distribution of Human Leukocyte Antigen (HLA-E alleles and their association with blood-borne pathogen infections/co-infections are limited for many populations, including Indonesia. Aims: The aim of this study was to analyze the association between HLA-E allelic variants and infection with blood-borne pathogens such as hepatitis B virus (HBV, hepatitis C virus (HCV, hepatitis D virus (HDV, torque teno virus (TTV, GB virus C (GBV-C, and Toxoplasma gondii (T. gondii in Indonesian Javanese human immunodeficiency virus (HIV patients. Settings and Design: A total of 320 anti-HIV-positive blood samples were analyzed for HBV, HCV, HDV, TTV, GBV-C, and T. gondii infection status and its association with HLA-E allelic variants. Materials and Methods: Nucleic acid was extracted from plasma samples and used for the molecular detection of HBV DNA, HCV RNA, HDV RNA, TTV DNA, and GBV-C RNA, whereas hepatitis B surface antigen, anti-HCV, immunoglobulin M and G (IgM and IgG anti-T. gondii were detected through serological testing. The blood samples were genotyped for HLA-E loci using a sequence-specific primer-polymerase chain reaction. Statistical Analysis Used: Either the Chi-square or Fisher′s exact test was performed to analyze the frequency of HLA-E alleles and blood-borne pathogen infections in the population. Odds ratios (ORs were calculated to measure the association between the antibodies found and the participants′ possible risk behaviors. A logistic regression analysis was used to assess the associations. Results: HLA-EFNx010101/0101 was associated with HCV/TTV co-infection (adjusted OR [aOR]: 3.5; 95% confidence interval [CI]: 1.156-10.734; P = 0.027 and IgM/IgG anti-Toxo positivity (aOR: 27.0; 95% CI: 3.626-200.472; P = 0.001. HLA-EFNx010103/0103 was associated with TTV co-infection (aOR: 2.7; 95% CI: 1.509-4.796; P = 0.001. Conclusions: HLA-E alleles in Indonesian Javanese HIV patients were found to be associated

  9. Antigen test for early diagnosis of active cytomegalo-virus infection in heart-transplant recipients

    NARCIS (Netherlands)

    van der Bij, W; van Dijk, R. B.; van Son, W. J.; Torensma, R; Prenger, K. B.; Prop, J.; Tegzess, A. M.; The, T. H.

    An assay was developed for the detection of cytomegalovirus (CMV) antigens in blood leukocytes and evaluated for its diagnostic significance in six heart transplant recipients. Slides of cytocentrifuged blood leukocytes were prepared at regular intervals during the posttransplantation period and

  10. Technique of leukocyte harvesting and labeling: problems and perspectives

    International Nuclear Information System (INIS)

    McAfee, J.G.; Subramanian, G.; Gagne, G.

    1984-01-01

    Mixed leukocyte suspensions obtained after gravity sedimentation of red cells and labeled with 111 In lipophilic chelates are now widely used clinically for abscess localization at many medical centers. So far, labeling with 111 In-oxine or tropolone has been more successful than any 99 mTc method. More sophisticated approaches are available for isolation and labeling of specific leukocyte cell types, to study their migration in vivo. The most significant advances in cell harvesting include newer density gradients for isopyknic centrifugation, centrifugal elutriation, and flow cytometry. Unlike current radioactive agents which label many cell types indiscriminately, more selective ligands are being developed which bind to specific cell surface receptors. These will label certain leukocyte populations or subtypes while not reacting with others, thereby avoiding laborious separation techniques. Monoclonal antibodies against leukocyte cell-surface antigens appear particularly promising as agents for selective cell labeling

  11. Endothelial signaling in leukocyte transmigration

    NARCIS (Netherlands)

    Hordijk, Peter

    2003-01-01

    Leukocyte transendothelial migration is a multistep process coordinated by chemokine receptors, integrins and cell adhesion molecules. The interaction between leukocytes and endothelial cells is accompanied by bidirectional signaling in both cell types, which is initiated following formation of

  12. TOGOG & SEMAR: DEHUMANIZATION, ANTI-HUMAN, POST-HUMAN

    Directory of Open Access Journals (Sweden)

    Imam Setyobudi

    2018-01-01

    Full Text Available The core of Wayang stories (Mahabharata, Bharatayuda, Ramayana is the reflection of human that is always continuously in crisis and emergency situations and conditions. Tragic. Wayang stories raise humanity problems so that the existences of human conception experience the perpetuity of dehumanization, existential instability and ambiguous. The killing of the essence of the human existence purpose on earth. It is an issue fundamentally of anti-human. Shadow play perspective does not rest on human understanding or Knight  (Pandawa, Kurawa, Rama, Giant, the heaven God (Bathara Guru, and/or Prabu Khresna, incarnation of Wisnhu God. Wayang stories evoke Togog and Semar angle. Liyan. Grassroots. The general public. Amorphous: No Man is not a knight instead of a brahmana is not god instead of giant. Arises a question that is closely related to the presence of Togog and Semar. Why do shadow play stories present the figure of the them, while the authentic story of the Mahabharata and Ramayana India version does not exist at all? Are Togog and Semar truly actualization of post-human aesthetic and post-human anthropology ideas? The substance of this writing ask us to discuss regarding the idea of Togog and Semar in shadow play into the realm of post-human discourse as a result of dehumanization signs in the frame of shadow play stories. The main focus of the discussion focused on the position of Togog and Semar as the figure as linuwih or great beyond human (knight and god. Study restriction on the context of Purwa Java Gagrak Jogja and Solo wayang; similarly in East Java, Sunda and Bali, there are also those two figures.

  13. Anti-human SIRPα antibody is a new tool for cancer immunotherapy.

    Science.gov (United States)

    Murata, Yoji; Tanaka, Daisuke; Hazama, Daisuke; Yanagita, Tadahiko; Saito, Yasuyuki; Kotani, Takenori; Oldenborg, Per-Arne; Matozaki, Takashi

    2018-02-23

    Interaction of signal regulatory protein α (SIRPα) expressed on the surface of macrophages with its ligand CD47 expressed on target cells negatively regulates phagocytosis of the latter cells by the former. We recently showed that blocking Abs to mouse SIRPα enhanced both the Ab-dependent cellular phagocytosis (ADCP) activity of mouse macrophages for Burkitt's lymphoma Raji cells opsonized with an Ab to CD20 (rituximab) in vitro as well as the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in nonobese diabetic (NOD)/SCID mice. However, the effects of blocking Abs to human SIRPα in preclinical cancer models have remained unclear given that such Abs have failed to interact with endogenous SIRPα expressed on macrophages of immunodeficient mice. With the use of Rag2 -/- γ c -/- mice harboring a transgene for human SIRPα under the control of human regulatory elements (hSIRPα-DKO mice), we here show that a blocking Ab to human SIRPα significantly enhanced the ADCP activity of macrophages derived from these mice for human cancer cells. The anti-human SIRPα Ab also markedly enhanced the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in hSIRPα-DKO mice. Our results thus suggest that the combination of Abs to human SIRPα with therapeutic Abs specific for tumor antigens warrants further investigation for potential application to cancer immunotherapy. In addition, humanized mice, such as hSIRPα-DKO mice, should prove useful for validation of the antitumor effects of checkpoint inhibitors before testing in clinical trials. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  14. Role of a Novel Human Leukocyte Antigen-DQA1*01:02;DRB1*15:01 Mixed Isotype Heterodimer in the Pathogenesis of “Humanized” Multiple Sclerosis-like Disease*

    Science.gov (United States)

    Kaushansky, Nathali; Eisenstein, Miriam; Boura-Halfon, Sigalit; Hansen, Bjarke Endel; Nielsen, Claus Henrik; Milo, Ron; Zeilig, Gabriel; Lassmann, Hans; Altmann, Daniel M.; Ben-Nun, Avraham

    2015-01-01

    Gene-wide association and candidate gene studies indicate that the greatest effect on multiple sclerosis (MS) risk is driven by the HLA-DRB1*15:01 allele within the HLA-DR15 haplotype (HLA-DRB1*15:01-DQA1*01:02-DQB1*0602-DRB5*01:01). Nevertheless, linkage disequilibrium makes it difficult to define, without functional studies, whether the functionally relevant effect derives from DRB1*15:01 only, from its neighboring DQA1*01:02-DQB1*06:02 or DRB5*01:01 genes of HLA-DR15 haplotype, or from their combinations or epistatic interactions. Here, we analyzed the impact of the different HLA-DR15 haplotype alleles on disease susceptibility in a new “humanized” model of MS induced in HLA-transgenic (Tg) mice by human oligodendrocyte-specific protein (OSP)/claudin-11 (hOSP), one of the bona fide potential primary target antigens in MS. We show that the hOSP-associated MS-like disease is dominated by the DRB1*15:01 allele not only as the DRA1*01:01;DRB1*15:01 isotypic heterodimer but also, unexpectedly, as a functional DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. The contribution of HLA-DQA1/DRB1 mixed isotype heterodimer to OSP pathogenesis was revealed in (DRB1*1501xDQB1*0602)F1 double-Tg mice immunized with hOSP(142–161) peptide, where the encephalitogenic potential of prevalent DRB1*1501/hOSP(142–161)-reactive Th1/Th17 cells is hindered due to a single amino acid difference in the OSP(142–161) region between humans and mice; this impedes binding of DRB1*1501 to the mouse OSP(142–161) epitope in the mouse CNS while exposing functional binding of mouse OSP(142–161) to DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. This study, which shows for the first time a functional HLA-DQA1/DRB1 mixed isotype heterodimer and its potential association with disease susceptibility, provides a rationale for a potential effect on MS risk from DQA1*01:02 through functional DQA1*01:02;DRB1*15:01 antigen presentation. Furthermore, it highlights a potential contribution to MS

  15. Correlation between Leukocyte Numbers and Body Size of Rainbow Trout

    DEFF Research Database (Denmark)

    Mohammad, Rezkar Jaafar; Otani, Maki; Kania, Per Walter

    2016-01-01

    towards an antigen to be initiated even in fry. The number of leukocytes in individual fish at different developmental stages is likely to influence the capacity of the fish to respond simultaneously to several antigens (pathogens and vaccine components). This parameter may therefore be crucial for both...... - 780 g (group IV) were investigated. The number of lymphocytes was generally higher in head kidney compared to blood and spleen but they dominated in all samples (blood, head kidney and spleen) and their numbers increased exponentially with fish size. Percentages of lymphocytes in relation...

  16. Estudo de associação entre antígenos leucocitários humanos e doença de Jorge Lobo Study of the association between human leukocyte antigens and Jorge Lobo's disease

    Directory of Open Access Journals (Sweden)

    Elaine Valim Camarinha Marcos

    2005-10-01

    Full Text Available A doença de Jorge Lobo é uma micose cutânea/subcutânea de evolução crônica, causada pelo fungo Lacazia loboi. Devido às características epidemiológicas e poucos estudos relacionados aos aspectos imunológicos dessa doença, o objetivo do trabalho foi investigar uma possível associação das especificidades HLA de classe II em 21 pacientes portadores da doença de Jorge Lobo, comparando com indivíduos sadios de mesma etnia. As tipificações HLA foram realizadas pelo método de PCR-SSP. O resultado não revelou qualquer tipo de associação entre os antígenos HLA e doença de Jorge Lobo. Embora sem significância estatística, foi observada a diminuição da freqüência do antígeno HLA-DR7 no grupo dos pacientes em relação aos controles (0% x 18%, sugerindo uma associação negativa (protetora entre HLA-DR7 e doença de Jorge Lobo. Contudo, estudos devem ser continuados, objetivando melhor entendimento nos mecanismos envolvidos na suscetibilidade e/ou proteção dessa doença.Jorge Lobo's disease is a cutaneous/subcutaneous mycosis with a chronic course, caused by the fungus Lacazia loboi. Considering its epidemiology and the few studies on immunological aspects of this disease, the objective of the present study was to investigate a possible association between HLA class II specificities in 21 Jorge Lobo's disease patients, by comparing them with healthy individual of the same ethnic group. HLA typing was performed using PCR-SSP method. The result did not show any association between HLA antigens and Jorge Lobo's disease. Although not statistically significant, a decreased frequency of HLA-DR7 was observed in the patients compared to the controls (0% x 18%. This suggests a negative association (protective between HLA-DR7 and Jorge Lobo's disease. Further studies, however, are needed for a better understanding of the susceptibility and/or protection mechanisms involved.

  17. Detection of Signal Regulatory Protein α in Saimiri sciureus (Squirrel Monkey) by Anti-Human Monoclonal Antibody

    Science.gov (United States)

    de Souza, Hugo Amorim dos Santos; Costa-Correa, Edmar Henrique; Bianco-Junior, Cesare; Andrade, Márcia Cristina Ribeiro; Lima-Junior, Josué da Costa; Pratt-Riccio, Lilian Rose; Daniel-Ribeiro, Cláudio Tadeu; Totino, Paulo Renato Rivas

    2017-01-01

    Non-human primates (NHP) are suitable models for studying different aspects of the human system, including pathogenesis and protective immunity to many diseases. However, the lack of specific immunological reagents for neo-tropical monkeys, such as Saimiri sciureus, is still a major factor limiting studies in these models. An alternative strategy to circumvent this obstacle has been the selection of immunological reagents directed to humans, which present cross-reactivity with NHP molecules. In this context and considering the key role of inhibitory immunoreceptors—such as the signal regulatory protein α (SIRPα)—in the regulation of immune responses, in the present study, we attempted to evaluate the ability of anti-human SIRPα monoclonal antibodies to recognize SIRPα in antigen-presenting S. sciureus peripheral blood mononuclear cells (PBMC). As shown by flow cytometry analysis, the profile of anti-SIRPα staining as well as the levels of SIRPα-positive cells in PBMC from S. sciureus were similar to those observed in human PBMC. Furthermore, using anti-SIRPα monoclonal antibody, it was possible to detect a decrease of the SIRPα levels on surface of S. sciureus cells after in vitro stimulation with lipopolysaccharides. Finally, using computed-based analysis, we observed a high degree of conservation of SIRPα across six species of primates and the presence of shared epitopes in the extracellular domain between humans and Saimiri genus that could be targeted by antibodies. In conclusion, we have identified a commercially available anti-human monoclonal antibody that is able to detect SIRPα of S. sciureus monkeys and that, therefore, can facilitate the study of the immunomodulatory role of SIRPα when S. sciureus is used as a model. PMID:29312325

  18. Detection of Signal Regulatory Protein α in Saimiri sciureus (Squirrel Monkey by Anti-Human Monoclonal Antibody

    Directory of Open Access Journals (Sweden)

    Hugo Amorim dos Santos de Souza

    2017-12-01

    Full Text Available Non-human primates (NHP are suitable models for studying different aspects of the human system, including pathogenesis and protective immunity to many diseases. However, the lack of specific immunological reagents for neo-tropical monkeys, such as Saimiri sciureus, is still a major factor limiting studies in these models. An alternative strategy to circumvent this obstacle has been the selection of immunological reagents directed to humans, which present cross-reactivity with NHP molecules. In this context and considering the key role of inhibitory immunoreceptors—such as the signal regulatory protein α (SIRPα—in the regulation of immune responses, in the present study, we attempted to evaluate the ability of anti-human SIRPα monoclonal antibodies to recognize SIRPα in antigen-presenting S. sciureus peripheral blood mononuclear cells (PBMC. As shown by flow cytometry analysis, the profile of anti-SIRPα staining as well as the levels of SIRPα-positive cells in PBMC from S. sciureus were similar to those observed in human PBMC. Furthermore, using anti-SIRPα monoclonal antibody, it was possible to detect a decrease of the SIRPα levels on surface of S. sciureus cells after in vitro stimulation with lipopolysaccharides. Finally, using computed-based analysis, we observed a high degree of conservation of SIRPα across six species of primates and the presence of shared epitopes in the extracellular domain between humans and Saimiri genus that could be targeted by antibodies. In conclusion, we have identified a commercially available anti-human monoclonal antibody that is able to detect SIRPα of S. sciureus monkeys and that, therefore, can facilitate the study of the immunomodulatory role of SIRPα when S. sciureus is used as a model.

  19. Integrin activation by P-Rex1 is required for selectin-mediated slow leukocyte rolling and intravascular crawling.

    Science.gov (United States)

    Herter, Jan M; Rossaint, Jan; Block, Helena; Welch, Heidi; Zarbock, Alexander

    2013-03-21

    Integrin activation is essential for the function of leukocytes. Impaired integrin activation on leukocytes is the hallmark of the leukocyte adhesion deficiency syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. In inflammation, leukocytes collect different signals during the contact with the microvasculature, which activate signaling pathways leading to integrin activation and leukocyte recruitment. We report the role of P-Rex1, a Rac-specific guanine nucleotide exchanging factor, in integrin activation and leukocyte recruitment. We find that P-Rex1 is required for inducing selectin-mediated lymphocyte function-associated antigen-1 (LFA-1) extension that corresponds to intermediate affinity and induces slow leukocyte rolling, whereas P-Rex1 is not involved in the induction of the high-affinity conformation of LFA-1 obligatory for leukocyte arrest. Furthermore, we demonstrate that P-Rex1 is involved in Mac-1-dependent intravascular crawling. In vivo, both LFA-1-dependent slow rolling and Mac-1-dependent crawling are defective in P-Rex1(-/-) leukocytes, whereas chemokine-induced arrest and postadhesion strengthening remain intact in P-Rex1-deficient leukocytes. Rac1 is involved in E-selectin-mediated slow rolling and crawling. In vivo, in an ischemia-reperfusion-induced model of acute kidney injury, abolished selectin-mediated integrin activation contributed to decreased neutrophil recruitment and reduced kidney damage in P-Rex1-deficient mice. We conclude that P-Rex1 serves distinct functions in LFA-1 and Mac-1 activation.

  20. Effect of fatty acids on leukocyte function

    Directory of Open Access Journals (Sweden)

    Pompéia C.

    2000-01-01

    Full Text Available Fatty acids have various effects on immune and inflammatory responses, acting as intracellular and intercellular mediators. Polyunsaturated fatty acids (PUFAs of the omega-3 family have overall suppressive effects, inhibiting lymphocyte proliferation, antibody and cytokine production, adhesion molecule expression, natural killer cell activity and triggering cell death. The omega-6 PUFAs have both inhibitory and stimulatory effects. The most studied of these is arachidonic acid that can be oxidized to eicosanoids, such as prostaglandins, leukotrienes and thromboxanes, all of which are potent mediators of inflammation. Nevertheless, it has been found that many of the effects of PUFA on immune and inflammatory responses are not dependent on eicosanoid generation. Fatty acids have also been found to modulate phagocytosis, reactive oxygen species production, cytokine production and leukocyte migration, also interfering with antigen presentation by macrophages. The importance of fatty acids in immune function has been corroborated by many clinical trials in which patients show improvement when submitted to fatty acid supplementation. Several mechanisms have been proposed to explain fatty acid modulation of immune response, such as changes in membrane fluidity and signal transduction pathways, regulation of gene transcription, protein acylation, and calcium release. In this review, evidence is presented to support the proposition that changes in cell metabolism also play an important role in the effect of fatty acids on leukocyte functioning, as fatty acids regulate glucose and glutamine metabolism and mitochondrial depolarization.

  1. The effect of HLA mismatches, shared cross-reactive antigen groups, and shared HLA-DR antigens on the outcome after pediatric liver transplantation

    NARCIS (Netherlands)

    Sieders, E; Hepkema, BG; Peeters, PMJG; Ten Vergert, EM; De Jong, KP; Porte, RJ; Bijleveld, CMA; van den Berg, AP; Lems, SPM; Gouw, ASH; Slooff, MJH

    2005-01-01

    The aim of this study was to analyze the effect of human leukocyte antigen (HLA) class I and HLA-DR mismatching, sharing cross-reactive antigen groups (CREGs), and sharing HLA-DR antigens on the outcome after pediatric liver transplantation. Outcome parameters were graft survival, acute rejection,

  2. Prenatal diagnostic procedure for leukocyte adhesion deficiency

    NARCIS (Netherlands)

    Weening, R. S.; Bredius, R. G.; Wolf, H.; van der Schoot, C. E.

    1991-01-01

    Leukocyte adhesion deficiency (LAD) is a rare autosomal recessive disorder which leads to recurrent severe infections due to impaired leukocyte functions. The disorder is caused by an absence or deficiency of leukocyte cell adhesion molecules (LeuCAMs) on the leukocyte membranes. The diagnosis is

  3. A Model System for Concurrent Detection of Antigen and Antibody Based on Immunological Fluorescent Method

    Directory of Open Access Journals (Sweden)

    Yuan-Cheng Cao

    2015-01-01

    Full Text Available This paper describes a combined antigen/antibody immunoassay implemented in a 96-well plate using fluorescent spectroscopic method. First, goat anti-human IgG was used to capture human IgG (model antigen; goat anti-human IgG (Cy3 or FITC was used to detect the model antigen; a saturating level of model antigen was then added followed by unlabelled goat anti-human IgG (model antibody; finally, Cy3 labelled rabbit anti-goat IgG was used to detect the model antibody. Two approaches were applied to the concomitant assay to analyze the feasibility. The first approach applied FITC and Cy3 when both targets were present at the same time, resulting in 50 ng/mL of the antibody detection limit and 10 ng/mL of antigen detection limit in the quantitative measurements of target concentration, taking the consideration of FRET efficiency of 68% between donor and acceptor. The sequential approach tended to lower the signal/noise (S/N ratio and the detection of the model antigen (lower than 1 ng/mL had better sensitivity than the model antibody (lower than 50 ng/mL. This combined antigen/antibody method might be useful for combined detection of antigens and antibodies. It will be helpful to screen for both antigen and antibody particularly in the situations of the multiserotype and high-frequency mutant virus infections.

  4. Phenotyping of Leukocytes and Leukocyte-Derived Extracellular Vesicles.

    Science.gov (United States)

    Pugholm, Lotte Hatting; Bæk, Rikke; Søndergaard, Evo Kristina Lindersson; Revenfeld, Anne Louise Schacht; Jørgensen, Malene Møller; Varming, Kim

    2016-01-01

    Extracellular vesicles (EVs) have a demonstrated involvement in modulating the immune system. It has been proposed that EVs could be used as biomarkers for detection of inflammatory and immunological disorders. Consequently, it is of great interest to investigate EVs in more detail with focus on immunological markers. In this study, five major leukocyte subpopulations and the corresponding leukocyte-derived EVs were phenotyped with focus on selected immunological lineage-specific markers and selected vesicle-related markers. The leukocyte-derived EVs displayed phenotypic differences in the 34 markers investigated. The majority of the lineage-specific markers used for identification of the parent cell types could not be detected on EVs released from monocultures of the associated cell types. In contrast, the vesicular presentation of CD9, CD63, and CD81 correlated to the cell surface expression of these markers, however, with few exceptions. Furthermore, the cellular expression of CD9, CD63, and CD81 varied between leukocytes present in whole blood and cultured leukocytes. In summary, these data demonstrate that the cellular and vesicular presentation of selected lineage-specific and vesicle-related markers may differ, supporting the accumulating observations that sorting of molecular cargo into EVs is tightly controlled.

  5. Cytomegalovirus infectivity in whole blood following leukocyte reduction by filtration.

    Science.gov (United States)

    Lipson, S M; Shepp, D H; Match, M E; Axelrod, F B; Whitbread, J A

    2001-07-01

    Cytomegalovirus (CMV) may be transmitted by transfusion of whole blood and cellular components processed according to standard processing procedures. A need exists to develop new procedures to remove CMV and other leukocyte-borne viruses from donor blood. Ten patients (AIDS/bone marrow transplants) who were CMV antigenemic (virus subsequently confirmed by isolation), donated 50 mL of venous blood within 24 to 72 hours of the initial antigen detection. Twenty-five-milliliter aliquots of each specimen were passed through Purecell Neo Neonatal Leukocyte Reduction Filters (Pall, East Hills, NY). The remaining 25-mL nonfiltered aliquots, as well as the blood filtrates, were subjected to infectivity endpoint determinations. The Purecell Neo filter effected a 3 to 4 log10 leukocyte reduction. CMV input titers ranged from less than 10 to 7.3 x 10(1) median tissue culture infectious dose (TCID50) per milliliter. CMV was not isolated from any postfiltration effluent (i.e., leukocytes, erythrocytes, or plasma). CMV DNA was not detected by nested polymerase chain reaction in 8 of 10 postfiltrate blood specimens. The Purecell Neo filter was efficacious in eliminating or significantly reducing viral (CMV) load in venous blood.

  6. Role of Human Leukocyte Antigens (HLA) in Autoimmune Diseases.

    Science.gov (United States)

    Bodis, Gergely; Toth, Victoria; Schwarting, Andreas

    2018-03-07

    Since the discovery of HLA 60 years ago, it has contributed to the understanding of the immune system as well as of the pathogenesis of several diseases. Aside from its essential role in determining donor-recipient immune compatibility in organ transplantation, HLA genotyping is meanwhile performed routinely as part of the diagnostic work-up of certain autoimmune diseases. Considering the ability of HLA to influence thymic selection as well as peripheral anergy of T cells, its role in the pathogenesis of autoimmunity is understandable. The aim of this paper is to provide a brief overview of the role and current clinical relevance of HLA-B27 in spondyloarthritis and HLA-B51 in Behçet's disease as well as HLA-DQ2/DQ8 in celiac disease and HLA-DRB1 in rheumatoid arthritis and to discuss possible future implications.

  7. Human leukocyte antigen (HLA)-G during pregnancy part I

    DEFF Research Database (Denmark)

    Klitkou, Louise; Dahl, Mette; Hviid, Thomas Vauvert F

    2015-01-01

    , as well as in umbilical cord blood samples. Soluble HLA-G levels declined by 38.4% in maternal blood from GW20 to term, and sHLA-G levels were significantly lower in maternal blood at term than in GW20 (P... blood (Pumbilical cord blood, were correlated (Pumbilical cord blood. The finding that s...

  8. Human leukocyte antigen-A genotype as a predictor of ...

    African Journals Online (AJOL)

    Reham Khalifa

    2016-01-18

    Jan 18, 2016 ... 4). Among the studied cases, 40% showed HLA-A*. 01–30 type. There was a significant difference (P = 0.05) among detected HLA types as regards. CMVpp65 ... Thus, HLA typing might be helpful in estimating the risk of CMV disease during the post- ..... recipients were serum CMV IgG positive (100%).

  9. HLA class I and II molecules present influenza virus antigens with different kinetics

    NARCIS (Netherlands)

    Kuijpers, K. C.; van Kemenade, F. J.; Hooibrink, B.; Neefjes, J. J.; Lucas, C. J.; van Lier, R. A.; Miedema, F.

    1992-01-01

    Human leukocyte antigen (HLA) class I and class II molecules differ with respect to their intracellular pathways and the compartments where they associate with processed antigen. To study possible consequences of these differences for the kinetics of antigen presentation by HLA class I and class II

  10. Leukocyte trafficking and vascular integrity

    NARCIS (Netherlands)

    Heemskerk, N.

    2017-01-01

    The endothelial cells that pave the inner lining of blood vessels maintain a tight barrier between the vasculature and the underlying tissues. However, disruptive stressors, such as transmigrating leukocytes and inflammatory mediators challenge blood vessel integrity every day. In this thesis, we

  11. BIOCOMPATIBILITY OF LEUKOCYTE REMOVAL FILTERS DURING BEDSIDE LEUKOCYTE FILTRATION OF RED-CELL CONCENTRATES

    NARCIS (Netherlands)

    GU, YJ; OBSTER, R; DEHAAN, J; HUET, RCGG; VANOEVEREN, W

    1992-01-01

    The biocompatibility of leukocyte removal filters was evaluated in four different types of leukocyte filters made from different materials during bedside leukocyte filtration of red cell concentrates (RCC). Two units of banked RCC were filtrated through each leukocyte filter inserted into the

  12. Leukocyte adhesion - a fundamental process in leukocyte physiology

    Directory of Open Access Journals (Sweden)

    Gahmberg C.G.

    1999-01-01

    Full Text Available Leukocyte adhesion is of pivotal functional importance. The adhesion involves several different adhesion molecules, the most important of which are the leukocyte ß2-integrins (CD11/CD18, the intercellular adhesion molecules, and the selectins. We and others have extensively studied the specificity and binding sites in the integrins and the intercellular adhesion molecules for their receptors and ligands. The integrins have to become activated to exert their functions but the possible mechanisms of activation remain poorly understood. Importantly, a few novel intercellular adhesion molecules have been recently described, which seem to function only in specific tissues. Furthermore, it is becoming increasingly apparent that changes in integrins and intercellular adhesion molecules are associated with a number of acute and chronic diseases.

  13. Leukocyte integrins: role in leukocyte recruitment and as therapeutic targets in inflammatory disease.

    Science.gov (United States)

    Mitroulis, Ioannis; Alexaki, Vasileia I; Kourtzelis, Ioannis; Ziogas, Athanassios; Hajishengallis, George; Chavakis, Triantafyllos

    2015-03-01

    Infection or sterile inflammation triggers site-specific attraction of leukocytes. Leukocyte recruitment is a process comprising several steps orchestrated by adhesion molecules, chemokines, cytokines and endogenous regulatory molecules. Distinct adhesive interactions between endothelial cells and leukocytes and signaling mechanisms contribute to the temporal and spatial fine-tuning of the leukocyte adhesion cascade. Central players in the leukocyte adhesion cascade include the leukocyte adhesion receptors of the β2-integrin family, such as the αLβ2 and αMβ2 integrins, or of the β1-integrin family, such as the α4β1-integrin. Given the central involvement of leukocyte recruitment in different inflammatory and autoimmune diseases, the leukocyte adhesion cascade in general, and leukocyte integrins in particular, represent key therapeutic targets. In this context, the present review focuses on the role of leukocyte integrins in the leukocyte adhesion cascade. Experimental evidence that has implicated leukocyte integrins as targets in animal models of inflammatory disorders, such as experimental autoimmune encephalomyelitis, psoriasis, inflammatory bone loss and inflammatory bowel disease as well as preclinical and clinical therapeutic applications of antibodies that target leukocyte integrins in various inflammatory disorders are presented. Finally, we review recent findings on endogenous inhibitors that modify leukocyte integrin function, which could emerge as promising therapeutic targets. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Periovulatory leukocyte infiltration in the rat ovary.

    Science.gov (United States)

    Oakley, Oliver R; Kim, HeyYoung; El-Amouri, Ismail; Lin, Po-Ching Patrick; Cho, Jongki; Bani-Ahmad, Mohammad; Ko, Chemyong

    2010-09-01

    Ovulation is preceded by intraovarian inflammatory reactions that occur in response to the preovulatory gonadotropin surge. As a main inflammatory event, leukocytes infiltrate the ovary and release proteolytic enzymes that degrade the extracellular matrix weakening the follicular wall, a required step for follicle rupture. This study aimed to quantitatively measure the infiltrating leukocytes, determine their cell types, and localize infiltration sites in the periovulatory rat ovary. Cycling adult and gonadotropin-stimulated immature rats were used as animal models. Ovaries were collected at five different stages of estrous cycle in the adult rats (diestrus, 1700 h; proestrus, 1500 h; proestrus, 2400 h; estrus, 0600 h; and metestrus, 1700 h) and at five different time points after superovulation induction in the immature rats (pregnant mare's serum gonadotrophin, 0 h; pregnant mare's serum gonadotrophin, 48 h; human chorionic gonadotropin, 6 h; human chorionic gonadotropin, 12 h; and human chorionic gonadotropin, 24 h). The ovaries were either dissociated into a single cell suspension for flow cytometric analysis or fixed for immunohistochemical localization of the leukocytes. Similar numbers of leukocytes were seen throughout the estrous cycle (approximately 500,000/ovary), except proestrus 2400 when 2-fold higher numbers of leukocytes were found (approximately 1.1 million/ovary). A similar trend of periovulatory rise of leukocyte numbers was seen in the superovulation-induced immature rat model, recapitulating a dramatic increase in leukocyte numbers upon gonadotropin stimulation. Both macrophage/granulocytes and lymphocytes were among the infiltrating leukocytes and were localized in the theca and interstitial tissues, where platelet-endothelial cell adhesion molecule-1 and intercellular adhesion molecule-1 may play roles in the transmigration of leukocytes, because their expressions correlates spatiotemporally with the infiltrating leukocytes. In addition, a

  15. Studying leukocyte recruitment under flow conditions.

    Science.gov (United States)

    Parsons, Sean A; Jurzinsky, Christophe; Cuvelier, Susan L; Patel, Kamala D

    2013-01-01

    Leukocyte recruitment from the vasculature occurs under conditions of haemodynamic shear stress. The parallel plate flow chamber apparatus is an in vitro system that is widely used to study leukocyte recruitment under shear conditions. The flow chamber is a versatile tool for examining adhesive interactions, as it can be used to study a variety of adhesive substrates, ranging from monolayers of primary cells to isolated adhesion molecules, and a variety of adhesive particles, ranging from leukocytes in whole blood to antibody-coated latex beads. We describe here methods for studying leukocyte recruitment to cytokine-stimulated, transfected or transduced endothelial cells using both whole blood and isolated leukocyte suspensions. These methods enable multiple parameters to be measured, including the total number of recruited leukocytes, the percentage of leukocytes that are rolling or firmly adherent, and the percentage of leukocytes that have transmigrated. Although these methods are described for interactions between leukocytes and endothelial cells, they are broadly applicable to the study of interactions between many combinations of adhesive substrates and adhesive particles.

  16. VSTM-v1, a potential myeloid differentiation antigen that is downregulated in bone marrow cells from myeloid leukemia patients

    OpenAIRE

    Xie, Min; Li, Ting; Li, Ning; Li, Jinlan; Yao, Qiumei; Han, Wenling; Ruan, Guorui

    2015-01-01

    Leukocyte differentiation antigens often represent important markers for the diagnosis, classification, prognosis, and therapeutic targeting of myeloid leukemia. Herein, we report a potential leukocyte differentiation antigen gene VSTM1 (V-set and transmembrane domain-containing 1) that was downregulated in bone marrow cells from leukemia patients and exhibited a higher degree of promoter methylation. The expression level of its predominant encoded product, VSTM1-v1, was positively correlated...

  17. Donor exosomes rather than passenger leukocytes initiate alloreactive T cell responses after transplantation

    Science.gov (United States)

    Marino, Jose; Babiker-Mohamed, Mohamed H.; Crosby-Bertorini, Patrick; Paster, Joshua T.; LeGuern, Christian; Germana, Sharon; Abdi, Reza; Uehara, Mayuko; Kim, James I.; Markmann, James F.; Tocco, Georges; Benichou, Gilles

    2016-01-01

    Transplantation of allogeneic organs and tissues represents a lifesaving procedure for a variety of patients affected with end-stage diseases. Although current immunosuppressive therapy prevents early acute rejection, it is associated with nephrotoxicity and increased risks for infection and neoplasia. This stresses the need for selective immune-based therapies relying on manipulation of lymphocyte recognition of donor antigens. The passenger leukocyte theory states that allograft rejection is initiated by recipient T cells recognizing donor major histocompatibility complex (MHC) molecules displayed on graft leukocytes migrating to the host’s lymphoid organs. We revisited this concept in mice transplanted with allogeneic skin, heart, or islet grafts using imaging flow cytometry. We observed no donor cells in the lymph nodes and spleen of skin-grafted mice, but we found high numbers of recipient cells displaying allogeneic MHC molecules (cross-dressed) acquired from donor microvesicles (exosomes). After heart or islet transplantation, we observed few donor leukocytes (100 per million) but large numbers of recipient cells cross-dressed with donor MHC (>90,000 per million). Last, we showed that purified allogeneic exosomes induced proinflammatory alloimmune responses by T cells in vitro and in vivo. Collectively, these results suggest that recipient antigen-presenting cells cross-dressed with donor MHC rather than passenger leukocytes trigger T cell responses after allotransplantation. PMID:27942611

  18. Plasmodium vivax: paroxysm-associated lipids mediate leukocyte aggregation

    Directory of Open Access Journals (Sweden)

    Mendis Kamini

    2007-05-01

    indicating that the parasite activity involved may be antigenically at least partially parasite species-specific. Conclusion Leukocyte aggregation was identified as associated with paroxysms in P. vivax infections. This phenomenon is mediated by plasma factors including host-derived cytokines and lipids of putative parasite origin. The characteristics of the phospholipid fraction in paroxysm plasma are congruent with those of the parasite-derived, TNF-inducing GPI moieties described by others. The more active cholesterol/triglyceride(s, however, represent a novel malarial toxin, which is a new class of biologically active lipid associated with the paroxysm of P. vivax malaria.

  19. Plasmodium vivax: paroxysm-associated lipids mediate leukocyte aggregation.

    Science.gov (United States)

    Karunaweera, Nadira; Wanasekara, Deepani; Chandrasekharan, Vishvanath; Mendis, Kamini; Carter, Richard

    2007-05-22

    antigenically at least partially parasite species-specific. Leukocyte aggregation was identified as associated with paroxysms in P. vivax infections. This phenomenon is mediated by plasma factors including host-derived cytokines and lipids of putative parasite origin. The characteristics of the phospholipid fraction in paroxysm plasma are congruent with those of the parasite-derived, TNF-inducing GPI moieties described by others. The more active cholesterol/triglyceride(s), however, represent a novel malarial toxin, which is a new class of biologically active lipid associated with the paroxysm of P. vivax malaria.

  20. Genetics Home Reference: leukocyte adhesion deficiency type 1

    Science.gov (United States)

    ... Home Health Conditions Leukocyte adhesion deficiency type 1 Leukocyte adhesion deficiency type 1 Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Leukocyte adhesion deficiency type 1 is a disorder that ...

  1. Docking onto the endothelium: Trio directs leukocyte extravasation

    NARCIS (Netherlands)

    van Rijssel, J.

    2011-01-01

    Leukocyte extravasation describes the process by which white blood cells (leukocytes) travel across the endothelium lining the vasculature, into the underlying tissue. Effi-cient and tightly controlled leukocyte extravasation is of key importance in physiological processes such as immune

  2. Leukocyte changes in pregnant Yankasa ewes experimentally ...

    African Journals Online (AJOL)

    Pregnancy and trypanosomosis are associated with leukocyte changes. The leukocyte response of pregnant Yankasa ewes during experimental Trypanosoma evansi infection was determined using twenty pregnant ewes. They ewes were divided into 3 groups with 6 ewes in group A, while groups B and C were made up of ...

  3. Discriminating between Interstitial and Circulating Leukocytes in Tissues of the Murine Oral Mucosa Avoiding Nasal-Associated Lymphoid Tissue Contamination.

    Science.gov (United States)

    Bittner-Eddy, Peter D; Fischer, Lori A; Tu, Andy A; Allman, Daniel A; Costalonga, Massimo

    2017-01-01

    Periodontitis is a chronic inflammatory response to a microbial biofilm that destroys bone and soft tissues supporting the teeth. Murine models of periodontitis based on Porphyromonas gingivalis ( Pg ) colonization have shown that extravasation of leukocytes into oral tissue is critical to driving alveolar bone destruction. Identifying interstitial leukocytes is key to understanding the immunopathogenesis of periodontitis. Here, we describe a robust flow cytometry assay based on intravenous FITC-conjugated anti-mouse CD45 mAb that distinguishes interstitial leukocytes in the oral mucosa of mice from those circulating within the vasculature or in post-dissection contaminating blood. Unaccounted circulating leukocytes skewed the relative frequency of B cells and granulocytes and inflated the numbers of all leukocyte cell types. We also describe a dissection technique that avoids contamination of oral mucosal tissues with nasal-associated lymphoid tissues (NALT), a B cell rich organ that can inflate leukocyte numbers at least 10-fold and skew the assessment of interstitial CD4 T cell phenotypes. Unlike circulating CD4 T cells, interstitial CD4 T cells were almost exclusively antigen-experienced cells (CD44 hi ). We report for the first time the presence of antigen-experienced Pg -specific CD4 T cells in NALT following oral feeding of mice with Pg . This new combined flow cytometry and dissection approach allows identification of leukocytes infiltrating the connective tissues of the murine oral mucosa and avoids confounding analyses of leukocytes not recruited to inflamed oral mucosal tissues in disease conditions like periodontitis, candidiasis, or sialadenitis.

  4. Lym-1 Chimeric Antigen Receptor T Cells Exhibit Potent Anti-Tumor Effects against B-Cell Lymphoma

    OpenAIRE

    Long Zheng; Peisheng Hu; Brandon Wolfe; Caryn Gonsalves; Luqing Ren; Leslie A. Khawli; Harvey R. Kaslow; Alan L. Epstein

    2017-01-01

    T cells expressing chimeric antigen receptors (CARs) recognizing CD19 epitopes have produced remarkable anti-tumor effects in patients with B-cell malignancies. However, cancer cells lacking recognized epitopes can emerge, leading to relapse and death. Thus, CAR T cells targeting different epitopes on different antigens could improve immunotherapy. The Lym-1 antibody targets a conformational epitope of Human Leukocyte Antigen-antigen D Related (HLA-DR) on the surface of human B-cell lymphomas...

  5. Reactivity of eleven anti-human leucocyte monoclonal antibodies with lymphocytes from several domestic animals

    DEFF Research Database (Denmark)

    Aasted, Bent; Blixenkrone-Møller, Merete; Larsen, Else Bang

    1988-01-01

    Nine commercially available monoclonal antibodies and two monoclonal antibodies from The American Type Culture Collection, raised against various human leucocyte surface antigens, were tested on lymphocytes from cow, sheep, goat, swine, horse, cat, dog, mink, and rabbit as well as man. Four...... antibodies bound to lymphocytes from some of the animals. These were the antibodies against CD8 and CD4 antigen, the antibody to C3b-receptor, and the antibody to the HLA-DR antigen. The CD8 antigen-reactive antibody reacted with lymphocytes from mink, cat, dog, and sheep, while the CD4 antigen......-reactive antibody reacted with lymphocytes from mink. The anti-C3b-R antibody reacted with lymphocytes from horse, swine, dog, and cat, and the anti-HLA-DR reacted with lymphocytes from cow, goat, sheep, horse, dog, cat, and mink....

  6. Leukocyte nucleus segmentation and nucleus lobe counting.

    Science.gov (United States)

    Chan, Yung-Kuan; Tsai, Meng-Hsiun; Huang, Der-Chen; Zheng, Zong-Han; Hung, Kun-Ding

    2010-11-12

    Leukocytes play an important role in the human immune system. The family of leukocytes is comprised of lymphocytes, monocytes, eosinophils, basophils, and neutrophils. Any infection or acute stress may increase or decrease the number of leukocytes. An increased percentage of neutrophils may be caused by an acute infection, while an increased percentage of lymphocytes can be caused by a chronic bacterial infection. It is important to realize an abnormal variation in the leukocytes. The five types of leukocytes can be distinguished by their cytoplasmic granules, staining properties of the granules, size of cell, the proportion of the nuclear to the cytoplasmic material, and the type of nucleolar lobes. The number of lobes increased when leukemia, chronic nephritis, liver disease, cancer, sepsis, and vitamin B12 or folate deficiency occurred. Clinical neutrophil hypersegmentation has been widely used as an indicator of B12 or folate deficiency.Biomedical technologists can currently recognize abnormal leukocytes using human eyes. However, the quality and efficiency of diagnosis may be compromised due to the limitations of the biomedical technologists' eyesight, strength, and medical knowledge. Therefore, the development of an automatic leukocyte recognition system is feasible and necessary. It is essential to extract the leukocyte region from a blood smear image in order to develop an automatic leukocyte recognition system. The number of lobes increased when leukemia, chronic nephritis, liver disease, cancer, sepsis, and vitamin B12 or folate deficiency occurred. Clinical neutrophil hypersegmentation has been widely used as an indicator of B12 or folate deficiency. The purpose of this paper is to contribute an automatic leukocyte nuclei image segmentation method for such recognition technology. The other goal of this paper is to develop the method of counting the number of lobes in a cell nucleus. The experimental results demonstrated impressive segmentation accuracy

  7. Lea blood group antigen on human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Dunstan, R.A.; Simpson, M.B.; Rosse, W.F.

    1985-01-01

    One- and two-stage radioligand assays were used to determine if human platelets possess the Lea antigen. Goat IgG anti-Lea antibody was purified by multiple adsorptions with Le(a-b-) human red blood cells, followed by affinity chromatography with synthetic Lea substance and labeling with /sup 125/I. Human IgG anti-Lea antibody was used either in a two stage radioassay with /sup 125/I-labeled mouse monoclonal IgG anti-human IgG as the second antibody or, alternatively, purified by Staph protein A chromatography, labeled with /sup 125/I, and used in a one-stage radioassay. Platelets from donors of appropriate red blood cell phenotypes were incubated with the antisera, centrifuged through phthalate esters, and assayed in a gamma scintillation counter. Dose response and saturation curve analysis demonstrate the presence of Lewis a antigen on platelets from Lea+ donors. Furthermore, platelets from an Le(a-b-) donor incubated in Le (a+b-) plasma adsorb Lea antigen in a similar manner to red blood cells. The clinical significance of these antigens in platelet transfusion remains undefined.

  8. QSAR modeling for anti-human African trypanosomiasis activity of substituted 2-Phenylimidazopyridines

    Science.gov (United States)

    Masand, Vijay H.; El-Sayed, Nahed N. E.; Mahajan, Devidas T.; Mercader, Andrew G.; Alafeefy, Ahmed M.; Shibi, I. G.

    2017-02-01

    In the present work, sixty substituted 2-Phenylimidazopyridines previously reported with potent anti-human African trypanosomiasis (HAT) activity were selected to build genetic algorithm (GA) based QSAR models to determine the structural features that have significant correlation with the activity. Multiple QSAR models were built using easily interpretable descriptors that are directly associated with the presence or the absence of a structural scaffold, or a specific atom. All the QSAR models have been thoroughly validated according to the OECD principles. All the QSAR models are statistically very robust (R2 = 0.80-0.87) with high external predictive ability (CCCex = 0.81-0.92). The QSAR analysis reveals that the HAT activity has good correlation with the presence of five membered rings in the molecule.

  9. Leukocyte integrins and their ligand interactions

    Science.gov (United States)

    Hyun, Young-Min; Lefort, Craig T.; Kim, Minsoo

    2010-01-01

    Although critical for cell adhesion and migration during normal immune-mediated reactions, leukocyte integrins are also involved in the pathogenesis of diverse clinical conditions including autoimmune diseases and chronic inflammation. Leukocyte integrins therefore have been targets for anti-adhesive therapies to treat the inflammatory disorders. Recently, the therapeutic potential of integrin antagonists has been demonstrated in psoriasis and multiple sclerosis. However, current therapeutics broadly affect integrin functions and, thus, yield unfavorable side effects. This review discusses the major leukocyte integrins and the anti-adhesion strategies for treating immune diseases. PMID:19184539

  10. Metabolism of phospholipids by polymorphonuclear leukocytes

    NARCIS (Netherlands)

    Elsbach, P.; Berg, J.W.O. van den; Bosch, H. van den; Deenen, L.L.M. van

    1965-01-01

    By incubating homogenates of polymorphonuclear leukocytes obtained from rabbit-peritoneal exudates with various 32P-labeled phosphoglycerides the following reactions were identified: Lecithin → Lysolecithin and fatty acid (1) Lysolecithin → Glycerylphosphorylcholine and fatty acid (2) Lysolecithin →

  11. Leukocyte Adhesion Molecules in Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Kousuke Noda

    2012-01-01

    Full Text Available Diabetes is a systemic disease that causes a number of metabolic and physiologic abnormalities. One of the major microvascular complications of diabetes is diabetic retinopathy (DR, a leading cause of blindness in people over age 50. The mechanisms underlying the development of DR are not fully understood; however, extensive studies have recently implicated chronic, low-grade inflammation in the pathophysiology of DR. During inflammation leukocytes undergo sequential adhesive interactions with endothelial cells to migrate into the inflamed tissues, a process known as the “leukocyte recruitment cascade” which is orchestrated by precise adhesion molecule expression on the cell surface of leukocytes and the endothelium. This paper summarizes the recent clinical and preclinical works on the roles of leukocyte adhesion molecules in DR.

  12. Estimation of malaria parasite density using leukocyte counts as an ...

    African Journals Online (AJOL)

    Leukocyte counts and screening for malaria parasites were carried out on 252 apparently healthy blood donors attending a transfusion centre in Ibadan. The leukocyte count range for the donors was 2.5-9.6 x 109 /l; the mean leukocyte count being 4.98 x 109 /l. 193 (76.6%) had leukocyte count less than 6.0 x 109 /l.

  13. A mathematical model for the leukocyte filtration process

    NARCIS (Netherlands)

    Bruil, A.; Bruil, Anton; Beugeling, T.; Beugeling, Tom; Feijen, Jan

    1995-01-01

    Leukocyte filters are applied clinically to remove leukocytes from blood. In order to optimize leukocyte filters, a mathematical model to describe the leukocyte filtration process was developed by modification of a general theoretical model for depth filtration. The model presented here can be used

  14. 21 CFR 864.7660 - Leukocyte alkaline phosphatase test.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Leukocyte alkaline phosphatase test. 864.7660... Leukocyte alkaline phosphatase test. (a) Identification. A leukocyte alkaline phosphatase test is a device used to identify the enzyme leukocyte alkaline phosphatase in neutrophilic granulocytes (granular...

  15. The multiple faces of leukocyte interstitial migration

    Science.gov (United States)

    Lämmermann, Tim; Germain, Ronald N.

    2014-01-01

    Spatiotemporal control of leukocyte dynamics within tissues is critical for successful innate and adaptive immune responses. Homeostatic trafficking and coordinated infiltration into and within sites of inflammation and infection rely on signaling in response to extracellular cues that in turn controls a variety of intracellular protein networks regulating leukocyte motility, migration, chemotaxis, positioning, and cell–cell interaction. In contrast to mesenchymal cells, leukocytes migrate in an amoeboid fashion by rapid cycles of actin polymerization and actomyosin contraction, and their migration in tissues is generally referred to as low adhesive and nonproteolytic. The interplay of actin network expansion, contraction, and adhesion shapes the exact mode of amoeboid migration, and in this review, we explore how leukocyte subsets potentially harness the same basic biomechanical mechanisms in a cell-type-specific manner. Most of our detailed understanding of these processes derives from in vitro migration studies in three-dimensional gels and confined spaces that mimic geometrical aspects of physiological tissues. We summarize these in vitro results and then critically compare them to data from intravital imaging of leukocyte interstitial migration in mouse tissues. We outline the technical challenges of obtaining conclusive mechanistic results from intravital studies, discuss leukocyte migration strategies in vivo, and present examples of mode switching during physiological interstitial migration. These findings are also placed in the context of leukocyte migration defects in primary immunodeficiencies. This overview of both in vitro and in vivo studies highlights recent progress in understanding the molecular and biophysical mechanisms that shape robust leukocyte migration responses in physiologically complex and heterogeneous environments. PMID:24573488

  16. Initial afferent lymphatic vessels controlling outbound leukocyte traffic from skin to lymph nodes.

    Science.gov (United States)

    Teijeira, Alvaro; Rouzaut, Ana; Melero, Ignacio

    2013-12-09

    Tissue drains fluid and macromolecules through lymphatic vessels (LVs), which are lined by a specialized endothelium that expresses peculiar differentiation proteins, not found in blood vessels (i.e., LYVE-1, Podoplanin, PROX-1, and VEGFR-3). Lymphatic capillaries are characteristically devoid of a continuous basal membrane and are anchored to the ECM by elastic fibers that act as pulling ropes which open the vessel to avoid edema if tissue volume increases, as it occurs upon inflammation. LVs are also crucial for the transit of T lymphocytes and antigen presenting cells from tissue to draining lymph nodes (LN). Importantly, cell traffic control across lymphatic endothelium is differently regulated under resting and inflammatory conditions. Under steady-state non-inflammatory conditions, leukocytes enter into the lymphatic capillaries through basal membrane gaps (portals). This entrance is integrin-independent and seems to be mainly guided by CCL21 chemokine gradients acting on leukocytes expressing CCR7. In contrast, inflammatory processes in lymphatic capillaries involve a plethora of cytokines, chemokines, leukocyte integrins, and other adhesion molecules. Importantly, under inflammation a role for integrins and their ligands becomes apparent and, as a consequence, the number of leukocytes entering the lymphatic capillaries multiplies several-fold. Enhancing transmigration of dendritic cells en route to LN is conceivably useful for vaccination and cancer immunotherapy, whereas interference with such key mechanisms may ameliorate autoimmunity or excessive inflammation. Recent findings illustrate how, transient cell-to-cell interactions between lymphatic endothelial cells and leukocytes contribute to shape the subsequent behavior of leukocytes and condition the LV for subsequent trans-migratory events.

  17. Initial afferent lymphatic vessels controlling outbound leukocyte traffic from skin to lymph nodes.

    Directory of Open Access Journals (Sweden)

    Ignacio eMelero

    2013-12-01

    Full Text Available Tissue drains fluid and macromolecules through lymphatic vessels, which are lined by a specialized endothelium that expresses peculiar differentiation proteins, not found in blood vessels (i.e: LYVE-1, Podoplanin, PROX-1 and VEGFR-3. Lymphatic capillaries are characteristically devoid of a continuous basal membrane and are anchored to the ECM by elastic fibers that act as pulling ropes which open the vessel to avoid oedema if tissue volume increases, as it occurs upon inflammation. Lymphatic vessels are also crucial for the transit of T lymphocytes and antigen presenting cells from tissue to draining lymph nodes. Importantly, cell traffic control across lymphatic endothelium is differently regulated under resting and inflammatory conditions. Under steady-state non-inflammatory conditions, leukocytes enter into the lymphatic capillaries through basal membrane gaps (portals. This entrance is integrin-independent and seems to be mainly guided by CCL21 chemokine gradients acting on leukocytes expressing CCR7. In contrast, inflammatory processes in lymphatic capillaries involve a plethora of cytokines, chemokines, leukocyte integrins and other adhesion molecules. Importantly, under inflammation a role for integrins and their ligands becomes apparent and, as a consequence, the number of leukocytes entering the lymphatic capillaries multiplies several-fold. Enhancing transmigration of dendritic cells en route to lymph nodes is conceivably useful for vaccination and cancer immunotherapy, whereas interference with such key mechanisms may ameliorate autoimmunity or excessive inflammation. Recent findings illustrate how, transient cell-to-cell interactions between lymphatic endothelial cells and leukocytes contribute to shape the subsequent behaviour of leukocytes and condition the lymphatic vessel for subsequent trans-migratory events.

  18. The Dominant Source of CD4+ and CD8+ T-Cell Activation in HIV Infection Is Antigenic Stimulation

    NARCIS (Netherlands)

    Cohen Stuart, J.W.T. (James Willem Theodoor); Hazebergh, M.D. (Mette); Hamann, D. (Dörte); Otto, S.A.; Borleffs, J.C.C.; Miedema, F.; Boucher, C.A.B.; Boer, R.J. de

    2000-01-01

    To distinguish between antigenic stimulation and CD4+ T-cell homeostasis as the cause of T-cell hyperactivation in HIV infection, we studied T-cell activation in 47 patients before and during highly active antiretroviral therapy (HAART). We show that expression of human leukocyte antigen

  19. Angiotensin receptor-binding molecule in leukocytes in association with the systemic and leukocyte inflammatory profile.

    Science.gov (United States)

    Haruhara, Kotaro; Wakui, Hiromichi; Azushima, Kengo; Kurotaki, Daisuke; Kawase, Wataru; Uneda, Kazushi; Haku, Sona; Kobayashi, Ryu; Ohki, Kohji; Kinguchi, Sho; Ohsawa, Masato; Minegishi, Shintaro; Ishigami, Tomoaki; Matsuda, Miyuki; Yamashita, Akio; Nakajima, Hideaki; Tamura, Tomohiko; Tsuboi, Nobuo; Yokoo, Takashi; Tamura, Kouichi

    2018-02-01

    The components of the renin-angiotensin system in leukocytes is involved in the pathophysiology of non-communicable diseases (NCDs), including hypertension, atherosclerosis and chronic kidney disease. Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP) is an AT1R-specific binding protein, and is able to inhibit the pathological activation of AT1R signaling in certain animal models of NCDs. The aim of the present study was to investigate the expression and regulation of ATRAP in leukocytes. Human leukocyte ATRAP mRNA was measured with droplet digital polymerase chain reaction system, and analyzed in relation to the clinical variables. We also examined the leukocyte cytokines mRNA in bone-marrow ATRAP-deficient and wild-type chimeric mice after injection of low-dose lipopolysaccharide. The ATRAP mRNA was abundantly expressed in leukocytes, predominantly granulocytes and monocytes, of healthy subjects. In 86 outpatients with NCDs, leukocyte ATRAP mRNA levels correlated positively with granulocyte and monocyte counts and serum C-reactive protein levels. These positive relationships remained significant even after adjustment. Furthermore, the leukocyte ATRAP mRNA was significantly associated with the interleukin-1β, tumor necrosis factor-α and monocyte chemotactic protein-1 mRNA levels in leukocytes of NCDs patients. In addition, the leukocyte interleukin-1β mRNA level was significantly upregulated in bone marrow ATRAP-deficient chimeric mice in comparison to wild-type chimeric mice after injection of lipopolysaccharide. These results suggest that leukocyte ATRAP is an emerging marker capable of reflecting the systemic and leukocyte inflammatory profile, and plays a role as an anti-inflammatory factor in the pathophysiology of NCDs. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Design of indirect solid-phase immunosorbent methods for detecting arenavirus antigens and antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, A.P.; Rezapkin, G.V.; Dzagurova, T.K.; Tkachenko, E.A.

    1984-05-01

    Specifications have been elaborated for formulating indirect solid-phase enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (SPRIA) methods that employ anti-human and anti-mice G class immunoglobulin (IgG), conjugated with horseradish peroxidase and /sup 125/I for detecting the arenaviruses Junin, Machupo, Tacaribe, Amalpari, Tamiami, Lassa, and LCM (lymphocytic choriomeningitis). These methods make it possible to identify with a high degree of sensitivity arenavirus antigens and antibodies in various kinds of material.

  1. Identification of compounds with anti-human cytomegalovirus activity that inhibit production of IE2 proteins.

    Science.gov (United States)

    Beelontally, Rooksarr; Wilkie, Gavin S; Lau, Betty; Goodmaker, Charles J; Ho, Catherine M K; Swanson, Chad M; Deng, Xianming; Wang, Jinhua; Gray, Nathanael S; Davison, Andrew J; Strang, Blair L

    2017-02-01

    Using a high throughput screening methodology we surveyed a collection of largely uncharacterized validated or suspected kinase inhibitors for anti-human cytomegalovirus (HCMV) activity. From this screen we identified three structurally related 5-aminopyrazine compounds (XMD7-1, -2 and -27) that inhibited HCMV replication in virus yield reduction assays at low micromolar concentrations. Kinase selectivity assays indicated that each compound was a kinase inhibitor capable of inhibiting a range of cellular protein kinases. Western blotting and RNA sequencing demonstrated that treatment of infected cells with XMD7 compounds resulted in a defect in the production of the major HCMV transcriptional transactivator IE2 proteins (IE2-86, IE2-60 and IE2-40) and an overall reduction in transcription from the viral genome. However, production of certain viral proteins was not compromised by treatment with XMD7 compounds. Thus, these novel anti-HCMV compounds likely inhibited transcription from the viral genome and suppressed production of a subset of viral proteins by inhibiting IE2 protein production. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Diphtheria toxin-based anti-human CD19 immunotoxin for targeting human CD19+tumors.

    Science.gov (United States)

    Zheng, Qian; Wang, Zhaohui; Zhang, Huiping; Huang, Qi; Madsen, Joren C; Sachs, David H; Huang, Christene A; Wang, Zhirui

    2017-05-01

    CD19 is expressed on normal and neoplastic B cells and is a promising target for immunotherapy. However, there is still an unmet need to further develop novel therapeutic drugs for the treatment of the refractory/relapsing human CD19 + tumors. We have developed a diphtheria toxin-based anti-human CD19 immunotoxin for targeting human CD19 + tumors. We have constructed three isoforms of the CD19 immunotoxin: monovalent, bivalent, and foldback diabody. In vitro binding affinity and efficacy analysis demonstrated that the bivalent isoform had the highest binding affinity and in vitro efficacy. The in vivo efficacy of the CD19 immunotoxins was assessed using human CD19 + JeKo-1 tumor-bearing NOD/SCID IL-2 receptor γ -/- (NSG) mouse model. In these animals, CD19 immunotoxins significantly prolonged the median survival from 31 days in controls to 34, 36, and 40 days in animals receiving the monovalent isoform, foldback diabody isoform, and bivalent isoform, respectively. The bivalent CD19 immunotoxin is a promising therapeutic drug candidate for targeting relapsing/refractory human CD19 + tumors. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  3. [Preparation and preliminary application of rabbit anti-human PON2 antibodies(paraoxonase-2)].

    Science.gov (United States)

    Chen, Miao; Yang, Jin-Ju; Li, Shu-Zhen; Liu, Xiao-Lan; Liu, Ying; Zhang, Lin-Jie; Gao, Jian-En; Sun, Qi-Hong

    2008-07-01

    To preparation and characterize the rabbit polyclonal antibodies against human PON2 (paraoxonase-2). A fragment of human PON2 gene which was of low homology with rabbits but of higher hydrophilicity and immunogenicity was selected for recombinant expression in prokaryotic expression system. The rabbits were immunized with the purified GST fusion protein 3 times. The specificity and sensitivity of the anti-human PON2 polyclonal antibodies were detected by Western blot and indirect immunofluorescence. The GST-PON2 fusion protein was highly expressed in Ecoli with a molecular weight of 46 kDa. Western blot analysis proved the rabbit polyclonal antibodies could specifically recognize 39 kDa native PON2 protein expressed in several cells and tissues, such as HeLa cells, U937 cells, and human liver tissue. Indirect immunofluorescence analysis confirmed that PON2 protein was located in the cytoplasm of SY5Y cells. The rabbit polyclonal antibodies against human PON2 can specifically recognize natural protein expressed in human cells and tissues, Which can be used for further study and clinical detection of human PON2.

  4. Imaging Leukocyte Responses in the Kidney.

    Science.gov (United States)

    Finsterbusch, Michaela; Kitching, A Richard; Hickey, Michael J

    2017-03-01

    The kidney can be negatively affected by a range of innate and adaptive immune responses, resulting in alterations in the functions of the kidney and, in some cases, progression to renal failure. In many of these responses, infiltration of blood-borne leukocytes into the kidney is central to the response. In addition, a large population of mononuclear phagocytes resident in the kidney can modulate these responses. A great deal of research has investigated both the mechanisms of leukocyte recruitment to the kidney and the actions of immune cells resident within the kidney. Because of the dynamic nature of the processes whereby leukocytes enter sites of inflammation, in vivo imaging has been one of the key approaches used for understanding leukocyte recruitment as it occurs throughout the body, and this is also true for kidney. However, imaging this organ and its complicated microvasculature during different forms of renal pathology presents a unique set of challenges. In this review, we examine the approaches used for intravital imaging of the kidney and summarize the insights gained from these studies regarding the mechanisms of leukocyte entry into the kidney during inflammation and the actions of immune cells within this organ.

  5. Leukocyte transendothelial migration: A local affair

    Science.gov (United States)

    Schimmel, Lilian; Heemskerk, Niels; van Buul, Jaap D.

    2017-01-01

    ABSTRACT Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens. It serves as a protective response that involves leukocytes, blood vessels and molecular mediators with the purpose to eliminate the initial cause of cell injury and to initiate tissue repair. Inflammation is tightly regulated by the body and is associated with transient crossing of leukocytes through the blood vessel wall, a process called transendothelial migration (TEM) or diapedesis. TEM is a close collaboration between leukocytes on one hand and the endothelium on the other. Limiting vascular leakage during TEM but also when the leukocyte has crossed the endothelium is essential for maintaining vascular homeostasis. Although many details have been uncovered during the recent years, the molecular mechanisms from the vascular part that drive TEM still shows significant gaps in our understanding. This review will focus on the local signals that are induced in the endothelium that regulate leukocyte TEM and simultaneous preservation of endothelial barrier function. PMID:27715453

  6. Carcinoma-associated antigens

    International Nuclear Information System (INIS)

    Bartorelli, A.; Accinni, R.

    1981-01-01

    This invention relates to novel antigens associated with breast carcinoma, anti-sera specific to said antigens, 125 I-labeled forms of said antigens and methods of detecting said antigens in serum or plasma. The invention also relates to a diagnostic kit containing standardised antigens or antisera or marked forms thereof for the detection of said antigens in human blood, serum or plasma. (author)

  7. A radioimmunoassay for human antibody specific for microbial antigens

    International Nuclear Information System (INIS)

    Tew, J.G.; Burmeister, J.; Greene, E.J.; Pflaumer, S.K.; Goldstein, J.

    1977-01-01

    A simple and sensitive method for detecting and quantitating antibody specific or microbial antigens is described. Bacterial, fungal, parasitic or viral antigens attached to bromoacetyl cellulose or the intact cells themselves were added to a series of two-fold dilutions of human serum. After a short incubation period, which allowed human antibody to attach to the antigens, the complex was thoroughly washed and carbon-14 labeled anti-human light chain antibody was added to each dilution. The resulting complex was washed, collected on a filter pad, placed in a scintillation vial and radioassayed. The relationship between radioactivity bound and -log 2 of the serum dilution was linear. The endpoint for each assay and a confidence interval was calculated by doing inverse prediction from simple linear regression. Results obtained using this assay indicated the presence of antibody in a pool of normal human sera specific for herpes virus and for both cell surface and intracellular antigens of Streptococcus mutans, Naegleria fowleri and Cryptococcus neoformans. In general the dominant response was against the intracellular antigens rather than cell surface antigens

  8. Leukocyte scintiscanning for the diagnosis of inflammations

    International Nuclear Information System (INIS)

    Becker, W.

    1988-01-01

    The value of leukocyte scintiscanning for clinical diagnostics is examined with regard to various areas of indications, and as a method of first examination, or as an alternative to, or additional method to be combined with, the other usual techniques. Leukocyte scintiscanning is indicated as a good first examination method in case of chronic enteritis in a highly active stage, stenosis of the colon, or when abscess is suspected, or infected renal cysts, or infection of angioplasty, osteomyelitis, or in case of fiever of unknown origin and impossible focal diagnosis. It also is applicable for follow-up diagnostics in chronic enteritis, suspected abdominal abscess, prosthetic valvular endocarditis, and infection of hip joint prothesis. The method also may yield additional information in case of renal graft rejection, coronary inflammations, for differential diagnosis of brain tumor or abcess, edematous or antodigestive pancreatitis, and in chronic polyarthritis. For leukocyte labelling, indium-111 and Tc-99m are primarily used. (ECB) [de

  9. Intravascular leukocyte migration through platelet thrombi: directing leukocytes to sites of vascular injury.

    Science.gov (United States)

    Ghasemzadeh, Mehran; Hosseini, Ehteramolsadat

    2015-06-01

    Leukocytes recruitment to thrombi supports an intimate cellular interaction leading to the enhancement of pro-coagulant functions and pro-inflammatory responses at site of vascular injury. Recent observations of neutrophil extracellular traps (NETs) formation and its mutual reactions with platelet thrombi adds more clinical interest to the growing body of knowledge in the field of platelet-leukocyte cross-talk. However, having considered thrombus as a barrier between leukocytes and injured endothelium, the full inflammatory roles of these cells during thrombosis is still ill defined. The most recent observation of neutrophils migration into the thrombi is a phenomenon that highlights the inflammatory functions of leukocytes at the site of injury. It has been hypothesised that leukocytes migration might be associated with the conveyance of highly reactive pro-inflammatory and/or pro-coagulant mediators to sites of vascular injury. In addition, the evidence of neutrophils migration into arterial thrombi following traumatic and ischaemia-reperfusion injury highlights the already described role of these cells in atherosclerosis. Regardless of the mechanisms behind leukocyte migration, whether these migrated cells benefit normal homeostasis by their involvement in wound healing and vascular rebuilding or they increase unwilling inflammatory responses, could be of interest for future researches that provide new insight into biological importance of leukocyte recruitment to thrombi.

  10. Immunohistochemical Analysis of Inflammatory Rheumatoid Synovial Tissues Using Anti-Human Podoplanin Monoclonal Antibody Panel.

    Science.gov (United States)

    Suzuki, Tomoto; Takakubo, Yuya; Oki, Hiroharu; Liu, Xing; Honma, Ryusuke; Naganuma, Yasushi; Goodman, Stuart B; Kaneko, Mika K; Kato, Yukinari; Takagi, Michiaki

    2018-02-01

    Podoplanin (PDPN) is a transmembrane sialoglycoprotein, which is expressed in several normal tissues and malignant tumors. Although PDPN expression in rheumatoid arthritis (RA) has been reported, the role of PDPN in RA and other arthritic conditions has not been fully elucidated. In this study, we examined PDPN expression in inflammatory synovial tissues using an anti-human PDPN (hPDPN) monoclonal antibody (mAb) panel to select the most useful one for evaluation of synovitis. Synovial tissue samples were obtained from 11 RA patients and 9 osteoarthritis (OA) patients undergoing joint surgery. PDPN-positive cells were immunostained by a panel of PDPN mAbs (NZ-1, LpMab-3, LpMab-7, LpMab-10, LpMab-12, LpMab-13, and LpMab-17), followed by cell grading of inflammation and cell counting of PDPN-positivity by a quantitative analyzer. Immunohistochemistry showed that PDPN was markedly expressed in both macrophage-like type A and fibroblast-like type B lining cells of the hyperplastic synovial lining cell layer, and macrophages and fibroblasts in the stroma of RA. Among anti-PDPN mAbs, LpMab-12 showed the highest score. In inflammatory OA synovium, PDPN expression was also detectable. Although LpMab-12 also showed the highest score in OA, the difference was not statistically significant. The inflammatory synovitis score of RA was significantly higher than that of OA. PDPN was expressed in inflammatory lining cells and sublining stroma of RA and OA synovium. In the seven anti-hPDPN antibodies examined, LpMab-12 was the most stainable antibody for PDPN in RA synovitis. Thus, LpMab-12 for PDPN has a possible and promising specific biomarker for evaluating synovitis in RA and inflammatory OA.

  11. Clinical significance of serum anti-human papillomavirus 16 and 18 antibodies in cervical neoplasia.

    Science.gov (United States)

    Chay, Doo Byung; Cho, Hanbyoul; Kim, Bo Wook; Kang, Eun Suk; Song, Eunseop; Kim, Jae-Hoon

    2013-02-01

    To estimate the clinical significance of serum anti-human papillomavirus (HPV) antibodies and high-risk cervical HPV DNA in cervical neoplasia. The study population comprised patients who were histopathologically diagnosed with cervical intraepithelial neoplasia (CIN) 1 (n=64), CIN 2 and 3 (n=241), cervical cancer (n=170), and normal control participants (n=975). Cervical HPV DNA tests were performed through nucleic acid hybridization assay tests, and serum anti-HPV 16 and 18 antibodies were measured by competitive immunoassay. The associations of HPV DNA and anti-HPV antibodies were evaluated with demographic characteristics and compared according to the levels of disease severity. Anti-HPV antibodies were also investigated with clinicopathologic parameters, including survival data. Among various demographic characteristics, factors involving sexual behavior had a higher tendency of HPV DNA positivity and HPV seropositivity. Human papillomavirus DNA mean titer and positivity were both increased in patients with cervical neoplasia compared with those with normal control participants, but there was no statistical difference among types of cervical neoplasia. Serum anti-HPV 16 antibodies were also able to differentiate cervical neoplasia from a normal control participant and furthermore distinguished CIN 1 from CIN 2 and 3 (odd ratio 2.87 [1.43-5.78], P=.002). In cervical cancer, HPV 16 seropositivity was associated with prolonged disease-free survival according to the univariable analysis (hazard ratio=0.12 [0.01-0.94], P=.044). Serum anti-HPV 16 antibodies can distinguish cervical neoplasia from a normal control and has the advantage of identifying high-grade CIN. Moreover, in cervical cancer, HPV 16 seropositivity may be associated with a more favorable prognosis. II.

  12. Modeling leukocyte-leukocyte non-contact interactions in a lymph node.

    Directory of Open Access Journals (Sweden)

    Nicola Gritti

    Full Text Available The interaction among leukocytes is at the basis of the innate and adaptive immune-response and it is largely ascribed to direct cell-cell contacts. However, the exchange of a number of chemical stimuli (chemokines allows also non-contact interaction during the immunological response. We want here to evaluate the extent of the effect of the non-contact interactions on the observed leukocyte-leukocyte kinematics and their interaction duration. To this aim we adopt a simplified mean field description inspired by the Keller-Segel chemotaxis model, of which we report an analytical solution suited for slowly varying sources of chemokines. Since our focus is on the non-contact interactions, leukocyte-leukocyte contact interactions are simulated only by means of a space dependent friction coefficient of the cells. The analytical solution of the Keller-Segel model is then taken as the basis of numerical simulations of interactions between leukocytes and their duration. The mean field interaction force that we derive has a time-space separable form and depends on the chemotaxis sensitivity parameter as well as on the chemokines diffusion coefficient and their degradation rate. All these parameters affect the distribution of the interaction durations. We draw a successful qualitative comparison between simulated data and sets of experimental data for DC-NK cells interaction duration and other kinematic parameters. Remarkably, the predicted percentage of the leukocyte-leukocyte interactions falls in the experimental range and depends (~25% increase upon the chemotactic parameter indicating a non-negligible direct effect of the non-contact interaction on the leukocyte interactions.

  13. Modeling leukocyte-leukocyte non-contact interactions in a lymph node.

    Science.gov (United States)

    Gritti, Nicola; Caccia, Michele; Sironi, Laura; Collini, Maddalena; D'Alfonso, Laura; Granucci, Francesca; Zanoni, Ivan; Chirico, Giuseppe

    2013-01-01

    The interaction among leukocytes is at the basis of the innate and adaptive immune-response and it is largely ascribed to direct cell-cell contacts. However, the exchange of a number of chemical stimuli (chemokines) allows also non-contact interaction during the immunological response. We want here to evaluate the extent of the effect of the non-contact interactions on the observed leukocyte-leukocyte kinematics and their interaction duration. To this aim we adopt a simplified mean field description inspired by the Keller-Segel chemotaxis model, of which we report an analytical solution suited for slowly varying sources of chemokines. Since our focus is on the non-contact interactions, leukocyte-leukocyte contact interactions are simulated only by means of a space dependent friction coefficient of the cells. The analytical solution of the Keller-Segel model is then taken as the basis of numerical simulations of interactions between leukocytes and their duration. The mean field interaction force that we derive has a time-space separable form and depends on the chemotaxis sensitivity parameter as well as on the chemokines diffusion coefficient and their degradation rate. All these parameters affect the distribution of the interaction durations. We draw a successful qualitative comparison between simulated data and sets of experimental data for DC-NK cells interaction duration and other kinematic parameters. Remarkably, the predicted percentage of the leukocyte-leukocyte interactions falls in the experimental range and depends (~25% increase) upon the chemotactic parameter indicating a non-negligible direct effect of the non-contact interaction on the leukocyte interactions.

  14. Filter Buffy Coats (FBC): a source of peripheral blood leukocytes recovered from leukocyte depletion filters.

    Science.gov (United States)

    Meyer, T P H; Zehnter, I; Hofmann, B; Zaisserer, J; Burkhart, J; Rapp, S; Weinauer, F; Schmitz, J; Illert, W E

    2005-12-20

    In compliance with federal regulations, blood banks routinely use leukocyte depletion filters to eliminate contaminating leukocytes from blood products such as red blood cell and platelet concentrates. We developed and optimized conditions to elute leukocytes adsorbed to these filters; resulting in leukocyte suspensions which we termed Filter Buffy Coats (FBCs). These Filter Buffy Coats can replace standard buffy coats for various research applications. After optimizing both the filter elution medium as well as elution protocols, we compared commonly used leukocyte depletion filters from four different manufacturers. Relative fractions as well as total recoveries of leukocyte subsets, such as lymphocytes, monocytes and granulocytes, found in Filter Buffy Coats were identified and compared among the filters as well as to standard buffy coats and whole blood. Flow cytometric analysis of Filter Buffy Coats confirmed the presence of T- and B-lymphocytes, NK cells and monocytes. Furthermore, a significant quantity of CD34(+) hematopoietic stem or progenitor cells (HSC/HPC) was detected in Filter Buffy Coats prepared from different filters, thus making FBCs a valuable source for research on HSC/HPC. Colony assays revealed that most of these CD34(+) cells are functional. Using immunomagnetic cell sorting (MACS), we isolated a variety of leukocyte populations from FBC mononuclear cells (Filter-PBMCs) including T lymphocytes (CD4(+), CD8(+), CD3(+)), B lymphocytes (CD19(+)), NK cells (CD56(+)), HSC/HPC (CD34(+), CD133(+)) or dendritic cells (BDCA-4(+)). Functional properties of Filter-PBMCs, as well as of some of these isolated leukocyte populations, were confirmed using standard assays. In summary, Filter Buffy Coats are a valuable and convenient source of different peripheral leukocyte populations and can replace standard buffy coat preparations for research applications.

  15. ANTIGENIC PROMOTION

    Science.gov (United States)

    Wu, Chin-Yu; Cinader, Bernard

    1971-01-01

    Rabbits were immunized with p-azobenzene arsonic acid derivatives of human serum albumin (HA-As) or of dissociated keyhole limpet hemocyanin. The IgM response to the hapten was evaluated in terms of the number of hapten-specific plaque-forming cells in the lymph node draining the injection site. In some experiments, antibody was measured by agglutination of tanned and sensitized erythrocytes. The hapten response of animals immunized with HA-As was increased (promoting effect) when the animals were injected with one of several structurally unrelated macromolecules: keyhole limpet hemocyanin (KLH), horse spleen ferritin (HSF), lysozyme (Lys), alum-precipitated human gamma globulin (alum-precipitated HGG). Different macromolecules differed in the magnitude of the promoting effect they induced, e.g., promotion by the associated form of KLH was greater than that by the dissociated form; alum-precipitated HGG was a better promoter than was soluble HGG. The relative magnitude of promotion by different macromolecules (associated vs. dissociated KLH, alum-precipitated vs. soluble HGG) correlated with the relative magnitude of the carrier effect, as judged by the hapten response induced by p-azobenzene arsonic acid conjugated to various proteins. Promotion was detected by agglutination assay of circulating antibody, by plaque assay of cells from the popliteal lymph node draining the site of preinjection, but not by plaque assay of cells from the contralateral lymph node. Promotion was dependent on the dose of the promoting macromolecule and on the dose of the hapten-protein conjugate. It was not observed in animals tolerant to the promoting macromolecule. Inhibition (i.e. antigenic competition), rather than promotion, was observed upon a secondary response to the preinjected macromolecule or when the hapten-protein conjugate was incorporated in Freund's adjuvant. PMID:15776570

  16. Anthocyanin contents in the seed coat of black soya bean and their anti-human tyrosinase activity and antioxidative activity.

    Science.gov (United States)

    Jhan, J-K; Chung, Y-C; Chen, G-H; Chang, C-H; Lu, Y-C; Hsu, C-K

    2016-06-01

    The seed coat of black soya bean (SCBS) contains high amount of anthocyanins and shows antioxidant and anti-mushroom tyrosinase activities. The objectives of this study were to analyse the anthocyanins in SCBS with different solvents and to find the relationship between anthocyanin profile with anti-human and anti-mushroom tyrosinase activities. SCBS was extracted with hot water, 50 and 80% ethanol, 50 and 80% acetone and 50 and 80% acidified acetone. Total phenol and total flavonoid contents in the extracts were determined. Anthocyanins in the extracts were analysed using HPLC and LC/MS/MS. A genetically engineered human tyrosinase was used to evaluate the anti-tyrosinase potential of the extracts from SCBS. 80% acetone extract from SCBS obtained the highest total phenol, total flavonoid and cyanidin-3-O-glucoside (C3G) contents among all the extracts, whereas the hot water extract showed the lowest antioxidant contents. Three anthocyanin compounds were found in all the extracts from SCBS, and the analysis of HPLC and LC/MS/MS indicated that they were C3G, delphinidin-3-O-glucoside (D3G) and peonidin-3-O-glucoside (P3G). The ratios of C3G (2.84 mg g(-1) ), D3G (0.34 mg g(-1) ) and P3G (0.35 mg g(-1) ) in 80% acidified acetone extract were 76.6, 9.1 and 9.3%, respectively. All the extracts from SCBS possessed anti-human tyrosinase activity. Moreover, a good correlation was found between the anti-human tyrosinase activities and C3G contents in the extracts. Antioxidants in SCBS also possess anti-human and anti-mushroom tyrosinase activities. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  17. Matrix Metalloproteinase-3 (MMP-3 Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Directory of Open Access Journals (Sweden)

    Arturo Flores-Pliego

    Full Text Available The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9 it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation.Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence.Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05, when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05 and up to 72 h (P≤0.001, when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005 when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells.In this work we confirm that placental leukocytes from

  18. Matrix Metalloproteinase-3 (MMP-3) Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Science.gov (United States)

    Flores-Pliego, Arturo; Espejel-Nuñez, Aurora; Castillo-Castrejon, Marisol; Meraz-Cruz, Noemi; Beltran-Montoya, Jorge; Zaga-Clavellina, Veronica; Nava-Salazar, Sonia; Sanchez-Martinez, Maribel; Vadillo-Ortega, Felipe; Estrada-Gutierrez, Guadalupe

    2015-01-01

    The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9) it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation. Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence. Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05), when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05) and up to 72 h (P≤0.001), when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005) when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells. In this work we confirm that placental leukocytes from human term

  19. Screening of multiple myeloma by polyclonal rabbit anti-human plasmacytoma cell immunoglobulin.

    Directory of Open Access Journals (Sweden)

    Bo Mu

    Full Text Available Antibody-based immunotherapy has been effectively used for tumor treatment. However, to date, only a few tumor-associated antigens (TAAs or therapeutic targets have been identified. Identification of more immunogenic antigens is essential for improvements in multiple myeloma (MM diagnosis and therapy. In this study, we synthesized a polyclonal antibody (PAb by immunizing rabbits with whole human plasmacytoma ARH-77 cells and identified MM-associated antigens, including enlonase, adipophilin, and HSP90s, among others, via proteomic technologies. 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay showed that 200 µg/mL PAb inhibits the proliferation of ARH-77 cells by over 50% within 48 h. Flow cytometric assay indicated that PAb treatment significantly increases the number of apoptotic cells compared with other treatments (52.1% vs. NS, 7.3% or control rabbit IgG, 9.9%. In vivo, PAb delayed tumor growth and prolonged the lifespan of mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that PAb also induces statistically significant changes in apoptosis compared with other treatments (P<0.05. We therefore conclude that PAb could be used for the effective screening and identification of TAA. PAb may have certain anti-tumor functions in vitro and in vivo. As such, its combination with proteomic technologies could be a promising approach for sieving TAA for the diagnosis and therapy of MM.

  20. cAMP signaling in leukocyte transendothelial migration

    NARCIS (Netherlands)

    Lorenowicz, Magdalena J.; Fernandez-Borja, Mar; Hordijk, Peter L.

    2007-01-01

    The migration of leukocytes across the vascular endothelium is crucial for immunosurveillance as well as for inflammatory responses. Uncontrolled leukocyte transendothelial migration results in pathologies such as asthma, rheumatoid arthritis, and atherosclerosis. The molecular mechanisms that

  1. Ex vivo simulation of leukocyte function: stimulation of specific subset of leukocytes in whole blood followed by the measurement of function-associated mRNAs.

    Science.gov (United States)

    Mitsuhashi, Masato

    2010-12-15

    In order to characterize a wide spectrum of leukocyte functions with clinically applicable procedures, 0.06 ml each of heparinized whole blood was stimulated in triplicate for 4h with phytohemagglutinin (T cell stimulator), heat aggregated IgG (IgG Fc receptor stimulator), lipopolysaccharide (toll-like receptor (TLR)-4 stimulator), zymosan (TLR-2 stimulator), monoclonal antibody against T-cell receptor alpha/beta chain, recombinant interleukin-2, and solvent controls, then 32 different leukocyte function-associated mRNAs were quantified by the method reported previously (Mitsuhashi et al. Clin. Chem. 2006). Two control genes (beta-actin, beta-2-microglobulin) were not affected by these stimulations, whereas the induction of CCL chemokines-2, 4, 8, 20, CXCL chemokines-3, 10, interleukin (IL)-8 (markers of leukocyte accumulation/recruit), granzyme B, perforin 1, tumor necrosis factor superfamily-1, 2, 5, 14, 15, CD16 (markers of cell killing), IL10, transforming growth factor beta 1 (humoral factors of immune suppression), forkhead box P3, CD25, arginase (cellular markers of immune suppression), IL2, IL4, interferon-gamma, IL17 (markers of various subsets of T helper cells), granulocyte-macrophage colony-stimulating factor (marker of antigen presenting cells), immunoglobulin heavy locus (marker of B-cells), vascular endothelial growth factor (marker of angiogenesis), pro-opiomelanocortin (marker of local pain), and CD11a mRNA (marker of leukocyte adherence to endothelium) were identified by these stimulations. The blood volume in this assay was 1.44 ml, and 4 h' incubation in whole blood was physiological. Using triplicate aliquots of whole blood for both stimulant and solvent control, statistical conclusion was drawn for each stimulant for each mRNA. The method introduced in this study will be a new paradigm for clinical cellular immunology. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Palmitoylated transmembrane adaptor proteins in leukocyte signaling

    Czech Academy of Sciences Publication Activity Database

    Štěpánek, Ondřej; Dráber, Peter; Hořejší, Václav

    2014-01-01

    Roč. 26, č. 5 (2014), s. 895-902 ISSN 0898-6568 R&D Projects: GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : Leukocyte * Adaptor * Palmitoylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.315, year: 2014

  3. x ORIGINAL ARTICLE ASSESSMENT OF LEUKOCYTE ESTERASE ...

    African Journals Online (AJOL)

    Dr Oboro VO

    ABSTRACT. This is a prospective study of urinary tract infection in 65 children (38 males and 27 females, M: F ratio 1: 0.7). Urine samples were evaluated by culture, microscopy and leukocyte esterase dipstick test. Positive urine culture, with significant bacteriuria was found in 19(29.2%). Urine microscopy for leukocyturia ...

  4. Modulation of polymorphonuclear leukocytes function by incubation ...

    Indian Academy of Sciences (India)

    Unknown

    Tel-Aviv University, Tel-Aviv, Israel. *Corresponding author (Fax, 972-4-8542092; Email, erica@rambam.health.gov.il). Polymorphonuclear leukocytes (PMN) from healthy donors were tested for stimulated release of superoxide anions after being incubated with serum of welders and of a group of unexposed individuals.

  5. Modulation of polymorphonuclear leukocytes function by incubation

    Indian Academy of Sciences (India)

    Polymorphonuclear leukocytes (PMN) from healthy donors were tested for stimulated release of superoxide anions after being incubated with serum of welders and of a group of unexposed individuals. These two groups were further subdivided either according to age or to smoking habits. The experiments showed that ...

  6. Modulation of polymorphonuclear leukocytes function by incubation ...

    Indian Academy of Sciences (India)

    Polymorphonuclear leukocytes (PMN) from healthy donors were tested for stimulated release of superoxide anions after being incubated with serum of welders and of a group of unexposed individuals. These two groups were further subdivided either according to age or to smoking habits. The experiments showed that ...

  7. Glycan microarray reveal induced IgGs repertoire shift against a dietary carbohydrate in response to rabbit anti-human thymocyte therapy

    Science.gov (United States)

    Amon, Ron; Ben-Arye, Shani Leviatan; Engler, Limor; Yu, Hai; Lim, Noha; Berre, Ludmilla Le; Harris, Kristina M.; Ehlers, Mario R.; Gitelman, Stephen E.; Chen, Xi; Soulillou, Jean-Paul; Padler-Karavani, Vered

    2017-01-01

    Humans have circulating antibodies against diverse glycans containing N-glycolylneuraminic acid (Neu5Gc) due to function-loss mutation of the CMAH gene. This xenogenic non-human carbohydrate is abundant in red meat, xenografts and biotherapeutics. Low levels of diet-derived Neu5Gc is also present on normal human endothelial cells, and together with anti-Neu5Gc antibodies could potentially mediate “xenosialitis” chronic-inflammation. Rabbit anti-human thymocyte globulin (ATG) is a drug containing polyclonal IgG glycoproteins commonly used as an immunosuppressant in human transplantation and autoimmune diseases. In type-1 diabetes patients, infusion of Neu5Gc-glycosylated ATG caused increased global anti-Neu5Gc response. Here, for the first time we explore changes in anti-Neu5Gc IgG repertoire following the immunization elicited by ATG, compared with the basal antibodies repertoire that reflect exposure to dietary-Neu5Gc. We used glycan microarrays with multiple Neu5Gc-glycans and controls to elucidate eventual differences in ATG-elicited repertoire, before/after ATG administration and track their kinetics (0, 1, 18 and 24 months). Response of all basal-pre-existing Neu5Gc-specific antibodies rapidly increased. This response peaked at one month post-ATG, with enhanced affinity, then resolved at 18–24 months. Induced-antibodies showed expanded diversity and de-novo recognition of different Neu5Gc-glycans, including endogenous glycolipids, that was further validated by affinity-purified anti-Neu5Gc antibodies from patients’ sera. These findings strongly suggest that ATG-induced anti-Neu5Gc IgGs represent a secondary exposure to this dietary carbohydrate-antigen in humans, with immune memory. Given their modified recognition patterns, ATG-evoked anti-Neu5Gc antibodies could potentially mediate biological effects different from pre-existing antibodies. PMID:29348821

  8. 21 CFR 864.7675 - Leukocyte peroxidase test.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Leukocyte peroxidase test. 864.7675 Section 864...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7675 Leukocyte peroxidase test. (a) Identification. A leukocyte peroxidase test is a device used to distinguish certain...

  9. Technetium-99m labelled anti-human chorionic gonadotropin, technetium-99m labelled anti-human chorionic gonadotropin-beta or its combinations along with a diagnostic kit for forming a composition useful in identifying cancer cell and/or a malignant tumour

    International Nuclear Information System (INIS)

    Crockford, D.R.; Rhodes, B.A.

    1979-01-01

    Anti-human chorionic gonadotropin and anti-human chorionic gonadotropin-beta have been labelled with technetium 99m, and applied separately or in mixture for scintiscanning of malignant tumors. Besides the labelled compound, the diagnostic kit includes an anionic exchange resin capable of selectively removing pertechnetate ion from aqueous solution from a protein labelled with Tcsup(99m). (E.G.)

  10. A molecular basis for the presentation of phosphorylated peptides by HLA-B antigens

    NARCIS (Netherlands)

    Alpízar, Adán; Marino, Fabio; Ramos-Fernández, Antonio; Lombardía, Manuel; Jeko, Anita; Pazos, Florencio; Paradela, Alberto; Santiago, César; Heck, Albert J R; Marcilla, Miguel

    2017-01-01

    As aberrant protein phosphorylation is a hallmark of tumor cells, the display of tumor-specific phosphopeptides by Human Leukocyte Antigen (HLA) class I molecules can be exploited in the treatment of cancer by T-cell-based immunotherapy. Yet, the characterization and prediction of HLA-I

  11. Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens

    Science.gov (United States)

    Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens. A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte...

  12. Chemokines in the corpus luteum: Implications of leukocyte chemotaxis

    Directory of Open Access Journals (Sweden)

    Liptak Amy R

    2003-11-01

    Full Text Available Abstract Chemokines are small molecular weight peptides responsible for adhesion, activation, and recruitment of leukocytes into tissues. Leukocytes are thought to influence follicular atresia, ovulation, and luteal function. Many studies in recent years have focused attention on the characterization of leukocyte populations within the ovary, the importance of leukocyte-ovarian cell interactions, and more recently, the mechanisms of ovarian leukocyte recruitment. Information about the role of chemokines and leukocyte trafficking (chemotaxis during ovarian function is important to understanding paracrine-autocrine relationships shared between reproductive and immune systems. Recent advances regarding chemokine expression and leukocyte accumulation within the ovulatory follicle and the corpus luteum are the subject of this mini-review.

  13. Clopidogrel affects leukocyte dependent platelet aggregation by P2Y12 expressing leukocytes.

    Science.gov (United States)

    Diehl, Philipp; Olivier, Christoph; Halscheid, Christoph; Helbing, Thomas; Bode, Christoph; Moser, Martin

    2010-05-01

    Up to 30% of all patients who are treated with a coronary stent do not respond sufficiently to antiplatelet therapy. This condition results in an increased risk for thrombotic complications such as stent thrombosis and myocardial infarction. The aim of the study was to determine clinical parameters modulating ASA and clopidogrel responsiveness. Patients were enrolled into three groups: (A) Patients with coronary artery disease without recent PCI treated with 100 mg/day ASA (n = 67). (B) Patients who underwent coronary stent implantation taking 100 mg/day ASA and 75 mg/day clopidogrel (n = 87). (C) Patients in whom CAD was excluded by angiography and who were not treated with anti-platelet medication served as controls (n = 32). Platelet aggregation was determined by impedance aggregometry using the Multiplate point of care device. Drug response was differentiated by stimulation of whole blood with arachidonic acid (AA, ASA responsiveness) or adenosine diphosphate (ADP, clopidogrel responsiveness). P2Y(12) receptor expression was determined by RT-PCR. ADP induced platelet aggregation correlated with the leukocyte count (r = 0.61, p leukocytes interact functionally. Clopidogrel treatment abolished the influence of leukocytes on platelets and caused decreased leukocyte activation. We detected the expression of the clopidogrel target P2Y(12) on leukocytes suggesting that clopidogrel may act directly on these cells and not only on platelets. In contrast to ASA responsiveness, clopidogrel response correlated with body mass index (r = 0.34; p = 0.001). In conclusion, (1) leukocytes influence ADP induced platelet aggregation most likely by expression of the P2Y(12) receptor. This interaction is abolished by clopidogrel. Therefore, clopidogrel may act directly on leukocytes via the P2Y(12) receptor. (2) Clopidogrel may be under dosed in obese patients.

  14. Bovine Doppel (Dpl) and prion protein (PrP) expression on lymphoid tissue and circulating leukocytes.

    Science.gov (United States)

    Paltrinieri, Saverio; Comazzi, Stefano; Spagnolo, Valentina; Rondena, Marco; Ponti, Wilma; Ceciliani, Fabrizio

    2004-12-01

    Doppel (Dpl) protein shares some structural features with prion protein (PrP), whose pathologic isoform (PrPsc) is considered to be the causative agent of transmissible spongiform encephalopathies. Dpl is mainly expressed in testes but, when ectopically expressed in the central nervous system, is neurotoxic. We have examined the expression pattern of Dpl and PrP on bovine lymphoid tissues and circulating leukocytes. A polyclonal anti-Dpl antibody along with a panel of monoclonal antibodies specific for leukocyte membrane antigens or PrP were used to examine frozen sections from spleen, lymph nodes, and bone marrow by immunohistochemistry. Blood was analyzed by flow cytometry. Double staining was used to study the possible coexpression of the two proteins and to characterize cells expressing Dpl and/or PrP. Dpl was expressed in B-cells, in dendritic cells within lymphoid follicles, bone marrow, circulating myeloid cells, and circulating B-cells. The distribution of Dpl was quite similar to that of PrP. The only differences in expression observed concerned the low number of Dpl+ cells in lymph nodes and the strong Dpl positivity of circulating granulocytes. The two proteins were rarely co-expressed, suggesting an independent expression mechanism in resting cells. The role of Dpl+ leukocytes in the pathogenesis of Dpl- or PrP-induced diseases merits further investigation.

  15. Semen leukocytes and oxidative-dependent DNA damage of spermatozoa in male partners of subfertile couples with no symptoms of genital tract infection.

    Science.gov (United States)

    Micillo, A; Vassallo, M R C; Cordeschi, G; D'Andrea, S; Necozione, S; Francavilla, F; Francavilla, S; Barbonetti, A

    2016-09-01

    The influence of seminal leukocytes on generation of oxidative damage to sperm DNA was here investigated on male partners of subfertile couples asymptomatic for a genital tract infection. The study included 111 ejaculates from men attending the Andrology Centre at University of L'Aquila. Semen leukocytes subset included round cells expressing pan-leukocyte CD45 antigen, monocyte/macrophage lineage antigen CD14, and activated macrophages HLA-DR antigen. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression identified spermatozoa with DNA oxidative adducts while terminal deoxynucleotidyl transferase (TdT)-mediated fluorescein-dUTP nick end labeling (TUNEL) assay detected spermatozoa with DNA fragmentation. Flow cytometry and immunocytochemistry was used for determinations. Main outcome measure was the association of semen leukocyte subpopulations with spermatozoa showing oxidative-related DNA damage and with routine semen parameters. Leukocyte subpopulations were strictly correlated (p spermatozoa. The percentage of 8-OHdG-positive spermatozoa was positively correlated with the percentage of TUNEL-positive spermatozoa (r = 0.48; p spermatozoa independently contributed (β = -0.25, p = 0.008; β = 0.23, p = 0.05, respectively) to the variation in percentage of 8-OHdG-positive spermatozoa after adjusting for age, abstinence time, and smoking. In conclusion, oxidative-dependent DNA damage in spermatozoa was associated to poor semen quality but not to different leukocyte subpopulations in ejaculates of men asymptomatic for a genital tract infection. © 2016 American Society of Andrology and European Academy of Andrology.

  16. Leukocyte Ig-Like Receptors - A Model for MHC Class I Disease Associations.

    Science.gov (United States)

    Hudson, Laura Emily; Allen, Rachel Louise

    2016-01-01

    MHC class I (MHC-I) polymorphisms are associated with the outcome of some viral infections and autoimmune diseases. MHC-I proteins present antigenic peptides and are recognized by receptors on natural killer cells and cytotoxic T lymphocytes, thus enabling the immune system to detect self-antigens and eliminate targets lacking self or expressing foreign antigens. Recognition of MHC-I, however, extends beyond receptors on cytotoxic leukocytes. Members of the leukocyte Ig-like receptor (LILR) family are expressed on monocytic cells and can recognize both classical and non-classical MHC-I alleles. Despite their relatively broad specificity when compared to the T cell receptor or killer Ig-like receptors, variations in the strength of LILR binding between different MHC-I alleles have recently been shown to correlate with control of HIV infection. We suggest that LILR recognition may mediate MHC-I disease association in a manner that does not depend on a binary discrimination of self/non-self by cytotoxic cells. Instead, the effects of LILR activity following engagement by MHC-I may represent a "degrees of self" model, whereby strength of binding to different alleles determines the degree of influence exerted by these receptors on immune cell functions. LILRs are expressed by myelomonocytic cells and lymphocytes, extending their influence across antigen-presenting cell subsets including dendritic cells, macrophages, and B cells. They have been identified as important players in the response to infection, inflammatory diseases, and cancer, with recent literature to indicate that MHC-I recognition by these receptors and consequent allelic effects could extend an influence beyond the immune system.

  17. Leukocyte Ig-Like Receptors – a model for MHC class I disease associations

    Directory of Open Access Journals (Sweden)

    Rachel Louise Allen

    2016-07-01

    Full Text Available MHC class I (MHC-I polymorphisms are associated with the outcome of some viral infections and autoimmune diseases. MHC-I proteins present antigenic peptides and are recognised by receptors on Natural Killer cells and Cytotoxic T lymphocytes, thus enabling the immune system to detect self-antigens and eliminate targets lacking self or expressing foreign antigens. Recognition of MHC-I, however, extends beyond receptors on cytotoxic leukocytes. Members of the Leukocyte Ig-like receptor (LILR family are expressed on monocytic cells and can recognise both classical and non-classical MHC-I alleles. Despite their relatively broad specificity when compared to the T Cell Receptor or Killer Ig-like Receptors, variations in the strength of LILR binding between different MHC-I alleles have recently been shown to correlate with control of HIV infection. We suggest that LILR recognition may mediate MHC-I disease association in a manner that does not depend on a binary discrimination of self/non-self by cytotoxic cells. Instead, the effects of LILR activity following engagement by MHC-I may represent a degrees of self model, whereby strength of binding to different alleles determines the degree of influence exerted by these receptors on immune cell functions. LILR are expressed by myelomonocytic cells and lymphocytes, extending their influence across antigen presenting cell subsets including dendritic cells, macrophages and B cells. They have been identified as important players in the response to infection, inflammatory diseases and cancer, with recent literature to indicate that MHC-I recognition by these receptors and consequent allelic effects could extend an influence beyond the immune system.

  18. Getting Leukocytes to the Site of Inflammation

    Science.gov (United States)

    Muller, W. A.

    2013-01-01

    There is no “response” in either the innate or adaptive immune response unless leukocytes cross blood vessels. They do this through the process of diapedesis, in which the leukocyte moves in ameboid fashion through tightly apposed endothelial borders (paracellular transmigration) and in some cases through the endothelial cell itself (transcellular migration). This review summarizes the steps leading up to diapedesis, then focuses on the molecules and mechanisms responsible for transendothelial migration. Surprisingly, many of the same molecules and mechanisms that regulate paracellular migration also control transcellular migration, including a major role for membrane from the recently described lateral border recycling compartment. A hypothesis that integrates the various known mechanisms of transmigration is proposed. PMID:23345459

  19. Leukocyte migration in experimental inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    E. P. Van Rees

    1997-01-01

    Full Text Available Emigration of leukocytes from the circulation into tissue by transendothelial migration, is mediated subsequently by adhesion molecules such as selectins, chemokines and integrins. This multistep paradigm, with multiple molecular choices at each step, provides a diversity in signals. The influx of neutrophils, monocytes and lymphocytes into inflamed tissue is important in the pathogenesis of chronic inflammatory bowel disease. The importance of each of these groups of adhesion molecules in chronic inflammatory bowel disease, either in human disease or in animal models, will be discussed below. Furthermore, the possibilities of blocking these different steps in the process of leukocyte extravasation in an attempt to prevent further tissue damage, will be taken into account.

  20. Effect of leukocyte hydrolases on bacteria

    International Nuclear Information System (INIS)

    Cohen, D.; Michel, J.; Ferne, M.; Bergner-Rabinowitz, S.; Ginsburg, I.

    1979-01-01

    Leukocyte extracts, trypsin, and lysozyme are all capable of releasing the bulk of the LPS from S. typhi, S. typhimurium, and E. coli. Bacteria which have been killed by heat, ultraviolet irradiation, or by a variety of metabolic inhibitors and antibiotics which affect protein, DNA, RNA, and cell wall synthesis no longer yield soluble LPS following treatment with the releasing agents. On the other hand, bacteria which are resistant to certain of the antibiotics yield nearly the full amount of soluble LPS following treatment, suggesting that certain heatabile endogenous metabolic pathways collaborate with the releasing agents in the release of LPS from the bacteria. It is suggested that some of the beneficial effects of antibiotics on infections with gram-negative bacteria may be the prevention of massive release of endotoxin by leukocyte enzymes in inflammatory sites

  1. Leukocyte removal filtration of platelet concentrates

    International Nuclear Information System (INIS)

    Wadenvik, H.; Kutti, J.; Lindholm, A.

    1991-01-01

    111 In labelled platelets and gamma camera scintigraphy were used for the study of the platelet loss during leukocyte removal filtration of stored platelets. Two different filters were examined, Imugard IG500 and Pall PL100, and platelet pools containing varying number of platelet concentrates were filtered. It was found that a sizeable amount of the platelets was trapped within the filter. Some of the trapped platelets could be recovered by rinsing the filters with normal saline. The most appropriate rinsing volume to recover lost platelets seemed to match with the ''dead space'' volume within the filter. It is concluded that radiolabelled platelets and gamma camera scintigraphy appears to be an excellent method to investigate the dynamic events of platelet loss during leukocyte removal filtration. This technique should be well applicable for the study of technological advances in filter construction. (author)

  2. 2-Substituted benzoxazinone analogues as anti-human coronavirus (anti-HCoV) and ICAM-1 expression inhibition agents.

    Science.gov (United States)

    Hsieh, Pei-Wen; Chang, Fang-Rong; Chang, Cheng-Hsien; Cheng, Pei-Wen; Chiang, Lien-Chai; Zeng, Fu-Long; Lin, Kuei-Hsiang; Wu, Yang-Chang

    2004-09-20

    A series of 2-substituted benzoxazinones were synthesized and subjected to anti-human coronavirus and ICAM-1 expression inhibition assays. Among them, compounds 1, 3, 4, 5, 6, and 7 exhibited significant anti-HCoV activities, and the IC(50) value of these compounds are 6.08, 5.06, 6.83, 1.92, 7.59, and 5.79 microg/mL, respectively. Furthermore, compounds 1 and 6 showed significant inhibitory effect on ICAM-1 expression, the ED(50) values of 1 and 6 are 1.00 and 0.50 microg/mL, respectively.

  3. Fabrication of Anti-human Cardiac Troponin I Immunogold Nanorods for Sensing Acute Myocardial Damage

    Directory of Open Access Journals (Sweden)

    Fan X

    2009-01-01

    Full Text Available Abstract A facile, rapid, solution-phase method of detecting human cardiac troponin I for sensing myocardial damage has been described using gold nanorods-based biosensors. The sensing is demonstrated by the distinct change of the longitudinal surface plasmon resonance wavelength of the gold nanorods to specific antibody–antigen binding events. For a higher sensitivity, the aspect ratio of gold nanorods is increased up to ca 5.5 by simply adding small amount of HCl in seed-mediated growth solution. Experimental results show that the detecting limit of the present method is 10 ng/mL. Contrast tests reveal that these gold nanorods-based plasmonic biosensors hold much higher sensitivity than that of conventionally spherical gold nanoparticles.

  4. Comparison of technetium-99m-HM-PAO leukocytes with indium-111-oxine leukocytes for localizing intraabdominal sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Mountford, P.J.; Kettle, A.G.; O' Doherty, M.J.; Coakley, A.J. (Kent and Canterbury Hospital (England))

    1990-03-01

    Technetium-99m-HM-PAO (({sup 99m}Tc)HM-PAO) leukocyte and indium-111-oxine (111In-oxine) leukocyte scanning were carried out simultaneously in 41 patients at 4 hr and 24 hr after reinjection to determine whether the 4-hr {sup 99m}Tc scan could replace the 24-hr {sup 111}In scan for detecting intraabdominal sepsis. Abdominal infection was confirmed in 12 cases. The 4-hr {sup 99}Tc-leukocyte scan, the 4-hr {sup 111}In-leukocyte scan, and the 24-hr {sup 111}In-leukocyte scan yielded a sensitivity of 100%, 67%, and 100%, respectively, and a specificity of 62%, 90%, and 86%, respectively. The 24-hr {sup 99m}Tc-leukocyte scan also produced a sensitivity of 100%, but it was falsely positive in all 29 cases without infection due to physiologic bowel uptake. False-positive 4-hr {sup 99m}Tc-leukocyte scans were also produced by physiologic bowel uptake in seven cases all of whom had true-negative 4-hr and 24-hr {sup 111}In-leukocyte scans. Because of the high incidence of false-positive 4-hr ({sup 99m}Tc)HM-PAO leukocyte scans, it was concluded that they could not replace 24-hr {sup 111}In-leukocyte scans for detecting intraabdominal sepsis, and that serial {sup 99m}Tc leukocyte scans starting earlier than 4 hr after reinjection must be evaluated.

  5. Towards patient-specific tumor antigen selection for vaccination.

    Science.gov (United States)

    Rammensee, Hans-Georg; Weinschenk, Toni; Gouttefangeas, Cécile; Stevanović, Stefan

    2002-10-01

    In this review, we discuss the possibilities for combining the power of molecular analysis of the antigens expressed in a given individual tumor with the design of a tailored vaccine containing defined antigens. Step 1 is a differential gene expression analysis of tumor and corresponding normal tissue. Step 2 is the analysis of human leukocyte antigen (HLA) ligands on tumor cells. Step 3 is data mining with the aim to select those antigens that might be suitable for tumor attack by the adaptive immune system. Step 4 is the on-the-spot clinical grade production of the constituents of the patient tailored vaccine, e.g. peptides. Step 5 is then vaccination and monitoring. Although it will not be possible to cover all relevant antigens expressed in a tumor, the antigens that can be identified with our present technical possibilities might be enough for improved immunotherapy. The scope of the present review is to explore the possibilities and the formidable technical and logistical challenge for such individual patient-oriented antigen definition to be used for therapeutic immunization.

  6. Long leukocyte telomere length in prostate cancer patients at diagnosis is associated with poor metastasis-free and cancer-specific survival.

    Science.gov (United States)

    Svenson, Ulrika; Roos, Göran; Wikström, Pernilla

    2017-02-01

    Previous studies have suggested that leukocyte telomere length is associated with risk of developing prostate cancer. Investigations of leukocyte telomere length as a prognostic factor in prostate cancer are, however, lacking. In this study, leukocyte telomere length was investigated both as a risk marker, comparing control subjects and patient risk groups (based on serum levels of prostate-specific antigen, tumor differentiation, and tumor stage), and as a prognostic marker for metastasis-free and cancer-specific survival. Relative telomere length was measured by a well-established quantitative polymerase chain reaction method in 415 consecutively sampled individuals. Statistical evaluation included 162 control subjects without cancer development during follow-up and 110 untreated patients with newly diagnosed localized prostate cancer at the time of blood draw. Leukocyte telomere length did not differ significantly between control subjects and patients, or between patient risk groups. Interestingly, however, and in line with our previous results in breast and kidney cancer patients, relative telomere length at diagnosis was an independent prognostic factor. Patients with long leukocyte telomeres (⩾median) had a significantly worse prostate cancer-specific and metastasis-free survival compared to patients with short telomere length. In contrast, for patients who died of other causes than prostate cancer, long relative telomere length was not coupled to shorter survival time. To our knowledge, these results are novel and give further strength to our hypothesis that leukocyte telomere length might be used as a prognostic marker in malignancy.

  7. The effect of Ureaplasma diversum activated mononuclear leukocytes on the development and interferon-tau production by bovine IVF-derived embryos.

    Science.gov (United States)

    Chełmońska-Soyta, A; Katska, L; Kurpisz, M; Stefaniak, T; Zimecki, M

    2001-08-01

    Ureaplasma diversum is an opportunistic pathogen of the bovine genital tract causing herd outbreaks of granular vulvitis, abortion and infertility. Early embryonic death probably contributes to reduction of the reproductive performance in cows, however, pathogenesis of the disease remains obscure. The aim of the study was to examine whether activation of mononuclear leukocytes by U. diversum may affect embryo development and IFN-tau production. Bovine peripheral blood mononuclear leukocytes were cultured with U.diversum antigen for 24 h. The levels of IL-1, TNF-alpha, NO and GM-CSF in the cell culture supernatants were measured. IVF-derived embryos were cultured in the presence of supernatants from activated leukocytes. The development of embryos until day 6 postinsemination and the rate of morulae/blastocysts were determined. IFN-tau production in supernatants of cultured embryos was examined by inhibition of a virally-induced cytopathic effect. The results showed that U. diversum stimulated mononuclear leukocyte production of IL-1, TNF-alpha and NO. Supernatants from U. diversum-activated cells did not impair the rates of the embryo development and blastocyst formation. The products of activated leukocytes increased the IFN-tau production by cultured blastocysts. This suggest that U. diversum infection provides leukocyte-mediated signals for developing embryos for generation of additional production of cytokine - an important component of innate immunity.

  8. Alloactivated HLA class II-positive T-cell lines induce IL-2 reactivity but lack accessory cell function in mixed leukocyte culture

    DEFF Research Database (Denmark)

    Odum, N; Dickmeiss, E; Hofmann, B

    1989-01-01

    in the primary mixed leukocyte reaction (median counts per minute (cpm) 5.5 x 10(3] was significantly lower than that of peripheral blood mononuclear cells (cpm: 44.0 x 10(3]. The stimulation by Ta was almost only seen when the Ta were specifically directed against the class II antigens of the responder...... peripheral blood mononuclear cells (i.e., in combinations with "backstimulation") (median cpm: 21,000). In mixed leukocyte reaction combinations without backstimulation, significantly weaker reactions were seen (median cpm: 1,000). This observation may explain previous controversies concerning...

  9. Posttransplant chimeric antigen receptor therapy.

    Science.gov (United States)

    Smith, Melody; Zakrzewski, Johannes; James, Scott; Sadelain, Michel

    2018-03-08

    Therapeutic T-cell engineering is emerging as a powerful approach to treat refractory hematological malignancies. Its most successful embodiment to date is based on the use of second-generation chimeric antigen receptors (CARs) targeting CD19, a cell surface molecule found in most B-cell leukemias and lymphomas. Remarkable complete remissions have been obtained with autologous T cells expressing CD19 CARs in patients with relapsed, chemo-refractory B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. Allogeneic CAR T cells may also be harnessed to treat relapse after allogeneic hematopoietic stem cell transplantation. However, the use of donor T cells poses unique challenges owing to potential alloreactivity. We review different approaches to mitigate the risk of causing or aggravating graft-versus-host disease (GVHD), including CAR therapies based on donor leukocyte infusion, virus-specific T cells, T-cell receptor-deficient T cells, lymphoid progenitor cells, and regulatory T cells. Advances in CAR design, T-cell selection and gene editing are poised to enable the safe use of allogeneic CAR T cells without incurring GVHD. © 2018 by The American Society of Hematology.

  10. RAGE controls leukocyte adhesion in preterm and term infants.

    Science.gov (United States)

    Buschmann, Kirsten; Tschada, Raphaela; Metzger, Marie-Sophie; Braach, Natascha; Kuss, Navina; Hudalla, Hannes; Poeschl, Johannes; Frommhold, David

    2014-11-27

    Insufficient leukocyte recruitment may be one reason for the high incidence of life-threatening infections in preterm infants. Since the receptor of advanced glycation end products (RAGE) is a known leukocyte adhesion molecule and highly expressed during early development, we asked whether RAGE plays a role for leukocyte recruitment in preterm and term infants. Leukocyte adhesion was analyzed in dynamic flow chamber experiments using isolated leukocytes of cord blood from extremely premature (35 weeks of gestation) and compared to the results of adults. For fluorescent microscopy leukocytes were labeled with rhodamine 6G. In the respective age groups we also measured the plasma concentration of soluble RAGE (sRAGE) by ELISA and Mac-1 and LFA-1 expression on neutrophils by flow cytometry. The adhesive functions of fetal leukocytes significantly increase with gestational age. In all age groups, leukocyte adhesion was crucially dependent on RAGE. In particular, RAGE was equally effective to mediate leukocyte adhesion when compared to ICAM-1. The plasma levels of sRAGE were high in extremely premature infants and decreased with increasing gestational age. In contrast, expression of β2-Integrins Mac-1 and LFA-1 which are known ligands for RAGE and ICAM-1 did not change during fetal development. We conclude that RAGE is a crucial leukocyte adhesion molecule in both preterm and term infants.

  11. Blood leukocyte and spleen lymphocyte immune response of spleen lymphocytes and whole blood leukocytes of hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Peters, B.A.; Sothmann, M.; Wehrenberg, W.B. (Univ. of Wisconsin, Milwaukee (USA))

    1989-01-01

    This study was designed to evaluate the effects of chronic physical activity on the immune response of spleen lymphocytes and whole blood leukocytes of hamsters. Animals were kept sedentary or allowed to exercise spontaneously on running wheels for eight weeks. Physically active animals averaged 12 kilometers per day. The immune response of spleen lymphocytes whole blood leukocytes was evaluated by {sup 3}H-thymidine incorporation in response to Concanavalin A or lipopolysaccharide. There was no treatment effect between physically active and sedentary hamster in response of spleen lymphocytes. The immune response of whole blood leukocytes to these mitogens was significantly greater in physically active vs. sedentary hamsters. These results demonstrate that chronic physical activity has the capacity to modulate immunoresponses.

  12. Fluid Stresses on the Membrane of Migrating Leukocytes

    OpenAIRE

    Su, Susan S.; Schmid-Schönbein, Geert W.

    2007-01-01

    We recently demonstrated that migrating human leukocytes respond to normal physiologic fluid stresses (~1dyn/cm2) by active control of local cytoplasmic extensions (pseudopods). To better understand the governing mechanisms of this response, we determined the fluid stress distributions on individual migrating leukocytes whose shapes were reconstructed with serial confocal microscopy. The flow over adherent leukocytes was computed by solution of the Stokes equation for plasma motion over the c...

  13. [Relationship between leukocyte count and risk of hypertension].

    Science.gov (United States)

    Xi, Lu; Hao, Yongchen; Liu, Jing; Wang, Wei; Wang, Miao; Qi, Yue; Zhao, Fan; Xie, Wuxiang; Li, Yan; Liu, Jun; Sun, Jiayi; Qin, Lanping; Zhao, Dong

    2015-04-01

    To observe the association between the leukocyte count and blood pressure value and hypertension risk in a Chinese community-based population. A total of 4 188 participants who took part in the baseline examination in 1992 and the follow-up survey in 2007 from the Chinese Multi-Provincial Cohort Study were included in this study. The relationship of leukocyte and blood pressure value and hypertension risk were evaluated by cross-sectional analyses.The prospective association between baseline leukocyte count and blood pressure changes and risk of hypertension were analyzed in 2 954 normotensive individuals at baseline examination.The associations between leukocyte count and blood pressure was evaluated with Spearman's rank correlation analyses and linear regression models,and the associations between leukocyte count and risk of hypertension was evaluated with logistic regression models. (1) The cross-sectional study results showed that the correlation coefficient of leukocyte count and systolic blood pressure and diastolic blood pressure was 0.208 and 0.154 (both P leukocyte count was associated with 1.41 mmHg (1 mmHg = 0.133 kPa) systolic blood pressure increase (95% CI: 1.20-1.63 mmHg, P leukocyte count was associated with a 15% increased risk of hypertension (OR: 1.15, 95% CI: 1.12-1.19, P leukocyte count and systolic blood pressure change and diastolic blood pressure change was 0.062 (P = 0.003) and 0.102 (P leukocyte count was associated with 1.03 mmHg systolic blood pressure increase (95% CI: 0.74-1.32 mmHg, P leukocyte count was associated with a 9% increased risk of incident hypertension (OR: 1.09, 95% CI: 1.06-1.13, P leukocyte count is associated with increased blood pressure value and hypertension among Chinese community-based population, suggesting that inflammation may participate in the pathogenesis of hypertension.

  14. Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanized monoclonal antibody A33.

    Science.gov (United States)

    Ritter, G; Cohen, L S; Williams, C; Richards, E C; Old, L J; Welt, S

    2001-09-15

    Mouse monoclonal antibody A33 (mAb A33) recognizes a M(r) 43,000 cell surface glycoprotein (designated A33) expressed in human colonic epithelium and colon cancer but absent from most other normal tissues. In patients, mAb A33 localizes with high specificity to colon cancer and is retained for up to 6 weeks in the cancer but cleared rapidly from normal colon (5-6 days). As a carrier of (125)I or (131)I, mAb A33 has shown antitumor activity. Induction of strong human anti-mouse antibody (immunoglobulin; HAMA) responses in patients, however, limits the use of the murine mAb A33 to very few injections. A humanized version of this antibody (huAb A33) has been prepared for Phase I and II clinical studies in patients with colon cancer. In those studies, immunogenicity of huAb A33 has been monitored using a novel, highly sensitive BIACORE method, which allows measurement of human anti-human antibodies (HAHAs) without the use of secondary reagents. We found that 63% (26 of 41) of the patients treated with repeated doses of huAb A33 developed HAHAs against a conformational antigenic determinant located in the V(L) and V(H) regions of huAb A33. Detailed serological analysis showed two distinct types of HAHAs. HAHA of type I (49% of patients) was characterized by an early onset with peak HAHA levels after 2 weeks of treatment, which declined with ongoing huAb A33 treatment. HAHA of type II (17% of patients) was characterized by a typically later onset of HAHA than in type I and by progressively increasing HAHA levels with each subsequent huAb A33 administration. Colon cancer patients with type I HAHAs did not develop infusion-related adverse events. In contrast, HAHA of type II was indicative of infusion-related adverse events. By using this new method, we were able to distinguish these two types of HAHAs in patients while on antibody treatment, allowing patients to be removed from study prior to the onset of severe infusion-related adverse events.

  15. BIOCOMPATIBILITY OF LEUKOCYTE REMOVAL FILTERS DURING LEUKOCYTE FILTRATION OF CARDIOPULMONARY BYPASS PERFUSATE

    NARCIS (Netherlands)

    GU, YJ; OBSTER, R; HAAN, J; HUET, RCGG; EIJGELAAR, A; VANOEVEREN, W

    To evaluate the biocompatibility and the efficacy of leukocyte removal filters, we performed a prospective study by using the cardiopulmonary bypass perfusate taken from the heart-lung machine for 20 patients who underwent cardiac surgery and were randomly divided into four groups according to the

  16. Targeting novel antigens in the arterial wall in thromboangiitis obliterans.

    Directory of Open Access Journals (Sweden)

    Murat Akkus

    2010-06-01

    Full Text Available Thromboangiitis obliterans is an inflammatory disease possibly resulting from cigarette smoking as a primary etiologic factor, perhaps as a delayed type of hypersensitivity or toxic angiitis. As little is known about the pathogenesis of the disease, we aimed to determine novel antigens that might be responsible from the local inflammatory reactions and structural changes observed in this disease. An indirect immunoperoxidase technique is used to examine the tissue samples obtained from the dorsalis pedis artery of affected individuals with twenty monoclonal antibodies. Among these several antigens which are not previously reported in TAO like CD34, CD44 and CD90 were determined in the tissue samples examined. On the other hand, many other antigens like cytokine/chemokine receptors, several enzymes and leukocyte/lymphocyte antigens were lacking giving some clues about the local pathological reactions. We briefly discussed our findings for several critical antigens those first described in the present work, possibly having roles in the development of the disease. Expression of the CD90/CD11c receptor/ligand pair seems to play an important role in mononuclear cell recruitment to the damage site. Vascular invasion of not only tunica intima but also the tunica media in affected vessels is clearly demonstrated using endothelial cell specific antigens.

  17. Photon Counts Statistics in Leukocyte Cell Dynamics

    Science.gov (United States)

    van Wijk, Eduard; van der Greef, Jan; van Wijk, Roeland

    2011-12-01

    In the present experiment ultra-weak photon emission/ chemiluminescence from isolated neutrophils was recorded. It is associated with the production of reactive oxygen species (ROS) in the "respiratory burst" process which can be activated by PMA (Phorbol 12-Myristate 13-Acetate). Commonly, the reaction is demonstrated utilizing the enhancer luminol. However, with the use of highly sensitive photomultiplier equipment it is also recorded without enhancer. In that case, it can be hypothesized that photon count statistics may assist in understanding the underlying metabolic activity and cooperation of these cells. To study this hypothesis leukocytes were stimulated with PMA and increased photon signals were recorded in the quasi stable period utilizing Fano factor analysis at different window sizes. The Fano factor is defined by the variance over the mean of the number of photon within the observation time. The analysis demonstrated that the Fano factor of true signal and not of the surrogate signals obtained by random shuffling increases when the window size increased. It is concluded that photon count statistics, in particular Fano factor analysis, provides information regarding leukocyte interactions. It opens the perspective to utilize this analytical procedure in (in vivo) inflammation research. However, this needs further validation.

  18. Aberrant leukocyte telomere length in Birdshot Uveitis.

    Directory of Open Access Journals (Sweden)

    Nadia Vazirpanah

    Full Text Available Birdshot Uveitis (BU is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes.To study this in detail, we exploited a sensitive standardized quantitative real-time polymerase chain reaction to determine the peripheral blood leukocyte telomere length (LTL in 91 genotyped Dutch BU patients and 150 unaffected Dutch controls.Although LTL erosion rates were very similar between BU patients and healthy controls, we observed that BU patients displayed longer LTL, with a median of log (LTL = 4.87 (= 74131 base pair compared to 4.31 (= 20417 base pair in unaffected controls (P<0.0001. The cause underpinning the difference in LTL could not be explained by clinical parameters, immune cell-subtype distribution, nor genetic predisposition based upon the computed weighted genetic risk score of genotyped validated variants in TERC, TERT, NAF1, OBFC1 and RTEL1.These findings suggest that BU is accompanied by significantly longer LTL.

  19. Cell adhesion molecules in the development of inflammatory infiltrates in giant cell arteritis: inflammation-induced angiogenesis as the preferential site of leukocyte-endothelial cell interactions.

    Science.gov (United States)

    Cid, M C; Cebrián, M; Font, C; Coll-Vinent, B; Hernández-Rodríguez, J; Esparza, J; Urbano-Márquez, A; Grau, J M

    2000-01-01

    To investigate the expression pattern of adhesion molecules involved in leukocyte-endothelial cell interactions in giant cell arteritis (GCA). Immunohistochemical analysis was performed on frozen temporal artery sections from 32 patients with biopsy-proven GCA and from 12 control patients with other diseases. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), very late activation antigen 4 (VLA-4), Mac-1 (CD18/CD11b), and gp 150,95 (CD18/CD11c). Clinical and biochemical parameters of inflammation in the patients, as well as the duration of previous corticosteroid treatment, were prospectively recorded. Constitutive (PECAM-1, ICAM-1, ICAM-2, and P-selectin) and inducible (E-selectin and VCAM-1) endothelial adhesion molecules for leukocytes were mainly expressed by adventitial microvessels and neovessels within inflammatory infiltrates. Concurrent analysis of leukocyte receptors indicated a preferential use of VLA-4/VCAM-1 and LFA-1/ICAM-1 at the adventitia and Mac-1/ICAM-1 at the intima-media junction. The intensity of inducible endothelial adhesion molecule expression (E-selectin and VCAM-1) correlated with the intensity of the systemic inflammatory response. Previous corticosteroid treatment reduced, but did not completely abrogate, the expression of the inducible endothelial adhesion molecules E-selectin and VCAM-1. Inflammation-induced angiogenesis is the main site of leukocyte-endothelial cell interactions leading to the development of inflammatory infiltrates in GCA. The distribution of leukocyte-endothelial cell ligand pairs suggests a heterogeneity in leukocyte-endothelial cell interactions used by different functional cell subsets at distinct areas of the temporal artery.

  20. Computerized detection of leukocytes in microscopic leukorrhea images.

    Science.gov (United States)

    Zhang, Jing; Zhong, Ya; Wang, Xiangzhou; Ni, Guangming; Du, Xiaohui; Liu, Juanxiu; Liu, Lin; Liu, Yong

    2017-09-01

    Detection of leukocytes is critical for the routine leukorrhea exam, which is widely used in gynecological examinations. An elevated vaginal leukocyte count in women with bacterial vaginosis is a strong predictor of vaginal or cervical infections. In the routine leukorrhea exam, the counting of leukocytes is primarily performed by manual techniques. However, the viewing and counting of leukocytes from multiple high-power viewing fields on a glass slide under a microscope leads to subjectivity, low efficiency, and low accuracy. To date, many biological cells in stool, blood, and breast cancer have been studied to realize computerized detection; however, the detection of leukocytes in microscopic leukorrhea images has not been studied. Thus, there is an increasing need for computerized detection of leukocytes. There are two key processes in the computerized detection of leukocytes in digital image processing. One is segmentation; the other is intelligent classification. In this paper, we propose a combined ensemble to detect leukocytes in the microscopic leukorrhea image. After image segmentation and selecting likely leukocyte subimages, we obtain the leukocyte candidates. Then, for intelligent classification, we adopt two methods: feature extraction and classification by a support vector machine (SVM); applying a modified convolutional neural network (CNN) to the larger subimages. If different methods classify a candidate in the same category, the process is finished. If not, the outputs of the methods are provided to a classifier to further classify the candidate. After acquiring leukocyte candidates, we attempted three methods to perform classification. The first approach using features and SVM achieved 88% sensitivity, 97% specificity, and 92.5% accuracy. The second method using CNN achieved 95% sensitivity, 84% specificity, and 89.5% accuracy. Then, in the combination approach, we achieved 92% sensitivity, 95% specificity, and 93.5% accuracy. Finally, the images

  1. Anti-Human Endoglin (hCD105) Immunotoxin-Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1.

    Science.gov (United States)

    Barriuso, Begoña; Antolín, Pilar; Arias, F Javier; Girotti, Alessandra; Jiménez, Pilar; Cordoba-Diaz, Manuel; Cordoba-Diaz, Damián; Girbés, Tomás

    2016-06-10

    Endoglin (CD105) is an accessory component of the TGF-β receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endoglin with immunotoxins containing type 2 ribosome-inactivating proteins has proved an effective tool to reduce blood supply to B16 mice tumor xenografts. We prepared anti-endoglin immunotoxin (IT)-containing recombinant musarmin 1 (single chain ribosome-inactivating proteins) linked to the mouse anti-human CD105 44G4 mouse monoclonal antibody via N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). The immunotoxin specifically killed L929 fibroblast mouse cells transfected with the short form of human endoglin with IC50 values in the range of 5 × 10(-10) to 10(-9) M.

  2. Anti-Human Endoglin (hCD105 Immunotoxin—Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1

    Directory of Open Access Journals (Sweden)

    Begoña Barriuso

    2016-06-01

    Full Text Available Endoglin (CD105 is an accessory component of the TGF-β receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endoglin with immunotoxins containing type 2 ribosome-inactivating proteins has proved an effective tool to reduce blood supply to B16 mice tumor xenografts. We prepared anti-endoglin immunotoxin (IT—containing recombinant musarmin 1 (single chain ribosome-inactivating proteins linked to the mouse anti-human CD105 44G4 mouse monoclonal antibody via N-succinimidyl 3-(2-pyridyldithio propionate (SPDP. The immunotoxin specifically killed L929 fibroblast mouse cells transfected with the short form of human endoglin with IC50 values in the range of 5 × 10−10 to 10−9 M.

  3. AntigenMap 3D: an online antigenic cartography resource.

    Science.gov (United States)

    Barnett, J Lamar; Yang, Jialiang; Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2012-05-01

    Antigenic cartography is a useful technique to visualize and minimize errors in immunological data by projecting antigens to 2D or 3D cartography. However, a 2D cartography may not be sufficient to capture the antigenic relationship from high-dimensional immunological data. AntigenMap 3D presents an online, interactive, and robust 3D antigenic cartography construction and visualization resource. AntigenMap 3D can be applied to identify antigenic variants and vaccine strain candidates for pathogens with rapid antigenic variations, such as influenza A virus. http://sysbio.cvm.msstate.edu/AntigenMap3D

  4. Antigens of Streptococcus sanguis

    Science.gov (United States)

    Rosan, Burton

    1973-01-01

    An antigenic analysis of the alpha-hemolytic streptococci isolated from dental plaque was performed by use of antisera against a strain of Streptococcus sanguis (M-5) which was isolated from dental plaque. Immunoelectrophoretic and Ouchterlony tests of Rantz and Randall extracts of 45 strains gave positive reactions with the M-5 antisera. These strains represented 60% of the strains tested. The number of antigens which could be identified in these extracts varied from one to five and were designated a to e. The a antigen was found in 36 of the strains tested, including reference strains of S. sanguis and the group H streptococci. The strains reacting with the M-5 antisera were divided into two majors types: type I consisted of 23 strains in which the a antigen was found alone or with one or more of the c, d, and e antigens; type II consisted of 13 strains in which both the a and b antigens were found with or without one or more of the c, d, and e antigens. The remaining strains contained, either singly or in combination, the b, c, d, and e antigens but not the a antigen. Biochemical tests of representatives of each serotype and reference strains indicated that strains reacting with M-5 antisera were S. sanguis. These findings suggest that S. sanguis strains share common physiological and serological properties. Images PMID:4633291

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  1. File list: His.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.AllAg.Polymorphonuclear_leukocytes hg19 Histone Blood Polymorphonuclear ...leukocytes http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.20.AllAg.Polymorphonuclear_leukocytes.bed ...

  2. File list: Oth.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.AllAg.Polymorphonuclear_leukocytes hg19 TFs and others Blood Polymorphonuclear... leukocytes http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.05.AllAg.Polymorphonuclear_leukocytes.bed ...

  3. Recent insights into endothelial control of leukocyte extravasation

    NARCIS (Netherlands)

    Hordijk, Peter L.

    2016-01-01

    In the process of leukocyte migration from the circulation across the vascular wall, the crosstalk with endothelial cells that line the blood vessels is essential. It is now firmly established that in endothelial cells important signaling events are initiated upon leukocyte adhesion that impinge on

  4. Leukocyte adhesion and polarization: Role of glycosylphosphatidylinositol-anchored proteins.

    Science.gov (United States)

    Richardson, Dion D; Fernandez-Borja, Mar

    2015-01-01

    Leukocyte traffic out of the blood stream is crucial for an adequate immune response. Leukocyte extravasation is critically dependent on the binding of leukocyte integrins to their endothelial counterreceptors. This interaction enables the firm adhesion of leukocytes to the luminal side of the vascular wall and allows for leukocyte polarization, crawling and diapedesis. Leukocyte adhesion, polarization and migration requires the orchestrated regulation of integrin adhesion/de-adhesion dynamics and actin cytoskeleton rearrangements. Adhesion strength depends on conformational changes of integrin molecules (affinity) as well as the number of integrin molecules engaged at adhesion sites (valency). These two processes can be independently regulated and several molecules modulate either one or both processes. Cholesterol-rich membrane domains (lipid rafts) participate in integrin regulation and play an important role in leukocyte adhesion, polarization and motility. In particular, lipid raft-resident glycosyl-phosphatidyl-inositol-anchored proteins (GPI-APs) have been reported to regulate leukocyte adhesion, polarization and motility in both integrin-dependent and independent manners. Here, we present our recent discovery concerning the novel role of the GPI-AP prion protein (PrP) in the regulation of β1 integrin-mediated monocyte adhesion, migration and shape polarization in the context of existing literature on GPI-AP-dependent regulation of integrins.

  5. Leukocyte Profile in HIV Positive Adults in Owerri, Nigeria ...

    African Journals Online (AJOL)

    Leukocyte Profile in HIV Positive Adults in Owerri, Nigeria. USB Anyaehie, RO Nneli, P Amadi, ED Nwodobo. Abstract. Leukocyte profile of 102 HIV positive asymptomatic adults (aged 18 – 56 years) in Owerri was compared with that of 80 HIV-negative adults (aged 22 – 50 years). The goal was to define early indicators of ...

  6. Tenocytes, pro-inflammatory cytokines and leukocytes: a relationship?

    OpenAIRE

    Al-Sadi, Onays; Schulze-Tanzil, Gundula; Kohl, Benjamin; Lohan, Anke; Lemke, Marion; Ertel, Wolfgang; John, Thilo

    2012-01-01

    Leukocyte derived pro-inflammatory mediators could be involved in tendon healing and scar formation. Hence, the effect of autologous leukocytes (PBMCs, peripheral blood mononuclear cells and neutrophils) on primary rabbit Achilles tenocytes gene expression was tested in insert assisted co-cultures.

  7. Asymmetric membrane filters for the removal of leukocytes from blood

    NARCIS (Netherlands)

    Bruil, A.; Bruil, A.; van Aken, W.G.; Beugeling, T.; Beugeling, T.; Feijen, Jan; Steneker, I.; Huisman, J.G.; Prins, H.K.

    1991-01-01

    As part of a study on the mechanisms of leukocyte filtration, the influence of pore size distribution on filter efficiency was investigated. Conventional leukocyte filters are not suitable for model studies, as these filters are composed of tightly packed synthetic fibers, with a poorly defined

  8. The effects of stress on the enzymes of peripheral leukocytes

    Science.gov (United States)

    Leise, E. M.; Gray, I.

    1973-01-01

    Previous work showed an early response of rabbit and human leukocyte enzymes to the stress of bacterial infection. Since these represented a mixed population of leukocytes and since polymorphonuclear leukocytes (PMN) increased in these preparations, it was necessary to establish whether the observed increase in lactate dehydrenase (LDH) and protein was the result of an increase in any one particular cell type or in all cells. The need for the development of a simple reproducible method for the differential separation of peripheral leukocytes for the furtherance of our own studies was apparent. It was also becoming increasingly apparent that morphologically similar cells, such as small lymphocytes (L) and macrophages, were capable of different biological functions. A dextran gradient centrifugation method was developed which has provided an easily reproducible technique for separating L from PMN. During the course of this work, in which over 250 rabbits were examined, the pattern of daily leukocyte protein and enzyme variation became increasingly more apparent. This information could have some impact on future work with leukocyte enzymes, by our group and by other workers. The differences in normal protein and enzyme levels maintained by some individuals, and some inbred strains, were evaluated and reported separately. It has been shown that one type of leukocyte may react more to a given stress than other leukocytes.

  9. Leukocytes Crossing the Endothelium: A Matter of Communication

    NARCIS (Netherlands)

    Timmerman, Ilse; Daniel, Anna E.; Kroon, Jeffrey; van Buul, Jaap D.

    2016-01-01

    Leukocytes cross the endothelial vessel wall in a process called transendothelial migration (TEM). The purpose of leukocyte TEM is to clear the causing agents of inflammation in underlying tissues, for example, bacteria and viruses. During TEM, endothelial cells initiate signals that attract and

  10. Mercuric chloride-induced autoimmunity in the brown Norway rat. Cellular kinetics and major histocompatibility complex antigen expression

    NARCIS (Netherlands)

    Aten, J.; Bosman, C. B.; Rozing, J.; Stijnen, T.; Hoedemaeker, P. J.; Weening, J. J.

    1988-01-01

    HgCl2 induces an autoimmune syndrome in Brown Norway rats that involves synthesis of anti-glomerular basement membrane (GBM) antibodies and development of nephritis with high proteinuria. HgCl2-induced changes in the composition of leukocyte populations and in the expression of MHC antigens in

  11. Leukocyte diversity in resolving and nonresolving mechanisms of cardiac remodeling.

    Science.gov (United States)

    Tourki, Bochra; Halade, Ganesh

    2017-10-01

    In response to myocardial infarction (MI), time-dependent leukocyte infiltration is critical to program the acute inflammatory response. Post-MI leukocyte density, residence time in the infarcted area, and exit from the infarcted injury predict resolving or nonresolving inflammation. Overactive or unresolved inflammation is the primary determinant in heart failure pathology post-MI. Here, our review describes supporting evidence that the acute inflammatory response also guides the generation of healing and regenerative mediators after cardiac damage. Time-dependent leukocyte density and diversity and the magnitude of myocardial injury is responsible for the resolving and nonresolving pathway in myocardial healing. Post MI, the diversity of leukocytes, such as neutrophils, macrophages, and lymphocytes, has been explored that regulate the clearance of deceased cardiomyocytes by using the classic and reparative pathways. Among the innovative factors and intermediates that have been recognized as essential in acute the self-healing and clearance mechanism, we highlight specialized proresolving mediators as the emerging factor for post-MI reparative mechanisms-translational leukocyte modifiers, such as aging, the source of leukocytes, and the milieu around the leukocytes. In the clinical setting, it is possible that leukocyte diversity is more prominent as a result of risk factors, such as obesity, diabetes, and hypertension. Pharmacologic agents are critical modifiers of leukocyte diversity in healing mechanisms that may impair or stimulate the clearance mechanism. Future research is needed, with a focused approach to understand the molecular targets, cellular effectors, and receptors. A clear understanding of resolving and nonresolving inflammation in myocardial healing will help to develop novel targets with major emphasis on the resolution of inflammation in heart failure pathology.-Tourki, B., Halade, G. Leukocyte diversity in resolving and nonresolving mechanisms

  12. Eosinofil Sel Penyaji Antigen

    Directory of Open Access Journals (Sweden)

    Safari Wahyu Jatmiko

    2015-04-01

    Full Text Available Sel eosinofil merupakan jenis sel lekosit yang terlibat dalam berbagai patogenesis penyakit. Sel eosinofil pada awalnya dikenal sebagai sel efektor  dari sistem imunitas alamiah. Akan tetapi, kemampuan sel eosinofil dalam memfagositosis patogen menimbulkan dugaan bahwa sel eosinofil ikut berperan sebagai sel penyaji antigen. Hal ini dianalogikan dengan sel makrofag dan sel dendritik yang bisa memfagositosis dan menyajikan antigen sebagai hasil dari degradasi patogen yang difagositosis. Untuk menjawab permasalahan ini, penulis melakukan penelusuran artikel tentang eosinofil sebagai sel penyaji antigen melalui US National Library of Medicine National Institute of Healthdengan kata kunci eoshinophil dan antigen presenting cell. Hasil penelusuran adalah ditemukannya 10 artikel yang relevan dengan topik. Hasil dari sintesis kesepuluh jurnal tersebut adalah sel eosinofil mampu berperan sebagai sel penyaji antigen yang profesional (professionalantigenpresentng cell

  13. Leukocyte telomere dynamics in the elderly

    DEFF Research Database (Denmark)

    Steenstrup, Troels; Hjelmborg, Jacob V B; Mortensen, Laust Hvas

    2013-01-01

    of the Longitudinal Study of Aging Danish Twins. We measured LTL by Southern blots of the terminal restriction fragment length (TRFL) in 476 individuals (73-94 years) in a cross-sectional evaluation and in a subset of this cohort comprising 80 individuals (73-81 years at baseline) who were followed.......010). For the TRFL distribution, which captures telomeres of all lengths in the DNA sample, we observed significant shifts with age toward shorter telomeres. Based on the measurement error of the TRFLs, we computed that in the longitudinal evaluation 10.6 % of individuals would manifest LTL elongation over 10 years......, assuming a 340 bp attrition during this period. This was not significantly different from the empirical observation of 7.5 % of individuals showing LTL elongation. We conclude that accumulation of ultra-short telomeres in leukocytes of the elderly reflects a shift toward shorter telomeres in the entire...

  14. Association of leukocyte telomere length in peripheral blood leukocytes with endometrial cancer risk in Caucasian Americans.

    Science.gov (United States)

    Sun, Yuhui; Zhang, Liren; Zhao, Lina; Wu, Xifeng; Gu, Jian

    2015-11-01

    Telomeres are the protective structure at the ends of each chromosome and play an important role in maintaining genomic integrity. Interindividual variation of telomere length in peripheral blood leukocytes has been associated with the risks of developing many human diseases including several cancers. The association between leukocyte telomere length (LTL) and endometrial cancer risk is still inconsistent. Using a case-control study of endometrial cancer patients (n = 139) and control subjects (n = 139) in a Caucasian population, we assessed the association of relative LTL with the risk of endometrial cancer. We calculated odds ratios and 95% confidence intervals using multivariate logistic regression. We also determined the joint effects of LTL with established risk factors of endometrial cancer. The normalized LTL was significantly longer in endometrial cancer cases (median, 0.93; range, 0.19-1.62) than in controls (median, 0.70; range, 0.03-2.14) (P leukocytes is associated with a significantly increased risk of endometrial cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Maternal and fetal human leukocyte antigen class Ia and II alleles in severe preeclampsia and eclampsia

    DEFF Research Database (Denmark)

    Emmery, J.; Hachmon, R.; Pyo, C. W.

    2016-01-01

    and -DPB1) alleles and the risk of developing severe preeclampsia/eclampsia were investigated in a detailed and large-scale study. In total, 259 women diagnosed with severe preeclampsia or eclampsia and 260 matched control women with no preeclampsia, together with their neonates, were included in the study....... HLA genotyping for mothers and neonates was performed using next-generation sequencing. The HLA-DPB1*04:01:01G allele was significantly more frequent (Pc=0.044) among women diagnosed with severe preeclampsia/eclampsia compared with controls, and the DQA1*01:02:01G allele frequency was significantly...... lower (Pc=0.042) among newborns born by women with severe preeclampsia/eclampsia compared with controls. In mothers with severe preeclampsia/eclampsia, homozygosity was significantly more common compared with controls at the HLA-DPB1 locus (Pc=0.0028). Although the current large study shows some...

  16. Soluble human leukocyte antigen-G in seminal plasma is associated with HLA-G genotype

    DEFF Research Database (Denmark)

    Dahl, Mette; Perin, Trine L; Djurisic, Snezana

    2014-01-01

    PROBLEM: We have previously shown that human seminal plasma contains immunomodulatory soluble HLA-G (sHLA-G). We investigated whether sHLA-G levels in seminal plasma are associated with a specific 14 base pair (bp) insertion/deletion (ins/del) polymorphism in the 3'-untranslated region of the HLA......-G gene and/or with the outcome of assisted reproduction treatments (ART) in couples attending a fertility clinic. METHOD OF STUDY: In a total of 54 unselected couples, sHLA-G levels were measured in seminal plasma samples and blood samples, HLA-G genotyping was performed, and clinical data were collected...... for higher seminal plasma levels of sHLA-G/total protein and total sHLA-G in cases with reduced semen quality, where the female partner became pregnant after ART, compared with those couples in which no pregnancy was achieved. CONCLUSION: These first results are in accordance with a possible role of seminal...

  17. Study of the association between human leukocyte antigens (HLA) and pemphigus vulgaris in Brazilian patients.

    Science.gov (United States)

    Gil, Julio M; Weber, Raimar; Rosales, Claudia B; Rodrigues, Helcio; Sennes, Luiz U; Kalil, Jorge; Chagury, Azis; Miziara, Ivan D

    2017-05-01

    Pemphigus vulgaris is a mucocutaneous blistering autoimmune disease that manifests as painful blisters or erosions on the skin and/or mucosal surfaces. IgG autoantibodies target desmoglein, playing a major role in disease pathogenesis. Genetic predisposal to pemphigus vulgaris, especially the HLA DR and DQ alleles, has been known since the 1980s. The unique constitution of the Brazilian population favors exploratory genetic studies. The study group included 51 patients with a confirmed diagnosis of pemphigus vulgaris from a tertiary hospital in Sao Paulo city, Sao Paulo, southeast Brazil. DNA was extracted from peripheral blood, and HLA A, B, C, DR, and DQ typing was performed. The control group was composed of a database of 297 deceased donors from the city of São Paulo typed with the same method. The statistical significance level was adjusted using the Bonferroni correction depending on the phenotypic frequencies evaluated for HLA A, HLA B, HLA C, HLA DRB1, DQA1, and HLA DQB1. The alleles HLA-B*57, HLA-C*15, HLA-DRB1*04:02, HLA-DRB1*08:04, HLA-DRB1*14:01, DQA1*03:01, DQB1*03:02, and DQB1*05:03 were associated with susceptibility. Alleles HLA DRB1*04:02 and HLA-DRB1*14:01 and their respective haplotypes DRB1*04-DQA1*03:01-DQB1*03:02, and DRB1*14-DQA1*01:01-DQB1*05:03 conferred a risk of the disease. The DRB1*04:02 and DQB1*05:03 alleles are associated with pemphigus vulgaris in our study as well as in various populations. The association with HLA-DRB1*08:04 in our study was confirmed to be specific to this allele and not to linkage disequilibrium to any adjacent gene. The association between HLA-B*57 and pemphigus vulgaris is reported for the first time in the present study. © 2017 The International Society of Dermatology.

  18. Susceptibility to and severity of tuberculosis is genetically controlledby human leukocyte antigens

    International Nuclear Information System (INIS)

    Harfouch-Hammoud, Elham I.; Daher, Nizar A.

    2008-01-01

    Objective was to assess the role of HLA polymorphism in thesusceptibility to tuberculosis in Syria. We used the polymerase chainreaction with sequence specific primer method to study the DRB1* locus in 147Syrian patients with positive sputum smear or sputum culture forMycobacterium Tuberculosis strains, and 209 Syrian healthy matchingindividuals with negative tuberculin skin test. Patients were randomlyrecruited from Damascus Health Center of Tuberculosis and Pulmonary Diseasesduring 2005-2007. The study was carried out at the Laboratory for Researchand Genetic Consultations, in the Faculty of Medicine of Damascus University,Damascus, Syria. A significant decrease of the DRB1*11 allele was observed inpatients compared to controls (34.7% in patients versus 51% in control, oddsratio [OR] =0.51, p=0.003, corrected p=0.004), whereas the DRB1*04 allele wasincreased in patients (38.8% in patients versus 26.4% in controls, OR=1.77,p=0.01, corrected p>0.05). This increase became significant when individualswith DRB*11 allele were removed from both patients and controls (33% inDRB1*11 negative patients versus 17% in DRB1*11negative controls, OR=2.5,p=0.003, corrected p=0.003). In addition, pulmonary cavitation wassignificantly increased in the DRB1*04 positive patients compared to patientswithout the DRB1*04 allele (33% in DRB1*04 positive patients versus 16% inDRB1*04 negative patients, OR=2.7, p=0.04). The DRB1*04 allele is associatedwith susceptibility to pulmonary tuberculosis, whereas DRB1*11 is associatedwith protection from pulmonary tuberculosis in the Syrian population. Inaddition, cavity formation in patients with pulmonary tuberculosis seems tobe favored by presence of the DRB1*04 allele. (author)

  19. De nonklassiske humant leukocyt-antigen (HLA)-vaevstyper--fra implantation til transplantation

    DEFF Research Database (Denmark)

    Hviid, Thomas Vauvert F

    2006-01-01

    has a role in implantation. A very strong expression of HLA-G is observed in the invasive trophoblast cells in the placenta. HLA-G may be involved in certain complications of pregnancy and the genetic predisposition to these. Finally, HLA-G expression has been associated with a reduced risk...

  20. Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms.

    Directory of Open Access Journals (Sweden)

    Alienke J Monsuur

    Full Text Available BACKGROUND: The HLA genes, located in the MHC region on chromosome 6p21.3, play an important role in many autoimmune disorders, such as celiac disease (CD, type 1 diabetes (T1D, rheumatoid arthritis, multiple sclerosis, psoriasis and others. Known HLA variants that confer risk to CD, for example, include DQA1*05/DQB1*02 (DQ2.5 and DQA1*03/DQB1*0302 (DQ8. To diagnose the majority of CD patients and to study disease susceptibility and progression, typing these strongly associated HLA risk factors is of utmost importance. However, current genotyping methods for HLA risk factors involve many reactions, and are complicated and expensive. We sought a simple experimental approach using tagging SNPs that predict the CD-associated HLA risk factors. METHODOLOGY: Our tagging approach exploits linkage disequilibrium between single nucleotide polymorphism (SNPs and the CD-associated HLA risk factors DQ2.5 and DQ8 that indicate direct risk, and DQA1*0201/DQB1*0202 (DQ2.2 and DQA1*0505/DQB1*0301 (DQ7 that attribute to the risk of DQ2.5 to CD. To evaluate the predictive power of this approach, we performed an empirical comparison of the predicted DQ types, based on these six tag SNPs, with those executed with current validated laboratory typing methods of the HLA-DQA1 and -DQB1 genes in three large cohorts. The results were validated in three European celiac populations. CONCLUSION: Using this method, only six SNPs were needed to predict the risk types carried by >95% of CD patients. We determined that for this tagging approach the sensitivity was >0.991, specificity >0.996 and the predictive value >0.948. Our results show that this tag SNP method is very accurate and provides an excellent basis for population screening for CD. This method is broadly applicable in European populations.

  1. Human leukocyte antigens (HLA) associated with selective IgA deficiency in Iran and Sweden.

    Science.gov (United States)

    Mohammadi, Javad; Pourpak, Zahra; Jarefors, Sara; Saghafi, Shiva; Zendehdel, Kazem; Pourfathollah, Ali Akbar; Amirzargar, Ali Akbar; Aghamohammadi, Asghar; Moin, Mostafa; Hammarstrom, Lennart

    2008-12-01

    Selective IgA deficiency (IgAD) (serum IgA concentration of <0.07 g/l) is the most common primary immunodeficiency in Caucasians, with an estimated prevalence of 1/600. There are strong indications for involvement of genetic factors in development of the disease and the frequency of several extended major histocompatibility complex haplotypes (including HLA-A1, B8, DR3, DQ2) have previously been shown to be increased among Caucasian patients with IgAD.PCR was used to type HLA B, DR, and DQ alleles in 29 Iranian individuals with IgAD and 299 Swedish individuals with IgAD.The results indicate a strong association with the HLA B14, DR1 alleles in Iranian subjects and HLA B8, B12, B13, B14, B40, DR1, DR3, DR7, DQ2 and DQ5 alleles in Swedish subjects.Differences in HLA association of IgAD in Iran and Sweden confirm the notion of a genetic background of the disease and that multiple, potentially different genes within the MHC region might be involved in the pathogenesis of IgAD in different ethnic groups.

  2. Human Leukocyte Antigen-G and Regulatory T Cells during Specific Immunotherapy for Pollen Allergy

    DEFF Research Database (Denmark)

    Sørensen, Anja Elaine; Johnsen, Claus R; Dalgaard, Louise Torp

    2013-01-01

    Background: TH2-biased immune responses are important in allergy pathogenesis. Mechanisms of allergen-specific immunotherapy (SIT) might include the induction of regulatory T cells (Tregs) and immunoglobulin (Ig) G4 blocking antibodies, a reduction in the number of effector cells, and skewing...

  3. Association of human leukocyte antigen haplotypes with posttransplant lymphoproliferative disease after solid organ transplantation

    NARCIS (Netherlands)

    Subklewe, Marion; Marquis, Rene; Choquet, Sylvain; Leblond, Veronique; Garnier, Jeanne-Luce; Hetzer, Roland; Swinnen, Lode J.; Oertel, Stephan; Papp-Vary, Matthias; Gonzalez-Barca, Eva; Hepkema, Bouke G.; Schoenemann, Constanze; May, Juergen; Pezzutto, Antonio; Riess, Hanno

    2006-01-01

    Background. Posttransplant lymphoproliferative disease (PTLD) after solid organ transplantation (SOT) is commonly characterized by Epstein-Barr virus (EBV)-driven proliferation of recipient B cells due to impaired immune surveillance in the context of immunosuppression. Because EBV-specific T-cell

  4. An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity

    Directory of Open Access Journals (Sweden)

    Marcela V Maus

    2016-01-01

    Full Text Available Chimeric antigen receptors (CARs are synthetic receptors that usually redirect T cells to surface antigens independent of human leukocyte antigen (HLA. Here, we investigated a T cell receptor-like CAR based on an antibody that recognizes HLA-A*0201 presenting a peptide epitope derived from the cancer-testis antigen NY-ESO-1. We hypothesized that this CAR would efficiently redirect transduced T cells in an HLA-restricted, antigen-specific manner. However, we found that despite the specificity of the soluble Fab, the same antibody in the form of a CAR caused moderate lysis of HLA-A2 expressing targets independent of antigen owing to T cell avidity. We hypothesized that lowering the affinity of the CAR for HLA-A2 would improve its specificity. We undertook a rational approach of mutating residues that, in the crystal structure, were predicted to stabilize binding to HLA-A2. We found that one mutation (DN lowered the affinity of the Fab to T cell receptor-range and restored the epitope specificity of the CAR. DN CAR T cells lysed native tumor targets in vitro, and, in a xenogeneic mouse model implanted with two human melanoma lines (A2+/NYESO+ and A2+/NYESO−, DN CAR T cells specifically migrated to, and delayed progression of, only the HLA-A2+/NY-ESO-1+ melanoma. Thus, although maintaining MHC-restricted antigen specificity required T cell receptor-like affinity that decreased potency, there is exciting potential for CARs to expand their repertoire to include a broad range of intracellular antigens.

  5. Recovery and assessment of leukocytes from LR Express filters.

    Science.gov (United States)

    Wegehaupt, Abby K; Roufs, Ellen K; Hewitt, Cory R; Killian, Marisela L; Gorbatenko, Oxana; Anderson, Cynthia M; Killian, M Scott

    2017-09-01

    Leukocytes, or white blood cells, are used for a variety of investigational purposes and they offer advantages over laboratory-adapted cell lines. Leukocytes that are typically discarded by blood banks during the collection of red blood cells, platelets, and plasma can often be obtained for research use. However, the available leukocytes are frequently contained within a blood filtration device, such as the Terumo LR Express (TLRE) filter. In this study, procedures were evaluated for the ability to elute viable leukocytes from TLRE filters. The recovered leukocytes were assessed for composition, growth, and functionality. The large majority (>70%) of leukocytes were eluted with a single reverse-elution procedure and the recovered cells contained representative populations of the major leukocyte subsets. Purified T cells exhibited diverse T cell receptor repertoires, characteristic growth upon mitogen stimulation, and CD4 + T cells were able to support HIV-1 propagation. Purified monocytes were able to be differentiated into phenotypically characteristic populations of macrophages and dendritic cells. Overall, TLRE filters offer an attractive source of primary human cells for research and possibly clinical purposes. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  6. Leukocyte count and incidence of hospitalizations due to heart failure.

    Science.gov (United States)

    Engström, Gunnar; Melander, Olle; Hedblad, Bo

    2009-05-01

    Leukocyte concentration in blood is a classical marker of systemic inflammation. Whether high leukocyte counts are associated with incidence of heart failure (HF) is unknown. This population-based study explored whether the leukocyte concentrations were associated with incidence of hospitalizations due to HF. Leukocyte counts were measured in 16 940 men from the general population (mean age 44 years) without history of myocardial infarction or stroke. Incidence of hospitalizations due to HF (primary diagnosis) was monitored over 23 years of follow-up, in relation to quartiles of leukocytes. Subjects with myocardial infarction during follow-up were censored in the main analysis. During the follow-up, 436 men were hospitalized due to HF. Incidence of HF hospitalizations was increased in men with high leukocyte counts. After adjustments for confounding factors, the adjusted hazards ratio (HR, 95% CI) for HF hospitalization was 1.00 (reference), 1.26 (0.93 to 1.7), 1.24 (0.91 to 1.7), and 1.73 (1.3 to 2.3), respectively, for men with leukocytes in the 1st, 2nd, 3rd, and 4th (highest) quartiles (trend, Pleukocyte counts in middle-aged men were associated with increased long-term incidence of HF hospitalizations.

  7. Increased circulating leukocyte-derived microparticles in ischemic cerebrovascular disease.

    Science.gov (United States)

    He, Zhangping; Tang, Yanyan; Qin, Chao

    2017-06-01

    Circulating leukocyte-derived microparticles act as proinflammatory mediators that reflect vascular inflammation. In this study, we examined the hypothesis that the quantity of leukocyte-derived microparticles is increased in patients with ischemic cerebrovascular diseases, and investigated utility of various phenotypes of leukocyte-derived microparticles as specific biomarkers of vascular inflammation injury. Additionally we focused on identifying leukocyte-derived microparticles that may be correlated with stroke severity in acute ischemic stroke patients. The plasma concentration of leukocyte-derived microparticles obtained by a series of centrifugations of 76 consecutive patients with ischemic cerebrovascular diseases and 70 age-, sex-, and race-matched healthy controls were determined by flow cytometry. Significantly elevated numbers of leukocyte (CD45+), monocyte (CD14+), lymphocyte (CD4+), granulocyte (CD15+) derived microparticles were found in the plasma samples of patients ischemic cerebrovascular diseases, compared to healthy controls (pcerebrovascular diseases, compared with healthy controls. As proinflammatory mediators, leukocyte-derived microparticles may contribute to vascular inflammatory and the inflammatory process in acute ischemic stroke. Levels of CD14+ microparticles may be a promising biomarker of ischemic severity and outcome of stroke in the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Electrophoretic detection of protein p53 in human leukocytes

    International Nuclear Information System (INIS)

    Paponov, V.D.; Kupsik, E.G.; Shcheglova, E.G.; Yarullin, N.N.

    1986-01-01

    The authors have found an acid-soluble protein with mol. wt. of about 53 kD in peripheral blood leukocytes of persons with Down's syndrome. It was present in different quantities in all 20 patients tested, but was virtually not discovered in 12 healthy blood donors. This paper determines the possible identity of this protein with protein p53 from mouse ascites carcinoma by comparing their electrophoretic mobilities, because the accuracy of electrophoretic determination of the molecular weight of proteins is not sufficient to identify them. The paper also describes experiments to detect a protein with electrophoretic mobility identical with that of a protein in the leukocytes of patients with Down's syndrome in leukocytes of patients with leukemia. To discover if protein p53 is involved in cell proliferation, the protein composition of leukocytes from healthy blood donors, cultured in the presence and absence of phytohemagglutinin (PHA), was compared. Increased incorporation of H 3-thymidine by leukocytes of patients with Down's syndrome is explained by the presence of a population of immature leukocytes actively synthesizing DNA in the peripheral blood of these patients, and this can also explain the presence of protein p53 in the leukocytes of these patients

  9. Preparation and functional studies of hydroxyethyl chitosan nanoparticles loaded with anti-human death receptor 5 single-chain antibody

    Directory of Open Access Journals (Sweden)

    Yang J

    2014-05-01

    Full Text Available Jingjing Yang,1,3,* Xiaoping Huang,1,3,* Fanghong Luo,1 Xiaofeng Cheng,3 Lianna Cheng,3 Bin Liu,4 Lihong Chen,2 Ruyi Hu,1,3 Chunyan Shi,1,3 Guohong Zhuang,1,3 Ping Yin2 1Anti-Cancer Research Center, Medical College, Xiamen University, Fujian, People's Republic of China, 2The Department of Pathology, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China, 3Organ transplantation institution, Xiamen University, Xiamen, People's Republic of China, 4Jilin Vocational College of Industry and Technology, Jilin, People's Republic of China  *These authors contributed equally to this work Objective: To prepare hydroxyethyl chitosan nanoparticles loaded with anti-human death receptor 5 single-chain antibody, and study their characteristics, functions, and mechanisms of action. Materials and methods: The anti-human death receptor 5 single-chain antibody was constructed and expressed. Protein-loaded hydroxyethyl chitosan nanoparticles were prepared, and their size, morphology, particle-size distribution and surface zeta potential were measured by scanning electron microscopy and laser particle-size analysis. Mouse H22 hepatocellular carcinoma cells were cultured, and growth inhibition was examined using the CellTiter-Blue cell-viability assay. Flow cytometry and Hoechst 33342 were employed to measure cell apoptosis. Kunming mice with H22 tumor models were treated with protein-loaded hydroxyethyl chitosan nanoparticles, and their body weight and tumor size were measured, while hematoxylin and eosin staining was used to detect antitumor effects in vivo and side effects from tumors. Results: The protein-loaded hydroxyethyl chitosan nanoparticles had good stability; the zeta potential was -24.2±0.205, and the dispersion index was 0.203. The inhibition of the protein-loaded hydroxyethyl chitosan nanoparticles on H22 growth was both time- and dose-dependent. Increased expressions of active caspase 8, active caspase 3, and BAX were detected

  10. Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability

    Science.gov (United States)

    Palomba, R.; Parodi, A.; Evangelopoulos, M.; Acciardo, S.; Corbo, C.; De Rosa, E.; Yazdi, I. K.; Scaria, S.; Molinaro, R.; Furman, N. E. Toledano; You, J.; Ferrari, M.; Salvatore, F.; Tasciotti, E.

    2016-10-01

    Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability, and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are composed of a surface coating containing multiple receptors that are critical in the cross-talk with the endothelium, mediating cellular accumulation in the tumor microenvironment while decreasing vascular barrier function. We previously demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Herein, we provide a more comprehensive analysis of the working mechanism of LLV in vitro in activating this pathway and in vivo in enhancing vascular permeability. Our results suggest the biological activity of the leukocyte membrane can be retained upon transplant onto NPS and is critical in providing the particles with complex biological functions towards tumor vasculature.

  11. Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

    Directory of Open Access Journals (Sweden)

    Barja-Fidalgo C.

    2005-01-01

    Full Text Available Extracellular matrix proteins and cell adhesion receptors (integrins play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of the immune and inflammatory responses. The modulation of neutrophil activation through integrin-mediated pathways is important in the homeostatic control of the resolution of inflammatory states. In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects.

  12. Carcinoembryonic antigen (CEA)

    International Nuclear Information System (INIS)

    Ephraim, K.H.; Cox, P.H.; Hamer, C.J.A. v.d.; Berends, W.; Delhez, H.

    1977-01-01

    The carcinoembryonic antigen (CEA) is a complex of antigen determinants and also the carrier of these determinants. Chemically it is a glycoprotein. Its occurrence in blood serum or urine is correlated with malignant disease. Several radioimmunoassays (RIA) have been developed, one by Hoffmann-Laroche and one by the Rotterdam Radiotherapeutic Institute. Both methods and the Hoffmann assay kit are tested. Specifications are given for isolation of the antigen, preparation of the antiserum, and the execution of the RIA. Biochemical and clinical aspects are discussed

  13. Synthesis of Diethylpropione Derivatives and Their Leukocyte-Increasing Activities

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chung Gang; Sun, Yi Ping; Wang, Guo Ping; Tan, Xiang Duan [Guilin Medical University, Guilin (China)

    2014-09-15

    In search of new antileukopenia agents, twenty dithiolopyrrolone derivatives were synthesized and evaluated for their leukocyte-increasing activities in normal mice. Among the synthesized compounds 4-23, compounds 5 and 6 showed significant leukocyte-increasing activity ( p < 0.01), and compounds 4, 9 and 16 had a moderate effect ( p < 0.05). Compound 5 also displayed stronger leukocyte-increasing activity than that of the positive recombinant human granulocyte colony stimulating factor (rhG-CSF). Above all, compound 5 would be a potential antileukopenia agent which deserved further research.

  14. The anti-human trafficking collaboration model and serving victims: Providers' perspectives on the impact and experience.

    Science.gov (United States)

    Kim, Hea-Won; Park, Taekyung; Quiring, Stephanie; Barrett, Diana

    2018-01-01

    A coalition model is often used to serve victims of human trafficking but little is known about whether the model is adequately meeting the needs of the victims. The purpose of this study was to examine anti-human trafficking collaboration model in terms of its impact and the collaborative experience, including challenges and lessons learned from the service providers' perspective. Mixed methods study was conducted to evaluate the impact of a citywide anti-trafficking coalition model from the providers' perspectives. Web-based survey was administered with service providers (n = 32) and focus groups were conducted with Core Group members (n = 10). Providers reported the coalition model has made important impacts in the community by increasing coordination among the key agencies, law enforcement, and service providers and improving quality of service provision. Providers identified the improved and expanded partnerships among coalition members as the key contributing factor to the success of the coalition model. Several key strategies were suggested to improve the coalition model: improved referral tracking, key partner and protocol development, and information sharing.

  15. JC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants

    OpenAIRE

    Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens; Albrecht, Eva; Gieger, Christian; Khademi, Mohsen; Lima Bomfim, Izaura; Fogdell-Hahn, Anna; Link, Jenny; Alfredsson, Lars; Søndergaard, Helle Bach; Hillert, Jan; Oturai, Annette B; Hemme, Bernhard; Kockum, Ingrid

    2014-01-01

    JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA), ...

  16. JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants

    OpenAIRE

    Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens; Albrecht, Eva; Gieger, Christian; Khademi, Mohsen; Lima Bomfim, Izaura; Fogdell-Hahn, Anna; Link, Jenny; Alfredsson, Lars; Søndergaard, Helle Bach; Hillert, Jan; Oturai, Annette B.; Hemme, Bernhard; Kockum, Ingrid

    2014-01-01

    JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA), ...

  17. Polymorphonuclear leukocyte elastase in patients with stroke.

    Science.gov (United States)

    Vila, N; Elena, M; Deulofeu, R; Chamorro, A

    1999-12-01

    Polymorphonuclear leukocytes (PMNL) are involved in the pathogenesis of acute cerebral ischemia and atherosclerosis. Elastase is one of the proteolytic enzymes released by activated PMNL. We evaluated whether plasma levels of elastase-inhibitor complexes (EIC) are related to acute cerebral damage or with extension of carotid atherosclerosis in patients with stroke. Plasma levels of EIC were determined in 44 patients during acute and chronic phases of stroke. We recorded in all patients vascular risk factors, clinical severity on admission, infarct volume, and extension of carotid atherosclerosis using B-mode ultrasound exam. EIC levels were not different between acute and chronic phases of stroke. Eleven patients (25%) had increased values of EIC. On multiple regression analysis diabetes, dislipemia, and coronary disease were predictors of abnormal EIC levels. EIC levels were not related to neurological severity on admission, infarct volume, or carotid atherosclerosis. EIC levels in stroke patients are associated to the presence of vascular risk factors and may reflect cellular inflammatory aspects of chronic vessel disease. However, whether elastase contributes to the development of carotid atherosclerosis in patients with stroke remains unknown.

  18. Association between Snoring and Leukocyte Telomere Length.

    Science.gov (United States)

    Shin, Chol; Yun, Chang-Ho; Yoon, Dae Wui; Baik, Inkyung

    2016-04-01

    Data on the association between snoring and telomere length, an indicator of biological aging, are very limited. Moreover, no polysomnography (PSG) studies on this association in a general population have been conducted. Our study aimed to evaluate the association between snoring and leukocyte telomere length (LTL) using PSG and a questionnaire. A cross-sectional PSG study embedded in a population-based cohort from the Korean Genome Epidemiology Study was conducted in 2010-2013. During the same period, questionnaire-based interviews, blood collection, and relative LTL assays were conducted. A total of 887 Korean men and women aged 50-79 y with an apnea-hypopnea index (AHI) snoring during sleep (% time spent snoring) assessed by PSG was inversely associated with LTL even after adjusting for potential risk factors and AHI. In the linear regression association between tertiles of percentage of time spent snoring and log-transformed LTL, coefficient estimates (P value) were -0.076 (snoring status determined using PSG and questionnaire information, both primary snorers and those with mild sleep apnea (5 ≤ AHI snoring may influence telomere attrition independent of sleep apnea. © 2016 Associated Professional Sleep Societies, LLC.

  19. Leukocyte Telomere Length in Postmenopausal Women.

    Science.gov (United States)

    Jones, Holly J; Janson, Susan L; Lee, Kathryn A

    To compare leukocyte telomere length (LTL) by race and describe demographic, health, and psychosocial factors associated with LTL in postmenopausal women. Descriptive study with comparative analyses and correlations. Data were collected at the University of California-San Francisco, San Francisco Clinical and Translational Science Institute. Thirty-nine African American and White postmenopausal women between 58 and 65 years of age (mean age = 61.3 ± 1.83 years). Measures included demographics, blood pressure, anthropometrics, scores on the Perceived Stress Scale and the Center for Epidemiologic Studies-Depression, and blood samples for LTL. African American women (n = 14) had greater PSS-10 and CES-D scores, greater blood pressure, and greater body mass index than White women (n = 25; p stress (p = .036) were related to shorter LTL. Findings from this small sample support the association between age and LTL. The association between perceived stress, number of children, and shorter LTL in postmenopausal women requires further research and replication of findings in a larger, more diverse sample. Copyright © 2017 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

  20. Bayesian data analysis of the dynamics of rolling leukocytes

    Science.gov (United States)

    Moskopp, Mats Leif; Preuss, Roland; Deussen, Andreas; Chavakis, Triantafyllos; Dieterich, Peter

    2013-08-01

    The coordinated recruitment of leukocytes to sites of infection and inflammation is a central process of the immune system and proceeds in several steps. Here we focus on the dynamics of rolling leukocytes obtained from in vitro experiments. Trajectories of rolling leukocytes in small flow chambers are acquired with phase contrast microscopy under different levels of fluid shear stress and a variation of protein coatings of the (adhesive) surfaces. Bayesian data analysis of a random walk model including drift is applied to individual trajectories of leukocytes. The analysis allows the estimation of drift velocities and diffusion coefficients within an uncertainty of about 10% and shows a certain homogeneity of the cell groups. Drift velocities of cells saturate in spite of increasing fluid flow. In addition, the analysis reveals some correlated fluctuations of cells' translocations requiring a refinement of the stochastic model.

  1. Leukocyte depletion during cardiac operation : A new approach through the venous bypass circuit

    NARCIS (Netherlands)

    Gu, YJ; de Vries, AJ; Vos, P; Boonstra, PW; van Oeveren, W

    Background. Leukocyte depletion recently has been introduced for cardiac surgical patients to attenuate leukocyte-mediated inflammation and organ reperfusion injury. We evaluated the feasibility of a new leukocyte depletion method in which systemic leukocyte depletion is achieved through the venous

  2. Platelet-mediated adhesion facilitates leukocyte sequestration in hypoxia-reoxygenated microvessels.

    Science.gov (United States)

    Zheng, Senfeng; Cao, Yanting; Zhang, Wenjian; Liu, Honglin; You, Jia; Yin, Yiqing; Lou, Jinning; Li, Chenghui

    2016-03-01

    Leukocyte transendothelial migration and sequestration are two distinct outcomes following leukocyte adhesion to endothelium during ischemia-reperfusion injury, in which platelets may play a pivotal role. In the present study, we established an in vitro hypoxia-reoxygenation model to mimic ischemia-reperfusion injury and found platelet pre-incubation significantly increased leukocyte adhesion to endothelial cells after hyoxia-reoxygenation (over 67%). Blockade of endothelial-cell-expressed adhesion molecules inhibited leukocyte direct adhesion to endothelial cells, while platelet-mediated leukocyte adhesion was suppressed by blockade of platelet-expressed adhesion molecules. Further experiments revealed platelets acted as a bridge to mediate leukocyte adhesion, and platelet-mediated adhesion was the predominant pattern in the presence of platelets. However, platelet pre-incubation significantly suppressed leukocyte transendothelial migration after hypoxia-reoxygenation (over 31%), which could be aggravated by blockade of endothelial-cell-expressed adhesion molecules, but alleviated by blockade of platelet- expressed adhesion molecules. This would indicate that platelet-mediated adhesion disrupted leukocyte transendothelial migration. An in vivo mesenteric ischemia-reperfusion model demonstrated leukocyte transfusion alone caused mild leukocyte adhesion to reperfused vessels and subsequent leukocyte infiltration, while simultaneous leukocyte and platelet transfusion led to massive leukocyte adhesion and sequestration within reperfused microvessels. Our studies revealed platelets enhanced leukocyte adhesion to endothelial cells, but suppressed leukocyte transendothelial migration. Overall, this leads to leukocyte sequestration in hypoxia-reoxygenated microvessels.

  3. Leukodepletion blood filters: filter design and mechanisms of leukocyte removal.

    Science.gov (United States)

    Dzik, S

    1993-04-01

    Modern leukocyte removal filters have been developed after years of refinement in design. Current filters are composite filters in which synthetic microfiber material is prepared as a nonwoven web. The filter material may be surface modified to alter surface tension or charge to improve performance. The housing design promotes effective contact of blood with the filter material and decreases shear forces. The exact mechanisms by which these filters remove leukocytes from blood components are uncertain, but likely represent a combination of both physical and biological processes whose contributions to leukocyte removal are interdependent. Small-pore microfiber webs result in barrier phenomena that permit retention of individual cells and increase the total adsorptive area of the filter. Modifications in surface charge can increase or decrease cell attraction to the fibers. Optimum interfacial surface tensions between blood cells, plasma, and filter fibers not only permit effective blood flow through small fiber pores, but also facilitate cell contact with the material. Barrier retention is a common mechanism for all modern leukocyte-removal filters and applies to all leukocyte subtypes. Because barrier retention does not depend on cell viability, it is operative for cells of any age and will retain any nondeformable cell, including whole nuclei from lymphocytes or monocytes. Barrier retention is supplemented by retention by adhesion. RBCs, lymphocytes, monocytes, granulocytes, and platelets differ in their relative adhesiveness to filter fibers. Different adhesive mechanisms are used in filters designed for RBCs compared with filters designed for platelets. Although lymphocytes, monocytes, and granulocytes can adhere directly to filter fibers, the biological mechanisms underlying cell adhesion may differ for these cell types. These differences may depend on expression of cell adhesion molecules. In the case of filtration of fresh RBCs, platelet-leukocyte interaction

  4. MHC class I-presented tumor antigen appraisable for T-cell responses against ovarian cancer

    Directory of Open Access Journals (Sweden)

    Jing Yao Wang

    2015-08-01

    Full Text Available The purpose of this study is to assess whether MHC class I-presented tumor antigen is appraisable for T-cell responses against ovarian cancer. In ovarian cancer cell, human leukocyte antigen A2 (HLA-A2 associated with peptides was used to promote the activation of naive T cells so as to activate antigen-specific T cells. 7 or 4 patients were observed grade 1 or 2 injection site reactions, respectively. 5, 2 or 1 patients were observed grade 1, 2 or 3 pain reactions, respectively. 4 or 1 patients were observed grade 1 or 2 induration reactions. Total number mean value of patients experiencing response to the particular peptide was 7.73, and total number mean value of peptides to which the patients responded was 7.45. MHC class I-presented tumor antigen is appraisable for T-cell responses against ovarian cancer in China.

  5. Association between diabetes complications and leukocyte counts in Iranian patients

    Directory of Open Access Journals (Sweden)

    Moradi S

    2012-01-01

    Full Text Available Sedigheh Moradi1, Scott Reza Jafarian Kerman2, Farzaneh Rohani1, Fereshteh Salari21Endocrine and Metabolism Research Center (Firouzgar, Hemmat Campus, Tehran University of Medical Sciences, Tehran, Iran, 2Scientific Students Research Committee, Tehran University of Medical Sciences, Tehran, IranBackground: The long term complications of diabetes can be fatal. They are also renowned for being an economic burden. Previous studies have demonstrated a relationship between inflammatory markers and complications of diabetes. The objective of this study was to evaluate the relationship between leukocyte counts and these complications.Methods: The study included 184 patients diagnosed with type 2 diabetes. The study was carried out in Iran during 2007 and 2008. Data collected on the subjects were as follows: age, gender, weight, height, blood pressure, smoking history, lipid profile including low density lipoprotein (LDL, high density lipoprotein (HDL, total cholesterol, triglycerides, and leukocyte count, albuminuria, and retinopathy. Furthermore, information on cardiac history for 100 patients was collected. The subjects were split into two groups according to their leukocyte levels: low (≤7000/mm³ and high (>7000/mm³; and then analyzed by Student's t-test or Mann–Whitney U-test as appropriate.Results: The average leukocyte count in these patients was 7594 ± 1965/mm³. Leukocyte count was significantly different in patients with and without retinopathy and albuminuria (P < 0.0001. According to this analysis, a leukocyte count of 6750/mm³ with a sensitivity of 80.2% and a specificity of 56.4%, and a count of 7550/mm³ with a sensitivity of 63.2% and a specificity of 74.6% indicated at least one diabetes complication.Conclusion: An elevated leukocyte count even within the normal range was associated with chronic complications in type 2 diabetes.Keywords: leukocytes, diabetes complications, inflammation

  6. The effect of high antigen density on solid-phase radioimmunoassays for antibody regardless of immunoglobulin class

    International Nuclear Information System (INIS)

    Rubin, R.L.; Hardtke, M.A.; Carr, R.I.

    1980-01-01

    Human sera containing antibody to casein or to bovine serum albumin were used to assess the validity and utility of a solid-phase assay for quantitating antibody activity. Rabbit anti-human immunoglobulin radiolabeled with 125 I and capable of reacting with all human immunoglobulin classes was used to detect antibody bound to antigen immobilized to polystyrene tubes by a new covalent technique. This method results in very high antigen concentrations in highly stable association with polystyrene tubes. Kinetic and absorption studies demonstrated that low avidity antibodies are better detected when antigen is immobilized by the covalent method than when passively adsorbed. Conditions are described for minimizing artifactual interactions and for obtaining results similar to those obtained with conventional, liquid-phase assays. Failure to reach equilibrium in solid-phase assays and other problems are proposed to explain, in part, the inability to obtain a better correlation between solid- and liquid-phase immunoassays. (Auth.)

  7. Infusion of leukocytes from HLA haplo-identical familial donors as an adjuvant in the HLH-2004 protocol to treat the virus-associated adult hemophagocytic lymphohistiocytosis: a retrospective study of 26 patients.

    Science.gov (United States)

    Zhang, Hui; Dai, Zhiming; Yang, Nan; Wang, Jin; He, Aili; Wang, Jianli; Zhang, Yang; Meng, Shan; Wang, Baiyan; Sun, Rong; Zhang, Wanggang

    2018-02-01

    Adult hemophagocytic lymphohistiocytosis (HLH) is a fatal disease with poor survival and a limited role of drug therapies. To help to recognize virus and enhance survival, we infused leukocytes derived from human leukocyte antigen (HLA) haplo-identical familial donors to patients. We retrospectively investigated 26 adult virus-associated hemophagocytic syndrome (VAHS) patients' medical records from 2006-2017. Eleven of the 26 patients accepted relatives' derived leukocytes infusions in addition to drug therapies recommended in the HLH-2004 protocol. The leukocyte doses ranged from 0.75 to 3.30×10 8 per kilogram of body weight. The other 15 patients accepted immunosuppressive and supportive therapies referred to in the HLH-2004 protocol. We compared the treatment outcomes of the two groups of patients. Patients in the cell infusion group had a lower viral load (P = 0.023) and better laboratory results and prolonged overall survival (60.44 vs. 20.18 weeks, P = 0.047). A factor that might relate to overall survival is platelet count (P = 0.032), except for the leukocyte infusions (P = 0.012). For patients without acceptable donors, infusions of leukocytes from HLA haplo-identical familial donors could be a feasible treatment to prolong overall survival as an adjuvant to drug therapies.

  8. Physiological levels of testosterone kill salmonid leukocytes in vitro

    Science.gov (United States)

    Slater, C.H.; Schreck, C.B.

    1997-01-01

    Adult spring chinook salmon (Oncorhynchus tshawytscha) elaborate high plasma concentrations of testosterone during sexual maturation, and these levels of testosterone have been shown to reduce the salmonid immune response in vitro. Our search for the mechanism of testosterone's immunosuppressive action has led to the characterization of an androgen receptor in salmonid leukocytes. In the present study we examined the specific effects that testosterone had on salmonid leukocytes. Direct counts of viable leukocytes after incubation with and without physiological levels of testosterone demonstrate a significant loss of leukocytes in cultures exposed to testosterone. At least 5 days of contact with testosterone was required to produce significant immunosuppression and addition of a 'conditioned media' (supernatant from proliferating lymphocytes not exposed to testosterone) did not reverse the immunosuppressive effects of testosterone. These data lead us to conclude that testosterone may exert its immunosuppressive effects by direct action on salmonid leukocytes, through the androgen receptor described, and that this action leads to the death of a significant number of these leukocytes.

  9. Granulocytes: New Members of the Antigen-Presenting Cell Family

    Directory of Open Access Journals (Sweden)

    Ang Lin

    2017-12-01

    Full Text Available Granulocytes, the most abundant types of leukocytes, are the first line of defense against pathogen invasion. However, the plasticity and diversity of granulocytes have been increasingly revealed, especially with regard to their versatile functions in orchestrating adaptive immune responses. A substantial body of recent evidence demonstrates that granulocytes can acquire the function as antigen-presenting cells under pathological or inflammatory conditions. In addition, they can acquire surface expression of MHC class II and costimulatory molecules as well as T cell stimulatory behavior when cultured with selected cytokines. The classic view of granulocytes as terminally differentiated, short-lived phagocytes is therefore changing to phenotypically and functionally heterogeneous cells that are engaged in cross-talk with other leukocyte populations and provide an additional link between innate and adaptive immunity. In this brief review, we summarize the current knowledge on the antigen-presenting capacity of granulocyte subsets (neutrophils, eosinophils, and basophils. Underlying mechanisms, relevant physiological significance and potential controversies are also discussed.

  10. C-type natriuretic peptide inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of P-selectin expression

    Science.gov (United States)

    Scotland, Ramona S.; Cohen, Marc; Foster, Paul; Lovell, Matthew; Mathur, Anthony; Ahluwalia, Amrita; Hobbs, Adrian J.

    2005-10-01

    The multifaceted process of immune cell recruitment to sites of tissue injury is key to the development of an inflammatory response and involved in the pathogenesis of numerous cardiovascular disorders. We recently identified C-type natriuretic peptide (CNP) as an important endothelium-derived mediator that regulates vascular tone and protects against myocardial ischemia/reperfusion injury. Herein, we investigated whether CNP inhibits leukocyte recruitment and platelet aggregation and thereby exerts a potential antiinflammatory influence on the blood vessel wall. We assessed the effects of CNP on leukocyte-endothelial cell interactions in mouse mesenteric postcapillary venules in vivo in animals with high basal leukocyte activation (endothelial nitric oxide synthase knockout mice, eNOS-/-) or under acute inflammatory conditions (induced by interleukin-1 or histamine). CNP suppressed basal leukocyte rolling in eNOS-/- mice in a rapid, reversible, and concentration-dependent manner. These effects of CNP were mimicked by the selective natriuretic peptide receptor-C agonist cANF4-23. CNP also suppressed leukocyte rolling induced by IL-1 or histamine, inhibited platelet-leukocyte interactions, and prevented thrombin-induced platelet aggregation of human blood. Furthermore, analysis of human umbilical vein endothelial cells, leukocytes, and platelets revealed that CNP selectively attenuates expression of P-selectin. Thus, CNP is a modulator of acute inflammation in the blood vessel wall characterized by leukocyte and platelet activation. These antiinflammatory effects appear to be mediated, at least in part, via suppression of P-selectin expression. These observations suggest that endothelial CNP might maintain an anti-atherogenic influence on the blood vessel wall and represent a target for therapeutic intervention in inflammatory cardiovascular disorders. endothelium | natriuretic peptide receptor type C | atherosclerosis | thrombosis

  11. Cetuximab in combination with anti-human IgG antibodies efficiently down-regulates the EGF receptor by macropinocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene [Institute of Pathology, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Stang, Espen, E-mail: espsta@rr-research.no [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)

    2012-12-10

    The monoclonal antibody C225 (Cetuximab) blocks binding of ligand to the epidermal growth factor receptor (EGFR). In addition, it is known that incubation with C225 induces endocytosis of the EGFR. This endocytosis has previously been shown to be increased when C225 is combined with an additional monoclonal anti-EGFR antibody. However, the effects of antibody combinations on EGFR activation, endocytosis, trafficking and degradation have been unclear. By binding a secondary antibody to the C225-EGFR complex, we here demonstrate that a combination of antibodies can efficiently internalize and degrade the EGFR. Although the combination of antibodies activated the EGFR kinase and induced ubiquitination of the EGFR, the kinase activity was not required for internalization of the EGFR. In contrast to EGF-induced EGFR down-regulation, the antibody combination efficiently degraded the EGFR without initiating downstream proliferative signaling. The antibody-induced internalization of EGFR was found not to depend on clathrin and/or dynamin, but depended on actin polymerization, suggesting induction of macropinocytosis. Macropinocytosis may cause internalization of large membrane areas, and this could explain the highly efficient internalization of the EGFR induced by combination of antibodies. -- Highlight: Black-Right-Pointing-Pointer Cetuximab induced endocytosis of EGFR increases upon combination with anti-human IgG. Black-Right-Pointing-Pointer Antibody combination causes internalization of EGFR by macropinocytosis. Black-Right-Pointing-Pointer Antibody-induced internalization of EGFR is independent of EGFR kinase activity. Black-Right-Pointing-Pointer Antibody combination may have a zipper effect and cross-link EGFRs on neighboring cells.

  12. Cetuximab in combination with anti-human IgG antibodies efficiently down-regulates the EGF receptor by macropinocytosis

    International Nuclear Information System (INIS)

    Berger, Christian; Madshus, Inger Helene; Stang, Espen

    2012-01-01

    The monoclonal antibody C225 (Cetuximab) blocks binding of ligand to the epidermal growth factor receptor (EGFR). In addition, it is known that incubation with C225 induces endocytosis of the EGFR. This endocytosis has previously been shown to be increased when C225 is combined with an additional monoclonal anti-EGFR antibody. However, the effects of antibody combinations on EGFR activation, endocytosis, trafficking and degradation have been unclear. By binding a secondary antibody to the C225-EGFR complex, we here demonstrate that a combination of antibodies can efficiently internalize and degrade the EGFR. Although the combination of antibodies activated the EGFR kinase and induced ubiquitination of the EGFR, the kinase activity was not required for internalization of the EGFR. In contrast to EGF-induced EGFR down-regulation, the antibody combination efficiently degraded the EGFR without initiating downstream proliferative signaling. The antibody-induced internalization of EGFR was found not to depend on clathrin and/or dynamin, but depended on actin polymerization, suggesting induction of macropinocytosis. Macropinocytosis may cause internalization of large membrane areas, and this could explain the highly efficient internalization of the EGFR induced by combination of antibodies. -- Highlight: ► Cetuximab induced endocytosis of EGFR increases upon combination with anti-human IgG. ► Antibody combination causes internalization of EGFR by macropinocytosis. ► Antibody-induced internalization of EGFR is independent of EGFR kinase activity. ► Antibody combination may have a zipper effect and cross-link EGFRs on neighboring cells.

  13. Leukocyte-derived microparticles in vascular homeostasis.

    Science.gov (United States)

    Angelillo-Scherrer, Anne

    2012-01-20

    Leukocyte-derived microparticles (LMPs) may originate from neutrophils, monocytes/macrophages, and lymphocytes. They express markers from their parental cells and harbor membrane and cytoplasmic proteins as well as bioactive lipids implicated in a variety of mechanisms, maintaining or disrupting vascular homeostasis. When they carry tissue factor or coagulation inhibitors, they participate in hemostasis and pathological thrombosis. Both proinflammatory and anti-inflammatory processes can be affected by LMPs, thus ensuring an appropriate inflammatory response. LMPs also play a dual role in the endothelium by either improving the endothelial function or inducing an endothelial dysfunction. LMPs are implicated in all stages of atherosclerosis. They circulate at a high level in the bloodstream of patients with high atherothrombotic risk, such as smokers, diabetics, and subjects with obstructive sleep apnea, where their prolonged contact with the vessel wall may contribute to its overall deterioration. Numbering microparticles, including LMPs, might be useful in predicting cardiovascular events. LMPs modify the endothelial function and promote the recruitment of inflammatory cells in the vascular wall, necessary processes for the progression of the atherosclerotic lesion. In addition, LMPs favor the neovascularization within the vulnerable plaque and, in the ruptured plaque, they take part in coagulation and platelet activation. Finally, LMPs participate in angiogenesis. They might represent a novel therapeutic tool to reset the angiogenic switch in pathologies with altered angiogenesis. Additional studies are needed to further investigate the role of LMPs in cardiovascular diseases. However, large-scale studies are currently difficult to set up because microparticle measurement still requires elaborate techniques which lack standardization.

  14. Antigenic proteins of Helicobacter pylori of potential diagnostic value.

    Science.gov (United States)

    Khalilpour, Akbar; Santhanam, Amutha; Wei, Lee Chun; Saadatnia, Geita; Velusamy, Nagarajan; Osman, Sabariah; Mohamad, Ahmad Munir; Noordin, Rahmah

    2013-01-01

    Helicobacter pylori antigen was prepared from an isolate from a patient with a duodenal ulcer. Serum samples were obtained from culture-positive H. pylori infected patients with duodenal ulcers, gastric ulcers and gastritis (n=30). As controls, three kinds of sera without detectable H. pylori IgG antibodies were used: 30 from healthy individuals without history of gastric disorders, 30 from patients who were seen in the endoscopy clinic but were H. pylori culture negative and 30 from people with other diseases. OFF-GEL electrophoresis, SDS-PAGE and Western blots of individual serum samples were used to identify protein bands with good sensitivity and specificity when probed with the above sera and HRP-conjugated anti-human IgG. Four H. pylori protein bands showed good (≥ 70%) sensitivity and high specificity (98-100%) towards anti-Helicobacter IgG antibody in culture- positive patients sera and control sera, respectively. The identities of the antigenic proteins were elucidated by mass spectrometry. The relative molecular weights and the identities of the proteins, based on MALDI TOF/ TOF, were as follows: CagI (25 kDa), urease G accessory protein (25 kDa), UreB (63 kDa) and proline/pyrroline- 5-carboxylate dehydrogenase (118 KDa). These identified proteins, singly and/or in combinations, may be useful for diagnosis of H. pylori infection in patients.

  15. Evaluation of Activated Leukocyte Cell Adhesion Molecule as a Biomarker for Breast Cancer in Egyptian Patients

    International Nuclear Information System (INIS)

    El-Shepiny, M.S.E.M.

    2013-01-01

    In this study, serum activated leukocyte cell adhesion molecule (ALCAM) levels were evaluated in 41 primary breast cancer patients and 20 healthy females, and its diagnostic value was quantified, and compared with those of carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA). Also, its prognostic value was examined. Serum ALCAM levels were also evaluated before and after surgical treatment. Serum levels of ALCAM and CA 15-3 were significantly higher in breast cancer patients than healthy controls (P=0.002, P=0.043 respectively), but the difference in serum CEA levels did not reach statistical significance. Serum ALCAM levels had significant area under the curve (AUC) (P=0.002), but serum levels of CA 15-3 and CEA had nonsignificant AUCs, and various combinations between them did not result in any improvement. A significant association was found between serum levels of ALCAM and CEA with age and menopausal status in breast cancer patients. Non-significant difference was shown in serum levels of ALCAM, CA 15-3 and CEA before and after surgical treatment. In conclusion, this study suggests that serum ALCAM may represent a novel diagnostic bio marker for breast cancer

  16. Performance and reliability of five commercial enzyme-linked immunosorbent assay kits in screening for anti-human immunodeficiency virus antibody in high-risk subjects.

    OpenAIRE

    Ozanne, G; Fauvel, M

    1988-01-01

    Anti-human immunodeficiency virus enzyme-linked immunosorbent assay kits marketed by Electro-Nucleonics Inc. (ENI), Genetic Systems Corp. (GSC), Organon Teknika Inc. (OTI), Ortho Diagnostic Systems Inc. (ODSI), and Wellcome Diagnostics (WD) were evaluated by using 289 randomly selected serum samples from a high-risk population and 53 serum samples likely to produce false-positive results. The radioimmunoprecipitation assay was used as the reference test. Sensitivities ranged from 96.51% (ODSI...

  17. Heparan sulphate as a regulator of leukocyte recruitment in inflammation.

    Science.gov (United States)

    Kumar, Archana V; Katakam, Sampath K; Urbanowitz, Ann-Kathrin; Gotte, Martin

    2015-01-01

    A key event in inflammatory disease is the transendothelial recruitment of leukocytes from the circulation to the site of inflammation. Intense research in the past decades indicates that the polyanionic carbohydrate heparan sulphate (HS) modulates multiple steps in the leukocyte recruitment cascade. Leukocyte recruitment is initiated by endothelial cell activation and presentation of chemokines to rolling leukocytes, which, via integrin activation, results in adhesion and diapedesis through the vessel wall. Heparan sulfate proteoglycans (HSPGs) immobilize the chemokines on the luminal endothelial cells, rendering them more robust against mechanical or hydrodynamic perturbations. During inflammation, endothelial HSPGs serve as ligands to L-selectin on leukocytes, transport chemokines in a basolateral to apical direction across the endothelium, and present chemokines at the luminal surface of the endothelium to circulating cells. HSPGs also promote chemokine oligomerization, which influences chemokine receptor signaling. Furthermore, proteoglycans of the syndecan family are involved in modulating integrin-mediated tight adhesion of leukocytes to the endothelium. Creation of a chemokine gradient by a localized chemokine release influences the speed of leukocyte recruitment from the blood to the tissue by attracting crawling neutrophils to optimal sites for transmigration. The directionality of intraluminal crawling is thought to be influenced by both mechanotactic and haptotactic signals, which are modulated by HS-dependent signaling processes. Finally, diapedesis is influenced by HS regarding transendothelial chemokine gradient formation and integrin- CAM interactions, and further enhanced by heparanase-mediated degradation of the endothelial basement membrane. Overall, the multifunctional role of HS in inflammation marks it as a potential target of glycan-centered therapeutic approaches.

  18. 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

  19. Fetal antigen 2: an amniotic protein identified as the aminopropeptide of the alpha 1 chain of human procollagen type I

    DEFF Research Database (Denmark)

    Teisner, B; Rasmussen, H B; Højrup, P

    1992-01-01

    with the aminopropeptide of the alpha 1 chain of human procollagen type I as determined by nucleotide sequences. After oxidative procedures normally employed for radio-iodination (iodogen and chloramine-T), FA2 lost its immunoreactivity. An antigen which cross-reacted with polyclonal rabbit anti-human FA2 was demonstrated...... to that of FA2 in human skin. FA2 is a circulating form of the aminopropeptide of the alpha 1 chain of procollagen type I, and this is the first description of its isolation and structural characterization in humans. Udgivelsesdato: 1992-Dec...

  20. A high molecular weight melanoma-associated antigen-specific chimeric antigen receptor redirects lymphocytes to target human melanomas.

    Science.gov (United States)

    Burns, William R; Zhao, Yangbing; Frankel, Timothy L; Hinrichs, Christian S; Zheng, Zhili; Xu, Hui; Feldman, Steven A; Ferrone, Soldano; Rosenberg, Steven A; Morgan, Richard A

    2010-04-15

    Immunotherapy, particularly the adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL), is a very promising therapy for metastatic melanoma. Some patients unable to receive TIL have been successfully treated with autologous peripheral blood lymphocytes (PBL), genetically modified to express human leukocyte antigen (HLA) class I antigen-restricted, melanoma antigen-reactive T-cell receptors; however, substantial numbers of patients remain ineligible due to the lack of expression of the restricting HLA class I allele. We sought to overcome this limitation by designing a non-MHC-restricted, chimeric antigen receptor (CAR) targeting the high molecular weight melanoma-associated antigen (HMW-MAA), which is highly expressed on more than 90% of human melanomas but has a restricted distribution in normal tissues. HMW-MAA-specific CARs containing an antigen recognition domain based on variations of the HMW-MAA-specific monoclonal antibody 225.28S and a T-cell activation domain based on combinations of CD28, 4-1BB, and CD3zeta activation motifs were constructed within a retroviral vector to allow stable gene transfer into cells and their progeny. Following optimization of the HMW-MAA-specific CAR for expression and function in human PBL, these gene-modified T cells secreted cytokines, were cytolytic, and proliferated in response to HMW-MAA-expressing cell lines. Furthermore, the receptor functioned in both CD4(+) and CD8(+) cells, was non-MHC restricted, and reacted against explanted human melanomas. To evaluate this HMW-MAA-specific CAR in patients with metastatic melanoma, we developed a clinical-grade retroviral packaging line. This may represent a novel means to treat the majority of patients with advanced melanoma, most notably those unable to receive current ACT therapies. (c)2010 AACR.

  1. A natural sulfated polysaccharide, calcium spirulan, isolated from Spirulina platensis: in vitro and ex vivo evaluation of anti-herpes simplex virus and anti-human immunodeficiency virus activities.

    Science.gov (United States)

    Hayashi, K; Hayashi, T; Kojima, I

    1996-10-10

    A sulfated polysaccharide named calcium spirulan (Ca-SP) has been isolated from a sea alga, Spirulina platensis, as an antiviral component. The anti-human immunodeficiency virus type 1 (HIV-1) and anti-herpes simplex virus type 1 (HSV-1) activities of Ca-SP were compared with those of dextran sulfate (DS) as a representative sulfated polysaccharide. Anti-HIV-1 activities of these agents were measured by three different assays: viability of acutely infected CD4-positive cells, or a cytopathology assay; determination of HIV-1 p24 antigen released into culture supernatants; and inhibition of HIV-induced syncytium formation. Anti-HSV-1 activity was assessed by plaque yield reduction. In addition, their effects on the blood coagulation processes and stability in the blood were evaluated. These data indicate that Ca-SP is a potent antiviral agent against both HIV-1 and HSV-1. Furthermore, Ca-SP is quite promising as an anti-HIV agent because even at low concentrations of Ca-SP an enhancement of virus-induced syncytium formation was not observed, as was observed in DS-treated cultures, Ca-SP had very low anticoagulant activity, and showed a much longer half-life in the blood of mice when compared with that of DS. Thus, Ca-SP can be a candidate agent for an anti-HIV therapeutic drug that might overcome the disadvantages observed in many sulfated polysaccharides. When the role of chelation of calcium ion with sulfate groups was examined by removing calcium or its replacement by sodium, the presence of calcium ion in the molecule was shown to be essential for the dose-dependent inhibition of cytopathic effect and syncytium formation induced by HIV-1.

  2. Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation.

    Science.gov (United States)

    Schnoor, Michael; Alcaide, Pilar; Voisin, Mathieu-Benoit; van Buul, Jaap D

    2015-01-01

    Leukocyte extravasation is one of the essential and first steps during the initiation of inflammation. Therefore, a better understanding of the key molecules that regulate this process may help to develop novel therapeutics for treatment of inflammation-based diseases such as atherosclerosis or rheumatoid arthritis. The endothelial adhesion molecules ICAM-1 and VCAM-1 are known as the central mediators of leukocyte adhesion to and transmigration across the endothelium. Engagement of these molecules by their leukocyte integrin receptors initiates the activation of several signaling pathways within both leukocytes and endothelium. Several of such events have been described to occur during transendothelial migration of all leukocyte subsets, whereas other mechanisms are known only for a single leukocyte subset. Here, we summarize current knowledge on regulatory mechanisms of leukocyte extravasation from a leukocyte and endothelial point of view, respectively. Specifically, we will focus on highlighting common and unique mechanisms that specific leukocyte subsets exploit to succeed in crossing endothelial monolayers.

  3. Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation

    Directory of Open Access Journals (Sweden)

    Michael Schnoor

    2015-01-01

    Full Text Available Leukocyte extravasation is one of the essential and first steps during the initiation of inflammation. Therefore, a better understanding of the key molecules that regulate this process may help to develop novel therapeutics for treatment of inflammation-based diseases such as atherosclerosis or rheumatoid arthritis. The endothelial adhesion molecules ICAM-1 and VCAM-1 are known as the central mediators of leukocyte adhesion to and transmigration across the endothelium. Engagement of these molecules by their leukocyte integrin receptors initiates the activation of several signaling pathways within both leukocytes and endothelium. Several of such events have been described to occur during transendothelial migration of all leukocyte subsets, whereas other mechanisms are known only for a single leukocyte subset. Here, we summarize current knowledge on regulatory mechanisms of leukocyte extravasation from a leukocyte and endothelial point of view, respectively. Specifically, we will focus on highlighting common and unique mechanisms that specific leukocyte subsets exploit to succeed in crossing endothelial monolayers.

  4. Contour Detection of Leukocyte Cell Nucleus Using Morphological Image

    Science.gov (United States)

    Supriyanti, R.; Satrio, G. P.; Ramadhani, Y.; Siswandari, W.

    2017-04-01

    Leukocytes are blood cells that do not contain color pigments. Leukocyte function to the tool body’s defenses. Abnormal forms of leukocytes can be a sign of serious diseases such example is leukemia. Most laboratories still use cell morphology examination to assist the diagnosis of illness associated with white blood cells such example is leukemia because of limited resources, both infrastructure, and human resources as happens in developing nations, such as Indonesia. This examination is less expensive and quicker process. However, morphological review requires the expertise of a specialist clinical pathology were limited. This process is sometimes less valid cause in some cases trying to differentiate morphology blast cells into the type of myoblasts, lymphoblast, monoblast, or erythroblast thus potentially misdiagnosis. The goal of this research is to develop a detection device types of blood cells automatically as lower-priced, easy to use and accurate so that the tool can be distributed across all units in existing health services throughout Indonesia and in particular for remote areas. However, because the variables used in the identification of abnormal leukocytes are very complex, in this paper, we emphasize on the contour detection of leukocyte cell nucleus using the morphological image. The results show that this method is promising for further development.

  5. A monkey antigen crossreacting with carcinoembryonic antigen, CEA.

    Science.gov (United States)

    Engvall, E.; Vuento, M.; Ruoslahti, E.

    1976-01-01

    Normal monkey tissues were found to contain an antigen which crossreacts immunologically with the carcinoembryonic antigen (CEA) of the human digestive tract. The monkey antigen reacted with complete or partial identity to the normal crossreacting antigen (NCA) in humans when tested in immunodiffusion against anti-CEA or anti-NCA. Extracts of monkey tissues inhibited in radioimmunoassays measuring human NCA. It is possible that monkey foetuses and colonic tumours contain CEA. Images Fig. 1 PMID:823952

  6. Antigen smuggling in tuberculosis.

    Science.gov (United States)

    Hudrisier, Denis; Neyrolles, Olivier

    2014-06-11

    The importance of CD4 T lymphocytes in immunity to M. tuberculosis is well established; however, how dendritic cells activate T cells in vivo remains obscure. In this issue of Cell Host & Microbe, Srivastava and Ernst (2014) report a mechanism of antigen transfer for efficient activation of antimycobacterial T cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 58, č. 6 (2001), s. 425-430 ISSN 0001-2815. [Conference on Human leucocyte differentiation antigens /7./. Harrogate, 20.06.2000-25.06.2000] Institutional research plan: CEZ:AV0Z5052915 Keywords : CD molecules, HLDA Subject RIV: EC - Immunology Impact factor: 2.864, year: 2001

  8. CD antigens 2002

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2002-01-01

    Roč. 99, č. 10 (2002), s. 3877-3880 ISSN 0006-4971. [Conference on Human leucocyte differentiation antigens /7./. Harrogate, 20.06.2000-25.06.2000] Institutional research plan: CEZ:AV0Z5052915 Keywords : CD molecules, HLDA Subject RIV: EC - Immunology Impact factor: 9.631, year: 2002

  9. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2002-01-01

    Roč. 168, č. 5 (2002), s. 2083-2086 ISSN 0022-1767. [Conference on Human leucocyte differentiation antigens /7./. Harrogate, 20.06.2000-25.06.2000] Institutional research plan: CEZ:AV0Z5052915 Keywords : CD molecules, HLDA Subject RIV: EC - Immunology Impact factor: 7.014, year: 2002

  10. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2002-01-01

    Roč. 15, č. 1 (2002), s. 71-76 ISSN 0893-3952. [Conference on Human leucocyte differentiation antigens /7./. Harrogate, 20.06.2000-25.06.2000] Institutional research plan: CEZ:AV0Z5052915 Keywords : CD molecules, HLDA Subject RIV: EC - Immunology Impact factor: 3.821, year: 2002

  11. β-endorphin antigen

    International Nuclear Information System (INIS)

    1981-01-01

    This invention relates to the production of antigens comprising β-endorphin, βsub(h)-endorphin, or βsub(c)-endorphin, in covalent conjugation with human gammaglobulin as immunogenic carrier material, and an antibody having the property of specifically binding β-endorphin or fragments thereof, containing the (6-15) residue sequence. (U.K.)

  12. Improving diagnosis of appendicitis. Early autologous leukocyte scanning.

    Science.gov (United States)

    DeLaney, A R; Raviola, C A; Weber, P N; McDonald, P T; Navarro, D A; Jasko, I

    1989-10-01

    A prospective nonrandomized study investigating the accuracy and utility of autologous leukocyte scanning in the diagnosis of apendicitis was performed. One hundred patients in whom the clinical diagnosis of appendicitis was uncertain underwent indium 111 oxyquinoline labelling of autologous leukocytes and underwent scanning 2 hours following reinjection. Of 32 patients with proved appendicitis, three scans revealed normal results (false-negative rate, 0.09). Of 68 patients without appendicitis, three scans had positive results (false-positive rate, 0.03; sensitivity, 0.91; specificity, 0.97; predictive value of positive scan, 0.94; predictive value of negative scan, 0.96; and overall accuracy, 0.95). Scan results altered clinical decisions in 19 patients. In 13 cases, the scan produced images consistent with diagnoses other than appendicitis, expediting appropriate management. Early-imaging111 In oxyquinoline autologous leukocyte scanning is a practical and highly accurate adjunct for diagnosing appendicitis.

  13. [Effect of ZL-004 on raising leukocyte count].

    Science.gov (United States)

    Sun, Hai-Yan; Li, Chun-Gang; Xiao, Lin; Wang, Guo-Ping; Liu, Quan-Hai

    2010-06-01

    This study is to investigate the effect of ZL-004 on normal mouse and mice with leukopenia induced by chemotherapeutic agents. 5-Fluorouracil were administered intraperitoneally to mice to develop leucopenia, and the mice were treated with ZL-004. The number of peripheral leukocytes and the percentage of granulocyte in total WBC were examined. The results are that ZL-004 markedly raise peripheral blood leukocytes in the normal mice and the mice model of leukopenia. So, ZL-004 could protect mice against 5-fluorouracil damage and raise peripheral blood leukocyte. Features of bone marrow smears is myeloproliferative hyperactivity in the mice, particularly the matured granulocytic series were observed. The mechanism of ZL-004 is to act on the mouse bone marrow causing proliferation and differentiation.

  14. Microchannel acoustophoresis does not impact survival or function of microglia, leukocytes or tumor cells.

    Directory of Open Access Journals (Sweden)

    Miguel A Burguillos

    Full Text Available The use of acoustic forces to manipulate particles or cells at the microfluidic scale (i.e. acoustophoresis, enables non-contact, label-free separation based on intrinsic cell properties such as size, density and compressibility. Acoustophoresis holds great promise as a cell separation technique in several research and clinical areas. However, it has been suggested that the force acting upon cells undergoing acoustophoresis may impact cell viability, proliferation or cell function via subtle phenotypic changes. If this were the case, it would suggest that the acoustophoresis method would be a less useful tool for many cell analysis applications as well as for cell therapy.We investigate, for the first time, several key aspects of cellular changes following acoustophoretic processing. We used two settings of ultrasonic actuation, one that is used for cell sorting (10 Vpp operating voltage and one that is close to the maximum of what the system can generate (20 Vpp. We used microglial cells and assessed cell viability and proliferation, as well as the inflammatory response that is indicative of more subtle changes in cellular phenotype. Furthermore, we adapted a similar methodology to monitor the response of human prostate cancer cells to acoustophoretic processing. Lastly, we analyzed the respiratory properties of human leukocytes and thrombocytes to explore if acoustophoretic processing has adverse effects.BV2 microglia were unaltered after acoustophoretic processing as measured by apoptosis and cell turnover assays as well as inflammatory cytokine response up to 48 h following acoustophoresis. Similarly, we found that acoustophoretic processing neither affected the cell viability of prostate cancer cells nor altered their prostate-specific antigen secretion following androgen receptor activation. Finally, human thrombocytes and leukocytes displayed unaltered mitochondrial respiratory function and integrity after acoustophoretic processing

  15. In Vivo Quantitation of Local Anesthetic Suppression of Leukocyte Adherence

    Science.gov (United States)

    Giddon, D. B.; Lindhe, J.

    1972-01-01

    Using intravital microscopy, topically applied amide-type local anesthetics suppressed the adherence of leukocytes to the venular endothelium within surgical defects in the hamster cheek pouch. The response was reversible with physiologic saline and was localized to venules within the defect. Quantitation in terms of the percent of initially adhering leukocytes remaining in place on the venule wall at each minute following application of lidocaine and physiologic saline, respectively, revealed the suppression to be reliably related to the concentration, viz: 20.0 >10.0 >5.0 >0.0 mg ml of commercially available Xylocaine® (lidocaine) HCl. ImagesFig 1Fig 1 PMID:5049429

  16. Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties.

    Science.gov (United States)

    Godlewska, Marlena; Arczewska, Katarzyna D; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław; Czarnocka, Barbara

    2017-01-01

    Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism.

  17. The Effect of Hemiscorpius lepturus (Scorpionida: Hemiscorpiidae Venom on Leukocytes and the Leukocyte Subgroups in Peripheral Blood of Rat

    Directory of Open Access Journals (Sweden)

    Mehri Ghafourian

    2016-01-01

    Full Text Available Background: The aim of this study was to investigate the effect of Hemiscorpius lepturus venom on leukocytes and the leukocyte subgroups in peripheral blood of rat.Methods: In this experimental study, sixty N-Mari rats were divided into three groups of 20 rats. Then the rats in each group were divided into four subgroups based on the blood sampling time that was 2, 6, 24 and 48 hours after the venom injection, respectively. The control group did not receive anything, however, the first and the second ex­perimental groups received 0.1 and 0.01mg/kg of venom, subcutaneously. In accordance with a designated four sam­pling times, the blood sampling was carried out in three groups. After RBC lysis, the leukocytes and leukocyte sub­populations were determined and counted using appropriate hematological standard methods.Results: The leukocyte and the neutrophil count at two (P<0.05, six (P<0.01 and 24 (P<0.05 hours after the venom injection showed a significant decline compared with the control group, this decrease was significant at the dose of 0.1 mg/kg until 48 hours after the venom injection (P<0.05. The lymphocyte count showed a significant decline throughout the all hours of the experiment, compared with the control group (P<0.05.Conclusion: Leukocytes are probably affected by the cytotoxicity effect of the H. lepturus venom in a dose-dependent manner. This could be a wakeup call for the medical staff to perform quick and accurate treatment in the least time possible.

  18. Leukocyte scintigraphy with 99mTc-exametazime-labeled leukocytes is not useful for follow-up of systemic vasculitis

    International Nuclear Information System (INIS)

    Staudenherz, A.; Kletter, K.; Deicher, R.; Haas, M.; Hoerl, W.H.; Jilma, B.; Becherer, A.; Dudczak, R.

    2002-01-01

    Background: The prognosis of systemic vasculitis, for instance Wegener's granulomatosis (WG), was greatly improved by the introduction of immunosuppressive treatment. However, relapses are frequent and predictors are scarce. 111 In-leukocytes have been found to indicate unknown manifestations of WG and to predict later relapse. We prospectively investigated the value of 99m Tc-Exametazime ( 99m Tc-HMPAO)-labeled leukocytes with regard to specific patterns and for their usefulness in the follow-up of patients with WG. Methods: The vasculitis group consisted of 8 patients with WG and 2 with idiopathic necrotizing glomerulonephritis (ING). Seven patients with different inflammatory diseases served as controls. Leukocyte labeling with 99m Tc-HMPAO was done using a slightly modified Hammersmith protocol. Cell viability after labeling was verified in vivo by the exclusion of early lung and splenic uptake and in vitro by means of propidium iodide and FACS analysis. Static gamma camera images from the head, chest, abdomen, and pelvis were obtained up to 18 hours after injection of approximately 300 MBq 99m Tc-HMPAO-labeled leukocytes. Scintigrams were analyzed visually; for semiquantitative analysis ROIs were drawn over the nasal region, the right lung, kidneys, and liver. Results: Increased nasal leukocyte accumulation was found in 7/8 patients with WG and in 2/2 patients with ING. Of 2 patients who had a relapse 6 months later, one presented with, and one without nasal uptake. The kidney/liver ratio was higher in controls (0.24 ± 0.07 vs. 0.37 ± 0.11, p 99m Tc-HMPAO leukocyte scintigraphy failed to indicate or exclude a later relapse and is therefore not suitable as a diagnostic tool in the management of patients with systemic vasculitis. (author)

  19. Leukocyte scintigraphy with 99mTc-exametazime-labeled leukocytes is not useful for follow-up of systemic vasculitis

    International Nuclear Information System (INIS)

    Becherer, A.; Dudczak, R.; Deicher, R.; Haas, M.; Hoerl, W.H.; Jilma, B.; Staudenherz, A.; Kletter, K.

    2002-01-01

    The prognosis of systemic vasculitis, for instance Wegener's granulomatosis (WG), was greatly improved by the introduction of immunosuppressive treatment. However, relapses are frequent and predictors are scarce. 111 In-leukocytes have been found to indicate unknown manifestations of WG and to predict later relapse. We prospectively investigated the value of 99m Tc-Exametazime ( 99m Tc-HMPAO)-labeled leukocytes with regard to specific patterns and for their usefulness in the follow-up of patients with WG. The vasculitis group consisted of 8 patients with WG and 2 with idiopathic necrotizing glomerulonephritis (ING). Seven patients with different inflammatory diseases served as controls. Leukocyte labeling with 99m Tc-HMPAO was done using a slightly modified Hammersmith protocol. Cell viability after labeling was verified in vivo by the exclusion of early lung and splenic uptake and in vitro by means of propidium iodide and FACS analysis. Static gamma camera images from the head, chest, abdomen, and pelvis were obtained up to 18 hours after injection of approximately 300 MBq 99m Tc-HMPAO-labeled leukocytes. Scintigrams were analyzed visually; for semiquantitative analysis ROls were drawn over the nasal region, the right lung, kidneys, and liver. Increased nasal leukocyte accumulation was found in 7/8 patients with WG and in 2/2 patients with ING. Of 2 patients who had a relapse 6 months later, one presented with, and one without nasal uptake. The kidney/liver ratio was higher in controls (0.24 ± 0.07 vs. 0.37 ± 0.11, p 99m Tc-HMPAO leukocyte scintigraphy failed to indicate or exclude a later relapse and is therefore not suitable as a diagnostic tool in the management of patients with systemic vasculitis. (author)

  20. Human platelet antigens - 2013.

    Science.gov (United States)

    Curtis, B R; McFarland, J G

    2014-02-01

    To date, 33 human platelet alloantigens (HPAs) have been identified on six functionally important platelet glycoprotein (GP) complexes and have been implicated in alloimmune platelet disorders including foetal and neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura (PTP) and multitransfusion platelet refractoriness (MPR). The greatest number of recognized HPA (20 of 33) resides on the GPIIb/IIIa complex, which serves as the receptor for ligands important in mediating haemostasis and inflammation. These include HPA-1a, the most commonly implicated HPA in FNAIT and PTP in Caucasian populations. Other platelet GP complexes, GPIb/V/IX, GPIa/IIa and CD109, express the remaining 13 HPAs. Of the recognized HPAs, 12 occur as six serologically and genetically defined biallelic 'systems' where the -a form designates the higher frequency allele and the -b form, the lower. Twenty-one other HPAs are low-frequency or rare antigens for which postulated higher frequency -a alleles have not yet been identified as antibody specificities. In addition to the HPA markers, platelets also express ABO and human leucocyte antigen (HLA) antigens; antibodies directed at the former are occasionally important in FNAIT, and to the latter, in MPR. © 2013 International Society of Blood Transfusion.

  1. Detection of Avian Antigen-Specific T Cells Induced by Viral Vaccines

    DEFF Research Database (Denmark)

    Dalgaard, Tina Sørensen; Norup, Liselotte Rothmann; Juul-Madsen, Helle Risdahl

    2016-01-01

    Live attenuated viral vaccines are widely used in commercial poultry production, but the development of new effective inactivated/subunit vaccines is needed. Studies of avian antigen-specific T cells are primarily based on analyses ex vivo after activating the cells with recall antigen....... There is a particular interest in developing robust high-throughput assays as chicken vaccine trials usually comprise many individuals. In many respects, the avian immune system differs from the mammalian, and T cell assessment protocols must be adjusted accordingly to account for, e.g., differences in leukocyte...... in the cells even throughout division. This leads to daughter cells containing half the fluorescence of their parents. When lymphocytes are loaded with CFSE prior to ex vivo stimulation with specific antigen, the measurement of serial halving of its fluorescence by flow cytometry identifies the cells...

  2. Roflumilast inhibits leukocyte-platelet interactions and prevents the prothrombotic functions of polymorphonuclear leukocytes and monocytes.

    Science.gov (United States)

    Totani, L; Amore, C; Di Santo, A; Dell'Elba, G; Piccoli, A; Martelli, N; Tenor, H; Beume, R; Evangelista, V

    2016-01-01

    ESSENTIALS: Thrombosis is a major comorbidity in patients with chronic obstructive pulmonary disease (COPD). Roflumilast is a selective phosphodiesterase type-4 (PDE4) inhibitor approved for treatment of severe COPD. PDE4 blockade by roflumilast inhibits prothrombotic functions of neutrophils and monocytes. PDE4 inhibitors may reduce thrombotic risk in COPD as well as in other vascular diseases. Roflumilast, an oral selective phosphodiesterase type 4 inhibitor, is approved for the treatment of severe chronic obstructive pulmonary disease (COPD). A recent meta-analysis of trials on COPD revealed that treatment with roflumilast was associated with a significant reduction in the rate of major cardiovascular events. The mechanisms of this effect remain unknown. We tested the hypothesis that roflumilast N-oxide (RNO), the active metabolite of roflumilast, curbs the molecular mechanisms required for leukocyte-platelet (PLT) interactions and prevents the prothrombotic functions of polymorphonuclear leukocytes (PMNs) and monocytes (MNs). Using well-characterized in vitro models, we analysed the effects of RNO on: (i) PMN adhesiveness; (ii) the release of neutrophil extracellular traps (NETs); and (iii) tissue factor expression in MNs. Key biochemical events underlying the inhibitory effects of RNO were defined. In PMNs, RNO prevented phosphoinositide 3-kinase (PI3K)-dependent phosphorylation of Akt on Ser473, and Src family kinase (SFK)-mediated Pyk2 phosphorylation on Tyr579-580, while inducing protein kinase A-mediated phosphorylation of C-terminal Src kinase, the major negative regulator of SFKs. Modulation of these signaling pathways by RNO resulted in a significant impairment of PMN adhesion to activated PLTs or human umbilical vein endothelial cells, mainly mediated by inhibition of the adhesive function of Mac-1. Moreover RNO curbed SFK/PI3K-mediated NET release by PMNs adherent on fibrinogen-coated surfaces. In MNs interacting with activated PLTs, RNO curbed PI3K

  3. Leukocyte depletion results in improved lung function and reduced inflammatory response after cardiac surgery

    NARCIS (Netherlands)

    Gu, YJ; Boonstra, PW; vanOeveren, W

    Leukocyte depletion during cardiopulmonary bypass has been demonstrated in animal experiments to improve pulmonary function, Conflicting results have been reported, however, with clinical depletion by arterial line filter of leukocytes at the beginning of cardiopulmonary bypass. In this study, we

  4. Study on immobilizations of ovine anti-human IgG and MCAb against EHF on radiation-modified silicone films

    International Nuclear Information System (INIS)

    Guo Jinhui; Ha Hongfei; Zhang Yuhua

    1990-01-01

    Films of silicone (silastic) were grafted by monomer acrylamide vis γ-radiation technology and then the ovine anti-human IgG, Epidemic hemorrhagic fever (EHF)-MCAb were immobilized on the silastic-AAM films with different grafting yields passthrough associate reactions. Measruements of relationships between grafting yields. Contents of immobilized antibodies and immunoactivities for immobilized silastic-AAM films were performed by using 125 I method ELISA method was used to measure the immunoactivities for the immobilized monoantibody. The results showed that the antibodies used can be immobilized on radiation-grafted silicone films and this immobilization method has its potential significance in clinical practice

  5. Changes In Peripheral Leukocyte And Body Fluids Of ...

    African Journals Online (AJOL)

    This study evaluated the peripheral leukocyte count and the presence of microfilariae in the body fluids of onchocerciasis patients treated with ivermectin. Fifty-three patients over the age 10 years were selected from Ipogun, an onchocerciasis endemic area in Ondo State, Nigeria. Before and after treatment, all patients ...

  6. Assessment Of Leukocyte Esterase Dipstick Test In Diagnosis Of ...

    African Journals Online (AJOL)

    This is a prospective study of urinary tract infection in 65 children (38 males and 27 females, M: F ratio 1: 0.7). Urine samples were evaluated by culture, microscopy and leukocyte esterase dipstick test. Positive urine culture, with significant bacteriuria was found in 19(29.2%). Urine microscopy for leukocyturia identified ...

  7. Leukocyte profile of adult Nigerian subjects with acute ...

    African Journals Online (AJOL)

    BACKGROUND: Leukocyte levels are evidently useful in trauma assessment, prognostication and management.1 Leukocytosis is a known physiologic response to trauma 2 but suggested to be absent among Africans origin3. The aim of present study is to investigate the existence of leukocytosis among adult Nigerians who ...

  8. Differential MSC activation leads to distinct mononuclear leukocyte binding mechanisms

    Science.gov (United States)

    Kota, Daniel J.; Dicarlo, Bryan; Hetz, Robert A.; Smith, Philippa; Cox, Charles S.; Olson, Scott D.

    2014-04-01

    Advances in the field of Multipotent Mesenchymal Stromal cell (MSC) biology have demonstrated that MSCs can improve disease outcome when `activated' to exert immunomodulatory effects. However, the precise mechanisms modulating MSC-immune cells interactions remain largely elusive. In here, we activated MSC based on a recent polarization paradigm, in which MSCs can be polarized towards a pro- or anti-inflammatory phenotype depending on the Toll-like receptor stimulated, to dissect the mechanisms through which MSCs physically interact with and modulate leukocytes in this context. Our data show that MSCs activated through the Toll-like receptor (TLR) 4 pathway increased VCAM-1 and ICAM-1 dependent binding of leukocytes. On the other hand, TLR3 stimulation strongly increases leukocytes affinity to MSC comparatively, through the formation of cable-like hyaluronic acid structures. In addition, TLR4 activation elicited secretion of pro-inflammatory mediators by MSCs, whereas TLR3-activated MSCs displayed a milder pro-inflammatory phenotype, similar to inactivated MSCs. However, the differently activated MSCs maintained their ability to suppress leukocyte activation at similar levels in our in vitro model, and this immunomodulatory property was shown here to be partially mediated by prostaglandin. These results reinforce the concept that alternate activation profiles control MSC responses and may impact the therapeutic use of MSCs.

  9. Leukocyte telomere length dynamics in women and men

    DEFF Research Database (Denmark)

    Dalgård, Christine; Benetos, Athanase; Verhulst, Simon

    2015-01-01

    BACKGROUND: A longer leukocyte telomere length (LTL) in women than men has been attributed to a slow rate of LTL attrition in women, perhaps due to high estrogen exposure during the premenopausal period. METHODS: To test this premise we performed a longitudinal study (an average follow-up of 12...

  10. Longitudinal Changes in Leukocyte Telomere Length and Mortality in Humans

    DEFF Research Database (Denmark)

    Bendix, Laila; Thinggaard, Mikael; Fenger, Mogens

    2014-01-01

    Leukocyte telomere length (LTL) ostensibly shortens with age and has been moderately associated with mortality. In humans, these findings have come almost solely from cross-sectional studies. Only recently has LTL shortening within individuals been analyzed in longitudinal studies. Such studies...

  11. Histamine, dithiaden and human polymorphonuclear leukocytes in vitro

    Czech Academy of Sciences Publication Activity Database

    Nosáľ, R.; Drábiková, K.; Jančinová, V.; Číž, Milan; Lojek, Antonín

    2003-01-01

    Roč. 52, Suppl. 1 (2003), s. S19-S20 ISSN 1023-3830 R&D Projects: GA MŠk ME 198 Grant - others:VEGA SR(SK) 2/1012/21 Institutional research plan: CEZ:AV0Z5004920 Keywords : dithiaden * histamine * polymorphonuclear leukocytes Subject RIV: BO - Biophysics Impact factor: 1.498, year: 2003

  12. Improved survival of newborns receiving leukocyte transfusions for sepsis

    International Nuclear Information System (INIS)

    Cairo, M.S.; Rucker, R.; Bennetts, G.A.; Hicks, D.; Worcester, C.; Amlie, R.; Johnson, S.; Katz, J.

    1984-01-01

    To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group compared with the group that did not receive transfusions

  13. Production and characterization of monoclonal antibodies against mink leukocytes

    DEFF Research Database (Denmark)

    Chen, W.S.; Pedersen, Mikael; Gram-Nielsen, S.

    1997-01-01

    Three monoclonal antibodies (mAbs) were generated against mink leukocytes. One antibody reacted with all T lymphocytes, one with all monocytes and one had platelet reactivity. Under reducing conditions, the T lymphocyte reactive antibody immunoprecipitated 18 kDa, 23 kDa, 25 kDa and 32-40 kDa pol...

  14. Effects of dexamethasone on leukocytic responses in pregnant ...

    African Journals Online (AJOL)

    Effects of dexamethasone on leukocytic responses of pregnant Yankasa sheep and Sahel does were investigated. In addition to its anti-inflammatory properties, dexamethasone regulates broad variety of immune cell functions and immune mediator expression at the molecular level and has become subject of considerable ...

  15. Activation of peripheral leukocytes in rat pregnancy and experimental preeclampsia

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Linton, EA; Sargent, IL; Redman, CWG

    OBJECTIVE: The aim of this study was to search for activation markers of peripheral leukocytes in experimental preeclampsia in the rat. STUDY DESIGN: Experimental preeclampsia was induced in 14-day-pregnant rats by infusion of endotoxin (1.0 mu g/kg body weight). For comparison, rats with normal

  16. CD18 activation epitopes induced by leukocyte activation

    NARCIS (Netherlands)

    Beals, C. R.; Edwards, A. C.; Gottschalk, R. J.; Kuijpers, T. W.; Staunton, D. E.

    2001-01-01

    The cell surface adhesion molecule LFA-1 coordinates leukocyte trafficking and is a costimulatory molecule for T cell activation. We developed a panel of mAbs that recognize activation epitopes on the CD18 subunit, and show that stimulation of T lymphocytes appears to be accompanied by a

  17. Leukocytes at the maternal-fetal interface in human pregnancy

    NARCIS (Netherlands)

    Sindram-Trujillo, Aliana Patricia

    2006-01-01

    The aim of this thesis was to gain a better understanding of the immunoregulatory mechanisms associated with maternal tolerance of the fetus during pregnancy. The distribution of decidual leukocytes, specifically uterine NK cells and T cells, in the decidua basalis and parietalis were studied in the

  18. Efficient leukocyte segmentation and recognition in peripheral blood image.

    Science.gov (United States)

    Shirazi, Syed H; Umar, Arif Iqbal; Naz, Saeeda; Razzak, Muhammad I

    2016-05-18

    Blood cell count, also known as differential count of various types of blood cells, provides valuable information in order to assess variety of diseases like AIDS, leukemia and blood cancer. Manual techniques are still used in diseases diagnosis that is very lingering and tedious process. However, machine based automatic analysis of leukocyte is a powerful tool that could reduce the human errors, improve the accuracy, and minimize the required time for blood cell analysis. However, leukocyte segmentation is a challenging process due to the complexity of the blood cell image; therefore, this task remains unresolved issue in the blood cell segmentation. The aim of this work is to develop an efficient leukocyte cell segmentation and classification system. This paper presents an efficient strategy to segment cell images. This has been achieved by using Wiener filter along with Curvelet transform for image enhancement and noise elimination in order to elude false edges. We have also used combination of entropy filter, thresholding and mathematical morphology for obtaining image segmentation and boundary detection, whereas we have used back-propagation neural network for leukocyte classification into its sub classes. As a result, the generated segmentation results are fruitful in a sense that we have overcome the problem of overlapping cells. We have obtained 100%, 96.15%, 92.30%, 92.30% and 96.15% accuracy for basophil, eosinophil, monocyte, lymphocyte and neutrophil respectively.

  19. Indium-111 leukocyte accumulation in intramuscular injection sites

    International Nuclear Information System (INIS)

    Swayne, L.C.; Dolgin, C.; Kabnick, L.S.; Filippone, A.

    1986-01-01

    We report four cases of indium-111 leukocyte concentration in previous intramuscular injection sites. Three patterns were observed: (1) small, discrete, and round; (2) linear; (3) irregular and large. The scintigraphic appearance did not necessarily correlate with the number of injections that the patient had received. (orig.)

  20. Pharmacological opportunities to control inflammatory diseases through inhibition of the leukocyte recruitment.

    Science.gov (United States)

    Peres, Raphael S; Menezes, Gustavo B; Teixeira, Mauro M; Cunha, Fernando Q

    2016-10-01

    Leukocyte recruitment to tissues is a highly orchestrated process and is one of the pillars of the inflammatory process. The contribution of leukocytes to tissue damage is very clear, suggesting that targeting leukocyte accumulation in tissue to be relevant for the development of novel therapies to treat chronic inflammatory diseases. Here, we review briefly known mechanisms of leukocyte recruitment and suggest potential targets for the development of novel anti-inflammatory therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Minor histocompatibility antigens on transfused leukoreduced units of red blood cells induce bone marrow transplant rejection in a mouse model

    OpenAIRE

    Desmarets, Maxime; Cadwell, Chantel M.; Peterson, Kenneth R.; Neades, Renee; Zimring, James C.

    2009-01-01

    When successful, human leukocyte antigen (HLA)–matched bone marrow transplantation with reduced-intensity conditioning is a cure for several nonmalignant hematologic disorders that require chronic transfusion, such as sickle cell disease and aplastic anemia. However, there are unusually high bone marrow transplant (BMT) rejection rates in these patients. Rejection correlates with the number of transfusions before bone marrow transplantation, and it has been hypothesized that preimmunization t...

  2. Leukocyte Populations in Human Preterm and Term Breast Milk Identified by Multicolour Flow Cytometry

    Science.gov (United States)

    Trend, Stephanie; de Jong, Emma; Lloyd, Megan L.; Kok, Chooi Heen; Richmond, Peter; Doherty, Dorota A.; Simmer, Karen; Kakulas, Foteini; Strunk, Tobias; Currie, Andrew

    2015-01-01

    Background Extremely preterm infants are highly susceptible to bacterial infections but breast milk provides some protection. It is unknown if leukocyte numbers and subsets in milk differ between term and preterm breast milk. This study serially characterised leukocyte populations in breast milk of mothers of preterm and term infants using multicolour flow cytometry methods for extended differential leukocyte counts in blood. Methods Sixty mothers of extremely preterm (leukocyte subsets analysed using flow cytometry. Results The major CD45+ leukocyte populations circulating in blood were also detectable in breast milk but at different frequencies. Progression of lactation was associated with decreasing CD45+ leukocyte concentration, as well as increases in the relative frequencies of neutrophils and immature granulocytes, and decreases in the relative frequencies of eosinophils, myeloid and B cell precursors, and CD16- monocytes. No differences were observed between preterm and term breast milk in leukocyte concentration, though minor differences between preterm groups in some leukocyte frequencies were observed. Conclusions Flow cytometry is a useful tool to identify and quantify leukocyte subsets in breast milk. The stage of lactation is associated with major changes in milk leukocyte composition in this population. Fresh preterm breast milk is not deficient in leukocytes, but shorter gestation may be associated with minor differences in leukocyte subset frequencies in preterm compared to term breast milk. PMID:26288195

  3. Efficiency and safety of leukocyte filtration during cardiopulmonary bypass for cardiac surgery

    NARCIS (Netherlands)

    Smit, JJJ; de Vries, AJ; Gu, YJ; van Oeveren, W

    Background. Leukocyte filtration of systemic blood during cardiopulmonary bypass surgery to reduce post-operative morbidity has not yet been established because of the enormous leukocyte release from the third space. This study was designed to examine the efficiency and safety of leukocyte

  4. Clinical efficacy and biocompatibility of three different leukocyte and fat removal filters during cardiac surgery

    NARCIS (Netherlands)

    de Vries, AJ; Vermeijden, WJ; Gu, YJ; Hagenaars, JAM; van Oeveren, W

    Activated leukocytes and fat particles are associated with organ injury after a cardiac surgery. Filters are currently used to remove either leukocytes or fat particles. A novel approach with a filter that combines leukocyte and fat removal might be clinically useful. As it is not known which type

  5. File list: NoD.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  7. File list: InP.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  12. File list: InP.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. Bacterial metabolism of human polymorphonuclear leukocyte-derived arachidonic acid.

    Science.gov (United States)

    Sorrell, T C; Muller, M; Sztelma, K

    1992-05-01

    Evidence for transcellular bacterial metabolism of phagocyte-derived arachidonic acid was sought by exposing human blood polymorphonuclear leukocytes, prelabelled with [3H]arachidonic acid, to opsonized, stationary-phase Pseudomonas aeruginosa (bacteria-to-phagocyte ratio of 50:1) for 90 min at 37 degrees C. Control leukocytes were stimulated with the calcium ionophore A23187 (5 microM) for 5 min. Radiochromatograms of arachidonic acid metabolites, extracted from A23187-stimulated cultures and then separated by reverse-phase high-performance liquid chromatography, revealed leukotriene B4, its omega-oxidation products, and 5-hydroxy-eicosatetraenoic acid. In contrast, two major metabolite peaks, distinct from known polymorphonuclear leukocyte arachidonic acid products by high-performance liquid chromatography or by thin-layer chromatography, were identified in cultures of P. aeruginosa with [3H]arachidonic acid-labelled polymorphonuclear leukocytes. Respective chromatographic characteristics of these novel products were identical to those of two major metabolite peaks produced by incubation of stationary-phase P. aeruginosa with [3H]arachidonic acid. Production of the metabolites was dependent upon pseudomonal viability. UV spectral data were consistent with a conjugated diene structure. Metabolism of arachidonic acid by P. aeruginosa was not influenced by the presence of catalase, superoxide dismutase, nordihydroguaiaretic acid, ethanol, dimethyl sulfoxide, or ferrous ions but was inhibited by carbon monoxide, ketoconazole, and 1,2-epoxy-3,3,3-trichloropropane. Our data suggest that pseudomonal metabolism of polymorphonuclear leukocyte-derived arachidonic acid occurs during phagocytosis, probably by enzymatic epoxidation and hydroxylation via an oxygenase. By this means, potential proinflammatory effects of arachidonic acid or its metabolites may be modulated by P. aeruginosa at sites of infection in vivo.

  14. VARIABILITY OF LEUKOCYTE COUNT AS AN INFLAMMATORY RESPONSE AMONG HYPERTENSIVES

    Directory of Open Access Journals (Sweden)

    Brinda

    2015-12-01

    Full Text Available INTRODUCTION Hypertension, a globally prevailing non communicable disease has been linked to various pathophysiological mechanisms. The new spotlight is on the inflammatory mechanism, which has been embarked on this study by utilising the White blood cell counts as the predominant marker. The pathogenesis behind this concept is the endothelial alteration which occurs in hypertension, causing increased oxidative stress and release of inflammatory mediators and further causing damage to the vascular walls and may result in sustained hypertension. OBJECTIVE To substantiate the difference in leukocyte count among the hypertensives and normotensives, to assess the variation in the leukocyte count among varied grades of hypertension. METHODS 80 subjects and 40 controls of both sex and age between 20-60 years were taken. Subjects with other chronic medical disorders, pregnancy, menstruation phase, history of infections in past 3 months, obesity, smokers and regular alcoholics were excluded. Three recordings of blood pressure were measured with a standard mercury sphygmomanometer. The differential leukocyte count was estimated with an automated counter. RESULTS Statistical analysis was done using independent sample t-test and one-way ANOVA. Total Leukocyte count (Mean = 8397.50 ± 1666.57 was raised significantly among the hypertensives, with P value <0.001. Comparison was done on the total count with the varied hypertensive years, which was suggestive of increase in total count among the pre hypertensives (systolic pressure and there was linear increase in total count with diastolic pressure though not statistically significant. CONCLUSION The elevation of white blood cell count is suggestive of underlying inflammatory mechanism among the hypertensives. The onset of inflammation could be at the onset of hypertension, as there is rise in total leukocyte count among the pre hypertensives which could also lead to sustained hypertension.

  15. Specificity for the tumor-associated self-antigen WT1 drives the development of fully functional memory T cells in the absence of vaccination.

    Science.gov (United States)

    Pospori, Constandina; Xue, Shao-An; Holler, Angelika; Voisine, Cecile; Perro, Mario; King, Judith; Fallah-Arani, Farnaz; Flutter, Barry; Chakraverty, Ronjon; Stauss, Hans J; Morris, Emma C

    2011-06-23

    Recently, vaccines against the Wilms Tumor antigen 1 (WT1) have been tested in cancer patients. However, it is currently not known whether physiologic levels of WT1 expression in stem and progenitor cells of normal tissue result in the deletion or tolerance induction of WT1-specific T cells. Here, we used an human leukocyte antigen-transgenic murine model to study the fate of human leukocyte antigen class-I restricted, WT1-specific T cells in the thymus and in the periphery. Thymocytes expressing a WT1-specific T-cell receptor derived from high avidity human CD8 T cells were positively selected into the single-positive CD8 population. In the periphery, T cells specific for the WT1 antigen differentiated into CD44-high memory phenotype cells, whereas T cells specific for a non-self-viral antigen retained a CD44(low) naive phenotype. Only the WT1-specific T cells, but not the virus-specific T cells, displayed rapid antigen-specific effector function without prior vaccination. Despite long-term persistence of WT1-specific memory T cells, the animals did not develop autoimmunity, and the function of hematopoietic stem and progenitor cells was unimpaired. This is the first demonstration that specificity for a tumor-associated self-antigen may drive differentiation of functionally competent memory T cells.

  16. Human peripheral blood monocytes display surface antigens recognized by monoclonal antinuclear antibodies

    International Nuclear Information System (INIS)

    Holers, V.M.; Kotzin, B.L.

    1985-01-01

    The authors used monoclonal anti-nuclear autoantibodies and indirect immunofluorescence to examine normal human peripheral blood mononuclear leukocytes for the presence of cell surface nuclear antigens. Only one monoclonal anti-histone antibody (MH-2) was found to bind to freshly isolated PBL, staining approximately 10% of large cells. However, after cells were placed into culture for 16-24 h, a high percentage (up to 60%) of large-sized cells were recognized by an anti-DNA (BWD-1) and several different antihistone monoclonal antibodies (BWH-1, MH-1, and MH-2). These antibodies recognize separate antigenic determinants on chromatin and histones extracted from chromatin. The histone antigen-positive cells were viable, and the monoclonal antibodies could be shown to be binding to the cell surface and not to the nucleus. Using monoclonal antibodies specific for monocytes and T cells, and complement-mediated cytotoxicity, the cells bearing histone antigens were shown to be primarily monocytes. The appearance of histone and DNA antigen-positive cells was nearly completely inhibited by the addition of low concentrations of cycloheximide at initiation of the cultures. In contrast, little effect on the percentage of positive cells was detected if cells were exposed to high doses of gamma irradiation before culture. These data further support the existence of cell surface nuclear antigens on selected cell subsets, which may provide insight into the immunopathogenesis of systemic lupus erythematosus and related autoimmune diseases

  17. Development of a complete human anti-human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer

    International Nuclear Information System (INIS)

    Nagai, Kentaro; Nakahata, Shingo; Shimosaki, Shunsuke; Tamura, Tomohiro; Kondo, Yuudai; Baba, Takashi; Taki, Tomohiko; Taniwaki, Masafumi; Kurosawa, Gene; Sudo, Yukio; Okada, Seiji; Sakoda, Sumio; Morishita, Kazuhiro

    2014-01-01

    Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. Up to 20% of oral dysplasia cases have been suggested to undergo malignant transformation to OSCC; however, there are no methods to predict OSCC development. In this study, to identify the genes associated with oral dysplasia progression, we performed genomic copy number analyses of genomic DNA samples isolated from primary oral dysplasia and OSCC via the microdissection method and found elevated expression of transferrin receptor C (TfR1/TFRC) with genomic amplification in oral dysplasia and OSCC. The expression rate of TFRC in OSCC was significantly higher than that in dysplasia, suggesting that OSCC disease progression might be related to TFRC expression. Additionally, we investigated the in vitro and in vivo impacts of a newly established anti-human TFRC monoclonal antibody, which was isolated from a human cDNA library using the phage-display method, on cell proliferation and survival. The anti-TFRC antibody blocked the interaction between transferrin and TFRC and consequently inhibited iron uptake, leading to the iron deprivation-mediated suppression of cell growth and induction of apoptosis. Moreover, we demonstrated that the anti-TFRC antibody efficiently inhibited tumor growth in a murine xenograft OSCC model. Therefore, we suggest our developed complete human anti-human TFRC antibody as a useful, novel treatment for oral dysplasia and OSCC

  18. Cancer testis antigen and immunotherapy

    Directory of Open Access Journals (Sweden)

    Krishnadas DK

    2013-04-01

    Full Text Available Deepa Kolaseri Krishnadas, Fanqi Bai, Kenneth G Lucas Department of Pediatrics, Division of Hematology/Oncology, University of Louisville, KY, USA Abstract: The identification of cancer testis (CT antigens has been an important advance in determining potential targets for cancer immunotherapy. Multiple previous studies have shown that CT antigen vaccines, using both peptides and dendritic cell vaccines, can elicit clinical and immunologic responses in several different tumors. This review details the expression of melanoma antigen family A, 1 (MAGE-A1, melanoma antigen family A, 3 (MAGE-A3, and New York esophageal squamous cell carcinoma-1 (NY-ESO-1 in various malignancies, and presents our current understanding of CT antigen based immunotherapy. Keywords: cancer testis antigens, immunotherapy, vaccine

  19. Leukocyte filtration to decrease the number of adherent leukocytes in the cerebral microcirculation after a period of deep hypothermic circulatory arrest.

    Science.gov (United States)

    Alaoja, Hanna; Niemelä, Eija; Anttila, Vesa; Dahlbacka, Sebastian; Mäkelä, Jussi; Kiviluoma, Kai; Laurila, Päivi; Kaakinen, Timo; Juvonen, Tatu

    2006-12-01

    Cardiopulmonary bypass and hypothermic circulatory arrest induce a systemic inflammatory response, including a cascade of leukocyte and endothelial cell activity, during the postischemic reperfusion phase. Accumulation of leukocytes in the brain can lead to neurologic problems after cardiac surgery. The beneficial effects of a leukocyte-depleting filter have been documented, but because of contradictory results the underlying function of the filter remains unclear. Twenty-two juvenile piglets (6 to 8 weeks) were randomly assigned to undergo cardiopulmonary bypass with or without a leukocyte-depleting filter 60 minutes before and 60 minutes after a 75-minute hypothermic circulatory arrest at 18 degrees C. The cerebral vessels were visualized with intravital microscopy through a cranial window placed over the parietal cortex. Rhodamine staining was used to observe adherent and rolling leukocytes in the cerebral postcapillary venules. The animals were electively killed 1 hour after weaning from cardiopulmonary bypass. There were no significant differences between the study groups regarding hemodynamic data. Numbers of adherent activated leukocytes were lower in the leukocyte filtration group, reaching borderline statistical significance when assessed throughout the experiment (between-groups P = .069) and actual statistical significance when assessed during the rewarming period (between-groups P = .029). The leukocyte-depleting filter succeeded in reducing the number of adherent leukocytes during the reperfusion period in an experimental operation with deep hypothermic circulatory arrest. Such a filter thus could mitigate cerebral reperfusion injury after cardiac surgery.

  20. HLA II class antigens and susceptibility to coeliac disease

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2011-01-01

    Full Text Available Coeliac disease (CD is a systemic autoimmune, complex and multifactorial disorder, which is caused by interactions between genetic and environmental factors. The only established genetic risk factors so far are the human leucocyte antigens. The aim of this study was to assess the distribution of II class human leukocyte antigens (HLA in patients with coeliac disease and to investigate the susceptibility to coeliac disease in family members. We typed HLA DR and DQ antigens in 37 patients from Vojvodina with coeliac disease, 23 first-degree relatives, and 210 controls, serologically using standard lymphocytotoxicity technique. HLA DQ5(1, DQ6(1, DR11(5, DQ7(3, DQ2 and DR15(2 were the most common antigens in the control group. Frequency of HLA DQ2, DR3 and DR7 was higher in CD patients than in the control group. The relative risks for HLA DQ2, DR3 and DR7 were 4.846, 6.986 and 2.106, respectively, while positive association was found between HLA DQ2 and DR3 and CD. Frequency of HLA DQ2, DR3 and DR16(2 was higher in first-degree relatives than in the control group while a positive association was found between HLA DQ2 and DR3. A negative association was found between HLA DQ5(1 and DQ6(1 in coeliac patients from Vojvodina and their relatives, in addition to HLA DR11(5 in the group of relatives (RR=0.363,PF=0.232. These findings indicate the impact of the HLA testing for CD in clinical practice in order to rule out the possibility to CD in doubtful cases or in at-risk subjects.

  1. Differences in leukocyte differentiation molecule abundances on domestic sheep (Ovis aries) and bighorn sheep (Ovis canadensis) neutrophils identified by flow cytometry.

    Science.gov (United States)

    Highland, Margaret A; Schneider, David A; White, Stephen N; Madsen-Bouterse, Sally A; Knowles, Donald P; Davis, William C

    2016-06-01

    Although both domestic sheep (DS) and bighorn sheep (BHS) are affected by similar respiratory bacterial pathogens, experimental and field data indicate BHS are more susceptible to pneumonia. Cross-reactive monoclonal antibodies (mAbs) for use in flow cytometry (FC) are valuable reagents for interspecies comparative immune system analyses. This study describes cross-reactive mAbs that recognize leukocyte differentiation molecules (LDMs) and major histocompatibility complex antigens on DS and BHS leukocytes. Characterization of multichannel eosinophil autofluorescence in this study permitted cell-type specific gating of granulocytes for evaluating LDMs, specifically on neutrophils, by single-label FC. Evaluation of relative abundances of LDMs by flow cytometry revealed greater CD11a, CD11b, CD18 (β2 integrins) and CD 172a (SIRPα) on DS neutrophils and greater CD14 (lipopolysaccharide receptor) on BHS neutrophils. Greater CD25 (IL-2) was identified on BHS lymphocytes following Concavalin A stimulation. While DS and BHS have similar total peripheral blood leukocyte counts, BHS have proportionately more neutrophils. Published by Elsevier Ltd.

  2. Distinct patterns of leukocyte recruitment in the pulmonary microvasculature in response to local and systemic inflammation.

    Science.gov (United States)

    Wang, Yongzhi; Roller, Jonas; Slotta, Jan E; Zhang, Su; Luo, Lingtao; Rahman, Milladur; Syk, Ingvar; Menger, Michael D; Thorlacius, Henrik

    2013-02-15

    The mechanisms of leukocyte recruitment in the pulmonary microvasculature in response to local and systemic inflammation remain elusive. Male C57BL/6 mice received lipopolysaccharide (LPS) intrapulmonary (intratracheally, it) or systemically (intravenously, iv) for 1-18 h. Leukocyte responses in lung were analyzed by use of intravital fluorescence microscopy. Plasma and lung levels of CXC chemokines as well as Mac-1 and F-actin expression in leukocytes and bronchoalveolar leukocytes were quantified. Venular leukocyte rolling was markedly increased in response to local LPS but only marginally after systemic LPS. Leukocyte adhesion in venules was enhanced in both groups although adhesion was higher in mice receiving LPS intratracheally compared with LPS intravenously. Systemic LPS caused more leukocytes trapping in capillaries compared with local LPS. The ratio of adherent leukocytes in venules compared with capillaries was higher in response to local LPS, suggesting that leukocytes were more prone to accumulate in venules in local inflammation and in capillaries in systemic inflammation. Systemic LPS triggered higher F-actin formation and Mac-1 expression in leukocytes compared with local LPS. Local and systemic LPS caused similar increases in CXC chemokines in the lung whereas intravenous endotoxin provoked higher levels of CXC chemokines in the circulation. Interestingly, intratracheal LPS increased recruitment of leukocytes in the alveolar space whereas intravenous LPS was ineffective in promoting leukocyte accumulation in the bronchoalveolar space. In conclusion, our data demonstrate that pulmonary microvascular recruitment of leukocytes differs in local and systemic inflammation, which might be related to premature activation and stiffening of circulating leukocytes in endotoxemia.

  3. Effect of radiographic contrast agents on leukocyte metabolic response

    Energy Technology Data Exchange (ETDEWEB)

    Hernanz-Schulman, M. [Dept. of Pediatric Radiology, Vanderbilt Children' s Hospital, Nashville, TN (United States); Vanholder, R.; Waterloos, M.A. [Dept. of Internal Medicine, Nephrology Section, University Hospital, Gent (Belgium); Hakim, R.; Schulman, G. [Department of Nephrology, Vanderbilt University Medical Center, Nashville, TN (United States)

    2000-06-01

    Barium, at clinical dilutions, causes a significant increase of baseline ''resting state'' phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media in bacteria was more complex (although inhibition is minor compared to barium). Our data demonstrate that barium is a significat activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these dsata serve to explain the enhanced adverse effect of barium in cased of fecal peritonitis. (orig.)

  4. Role of flexural stiffness of leukocyte microvilli in adhesion dynamics

    Science.gov (United States)

    Wu, Tai-Hsien; Qi, Dewei

    2018-03-01

    Previous work reported that microvillus deformation has an important influence on dynamics of cell adhesion. However, the existing studies were limited to the extensional deformation of microvilli and did not consider the effects of their bending deformation on cell adhesion. This Rapid Communication investigates the effects of flexural stiffness of microvilli on the rolling process related to adhesion of leukocytes by using a lattice-Boltzmann lattice-spring method (LLM) combined with adhesive dynamics (AD) simulations. The simulation results reveal that the flexural stiffness of microvilli and their bending deformation have a profound effect on rolling velocity and adhesive forces. As the flexural stiffness of the microvilli decreases, their bending angles increase, resulting in an increase in the number of receptor-ligand bonds and adhesive bonding force and a decrease in the rolling velocity of leukocytes. The effects of flexural stiffness on deformation and adhesion represent crucial factors involved in cell adhesion.

  5. Imaging Cytometry of Human Leukocytes with Third Harmonic Generation Microscopy

    Science.gov (United States)

    Wu, Cheng-Ham; Wang, Tzung-Dau; Hsieh, Chia-Hung; Huang, Shih-Hung; Lin, Jong-Wei; Hsu, Szu-Chun; Wu, Hau-Tieng; Wu, Yao-Ming; Liu, Tzu-Ming

    2016-11-01

    Based on third-harmonic-generation (THG) microscopy and a k-means clustering algorithm, we developed a label-free imaging cytometry method to differentiate and determine the types of human leukocytes. According to the size and average intensity of cells in THG images, in a two-dimensional scatter plot, the neutrophils, monocytes, and lymphocytes in peripheral blood samples from healthy volunteers were clustered into three differentiable groups. Using these features in THG images, we could count the number of each of the three leukocyte types both in vitro and in vivo. The THG imaging-based counting results agreed well with conventional blood count results. In the future, we believe that the combination of this THG microscopy-based imaging cytometry approach with advanced texture analysis of sub-cellular features can differentiate and count more types of blood cells with smaller quantities of blood.

  6. Scintigraphic demonstration of abscesses with radioactive gallium labeled leukocytes

    International Nuclear Information System (INIS)

    Burleson, R.L.; Holman, B.L.; Tow, D.E.

    1975-01-01

    Autologous peripheral blood leukocytes, labeled in vitro with 67 Ga citrate, have been studied in 20 patients as a radioactive carrier for the scintigraphic visualization of septic inflammatory areas. 67 Ga citrate was added to venous whole blood; following incubation, the blood was centrifuged, and the packed cells were reinfused. Scintiscans were obtained four and 24 hours later. The inflammatory process was demonstrated in nine of nine patients with confirmed sepsis. Eleven patients without sepsis had normal scans. There were no false-negative scans and one false-positive scan. The selective accumulation of the gallium labeled leukocytes in areas of septic inflammation was sufficient to allow scintigraphic demonstration of the inflammatory area

  7. Role of total leukocyte in diagnosis of acute appendicitis

    International Nuclear Information System (INIS)

    Kamran, H.; Naveed, D.; Ahmed, M.

    2008-01-01

    Acute appendicitis is a common surgical emergency. Diagnosis may be difficult with little help from radiological and laboratory investigations. Total leukocyte count is one of the helpful investigations, being evaluated in this study. The patients presenting with right lower quadrant abdominal pain whom were diagnosed as having acute appendicitis and later underwent appendicectomy were included in the study. The preoperative leukocyte count was compared with histo-pathology findings of removed appendix. Sensitivity and specificity of TLC was calculated by standard formulas. The sensitivity and specificity of TLC as calculated in this study is 76.5% and 73.7% respectively while positive predictive value is 92.5%. TLC although not a diagnostic criteria for acute appendicitis but still is helpful investigation in decision making. (author)

  8. Leukocytes: The Double-Edged Sword in Fibrosis

    Directory of Open Access Journals (Sweden)

    Jakub Kryczka

    2015-01-01

    Full Text Available Skin tissue scar formation and fibrosis are often characterized by the increased production and deposition of extracellular matrix components, accompanied by the accumulation of a vast number of myofibroblasts. Scaring is strongly associated with inflammation and wound healing to regain tissue integrity in response to skin tissue injury. However, increased and uncontrolled inflammation, repetitive injury, and individual predisposition might lead to fibrosis, a severe disorder resulting in the formation of dense and stiff tissue that loses the physical properties and physiological functions of normal tissue. Fibrosis is an extremely complicated and multistage process in which bone marrow-derived leukocytes act as both pro- and antifibrotic agents, and therefore, few, if any, effective therapies are available for the most severe and lethal forms of fibrosis. Herein, we discuss the current knowledge on the multidimensional impact of leukocytes on the induction of fibrosis, focusing on skin fibrosis.

  9. Does human leukocyte elastase degrade intact skin elastin?

    DEFF Research Database (Denmark)

    Schmelzer, Christian E H; Jung, Michael C; Wohlrab, Johannes

    2012-01-01

    and organs, including the aorta, lung, cartilage, elastic ligaments and skin, and is thus critical for their long-term function. Mature elastin is an insoluble and extremely durable protein that undergoes very little turnover, but sustained exposure to proteases may lead to irreversible and severe damage......This study aimed to investigate the susceptibility of intact fibrillar human elastin to human leukocyte elastase and cathepsin G. Elastin is a vital protein of the extracellular matrix of vertebrates, and provides exceptional properties including elasticity and tensile strength to many tissues...... small tissue samples to test enzymes for their elastolytic potential. This workflow was applied to skin samples from variously aged individuals, and it was found that strong differences exist in the degradability of the elastins investigated. In summary, human leukocyte elastase was unable to degrade...

  10. Inhibition of the mixed leukocyte reaction by alloantisera in man

    International Nuclear Information System (INIS)

    Jonker, M.; Leeuwen, A. van; Rood, J.J. van

    1977-01-01

    The incidence of MLC(mixed leukocyte culture)-inhibiting antibodies was determined in 42 pregnancy sera. MLC's were carried out between the cells from the serum donor and her husband in the presence of nonimmune AB serum and the test serum. Fifty per cent of the sera reduced the MLC response to less than 40% of the control values. Only four sera had lymphocytotoxic activity. The inhibition was strong against the specific immunizor, less strong against random unrelated cells and weak against cells which were SD(serologically defined)-identical with the serum donor. Absorptions with lymphocytes and platelets were carried out. Lymphocytes removed activity in three of the four sera tested. Platelets removed activity from one serum. It was concluded that both anti-LD(lymphocyte defined) and anti-SD antibodies were able to inhibit the MLR (mixed leukocyte reaction) at the stimulator cell level. (author)

  11. Influence of glucose on the leukocyte response in women athletes ...

    African Journals Online (AJOL)

    Objective. This study investigated the influence of carbohydrate versus placebo beverage intake on leukocyte and cortisol responses to 90 minutes of running on a treadmill at 70% VO 2max in women. Subjects. Ten moderately trained women athletes (age: 27.6±3.7 yr; VO 2max: 46.6±2.0ml.kg-1.min-1) from the local ...

  12. Indium-111 leukocyte localization in infected prosthetic graft

    International Nuclear Information System (INIS)

    Purnell, G.L.; Walker, C.W.; Allison, J.W.; Dalrymple, G.V.

    1990-01-01

    Infective endocarditis can be difficult to prove, even in the face of strong clinical suspicion. A case in which standard methods of diagnosis failed to demonstrate endocarditis in a patient with recurrent Staphylococcus aureus bacteremia and porcine aortic valve is reported. An In-111 labelled leukocyte SPECT study demonstrated uptake in the aortic root and leaflets, and autopsy demonstrated vegetations on the leaflets. In-111 may prove useful in demonstrating endocarditis in patients with prosthetic valve infection

  13. Indium-111 leukocyte localization in infected prosthetic graft

    Energy Technology Data Exchange (ETDEWEB)

    Purnell, G.L.; Walker, C.W.; Allison, J.W.; Dalrymple, G.V. (Univ. of Arkansas for Medical Sciences, Little Rock (USA))

    1990-08-01

    Infective endocarditis can be difficult to prove, even in the face of strong clinical suspicion. A case in which standard methods of diagnosis failed to demonstrate endocarditis in a patient with recurrent Staphylococcus aureus bacteremia and porcine aortic valve is reported. An In-111 labelled leukocyte SPECT study demonstrated uptake in the aortic root and leaflets, and autopsy demonstrated vegetations on the leaflets. In-111 may prove useful in demonstrating endocarditis in patients with prosthetic valve infection.

  14. Neisseria gonorrhoeae suppresses the oxidative burst of human polymorphonuclear leukocytes

    OpenAIRE

    Criss, Alison K.; Seifert, H. Steven

    2008-01-01

    Symptomatic infection with Neisseria gonorrhoeae (Gc) results in a potent polymorphonuclear leukocyte (PMN)-driven inflammatory response, but the mechanisms by which Gc withstands PMN attack are poorly defined. Here we report that Gc can suppress the PMN oxidative burst, a central component of the PMN antimicrobial arsenal. Primary human PMNs remained viable after exposure to liquid-grown, exponential-phase, opacity-associated protein (Opa)-negative Gc of strains FA1090 and MS11 but did not g...

  15. Quantitative and qualitative changes in leukocytes of psoriatic patients

    International Nuclear Information System (INIS)

    Mahesar, S.M.; Khand, A.A.

    2011-01-01

    Background: Psoriasis is a disease concerned with inflammation and scaling of skin. In psoriasis, cells of the skin come on surface quickly before their complete maturation. In psoriatic patients, T-cells produce an abnormally large amount of toxic chemicals and cause inflammation. This study was undertaken to find out values of prognostic significance for worsening of the disease at early stage and to evaluate the changes (quantitative and qualitative) occurring in white blood cells of psoriatic patients. Methods: A total of 158 subjects, 79 psoriatic patients (44 males and 35 females) and same numbers of normal control volunteers were recruited. Total and Differential Leukocyte Counts (TLC and DLC) were determined. Morphological examination was also undertaken. All results of patients were compared with normal control volunteers. Results : In 47.7% male and 54.2% female patients TLC was higher than controls while variation in differential count was observed in 61.3% male and 62.8% female patients. Overall, neutrophils in 45% patients, basophils in 30.3%, eosinophils in 65.8%, and monocytes in 15% of patients were elevated. In 77.2% psoriatic patients, lymphocytes were decreased. In volunteers total and differential leukocyte counts were within normal range. Total leukocyte count in normal males was 5,136 +- 31, and in psoriatic male subjects it was 10,498 +- 43, and it was 5,023 +- 35 against 11,390 +- 31 in normal versus psoriatic females ( p<0.001). Conclusion: Total leukocyte count was elevated in psoriatics while on DLC neutrophils, eosinophils and neutrophils were significantly raised where as lymphocytes were significantly decreased in psoriatic patients. Morphological changes were also noted. (author)

  16. Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

    Directory of Open Access Journals (Sweden)

    Gomez-Lopez Nardhy

    2013-01-01

    Full Text Available Abstract Background Parturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine activation and the systemic progesterone/estradiol shift. Methods Tissues and blood were collected from pregnant Long-Evans rats on gestational days (GD 17, 20 and 22 (term gestation. We employed a validated Boyden chamber assay, flow cytometry, quantitative real time-polymerase chain reaction, and enzyme-linked immunosorbent assays. Results We found that GD20 maternal peripheral leukocytes migrated more than those from GD17 when these were tested with GD22 uterus and cervix extracts. Leukocytes on GD20 also displayed a significant increase in chemokine (C-C motif ligand 2 (Ccl2 gene expression and this correlated with an increase in peripheral granulocyte proportions and a decrease in B cell and monocyte proportions. Tissue chemotactic activity and specific chemokines (CCL2, chemokine (C-X-C motif ligand 1/CXCL1, and CXCL10 were mostly unchanged from GD17 to GD20 and increased only on GD22. CXCL10 peaked on GD20 in cervical tissues. As expected, prostaglandin F2α receptor and oxytocin receptor gene expression increased dramatically between GD20 and 22. Progesterone concentrations fell and estradiol-17β concentrations increased in peripheral serum, cervical and uterine tissue extracts between GD20 and 22. Conclusion Maternal circulating leukocytes display early chemotactic responsiveness, which leads to their infiltration into the uterus where they may participate in the process of parturition.

  17. Removal of leukocytes from blood by fibre filtration. A comparison study on the performance of two commercially available filters

    NARCIS (Netherlands)

    Reesink, H. W.; Veldman, H.; Henrichs, H. J.; Prins, H. K.; Loos, J. A.

    1982-01-01

    Two different kinds of filters suitable for the almost complete removal of leukocytes from blood-cell concentrates were tested. The maximal retention of filter I was 1.9-3.4 x 10(9) leukocytes per filter, whereas filter II could retain 3.6 - 7.8 x 10(9) leukocytes per filter before the leukocyte

  18. Antigen antibody interactions

    CERN Document Server

    DeLisi, Charles

    1976-01-01

    1. 1 Organization of the Immune System One of the most important survival mechanisms of vertebrates is their ability to recognize and respond to the onslaught of pathogenic microbes to which they are conti- ously exposed. The collection of host cells and molecules involved in this recognition­ 12 response function constitutes its immune system. In man, it comprises about 10 cells 20 (lymphocytes) and 10 molecules (immunoglobulins). Its ontogenic development is c- strained by the requirement that it be capable of responding to an almost limitless variety of molecular configurations on foreign substances, while simultaneously remaining inert to those on self components. It has thus evolved to discriminate, with exquisite precision, between molecular patterns. The foreign substances which induce a response, called antigens, are typically large molecules such as proteins and polysaccharides. The portions of these with which immunoglobulins interact are called epitopes or determinants. A typical protein epitope m...

  19. Clinical relevance of HLA donor-specific antibodies detected by single antigen assay in kidney transplantation.

    Science.gov (United States)

    Caro-Oleas, José Luis; González-Escribano, María Francisca; González-Roncero, Francisco Manuel; Acevedo-Calado, María José; Cabello-Chaves, Virginia; Gentil-Govantes, Miguel Ángel; Núñez-Roldán, Antonio

    2012-03-01

    Clinical relevance of donor-specific antibodies (DSAs) detected by a single antigen Luminex virtual crossmatch in pre-transplant serum samples from patients with a negative cytotoxicity-dependent complement crossmatch is controversial. The aim of this study was to analyse the influence of a pre-transplant positive virtual crossmatch in the outcome of kidney transplantation. A total of 892 patients who received a graft from deceased donors after a negative cytotoxicity crossmatch were included. Presence of anti-human leucocyte antigen (HLA) antibodies was investigated using a Luminex screening assay and anti-HLA specificities were assigned performing a Luminex single antigen assay. Graft survival was significantly worse among patients with anti-HLA DSA compared to both patients with anti-HLA with no DSA (P = 0.001) and patients without HLA antibodies (P HLA with no DSA and no HLA antibodies patient groups were observed (P = 0.595). Influence of both anti-Class I and anti-Class II DSA was detected (P 1500 (global P > 0.05). The presence of preformed HLA DSA in transplanted patients with a negative cytotoxicity crossmatch is associated with a lower allograft survival. The detection of anti-HLA with no DSA has no influence in the graft outcome. Finally, there were no demonstrable effects of mean fluorescence intensity (MFI) values >1500 on graft survival.

  20. Biomechanics of the endothelium substrate influences leukocyte transmigration

    Science.gov (United States)

    Stroka, Kimberly; Aranda-Espinoza, Helim

    2012-02-01

    The effects of shear flow and cytokines on leukocyte transmigration are well understood. However, the effects of substrate stiffness on transmigration remain unexplored. We have developed an in vitro model that allows us to study leukocyte transmigration as a function of varying physiological substrate stiffness. Interestingly, leukocyte transmigration increased with increasing substrate stiffness below the endothelium. intercellular adhesion molecule-1 expression, stiffness, cytoskeletal arrangement, morphology, and cell-substrate adhesion could not account for the dependence of transmigration on substrate stiffness. We also explored the role of cell contraction and observed that (1) neutrophil transmigration caused large hole formation in monolayers on stiff substrates. (2) Neutrophil transmigration on soft substrates was increased by decreasing cell-cell adhesion. (3) Inhibition of myosin light chain kinase normalized the effects of substrate stiffness by reducing cell contraction on stiff substrates. These results demonstrate that neutrophil transmigration is regulated by MLCK-mediated generation of gaps at cell borders through substrate stiffness-dependent endothelial cell contraction.

  1. Curcumin modulates leukocyte and platelet adhesion in murine sepsis.

    Science.gov (United States)

    Vachharajani, Vidula; Wang, Si-Wei; Mishra, Nilamadhab; El Gazzar, Mohamed; Yoza, Barbara; McCall, Charles

    2010-08-01

    Circulating cell-endothelial cell interaction in sepsis is a rate-determining factor in organ dysfunction, and interventions targeting this process have a potential therapeutic value. In this project, we examined whether curcumin, an active ingredient of turmeric and an anti-inflammatory agent, could disrupt interactions between circulating blood cells and endothelium and improve survival in a murine model of sepsis. Mice were subjected to cecal ligation and puncture (CLP) to induce sepsis vs. sham surgery. We studied leukocyte and platelet adhesion in cerebral microcirculation using intravital fluorescent video microscopy technique, blood-brain barrier (BBB) dysfunction using Evans Blue (EB) leakage method, P-selectin expression using dual radiolabeling technique, and survival in mice subjected to Sham, CLP, and CLP with curcumin pre-treatment (CLP + curcumin). Curcumin significantly attenuated leukocyte and platelet adhesion in cerebral microcirculation, EB leakage in the brain tissue, and improved survival in mice with CLP. P-selectin expression in mice with CLP + curcumin was significantly attenuated compared with CLP in various microcirculatory beds, including brain. Reduction in platelet adhesion was predominantly via modulation of endothelium by curcumin. Curcumin pre-treatment modulates leukocyte and platelet adhesion and BBB dysfunction in mice with CLP via P-selectin expression and improves survival in mice with CLP.

  2. Increased oxidative DNA damage in mononuclear leukocytes in vitiligo

    Energy Technology Data Exchange (ETDEWEB)

    Giovannelli, Lisa [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy)]. E-mail: lisag@pharm.unifi.it; Bellandi, Serena [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Pitozzi, Vanessa [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Fabbri, Paolo [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Dolara, Piero [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Moretti, Silvia [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy)

    2004-11-22

    Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The autocytotoxic hypothesis suggests that melanocyte impairment could be related to increased oxidative stress. Evidences have been reported that in vitiligo oxidative stress might also be present systemically. We used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive sites, in peripheral blood cells from patients with active vitiligo and healthy controls. The basal level of oxidative DNA damage in mononuclear leukocytes was increased in vitiligo compared to normal subjects, whereas DNA strand breaks (SBs) were not changed. This alteration was not accompanied by a different capability to respond to in vitro oxidative challenge. No differences in the basal levels of DNA damage in polymorphonuclear leukocytes were found between patients and healthy subjects. Thus, this study supports the hypothesis that in vitiligo a systemic oxidative stress exists, and demonstrates for the first time the presence of oxidative alterations at the nuclear level. The increase in oxidative DNA damage shown in the mononuclear component of peripheral blood leukocytes from vitiligo patients was not particularly severe. However, these findings support an adjuvant role of antioxidant treatment in vitiligo.

  3. Imaging leukocytes in vivo with third harmonic generation microscopy

    Science.gov (United States)

    Tsai, Cheng-Kun; Chen, Chien-Kuo; Chen, Yu-Shing; Wu, Pei-Chun; Hsieh, Tsung-Yuan; Liu, Han-Wen; Yeh, Chiou-Yueh; Lin, Win-Li; Chia, Jean-San; Liu, Tzu-Ming

    2013-02-01

    Without a labeling, we demonstrated that lipid granules in leukocytes have distinctive third harmonic generation (THG) contrast. Excited by a 1230nm femtosecond laser, THG signals were generated at a significantly higher level in neutrophils than other mononuclear cells, whereas signals in agranular lymphocytes were one order smaller. These characteristic THG features can also be observed in vivo to trace the newly recruited leukocytes following lipopolysaccharide (LPS) challenge. Furthermore, using video-rate THG microscopy, we also captured images of blood cells in human capillaries. Quite different from red-blood-cells, every now and then, round and granule rich blood cells with strong THG contrast appeared in circulation. The corresponding volume densities in blood, evaluated from their frequencies of appearance and the velocity of circulation, fall within the physiological range of human white blood cell counts. These results suggested that labeling-free THG imaging may provide timely tracing of leukocyte movement and hematology inspection without disturbing the normal cellular or physiological status.

  4. Cancer antigen 125 and prognosis

    DEFF Research Database (Denmark)

    Høgdall, Estrid Vilma Solyom

    2008-01-01

    cancer antigen 125 determination may be implemented into clinical practice, cut-off levels must be evaluated and internationally defined. Studies examining serum cancer antigen 125 levels after surgery but before, during, or after treatment confirmed that changes in serum levels are of prognostic value...

  5. Radioimmunoassays of hidden viral antigens

    International Nuclear Information System (INIS)

    Neurath, A.R.; Strick, N.; Baker, L.; Krugman, S.

    1982-01-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure

  6. ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

    DEFF Research Database (Denmark)

    Faraco, Juliette; Lin, Ling; Kornum, Birgitte Rahbek

    2013-01-01

    Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals...... with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell...

  7. The CXCR1/2 ligand NAP-2 promotes directed intravascular leukocyte migration through platelet thrombi

    Science.gov (United States)

    Ghasemzadeh, Mehran; Kaplan, Zane S.; Alwis, Imala; Schoenwaelder, Simone M.; Ashworth, Katrina J.; Westein, Erik; Hosseini, Ehteramolsadat; Salem, Hatem H.; Slattery, Robyn; McColl, Shaun R.; Hickey, Michael J.; Ruggeri, Zaverio M.; Yuan, Yuping

    2013-01-01

    Thrombosis promotes leukocyte infiltration into inflamed tissues, leading to organ injury in a broad range of diseases; however, the mechanisms by which thrombi guide leukocytes to sites of vascular injury remain ill-defined. Using mouse models of endothelial injury (traumatic or ischemia reperfusion), we demonstrate a distinct process of leukocyte recruitment, termed “directed intravascular migration,” specifically mediated by platelet thrombi. Single adherent platelets and platelet aggregates stimulated leukocyte shape change at sites of endothelial injury; however, only thrombi were capable of inducing directed intravascular leukocyte migration. Leukocyte recruitment and migration induced by platelet thrombi occurred most prominently in veins but could also occur in arteries following ischemia-reperfusion injury. In vitro studies demonstrated a major role for platelet-derived NAP-2 (CXCL-7) and its CXCR1/2 receptor in regulating leukocyte polarization and motility. In vivo studies demonstrated the presence of an NAP-2 chemotactic gradient within the thrombus body. Pharmacologic blockade of CXCR1/2 as well as genetic deletion of NAP-2 markedly reduced leukocyte shape change and intrathrombus migration. These studies define a distinct process of leukocyte migration that is initiated by homotypic adhesive interactions between platelets, leading to the development of an NAP-2 chemotactic gradient within the thrombus body that guides leukocytes to sites of vascular injury. PMID:23550035

  8. The metalloproteinase ADAM8 promotes leukocyte recruitment in vitro and in acute lung inflammation.

    Science.gov (United States)

    Dreymueller, Daniela; Pruessmeyer, Jessica; Schumacher, Julian; Fellendorf, Sandra; Hess, Franz Martin; Seifert, Anke; Babendreyer, Aaron; Bartsch, Jörg W; Ludwig, Andreas

    2017-09-01

    Alveolar leukocyte recruitment is a hallmark of acute lung inflammation and involves transmigration of leukocytes through endothelial and epithelial layers. The disintegrin and metalloproteinase (ADAM) 8 is expressed on human isolated leukocytic cells and can be further upregulated on cultured endothelial and epithelial cells by proinflammatory cytokines. By shRNA-mediated knockdown we show that leukocytic ADAM8 is required on monocytic THP-1 cells for chemokine-induced chemotaxis as well as transendothelial and transepithelial migration. Furthermore, ADAM8 promotes α L -integrin upregulation and THP-1 cell adhesion to endothelial cells. On endothelial cells ADAM8 enhances transendothelial migration and increases cytokine-induced permeability. On epithelial cells the protease facilitates migration in a wound closure assay but does not affect transepithelial leukocyte migration. Blood leukocytes and bone marrow-derived macrophages (BMDM) from ADAM8-deficient mice show suppressed chemotactic response. Intranasal application of LPS to mice is accompanied with ADAM8 upregulation in the lung. In this model of acute lung inflammation ADAM8-deficient mice are protected against leukocyte infiltration. Finally, transfer experiments of BMDM in mice indicate that ADAM8 exerts a promigratory function predominantly on leukocytes. Our study provides in vitro and in vivo evidence that ADAM8 on leukocytes holds a proinflammatory function in acute lung inflammation by promoting alveolar leukocyte recruitment. Copyright © 2017 the American Physiological Society.

  9. Post-transfusion purpura in an African-American man due to human platelet antigen-5b alloantibody: a case report

    Directory of Open Access Journals (Sweden)

    Lynce Filipa

    2012-12-01

    Full Text Available Abstract Introduction Post-transfusion purpura is a rare immunohematological disorder characterized by severe thrombocytopenia following transfusion of blood components and induced by an alloantibody against a donor platelet antigen. It occurs primarily in women sensitized by pregnancy and is most commonly caused by anti-human platelet antigen-1a antibodies. Here, we describe what we believe to be the first documented case of an African-American man who developed post-transfusion purpura due to an anti-human platelet antigen-5b alloantibody after receiving multiple blood products. Case presentation A 68-year-old African-American man initially admitted with atrial flutter was started on anticoagulation treatment, which was complicated by severe hematemesis. On days 4 and 5 of hospitalization, he received six units of packed red blood cells, and on days 4, 13 and 14 he received plasma. His platelet count began to drop on day 25 and on day 32 reached a nadir of 7 × 109/L. His platelet count increased after receiving intravenous immune globulin. An antibody with reactivity to human platelet antigen-5b was detected by a solid-phase enzyme-linked immunoassay. Our patient was homozygous for human platelet antigen-5a. Conclusion This case emphasizes the importance of including post-transfusion purpura in the differential diagnosis for both men and women with acute onset of thrombocytopenia following transfusion of blood products. The prompt recognition of this entity is crucial for initiation of the appropriate management.

  10. Immunohistochemical detection of SWC3, CD2, CD3, CD4 and CD8 antigens in paraformaldehyde fixed and paraffin embedded porcine lymphoid tissue

    DEFF Research Database (Denmark)

    Tingstedt, Jens Erik; Tornehave, Ditte; Lind, Peter

    2003-01-01

    Identification of the different cell types of the immune system is important for in situ studies on the pathogenesis of infectious diseases in various animals, including the pig. Unfortunately, many monoclonal anti-leukocyte antibodies are only useful for staining frozen tissue sections with inhe......Identification of the different cell types of the immune system is important for in situ studies on the pathogenesis of infectious diseases in various animals, including the pig. Unfortunately, many monoclonal anti-leukocyte antibodies are only useful for staining frozen tissue sections...... with inherent poor tissue morphology, and are not readily adapted to formaldehyde fixed and paraffin embedded tissue with well preserved morphology. Seven well characterised monoclonal antibodies against porcine leukocyte antigens were tested on neutral buffered paraformaldehyde fixed and paraffin embedded...

  11. COLONOSCOPY AND CARCINOEMBRYONIC ANTIGEN VARIATIONS

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    Rita G SOUSA

    2014-03-01

    Full Text Available Context Colonoscopy is essential for synchronous and metachronous cancer detection. Carcinoembryonic antigen is a colorectal cancer tumor marker, important as a follow-up tool in patients with previous colorectal cancer. False-positive carcinoembryonic antigen elevation results in multiples exams and in patient anxiety. In literature, there is reference to transient carcinoembryonic antigen increase with colonoscopy. Objective To evaluate the influence of bowel preparation and colonoscopy in carcinoembryonic antigen blood levels. Methods We prospectively studied subjects that underwent routine colonoscopy in our institution. Blood samples were collected (1 before bowel cleaning, (2 before colonoscopy and (3 immediately after colonoscopy. Blood carcinoembryonic antigen levels were determined by “Sandwich” immunoassay. The statistical methods used were the paired t-test and ANOVA. Results Thirty-seven patients (22M/15F were included; age range 28-84 (mean 56 years. Mean carcinoembryonic antigen values were 1.9, 2 and 1.8 for (1, (2 and (3, respectively. An increase in value (2 compared with (1 was observed in 20/37 patients (P = 0.018, mainly in younger patients and in patients requiring more endoluminal interventions. In 29/37 patients, the CEA value decreased from (2 to (3 (P = 1.3x10-7. Conclusions A trend for carcinoembryonic antigen increase after bowel cleaning was observed, especially in younger patients and in patients with more endoluminal interventions, but without clinical meaning.

  12. Colonoscopy and carcinoembryonic antigen variations.

    Science.gov (United States)

    Sousa, Rita G; Nunes, Ana; Meira, Tânia; Carreira, Olga; Pires, Ana M; Freitas, João

    2014-01-01

    Colonoscopy is essential for synchronous and metachronous cancer detection. Carcinoembryonic antigen is a colorectal cancer tumor marker, important as a follow-up tool in patients with previous colorectal cancer. False-positive carcinoembryonic antigen elevation results in multiples exams and in patient anxiety. In literature, there is reference to transient carcinoembryonic antigen increase with colonoscopy. To evaluate the influence of bowel preparation and colonoscopy in carcinoembryonic antigen blood levels. We prospectively studied subjects that underwent routine colonoscopy in our institution. Blood samples were collected (1) before bowel cleaning, (2) before colonoscopy and (3) immediately after colonoscopy. Blood carcinoembryonic antigen levels were determined by "Sandwich" immunoassay. The statistical methods used were the paired t-test and ANOVA. Thirty-seven patients (22M/15F) were included; age range 28-84 (mean 56 years). Mean carcinoembryonic antigen values were 1.9, 2 and 1.8 for (1), (2) and (3), respectively. An increase in value (2) compared with (1) was observed in 20/37 patients (P = 0.018), mainly in younger patients and in patients requiring more endoluminal interventions. In 29/37 patients, the CEA value decreased from (2) to (3) (P = 1.3x10-7). A trend for carcinoembryonic antigen increase after bowel cleaning was observed, especially in younger patients and in patients with more endoluminal interventions, but without clinical meaning.

  13. Efficiency of Direct Microscopy of Stool Samples Using an Antigen-Specific Adhesin Test for Entamoeba Histolytica

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    Arzu İrvem

    2016-10-01

    Full Text Available Background: E. histolytica is among the common causes of acute gastroenteritis. The pathogenic species E. histolytica and the nonpathogenic species E. dispar cannot be morphologically differentiated, although correct identification of these protozoans is important for treatment and public health. In many laboratories, the screening of leukocytes, erythrocytes, amoebic cysts, trophozoites and parasite eggs is performed using Native-Lugol’s iodine for pre-diagnosis. Aims: In this study, we aimed to investigate the frequency of E. histolytica in stool samples collected from 788 patients residing in the Anatolian region of İstanbul who presented with gastrointestinal complaints. We used the information obtained to evaluate the effectiveness of microscopic examinations when used in combination with the E. histolytica adhesin antigen test. Study Design: Retrospective cross-sectional study Methods: Preparations of stool samples stained with Native-Lugol’s iodine were evaluated using the E. histolytica adhesin test and examined using standard light microscopy at ×40 magnification. Pearson’s Chi-square and Fisher’s exact tests were used for statistical analysis. Logistic regression analysis was used for multivariate analysis. Results: Of 788 samples, 38 (4.8% were positive for E. histolytica adhesin antigens. When evaluated together with the presences of erythrocytes, leukocytes, cysts, and trophozoites, respectively, using logistic regression analysis, leukocyte positivity was significantly higher. The odds ratio of leukocyte positivity increased adhesin test-positivity by 2,530-fold (95% CI=1.01–6.330. Adhesin test-positivity was significant (p=0.047. Conclusion: In line with these findings, the consistency between the presence of cysts and erythrocytes and adhesin test-positivity was found to be highly significant, but that of higher levels of leukocytes was found to be discordant. It was concluded that leukocytes and trophozoites were

  14. Efficiency of Direct Microscopy of Stool Samples Using an Antigen-Specific Adhesin Test for Entamoeba Histolytica.

    Science.gov (United States)

    İrvem, Arzu; Özdil, Kamil; Çalışkan, Zuhal; Yücel, Muhterem

    2016-09-01

    E. histolytica is among the common causes of acute gastroenteritis. The pathogenic species E. histolytica and the nonpathogenic species E. dispar cannot be morphologically differentiated, although correct identification of these protozoans is important for treatment and public health. In many laboratories, the screening of leukocytes, erythrocytes, amoebic cysts, trophozoites and parasite eggs is performed using Native-Lugol's iodine for pre-diagnosis. In this study, we aimed to investigate the frequency of E. histolytica in stool samples collected from 788 patients residing in the Anatolian region of İstanbul who presented with gastrointestinal complaints. We used the information obtained to evaluate the effectiveness of microscopic examinations when used in combination with the E. histolytica adhesin antigen test. Retrospective cross-sectional study. Preparations of stool samples stained with Native-Lugol's iodine were evaluated using the E. histolytica adhesin test and examined using standard light microscopy at ×40 magnification. Pearson's Chi-square and Fisher's exact tests were used for statistical analysis. Logistic regression analysis was used for multivariate analysis. Of 788 samples, 38 (4.8%) were positive for E. histolytica adhesin antigens. When evaluated together with the presences of erythrocytes, leukocytes, cysts, and trophozoites, respectively, using logistic regression analysis, leukocyte positivity was significantly higher. The odds ratio of leukocyte positivity increased adhesin test-positivity by 2,530-fold (95% CI=1.01-6.330). Adhesin test-positivity was significant (p=0.047). In line with these findings, the consistency between the presence of cysts and erythrocytes and adhesin test-positivity was found to be highly significant, but that of higher levels of leukocytes was found to be discordant. It was concluded that leukocytes and trophozoites were easily misjudged using direct microscopy. Although microscopic examination of samples

  15. Leukocyte Populations in Human Preterm and Term Breast Milk Identified by Multicolour Flow Cytometry.

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    Stephanie Trend

    Full Text Available Extremely preterm infants are highly susceptible to bacterial infections but breast milk provides some protection. It is unknown if leukocyte numbers and subsets in milk differ between term and preterm breast milk. This study serially characterised leukocyte populations in breast milk of mothers of preterm and term infants using multicolour flow cytometry methods for extended differential leukocyte counts in blood.Sixty mothers of extremely preterm (<28 weeks gestational age, very preterm (28-31 wk, and moderately preterm (32-36 wk, as well as term (37-41 wk infants were recruited. Colostrum (d2-5, transitional (d8-12 and mature milk (d26-30 samples were collected, cells isolated, and leukocyte subsets analysed using flow cytometry.The major CD45+ leukocyte populations circulating in blood were also detectable in breast milk but at different frequencies. Progression of lactation was associated with decreasing CD45+ leukocyte concentration, as well as increases in the relative frequencies of neutrophils and immature granulocytes, and decreases in the relative frequencies of eosinophils, myeloid and B cell precursors, and CD16- monocytes. No differences were observed between preterm and term breast milk in leukocyte concentration, though minor differences between preterm groups in some leukocyte frequencies were observed.Flow cytometry is a useful tool to identify and quantify leukocyte subsets in breast milk. The stage of lactation is associated with major changes in milk leukocyte composition in this population. Fresh preterm breast milk is not deficient in leukocytes, but shorter gestation may be associated with minor differences in leukocyte subset frequencies in preterm compared to term breast milk.

  16. Influenza A virus-induced polymorphonuclear leukocyte dysfunction in the pathogenesis of experimental pneumococcal otitis media.

    OpenAIRE

    Abramson, J S; Giebink, G S; Quie, P G

    1982-01-01

    The role of influenza A virus-induced polymorphonuclear leukocyte and eustachian tube dysfunction in the pathogenesis of acute purulent otitis media was studied in chinchillas. Polymorphonuclear leukocyte function, middle ear pressure, and the incidence of pneumococcal otitis media were observed after intranasal inoculation with influenza A virus, Streptococcus pneumoniae, or both. Results showed that depressed negative middle ear pressure and polymorphonuclear leukocyte chemiluminescence and...

  17. JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants

    DEFF Research Database (Denmark)

    Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens

    2014-01-01

    mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA), instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate...... antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and lays the ground for risk stratification for PML and development of therapy and prevention.......JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV...

  18. ImmunoChip study implicates antigen presentation to T cells in narcolepsy.

    Directory of Open Access Journals (Sweden)

    Juliette Faraco

    Full Text Available Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip. Three loci located outside the Human Leukocyte Antigen (HLA region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@, variants in two additional narcolepsy loci, Cathepsin H (CTSH and Tumor necrosis factor (ligand superfamily member 4 (TNFSF4, also called OX40L, attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.

  19. ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

    Science.gov (United States)

    Kornum, Birgitte Rahbek; Kenny, Eimear E.; Trynka, Gosia; Einen, Mali; Rico, Tom J.; Lichtner, Peter; Dauvilliers, Yves; Arnulf, Isabelle; Lecendreux, Michel; Javidi, Sirous; Geisler, Peter; Mayer, Geert; Pizza, Fabio; Poli, Francesca; Plazzi, Giuseppe; Overeem, Sebastiaan; Lammers, Gert Jan; Kemlink, David; Sonka, Karel; Nevsimalova, Sona; Rouleau, Guy; Desautels, Alex; Montplaisir, Jacques; Frauscher, Birgit; Ehrmann, Laura; Högl, Birgit; Jennum, Poul; Bourgin, Patrice; Peraita-Adrados, Rosa; Iranzo, Alex; Bassetti, Claudio; Chen, Wei-Min; Concannon, Patrick; Thompson, Susan D.; Damotte, Vincent; Fontaine, Bertrand; Breban, Maxime; Gieger, Christian; Klopp, Norman; Deloukas, Panos; Wijmenga, Cisca; Hallmayer, Joachim; Onengut-Gumuscu, Suna; Rich, Stephen S.; Winkelmann, Juliane; Mignot, Emmanuel

    2013-01-01

    Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease. PMID:23459209

  20. Defining the immunogenicity and antigenicity of HLA epitopes is crucial for optimal epitope matching in clinical renal transplantation.

    Science.gov (United States)

    Kramer, C S M; Roelen, D L; Heidt, S; Claas, F H J

    2017-07-01

    Transplantation of an human leukocyte antigen (HLA) mismatched graft can lead to the development of donor-specific antibodies (DSA), which can result in antibody mediated rejection and graft loss as well as complicate repeat transplantation. These DSA are induced by foreign epitopes present on the mismatched HLA antigens of the donor. However, not all epitopes appear to be equally effective in their ability to induce DSA. Understanding the characteristics of HLA epitopes is crucial for optimal epitope matching in clinical transplantation. In this review, the latest insights on HLA epitopes are described with a special focus on the definition of immunogenicity and antigenicity of HLA epitopes. Furthermore, the use of this knowledge to prevent HLA antibody formation and to select the optimal donor for sensitised transplant candidates will be discussed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.