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Sample records for selective iga deficiency

  1. A prospective study on oral manifestations in selective IgA deficient patients in children medical center of Tehran University of Medical Sciences (2000- 2001

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    Pourpak Z.

    2001-09-01

    Full Text Available "nAbstract: IgA selective deficiency is the most common immunodeficiency. The prevalence of it in different races varies from  to . Since secretary IgA has has a defensive role in the mucosal surfaces, supposing is thought that IgA deficiency will be accompanied by oral manifestations. The previous studies showed controversial results about that. The aim of this cohort study was to finding out oral manifestations in IgA- deficient individuals. As s result oral specialists can find the patients in early stages. 11 IgA- deficient patients (with IgA level < 10 mg/dl in serum and 11 normal volunteers with the same age and sex were compared. The ages of the people were between 3 and 18 years old and 5 girls and 6 boys were in each group. Their oral examination included DMFT (Decayed, Missed and Filled Teeth, periodontal condition, Plaque accumulation and oral mucosal lesions. Saliva immunoglobulin and secretary component levels were detected by enzyme- linked immunosorbent assay (ELISA and serum immunoglobulin levels were detected by single radial immunodiffusion (SRID methods. All of the IgA- deficient patients had the serum IgA level < 10 mg/dl and their immunoglobulin levels were normal.  of these patients didn't have SIgA and the rest of them had a little SIgA in their saliva(<  SIgA levels in sex and age matched normal group. IgA deficient patients showed no statistical significant difference about oral manifestations in comparison with normal group. It may be related to the increase of compensatory SIgM or assistance of other non- immunological defense factors in saliva, phagocytosis and cellular immunity. Thus IgA- deficiency cannot produce any oral manifestations as a criteria to diagnose it.

  2. Evaluation of natural regulatory T cells in subjects with selective IgA deficiency: from senior idea to novel opportunities.

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    Soheili, Habib; Abolhassani, Hassan; Arandi, Narges; Khazaei, Hossein Ali; Shahinpour, Shervin; Hirbod-Mobarakeh, Armin; Rezaei, Nima; Aghamohammadi, Asghar

    2013-01-01

    Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency disorder, which is characterized by significantly decreased serum levels of IgA. Abnormalities of CD4+CD25(high)forkhead box P3 (FoxP3)+ regulatory T cells (T(reg)) have been shown in association with autoimmune and inflammatory disorders. In order to evaluate the relationship between autoimmunity and T(reg) in SIgAD, we studied 26 IgA-deficient patients (aged 4-17 years) with serum IgA levels 2.36%. Autoimmunity was recorded in 9 patients (53.3%) of G1 and only 1 patient of G2, respectively (p = 0.034). Although a defect in class switching recombination was observed in 40% of the patients in G1, none of the G2 patients had such a defect (p = 0.028). This study showed decreased proportions of T(reg) in SIgAD patients, particularly in those with signs of chronic inflammation. Copyright © 2012 S. Karger AG, Basel.

  3. Class switch recombination in selective IgA-deficient subjects

    DEFF Research Database (Denmark)

    Jensen, Lone Hummelshøj; Ryder, L P; Nielsen, L K

    2006-01-01

    Selective IgA deficiency is a common immunodeficiency in Caucasians, but the molecular basis of the disorder remains elusive. To address this issue we examined the molecular events leading to IgA production. Naive IgD positive B cells were purified from four donors with IgA deficiency and four...

  4. Recombinant human immunoglobulin (Ig)A1 and IgA2 anti-D used for detection of IgA deficiency and anti-IgA

    DEFF Research Database (Denmark)

    Nielsen, Leif K; Dziegiel, Morten Hanefeld

    2008-01-01

    To avoid anaphylactic reactions, immunoglobulin (Ig)A-deficient patients with anti-IgA should be transfused with IgA-deficient blood components. There is a need for fast and robust assays for demonstration of IgA deficiency and for detection of anti-IgA.......To avoid anaphylactic reactions, immunoglobulin (Ig)A-deficient patients with anti-IgA should be transfused with IgA-deficient blood components. There is a need for fast and robust assays for demonstration of IgA deficiency and for detection of anti-IgA....

  5. Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease

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    Colin Reily

    2014-01-01

    Full Text Available Immunoglobulin A (IgA nephropathy (IgAN, the leading cause of primary glomerulonephritis, is characterized by IgA1-containing immunodeposits in the glomeruli. IgAN is a chronic disease, with up to 40% of patients progressing to end-stage renal disease, with no disease-specific treatment. Multiple studies of the origin of the glomerular immunodeposits have linked elevated circulating levels of aberrantly glycosylated IgA1 (galactose-deficient in some O-glycans; Gd-IgA1 with formation of nephritogenic Gd-IgA1-containing immune complexes. Gd-IgA1 is recognized as an autoantigen in susceptible individuals by anti-glycan autoantibodies, resulting in immune complexes that may ultimately deposit in the kidney and induce glomerular injury. Genetic studies have revealed that an elevated level of Gd-IgA1 in the circulation of IgAN patients is a hereditable trait. Moreover, recent genome-wide association studies have identified several immunity-related loci that associated with IgAN. Production of Gd-IgA1 by IgA1-secreting cells of IgAN patients has been attributed to abnormal expression and activity of several key glycosyltransferases. Substantial evidence is emerging that abnormal signaling in IgA1-producing cells is related to the production of Gd-IgA1. As Gd-IgA1 is the key autoantigen in IgAN, understanding the genetic, biochemical, and environmental aspects of the abnormal signaling in IgA1-producing cells will provide insight into possible targets for future disease-specific therapy.

  6. A rare case of Addison's disease, hepatitis, thyreoiditis, positive IgG anti-tissue transglutaminase antibodies and partial IgA deficiency.

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    Baleva, Marta P; Mihaylova, Snejina; Yankova, Petja; Atanasova, Iliana; Nikolova-Vlahova, Milena; Naumova, Elissaveta

    2016-01-01

    Selective IgA deficiency (IgAD) is the most prevalent type of primary immune deficiencies, but partial IgA deficiency is even more common. Addison's disease is a rare condition associated with primary adrenal insufficiency due to infection or autoimmune destruction of the adrenals. The association between IgA deficiency and Addison's disease is very rare. We observed a 22-year-old male patient with marked darkening of the skin, especially on the palms and areolae, jaundice on the skin and sclera, astheno-adynamia, hypotension (80/50 mm Hg), and pain in the right hypochondrium. The laboratory investigations revealed increased serum levels of total and indirect bilirubin, AST, ALT, GGT and LDH, negative HBsAg, anti-HBc IgM, anti-HCV and anti-HAV IgM, very low serum IgA levels (0.16 g/l) with normal IgG and IgM, negative ANA, ANCA, AMA, LKM-1, anti-GAD-60, anti-IA-2, anti-thyroglobulin antibodies, a mild increase in anti-TPO antibodies titer, a marked increase in IgG anti-tissue transglutaminase antibodies, with no typical changes in cellular immunity, negative T-SPOT-TB test, HLA - A*01; B*08; DRB1*03; DQB1*02, karyotype - 46, XY. We present a rare case of partial IgA deficiency with Addison's disease, hepatitis, thyroiditis and positive anti-tissue transglutaminase antibodies. IgAD and some autoimmune disorders share several predisposing HLA genes, thus explaining the increased prevalence of IgAD in certain patient groups.

  7. Antigen-specific IgA titres after 23-valent pneumococcal vaccine indicate transient antibody deficiency disease in children

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    Janssen, Willemijn J M; Nierkens, Stefan; Sanders, Elisabeth A; Boes, Marianne; van Montfrans, Joris M

    2015-01-01

    Paediatric patients with antibody deficiency may either be delayed in development of humoral immunity or may be persistently deficient in antibody production. To differentiate between these entities, we examined the 23-valent pneumococcal polysaccharide (PnPS) vaccine-induced IgM-, IgG- and IgA

  8. IgA deficiency evidence after anti-TNF-α treatment in a psoriatic arthritis patient: case report

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    R. Scarpa

    2012-03-01

    Full Text Available It is known that the use of anti-TNF-α drugs is related to an increased incidence of infective diseases. This therapy can not be administered to patients having active infections and it has to be considered with caution in case of acquired or congenital immunodeficiency diseases. We report the case of a 28-years-old man affected by psoriatic arthritis; he developed some infections during treatment with TNF-α blockers. The infections were caused by a selective IgA deficiency, that was not evident before the anti-TNF-α blockers administration and disappeared after withdrawing the biological therapy. This case-report draws our attention to the possibility of cases of subclinical immunodeficiency, unknown by the patients, but important in the prognosis and in the therapeutic approach to these diseases. Therefore, it is important to evaluate carefully the immunologic status of patients during the pre-therapeutic screening for TNF-α blocking therapy.

  9. Combined IL-12 receptor and IgA deficiency in an adult man intestinally infested by an unknown, non-cultivable mycobacterium

    DEFF Research Database (Denmark)

    Schejbel, L; Rasmussen, E M; Kemp, Helle Bruunsgaard

    2011-01-01

    deficiencies could promote illness. Even though the IgA deficiency in itself does not predispose to mycobacterial disease, the lack of secreted IgA may have disturbed the intestinal homoeostasis and increased the susceptibility to the low-virulent mycobacterium that the patient was not able to clear because...

  10. Interleukin-6-deficient mice refractory to IgA dysregulation but not anorexia induction by vomitoxin (deoxynivalenol) ingestion.

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    Pestka, J J; Zhou, H R

    2000-07-01

    Dietary exposure to the trichothecene vomitoxin (VT) causes feed refusal and elevates IgA production in the mouse. Based on the observations that IL-6 can cause anorexia and promote IgA production and that gene expression of this cytokine is increased in vivo and ex vivo on VT exposure, we hypothesized that IL-6 is an essential cytokine in VT-induced feed refusal and IgA dysregulation. To test this hypothesis, the effects of dietary VT on feed intake, weight gain, serum IgA levels and kidney mesangial IgA deposition in an IL-6-"knockout" mouse (B6129-IL6(tmi Kopf)) were compared to those in both a corresponding "wildtype" (B6129F2) and a previously characterized "sentinel" strain (B6C3F1) that possess the intact gene for this cytokine. IL-6 deficiency did not alter the capacity of VT to cause feed refusal or impair weight gain. VT-fed B6129F2 and B6C3F1 mice had significantly higher serum IgA concentrations than did their corresponding controls fed clean diet, whereas significant differences were not observed between IL-6 KO mice fed VT or control diets. Kidneys taken from VT-fed wild-type and sentinel mice had significantly increased mesangial IgA deposition as compared to controls. While slight increases in mesangial IgA were observed in VT-fed IL-6 KO mice, mean fluorescence intensities were significantly less than that found in the corresponding wild-type and sentinel strains. IL-6 KO mice appeared to be less prone to the development of microscopic haematuria following VT exposure than were the corresponding wild-type and sentinel strains. In total, the results suggested that IL-6-deficient mice were refractory to VT-induced dysregulation of IgA production and development of IgA nephropathy, whereas chronic VT-mediated nutritional effects related to feed intake and weight gain were unaffected.

  11. Genome-Wide Analyses Suggest Mechanisms Involving Early B-Cell Development in Canine IgA Deficiency.

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    Mia Olsson

    Full Text Available Immunoglobulin A deficiency (IgAD is the most common primary immune deficiency disorder in both humans and dogs, characterized by recurrent mucosal tract infections and a predisposition for allergic and other immune mediated diseases. In several dog breeds, low IgA levels have been observed at a high frequency and with a clinical resemblance to human IgAD. In this study, we used genome-wide association studies (GWAS to identify genomic regions associated with low IgA levels in dogs as a comparative model for human IgAD. We used a novel percentile groups-approach to establish breed-specific cut-offs and to perform analyses in a close to continuous manner. GWAS performed in four breeds prone to low IgA levels (German shepherd, Golden retriever, Labrador retriever and Shar-Pei identified 35 genomic loci suggestively associated (p <0.0005 to IgA levels. In German shepherd, three genomic regions (candidate genes include KIRREL3 and SERPINA9 were genome-wide significantly associated (p <0.0002 with IgA levels. A ~20kb long haplotype on CFA28, significantly associated (p = 0.0005 to IgA levels in Shar-Pei, was positioned within the first intron of the gene SLIT1. Both KIRREL3 and SLIT1 are highly expressed in the central nervous system and in bone marrow and are potentially important during B-cell development. SERPINA9 expression is restricted to B-cells and peaks at the time-point when B-cells proliferate into antibody-producing plasma cells. The suggestively associated regions were enriched for genes in Gene Ontology gene sets involving inflammation and early immune cell development.

  12. Selective excretion of IgA in rat bronchial secretions: lack of significant contribution from plasma IgA

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    Lemaitre-Coelho, I.; Yamakido, M.; Montgomery, P.C.; Langendries, A.E.; Vaerman, J.P.

    1982-01-01

    Concentrated rat bronchial washings (BW) were analyzed by gel-filtration and immunochemical methods. BW contained mainly albumin, transferrin and IgG. Free secretory component and secretory IgA were identified in BW; the BW-IgA had the same three sedimentation coefficients, i.e. +/- 11 S, 13 S, 15 S by sucrose density gradient ultracentrifugation, as rat milk and rat bile IgA; the three peaks were secretory IgA. Compared to serum, and relatively to albumin, BW were significantly enriched in IgA, although much less than rat bile. Purified polyclonal rat polymeric 125 I-IgA was injected intravenously into normal rats, and into rats with bile duct ligation or partial hepatectomy, which decrease the liver plasma-to-bile transfer of IgA. BW were then collected, one or four hours later, to assess the recovery of the 125 I-IgA in BW and to estimate the contribution of serum IgA to BW-IgA. Very little 125 I-IgA (less than 0.2%) was recovered in all BW. The specific activity, measured only in the rat with the highest recovery in BW, was 20 times lower in BW than in serum. The data demonstrate that rat serum IgA does not contribute significantly to IgA in BW

  13. Association of IgG co-deposition with serum levels of galactose-deficient IgA1 in pediatric IgA nephropathy

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    Eison, T. Matthew; Hastings, M. Colleen; Moldoveanu, Zina; Sanders, John T.; Gaber, Lillian; Walker, Patrick D.; Lau, Keith K; Julian, Bruce A.; Novak, Jan; Wyatt, Robert J.

    2012-01-01

    Objective: To determine whether the absence of mesangial IgG deposits is associated with the absence of elevated blood levels of galactose-deficient IgA1 (Gd-IgA1) in pediatric patients with IgA nephropathy (IgAN). Design and methods: Serum Gd-IgA1 levels were determined by ELISA using an N-acetylgalactosamine-specific lectin from Helix aspersa. Levels of Gd-IgA1 above the 90th percentile for healthy pediatric controls were considered to be elevated. Renal biopsy samples were examined by immunofluorescence for presence and intensity of staining for IgA, IgG, IgM, C3 and C1q and by light microscopy for histological changes. Findings were graded by a single pathologist (L. Gaber) at UTHSC until 2007 and by NephropathTM (Little Rock, AR, USA) thereafter. Staining for the mesangial deposits was considered negative when intensity was trace or less, and positive at greater intensity. Fisher’s exact-test was used to determine significance of 2 × 2 tables. Results: Serum samples were obtained from 30 patients with IgAN diagnosed before age 18 years. Male : female ratio was 2.3 : 1. Twenty were Caucasian and 10 were African-American. Blood was obtained within 3 months of biopsy (incident cases) for 12, while 18 provided blood > 3 months after biopsy (prevalent cases). Serum Gd-IgA1 level was elevated in 23 (77%) of cases and 20 (67%) had a biopsy positive for IgG. Of those 20 patients, 18 (90%) had an elevated serum Gd-IgA1 level, whereas 5 (50%) of patients with biopsies without IgG had a normal serum Gd-IgA1 level (p = 0.026). Summary: In this small study we found a weak association between the absence of IgG in the biopsy and normal serum Gd-IgA1 level. PMID:23006340

  14. Graves disease and IgA deficiency as manifestations of 22q11.2 deletion syndrome:

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    Silva, João Miguel de Almeida; Silva, Cecília Pereira; Melo, Flavio Fernando Nogueira de; Silva, Luis Alberto A.; Utagawa, Claudia Yamada

    2010-01-01

    A síndrome de deleção 22q11.2 (SD22q11.2) está associada à alta variabilidade fenotípica, abrangendo o espectro velocardiofacial/síndrome de DiGeorge. Manifestações autoimunes, endocrinológicas e de imunodeficiência vêm sendo relatadas associadas à síndrome. O objetivo deste estudo foi relatar um caso de SD22q11.2 associado à deficiência de IgA e à doença de Graves e rever a literatura visando verificar a frequência dessas alterações na SD22q11.2. Os distúrbios autoimunes, cada vez mais relac...

  15. THE IGA SYSTEM

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    South, Mary Ann; Cooper, Max D.; Wollheim, Frank A.; Hong, Richard; Good, Robert A.

    1966-01-01

    1. Five patients with congenital or acquired agammaglobulinemia, lacking detectable IgA in serum or saliva, were transfused with 1 to 2 liters of normal plasma. In 2 of these patients IgA was demonstrated in parotid saliva collected after transfusion, but in none of the 5 was salivary IgG or IgM found. This observation indicates the selective transport of IgA into saliva. 2. The observation by others of an immunochemical difference between serum and sahvary IgA globulin was confirmed. In contrast to serum IgA, salivary IgA is attached to a protein having antigenicity which migrates as a gamma1 globulin. We have termed this protein component "transport piece". 3. The transport piece has been found in an unbound form in the saliva of persons completely lacking IgA: agammaglobulinemic patients, ataxia-telangiectasia patients, a healthy person lacking IgA, and a newborn infant. Free transport piece still occurs in the normal child's saliva after IgA production begins. By adulthood there is usually no free transport piece in the saliva. 4. Heat-aggregated salivary IgA, like heat-aggregated serum IgA, does not fix complement. 5. Our findings offer support for the view that there is a distinct local antibody system for the protection of the mucous surfaces. PMID:4160397

  16. The association of IgA deficiency on infection rate, self-perceived health, and levels of C-reactive protein in healthy blood donors

    DEFF Research Database (Denmark)

    Hauge, Sabina Chaudhary; Jensen, Charlotte Kæstel; Nielsen, Leif Kofoed

    2018-01-01

    The clinical importance of immunoglobulin A (IgA) deficiency in otherwise healthy individuals is not well described. We aimed to investigate the self-reported mental and physical health and the risk of infection in IgA-deficient blood donors compared to healthy control blood donors. Infectious...... events, recorded in public health registries either as prescriptions filled of any antimicrobial medicine or as hospital infections, were compared between 177 IgA-deficient blood donors and 1770 control blood donors. A subset of the IgA-deficient donors were further characterized by self-reported health...... was found with hospital infections (hazard ratio = 1.02, p = 0.95) or self-reported physical health (p = 0.86). IgA-deficient blood donors have impaired self-reported mental health, enhanced inflammation and possibly an increased risk of infection. Despite these findings, this study does not provide...

  17. Class switch recombination in selective IgA-deficient subjects

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    Jensen, Lone Hummelshøj; Ryder, L P; Nielsen, L K

    2006-01-01

    -beta in combination, induced IgA production, albeit lower than found in B cells from controls. The B cells from the IgA-deficient subjects were less effective in differentiating into CD138(+) X-box binding protein 1 (XBP-1)(+) plasma cells when stimulated with TGF-beta, IFN-gamma or IL-10. Interestingly, when adding...

  18. Host Immune Selection of Rumen Bacteria through Salivary Secretory IgA

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    Janelle M. Fouhse

    2017-05-01

    Full Text Available The rumen microbiome is integral to efficient production in cattle and shows strong host specificity, yet little is known about what host factors shape rumen microbial composition. Secretory immunoglobulin A (SIgA is produced in large amounts in the saliva, can coat both commensal and pathogenic microbes within the gut, and presents a plausible mechanism of host specificity. However, the role salivary SIgA plays in commensal bacteria selection in ruminants remains elusive. The main objectives of this study were to develop an immuno-affinity benchtop method to isolate SIgA-tagged microbiota and to determine if salivary SIgA preferentially binds selected bacteria. We hypothesized that SIgA-tagged bacteria would differ from total bacteria, thus supporting a potential host-derived mechanism in commensal bacterial selection. Whole rumen (n = 9 and oral secretion samples (n = 10 were incubated with magnetic beads conjugated with anti-secretory IgA antibodies to enrich SIgA-tagged microbiota. Microbial DNA from the oral secretion, whole rumen, SIgA-tagged oral secretion, and SIgA-tagged rumen was isolated for amplicon sequencing of V1–V3 region of 16S rDNA genes. Whole rumen and oral secretion had distinctive (P < 0.05 bacterial compositions indicated by the non-parametric multidimensional scaling plot using Euclidean distance metrics. The SIgA-tagged microbiota from rumen and oral secretion had similar abundance of Bacteroidetes, Actinobacteria, Fibrobacter, candidate phyla TM7, and Tenericutes and are clustered tightly. Composition of SIgA-tagged oral secretion microbiota was more similar to whole rumen microbiota than whole oral secretion due to enrichment of rumen bacteria (Lachnospiraceae and depletion of oral taxa (Streptococcus, Rothia, Neisseriaceae, and Lactobacillales. In conclusion, SIgA-tagged oral secretion microbiota had an increased resemblance to whole rumen microbiota, suggesting salivary SIgA-coating may be one host

  19. Pili Annulati Coincident with Alopecia Areata, Autoimmune Thyroid Disease, and Primary IgA Deficiency: Case Report and Considerations on the Literature

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    E. Castelli

    2012-11-01

    Full Text Available Pili annulati is a rare autosomal dominant hair disorder clinically characterized by a pattern of alternating bright and dark bands of the hair, the bright bands appearing dark if observed by transmitted light. This pattern is due to the periodic occurrence of air-filled cavities along the hair cortex which scatter and reflect the light while precluding its transmission. A susceptibility region, including a possibly responsible Frizzled gene, has been mapped to the telomeric region of chromosome 12q, although a specific mutation has not been identified. The condition has sometimes been observed in concurrence with alopecia areata, and in this paper we report a case in whom the concomitant severe alopecia areata was associated with autoimmune thyroid disease and primary IgA deficiency – a quadruple complex which, to our knowledge, has never been previously described. The occurrence of multiple immune disorders in the same patient affected by pili annulati could represent a key to understanding the high prevalence of alopecia areata in this condition. Specifically, in individuals predisposed to autoimmune disease, the molecular alterations that cause the anatomical changes of pili annulati could prompt the immune response against the hair root that underlies alopecia areata.

  20. IgA Nephropathy and Henoch-Schoenlein Purpura Nephritis: Aberrant Glycosylation of IgA1, Formation of IgA1-Containing Immune Complexes, and Activation of Mesangial Cells

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    Novak, J.; Moldoveanu, Z.; Renfrow, M.B.

    2007-01-01

    IgA1 in the circulation and glomerular deposits of patients with IgA nephropathy (IgAN) is aberrantly glycosylated; the hinge-region O-linked glycans are galactose-deficient. The circulating IgA1 of patients with Henoch-Schoenlein purpura nephritis (HSPN) has a similar defect. This aberrancy...

  1. Aberrantly Glycosylated IgA1 as a Factor in the Pathogenesis of IgA Nephropathy

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    Mototsugu Tanaka

    2011-01-01

    Full Text Available Predominant or codominant immunoglobulin (Ig A deposition in the glomerular mesangium characterizes IgA nephropathy (IgAN. Accumulated glomerular IgA is limited to the IgA1 subclass and usually galactose-deficient. This underglycosylated IgA may play an important role in the pathogenesis of IgAN. Recently, antibodies against galactose-deficient IgA1 were found to be well associated with the development of IgAN. Several therapeutic strategies based on corticosteroids or other immunosuppressive agents have been shown to at least partially suppress the progression of IgAN. On the other hand, several case reports of kidney transplantation or acquired IgA deficiency uncovered a remarkable ability of human kidney to remove mesangial IgA deposition, resulting in the long-term stabilization of kidney function. Continuous exposure to circulating immune complexes containing aberrantly glycosylated IgA1 and sequential immune response seems to be essential in the disease progression of IgAN. Removal of mesangial IgA deposition may be a challenging, but fundamental approach in the treatment of IgAN.

  2. Inhibition of STAT3 Signaling Reduces IgA1 Autoantigen Production in IgA Nephropathy

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    Koshi Yamada

    2017-11-01

    Discussion: Our results revealed that IL-6−induced aberrant activation of STAT3-mediated overproduction of galactose-deficient IgA1. STAT3 signaling pathway may thus represent a new target for disease-specific therapy of IgA nephropathy.

  3. Malacoplakia associated with vesicoureteral reflux and selective immunoglobulin A deficiency.

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    Witherington, R; Branan, W J; Wray, B B; Best, G K

    1984-11-01

    A case of malacoplakia involving the lower urinary tract of a young black boy, with associated bilateral vesicoureteral reflux, hydronephrosis and selective immunoglobulin A deficiency is reported. Reflux was caused by the malacoplakia. Reflux and hydronephrosis persisted despite elimination of bacterial infection and malacoplakia by drug therapy. These abnormalities were corrected by a conventional antireflux operation. Malacoplakia appears to be related to immunologic incompetence and diminished levels of intracellular cyclic 3',5' guanine monophosphate. Cholinergic agonists reverse or prevent the pathological changes of malacoplakia.

  4. Human antibodies to immunoglobulin A (IgA)

    International Nuclear Information System (INIS)

    Munster, P.J.J. van; Nadorp, J.H.S.M.; Shuurman, H.J.

    1978-01-01

    In the sera of 12 out of 27 individuals with IgA deficiency (serum level below 0.02 mg IgA/m) class-specific anti-IgA antibodies were demonstrated by haemagglutination. These sera showed false-positive results in a solid-phase inhibition radioimmunoassay (RIST) (apparent IgA concentration between 0.6 and 13.7 μg IgA/ml) indicating that the RIST is not an appropriate test for the analysis of serum of IgA seficient individuals. A modification of the RIST is proposed (titration RIA) that permits differentiation between low levels of IgA and class-specific anti-IgA antibodies. With this test IgA deficient individuals could be classified as those with low but detectable levels of IgA and those with class-specific anti-IgA antibodies. A computer procedure was developed to calculate both the amount and the avidity (K) of the anti-IgA antibodies and to simulate the assay system. The K value calculated from experimental points proved to be an overestimation of the K value which fitted most adequately in the simulation. The comparison of the results with clinical findings indicated a possible correlation between the amount and the avidity of the anti-IgA antibodies and the appearence of anaphylactic reactions after transfusion of IgA. (Auth.)

  5. False-positive radioactive iodine uptake mimicking miliary lung metastases in a patient affected by papillary thyroid cancer and IgA deficiency

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    Demidowich, Andrew Paul; Reynolds, James C. [National Institutes of Health, Bethesda (United States); Kundu, Amartya [Dept. of MedicineUniversity of Massachusetts Medical School, Worcester (United States); Celi, Francesco S. [Div. of Endocrinology and MetabolismVirginia Commonwealth UniversityRichmond (United States)

    2016-09-15

    A 42-year-old female with immunoglobulin A deficiency and recurrent sinopulmonary infections underwent thyroidectomy for papillary thyroid cancer (PTC). Follow-up {sup 123}I scintigraphy demonstrated diffuse pulmonary uptake, suggesting metastatic disease. However, subsequent pathologic, biochemical and radiographic testing proved that she was in fact disease free, and the initial {sup 123}I pulmonary uptake was identified as a false positive. Inflammatory conditions may rarely cause iodine uptake in non-thyroidal tissues due to local retention, organification, and/or immunologic utilization. To avoid exposing patients to unnecessary treatments, it is critical for clinicians to recognize that comorbid pulmonary conditions may mimic metastatic PTC on radioiodine scintigraphy.

  6. Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry: implications for IgA nephropathy

    DEFF Research Database (Denmark)

    Renfrow, MB; Mackay, CL; Chalmers, MJ

    2007-01-01

    deficiency in IgA1 proteins occurs randomly or preferentially at specific sites. We have previously demonstrated the first direct localization of multiple O-glycosylation sites on a single IgA1 myeloma protein by use of activated ion-electron capture dissociation (AI-ECD) Fourier transform ion cyclotron...... resonance (FT-ICR) tandem mass spectrometry. Here, we report the analysis of IgA1 O-glycan heterogeneity by use of FT-ICR MS and liquid chromatography FT-ICR MS to obtain unbiased accurate mass profiles of IgA1 HR glycopeptides from three different IgA1 myeloma proteins. Additionally, we report the first AI......-ECD fragmentation on an individual IgA1 O-glycopeptide from an IgA1 HR preparation that is reproducible for each IgA1 myeloma protein. These results suggest that future analysis of IgA1 HR from IgAN patients and normal healthy controls should be feasible....

  7. IgA nephropathy enigma

    Czech Academy of Sciences Publication Activity Database

    Městecký, Jiří; Novák, J.; Moldoveanu, Z.; Raška, M.

    2016-01-01

    Roč. 172, NOV 2016 SI (2016), s. 72-77 ISSN 1521-6616 R&D Projects: GA MZd(CZ) NV15-33686A Institutional support: RVO:61388971 Keywords : IgA nephropathy * IgA subclasses * Autoimmunity Subject RIV: EE - Microbiology, Virology Impact factor: 3.990, year: 2016

  8. Selected systems engineering process deficiencies and their consequences

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    Thomas, L. Dale

    2007-06-01

    The systems engineering process is well established and well understood. While this statement could be argued in the light of the many systems engineering guidelines and that have been developed, comparative review of these respective descriptions reveal that they differ primarily in the number of discrete steps or other nuances, and are at their core essentially common. Likewise, the systems engineering textbooks differ primarily in the context for application of systems engineering or in the utilization of evolved tools and techniques, not in the basic method. Thus, failures in systems engineering cannot credibly be attributed to implementation of the wrong systems engineering process among alternatives. However, numerous system failures can be attributed to deficient implementation of the systems engineering process. What may clearly be perceived as a systems engineering deficiency in retrospect can appear to be a well considered system engineering efficiency in real time—an efficiency taken to reduce cost or meet a schedule, or more often both. Typically these efficiencies are grounded on apparently solid rationale, such as reuse of heritage hardware or software. Over time, unintended consequences of a systems engineering process deficiency may begin to be realized, and unfortunately often the consequence is systems failure. This paper describes several actual cases of system failures that resulted from deficiencies in their systems engineering process implementation, including the Ariane 5 and the Hubble Space Telescope.

  9. Select cognitive deficits in Vasoactive Intestinal Peptide deficient mice

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    Hagopian Arkady

    2008-07-01

    Full Text Available Abstract Background The neuropeptide vasoactive intestinal peptide (VIP is widely distributed in the adult central nervous system where this peptide functions to regulate synaptic transmission and neural excitability. The expression of VIP and its receptors in brain regions implicated in learning and memory functions, including the hippocampus, cortex, and amygdala, raise the possibility that this peptide may function to modulate learned behaviors. Among other actions, the loss of VIP has a profound effect on circadian timing and may specifically influence the temporal regulation of learning and memory functions. Results In the present study, we utilized transgenic VIP-deficient mice and the contextual fear conditioning paradigm to explore the impact of the loss of this peptide on a learned behavior. We found that VIP-deficient mice exhibited normal shock-evoked freezing behavior and increases in corticosterone. Similarly, these mutant mice exhibited no deficits in the acquisition or recall of the fear-conditioned behavior when tested 24-hours after training. The VIP-deficient mice exhibited a significant reduction in recall when tested 48-hours or longer after training. Surprisingly, we found that the VIP-deficient mice continued to express circadian rhythms in the recall of the training even in those individual mice whose wheel running wheel activity was arrhythmic. One mechanistic explanation is suggested by the finding that daily rhythms in the expression of the clock gene Period2 continue in the hippocampus of VIP-deficient mice. Conclusion Together these data suggest that the neuropeptide VIP regulates the recall of at least one learned behavior but does not impact the circadian regulation of this behavior.

  10. Present status of understanding on the G6PD deficiency and natural selection

    Directory of Open Access Journals (Sweden)

    Tripathy V

    2007-01-01

    Full Text Available G6PD deficiency is a common hemolytic genetic disorder, particularly in the areas endemic to malaria. Individuals are generally asymptomatic and hemolytic anemia occurs when some anti-malarial drugs or other oxidizing chemicals are administered. It has been proposed that G6PD deficiency provides protection against malaria. Maintaining of G6PD deficient alleles at polymorphic proportions is complicated because of the X-linked nature of G6PD deficiency. A comprehensive review of the literature on the hypothesis of malarial protection and the nature of the selection is being presented. Most of the epidemiological, in vitro and in vivo studies report selection for G6PD deficiency. Analysis of the G6PD gene also reveals that G6PD-deficient alleles show some signatures of selection. However, the question of how this polymorphism is being maintained remains unresolved because the selection/fitness coefficients for the different genotypes in the two sexes have not been established. Prevalence of G6PD deficiency in Indian caste and tribal populations and the different variants reported has also been reviewed.

  11. A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction.

    Science.gov (United States)

    Lafayette, Richard A; Canetta, Pietro A; Rovin, Brad H; Appel, Gerald B; Novak, Jan; Nath, Karl A; Sethi, Sanjeev; Tumlin, James A; Mehta, Kshama; Hogan, Marie; Erickson, Stephen; Julian, Bruce A; Leung, Nelson; Enders, Felicity T; Brown, Rhubell; Knoppova, Barbora; Hall, Stacy; Fervenza, Fernando C

    2017-04-01

    IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m 2 , to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy. Copyright © 2017 by the American Society of Nephrology.

  12. Iga viies SVH on ennetatav

    Index Scriptorium Estoniae

    2009-01-01

    ONTARGET uuring tõestab, et telmisartaan kaitseb kõrge kardiovaskulaarse riskiga patsiente sama tõhusalt kui ramipriil, kuid on paremini talutav. Uuringust võib järeldada, et telmisartaaniga saab ennetada iga viiendat tõsist kardiovaskulaarset juhtumit. Eesti arstidele tutvustati uuringut 6. mail toimunud sümpoosiumil

  13. Rhodium metalloinsertor binding generates a lesion with selective cytotoxicity for mismatch repair-deficient cells.

    Science.gov (United States)

    Bailis, Julie M; Weidmann, Alyson G; Mariano, Natalie F; Barton, Jacqueline K

    2017-07-03

    The DNA mismatch repair (MMR) pathway recognizes and repairs errors in base pairing and acts to maintain genome stability. Cancers that have lost MMR function are common and comprise an important clinical subtype that is resistant to many standard of care chemotherapeutics such as cisplatin. We have identified a family of rhodium metalloinsertors that bind DNA mismatches with high specificity and are preferentially cytotoxic to MMR-deficient cells. Here, we characterize the cellular mechanism of action of the most potent and selective complex in this family, [Rh(chrysi)(phen)(PPO)] 2+ (Rh-PPO). We find that Rh-PPO binding induces a lesion that triggers the DNA damage response (DDR). DDR activation results in cell-cycle blockade and inhibition of DNA replication and transcription. Significantly, the lesion induced by Rh-PPO is not repaired in MMR-deficient cells, resulting in selective cytotoxicity. The Rh-PPO mechanism is reminiscent of DNA repair enzymes that displace mismatched bases, and is differentiated from other DNA-targeted chemotherapeutics such as cisplatin by its potency, cellular mechanism, and selectivity for MMR-deficient cells.

  14. Selective Cytotoxicity of Rhodium Metalloinsertors in Mismatch Repair-Deficient Cells†

    Science.gov (United States)

    Ernst, Russell J.; Komor, Alexis C.; Barton, Jacqueline K.

    2011-01-01

    Mismatches in DNA occur naturally during replication and as a result of endogenous DNA damaging agents, but the mismatch repair (MMR) pathway acts to correct mismatches before subsequent rounds of replication. Rhodium metalloinsertors bind to DNA mismatches with high affinity and specificity and represent a promising strategy to target mismatches in cells. Here we examine the biological fate of rhodium metalloinsertors bearing dipyridylamine ancillary ligands in cells deficient in MMR versus those that are MMR-proficient. These complexes are shown to exhibit accelerated cellular uptake which permits the observation of various cellular responses, including disruption of the cell cycle, monitored by flow cytometry assays, and induction of necrosis, monitored by dye exclusion and caspase inhibition assays, that occur preferentially in the MMR-deficient cell line. These cellular responses provide insight into the mechanisms underlying the selective activity of this novel class of targeted anti-cancer agents. PMID:22103240

  15. Characterization and Selection of Phosphorus Deficiency Tolerant Rice Genotypes in Sri Lanka

    Directory of Open Access Journals (Sweden)

    Y.C. Aluwihare

    2016-07-01

    Full Text Available Phosphorus (P deficiency in soil is a major constrain for rice production. An important set of rice genotypes (landraces, old improved and new improved varieties were screened for P deficiency tolerance in two major cropping seasons of Sri Lanka, in 2012. The Ultisol soil, which was collected from a plot cultivated with rice without fertilizer application for past 40 years (P0 at the Rice Research and Development Institute (RRDI, Bathalagoda, Sri Lanka, was used as the potting medium for greenhouse trials. Two field trials were conducted in the same plots at RRDI. Both P0 and P30 (30 mg/kg P2O5 conditions were used in the two greenhouse trials. At the early vegetative (three weeks after transplanting, late vegetative (six weeks after transplanting and flowering stages, plant height and number of tillers per plant were recorded. At the flowering stage, shoots were harvested and shoot dry weight, shoot P concentration, shoot P uptake and P utilization efficiency were measured. All data were statistically analyzed using analysis of variance, regression and cluster procedures. The measured parameters were significantly different between P0 and P30 conditions (P < 0.05. Higher shoot dry weight was reported by the rice genotypes H4 and Marss under P0 conditions. The regression analysis between shoot dry weight and P utilization efficiency revealed that the studied rice genotypes could be categorized to three P deficiency tolerance classes. A total of 13 genotypes could be considered as highly tolerant and 4 genotypes as sensitive for P deficiency. These results could be used to select parental genotypes for breeding and genetic studies and also to select interesting varieties or landraces for organic rice production.

  16. Isolated lymphoid follicles are not IgA inductive sites for recombinant Salmonella

    International Nuclear Information System (INIS)

    Hashizume, Tomomi; Momoi, Fumiki; Kurita-Ochiai, Tomoko; Kaminogawa, Shuichi; Hosono, Akira; Kataoka, Kosuke; Shinozaki-Kuwahara, Noriko; Kweon, Mi-Na; Yamamoto, Masafumi

    2007-01-01

    In this study, we investigated whether isolated lymphoid follicles (ILF) play a role in the regulation of intestinal IgA antibody (Ab) responses. The transfer of wild type (WT) bone marrow (BM) to lymphotoxin-α-deficient (LTα -/- ) mice resulted in the formation of mature ILF containing T cells, B cells, and FDC clusters in the absence of mesenteric lymph nodes and Peyer's patches. Although the ILF restored total IgA Abs in the intestine, antigen (Ag)-specific IgA responses were not induced after oral immunization with recombinant Salmonella expressing fragment C of tetanus toxin. Moreover, Ag-specific cell proliferation was not detected in the ILF. Interestingly, no IgA anti-LPS Abs were detected in the fecal extracts of LTα -/- mice reconstituted with WT BM. On the basis of these findings, ILF can be presumed to play a role in the production of IgA Abs, but lymphoid nodules are not inductive sites for the regulation of Ag-specific intestinal IgA responses to recombinant Salmonella

  17. Truly selective primary IgM deficiency is probably very rare.

    Science.gov (United States)

    Janssen, L M A; Macken, T; Creemers, M C W; Pruijt, J F M; Eijk, J J J; de Vries, E

    2018-02-01

    Isolated decreased serum-immunoglobulin (Ig)M has been associated with severe and/or recurrent infections, atopy and autoimmunity. However, the reported high prevalence of clinical problems in IgM-deficient patients may reflect the skewed tertiary centre population studied so far. Also, many papers on IgM deficiency have included patients with more abnormalities than simply IgM-deficiency. We studied truly selective primary IgM deficiency according to the diagnostic criteria of the European Society for Immunodeficiencies (ESID) (true sIgMdef) by reviewing the literature (261 patients with primary decreased serum-IgM in 46 papers) and analysing retrospectively all patients with decreased serum-IgM in a large teaching hospital in 's-Hertogenbosch, the Netherlands [1 July 2005-23 March 2016; n = 8049 IgM < 0·4 g/l; n = 2064 solitary (IgG+IgA normal/IgM < age-matched reference)]. A total of 359 of 2064 (17%) cases from our cohort had primary isolated decreased serum-IgM, proven persistent in 45 of 359 (13%) cases; their medical charts were reviewed. Our main finding is that true sIgMdef is probably very rare. Only six of 261 (2%) literature cases and three of 45 (7%) cases from our cohort fulfilled the ESID criteria completely; 63 of 261 (24%) literature cases also had other immunological abnormalities and fulfilled the criteria for unclassified antibody deficiencies (unPAD) instead. The diagnosis was often uncertain (possible sIgMdef): data on IgG subclasses and/or vaccination responses were lacking in 192 of 261 (74%) literature cases and 42 of 45 (93%) cases from our cohort. Our results also illustrate the clinical challenge of determining the relevance of a serum sample with decreased IgM; a larger cohort of true sIgMdef patients is needed to explore fully its clinical consequences. The ESID online Registry would be a useful tool for this. © 2017 British Society for Immunology.

  18. Glomerular diseases: emerging tests and therapies for IgA nephropathy.

    Science.gov (United States)

    Canetta, Pietro A; Kiryluk, Krzysztof; Appel, Gerald B

    2014-03-01

    The last decade has seen major progress in understanding the pathogenesis as well as the prognosis and treatment of patients with IgA nephropathy (IgAN). Although the diagnostic criterion of a kidney biopsy demonstrating dominant or codominant IgA deposition remains unchanged, much more is known about the genetic and environmental factors predisposing to disease development and progression. These advances have led to the identification of novel diagnostic and prognostic markers. Among the most promising clinically are genetic profiling, quantification of galactose-deficient IgA1 levels, and measurement of anti-IgA1 immunoglobulins. While targeted treatment for IgAN remains elusive, there is mounting evidence for therapeutic interventions that alter the disease course. The appropriate validation and integration of these discoveries into clinical care represent a major challenge, but one that holds tremendous promise for refining prognostication, guiding therapy, and improving the lives of patients with IgAN.

  19. Low pretransplant IgA level is associated with early post-lung transplant seromucous infection.

    Science.gov (United States)

    Murthy, Sudish C; Avery, Robin K; Budev, Marie; Gupta, Sandeep; Pettersson, Gösta B; Nowicki, Edward R; Mehta, Atul; Chapman, Jeffrey T; Rajeswaran, Jeevanantham; Blackstone, Eugene H

    2018-04-13

    Infection is an important cause of morbidity and mortality after lung transplantation. Immunoglobulins are part of both seromucous (IgA) and serum (IgG) infection defense mechanisms. We therefore hypothesized that lower pretransplant IgA levels would be associated with more early post-lung transplant seromucous infections and greater mortality independent of IgG. From January 2000 to July 2010, 538 patients undergoing primary lung transplantation had pretransplant IgA (n = 429) and IgG (n = 488) measured as a clinical routine. Median IgA was 200 mg·dL -1 (2% < 70 mg·dL -1 , lower limit of normal); median IgG was 970 mg·dL -1 (5% < 600 mg·dL -1 ). Intensive microbiology review was used to categorize infections and their causative organisms within the first posttransplant year. In total, 397 seromucous infections were observed in 247 patients, most bacterial. Although IgA and IgG were moderately correlated (r = 0.5, P < .0001), low pretransplant IgA was a strong risk factor (P = .01) for seromucous infections, but pretransplant IgG was not (P ≥ .6). As pretransplant IgA levels fell below 200 mg·dL -1 , the risk of these posttransplant infections rose nearly linearly. Lower pretransplant levels of IgA were associated with greater posttransplant mortality to end of follow-up (P = .004), but pretransplant IgG was not (P ≥ .3). Low levels of preoperative IgA, an important immunoglobulin involved in mucosal immunologic defense, but not IgG, are associated with seromucous infections in the year after lung transplantation and increased follow-up mortality. It would appear prudent to identify patients with relative IgA deficiency at listing and to increase vigilance of monitoring for, and prophylaxis against, seromucous infection in this high-risk population. Copyright © 2018. Published by Elsevier Inc.

  20. Cleavage of a recombinant human immunoglobulin A2 (IgA2)-IgA1 hybrid antibody by certain bacterial IgA1 proteases

    DEFF Research Database (Denmark)

    Senior, B; Dunlop, JI; Batten, MR

    2000-01-01

    , Streptococcus pneumoniae, S. sanguis, Neisseria meningitidis types 1 and 2, N. gonorrhoeae types 1 and 2, and Haemophilus influenzae type 2. Thus, for these enzymes the recognition site for IgA1 cleavage is contained within half of the IgA1 hinge region; additional distal elements, if required, are provided...... by either an IgA1 or an IgA2 framework. In contrast, the IgA2/A1 hybrid appeared to be resistant to cleavage with S. oralis and some H. influenzae type 1 IgA1 proteases, suggesting these enzymes require additional determinants for efficient substrate recognition....

  1. Recurrence and graft loss after renal transplantation in adults with IgA vasculitis.

    Science.gov (United States)

    Kawabe, Mayuko; Yamamoto, Izumi; Komatsuzaki, Yo; Yamakawa, Takafumi; Katsumata, Haruki; Katsuma, Ai; Mafune, Aki; Nakada, Yasuyuki; Kobayashi, Akimitsu; Tanno, Yudo; Ohkido, Ichiro; Tsuboi, Nobuo; Yokoyama, Keitaro; Horita, Shigeru; Okumi, Masayoshi; Ishida, Hideki; Yamamoto, Hiroyasu; Yokoo, Takashi; Tanabe, Kazunari

    2017-08-01

    IgA vasculitis, a rare condition resulting in end-stage renal disease, is a small-vessel vasculitis that affects the kidney in 49-83 % of adults. The reported recurrence rate of IgA vasculitis in renal transplant recipients is 11.5-60 %, leading to graft loss in 0-50 % of these patients. However, limited data are available on recurrence and graft loss after renal transplantation. We evaluated renal transplant recipients seen from 1987 to 2015 at the Jikei University School of Medicine and the Department of Urology, Tokyo Women's Medical University. Using a 1:2 match, 21 patients with IgA vasculitis and 42 controls were selected. The mean post-transplant follow-up was 121 ± 69 months for IgA vasculitis and 147 ± 66 months for the controls. The 15-year patient survival was 100 % in IgA vasculitis and 97.6 % in the controls (p = 0.22). The 5-, 10-, and 15-year graft survival rates were 95.2, 90.5, and 81 % in IgA vasculitis and 100, 90.5, and 88.1 % in the controls, respectively (p = 0.63). The recurrence rate was 28.6 % (6 of 21 cases) and half of them (3 of 6 cases) showed histological activity (ISKDC III). We treated them with methylprednisolone pulse therapy and/or tonsillectomy. None of the recurrence cases lost the allograft. The long-term patient and graft survival of IgA vasculitis in renal transplantation were comparable with the previous reports. The recurrence rate was 28.6 %, but none of the recurrent cases showed allograft loss in this study. We speculate that methylprednisolone pulse therapy and/or tonsillectomy prevent the progression of recurrent IgA vasculitis.

  2. Gut TFH and IgA: key players for regulation of bacterial communities and immune homeostasis.

    Science.gov (United States)

    Kato, Lucia M; Kawamoto, Shimpei; Maruya, Mikako; Fagarasan, Sidonia

    2014-01-01

    The main function of the immune system is to protect the host against pathogens. However, unlike the systemic immune system, the gut immune system does not eliminate, but instead nourishes complex bacterial communities and establishes advanced symbiotic relationships. Immunoglobulin A (IgA) is the most abundant antibody isotype in mammals, produced mainly in the gut. The primary function of IgA is to maintain homeostasis at mucosal surfaces, and studies in mice have demonstrated that IgA diversification has an essential role in the regulation of gut microbiota. Dynamic diversification and constant adaptation of IgA responses to local microbiota require expression of activation-induced cytidine deaminase by B cells and control from T follicular helper and Foxp3(+) T cells in germinal centers (GCs). We discuss the finely tuned regulatory mechanisms for IgA synthesis in GCs of Peyer's patches and emphasize the roles of CD4(+) T cells for IgA selection and the maintenance of appropriate gut microbial communities required for immune homeostasis.

  3. Hyperammonaemic encephalopathy secondary to selective cobalamin deficiency in a juvenile Border collie.

    Science.gov (United States)

    Battersby, I A; Giger, U; Hall, E J

    2005-07-01

    An eight-month-old Border collie was presented with anorexia, cachexia, failure to thrive and stupor. Laboratory tests demonstrated a mild anaemia, neutropenia, proteinuria and hyperammonaemia. Serum bile acid concentrations were normal, but an ammonia tolerance test (ATT) was abnormal. The dog responded to symptomatic therapy for hepatoencephalopathy. When a low serum cobalamin (vitamin B12) concentration and methylmalonic aciduria were noted, the dog was given a supplement of parenteral cobalamin. Two weeks later, a repeat ATT was normal. Cobalamin supplementation was continued every two weeks, and all clinical signs, except for proteinuria, resolved despite withdrawing all therapy for hepatoencephalopathy. A presumptive diagnosis of hereditary selective cobalamin malabsorption was made, based on the young age, Border collie breed, low serum cobalamin concentration and methylmalonic aciduria. Although hereditary selective cobalamin malabsorption in Border collies, giant schnauzers, Australian shepherd dogs and beagles has previously been reported in North America, to the authors' knowledge this is the first report of the condition in the UK and the first to document an abnormal ATT in a cobalamin-deficient dog.

  4. Prevalence of G6PD deficiency in selected populations from two previously high malaria endemic areas of Sri Lanka.

    Directory of Open Access Journals (Sweden)

    Sharmini Gunawardena

    Full Text Available Glucose-6-Phosphate Dehydrogenase (G6PD enzyme deficiency is known to offer protection against malaria and an increased selection of mutant genes in malaria endemic regions is expected. However, anti-malarial drugs such as primaquine can cause haemolytic anaemia in persons with G6PD deficiency. We studied the extent of G6PD deficiency in selected persons attending Teaching Hospitals of Anuradhapura and Kurunegala, two previously high malaria endemic districts in Sri Lanka. A total of 2059 filter-paper blood spots collected between November 2013 and June 2014 were analysed for phenotypic G6PD deficiency using the modified WST-8/1-methoxy PMS method. Each assay was conducted with a set of controls and the colour development assessed visually as well as with a microplate reader at OD450-630nm. Overall, 142/1018 (13.95% and 83/1041 (7.97% were G6PD deficient in Anuradhapura and Kurunegala districts respectively. The G6PD prevalence was significantly greater in Anuradhapura when compared to Kurunegala (P0.05. Severe deficiency (<10% normal was seen among 28/1018 (2.75% in Anuradhapura (7 males; 21 females and 17/1041 (1.63% in Kurunegala (7 males; 10 females. Enzyme activity between 10-30% was observed among 114/1018 (11.20%; 28 males; 86 females in Anuradhapura while it was 66/1041 (6.34%; 18 males; 48 females in Kurunegala. Screening and educational programmes for G6PD deficiency are warranted in these high risk areas irrespective of gender for the prevention of disease states related to this condition.

  5. Selection of radioresistant cells by vitamin A deficiency in a small cell lung cancer cell line

    International Nuclear Information System (INIS)

    Terasaki, Takeo; Shimosato, Yukio; Wada, Makio; Yokota, Jun; Terada, Masaaki

    1990-01-01

    Radiation sensitivity of a human small cell lung cancer cell line, Lu-134-B cells, cultured in serum-supplemented medium and of cells transferred to and cultured in delipidized serum-supplemented (vitamin A-deficient) medium was studied. The cells cultured in serum-supplemented medium showed the phenotype of classic small cell lung cancer sensitive to radiation, while cells transferred to delipidized serum-supplemented medium showed partial squamous cell differentiation and became resistant to radiation. These results suggest that some small cell lung cancer cells in vitro change their morphology and radiosensitivity depending on the culture conditions. The change in radiosensitivity was reproducible, and was not reversible by culture of the radioresistant cells in delipidized serum-supplemented medium with addition of retinoic acid (vitamin A-sufficient medium) for two months, although squamous cells disappeared. Acquisition of radioresistancy was considered to occur as the result of clonal selective growth in delipidized medium of a minor cell population in the original cell culture, based on a study of chromosome number. It was also found that there was no association of myc-family oncogenes with the changes of radiosensitivity in this cell line. (author)

  6. Zinc content of selected tissues and taste perception in rats fed zinc deficient and zinc adequate rations

    International Nuclear Information System (INIS)

    Boeckner, L.S.; Kies, C.

    1986-01-01

    The objective of the study was to determine the effects of feeding zinc sufficient and zinc deficient rations on taste sensitivity and zinc contents of selected organs in rats. The 36 Sprague-Dawley male weanling rats were divided into 2 groups and fed zinc deficient or zinc adequate rations. The animals were subjected to 4 trial periods in which a choice of deionized distilled water or a solution of quinine sulfate at 1.28 x 10 -6 was given. A randomized schedule for rat sacrifice was used. No differences were found between zinc deficient and zinc adequate rats in taste preference aversion scores for quinine sulfate in the first three trial periods; however, in the last trial period rats in the zinc sufficient group drank somewhat less water containing quinine sulfate as a percentage of total water consumption than did rats fed the zinc deficient ration. Significantly higher zinc contents of kidney, brain and parotid salivary glands were seen in zinc adequate rats compared to zinc deficient rats at the end of the study. However, liver and tongue zinc levels were lower for both groups at the close of the study than were those of rats sacrificed at the beginning of the study

  7. Linear IgA Bullous Dermatosis

    DEFF Research Database (Denmark)

    Lings, Kristina; Bygum, Anette

    2015-01-01

    Linear IgA bullous dermatosis (LAD) is an autoimmune, chronic bullous disease affecting primarily young children and adults. Studies on LAD are relatively sparse and from Scandinavia we could only find a few case reports. Therefore we decided to conduct a retrospective investigation of patients...

  8. Phase Field Modeling Using PetIGA

    KAUST Repository

    Vignal, Philippe; Collier, Nathan; Calo, Victor M.

    2013-01-01

    , and having a highly efficient and parallel framework to solve them is necessary. In this work, a brief review on phase field models is given, followed by a short analysis of the Phase Field Crystal Model solved with Isogeometric Analysis us- ing PetIGA. We

  9. Pyoderma gangrenosum in association with microscopic colitis, idiopathic hypereosinophilic syndrome, selective IgE deficiency and diabetes mellitus.

    Science.gov (United States)

    Riyaz, N; Sasidharanpillai, S; Rahima, S; Bindu, V; Shaan, M; Raghavan, N T; Mohan, L; Janardhanan, A K

    2015-08-01

    Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown aetiology. We report a 27-year-old male patient with diabetes, who presented with a nonhealing ulcer on the left leg, pruritic hyperpigmented papules distributed over the trunk and limbs, and chronic diarrhoea. He had eosinophilia, low haemoglobin and serum IgE levels, and raised erythrocyte sedimentation rate. Histopathology of the leg ulcer was consistent with the diagnosis of PG, while the histology of the hyperpigmented papule revealed tissue eosinophilia. Subsequent evaluation was conclusive of the diagnosis of PG, idiopathic hypereosinophilic syndrome (IHES) and selective IgE deficiency. Dexamethasone pulse therapy achieved resolution of the ulcer and reduction in the eosinophilia. Further evaluation for the persistent diarrhoea led to a diagnosis of lymphocytic colitis (LC), which responded to budesonide. To our knowledge, the association of PG with IHES, selective IgE deficiency or LC has not been previously reported. © 2015 British Association of Dermatologists.

  10. Placental transfer of maternally-derived IgA precludes the use of guthrie card eluates as a screening tool for primary immunodeficiency diseases.

    Directory of Open Access Journals (Sweden)

    Stephan Borte

    Full Text Available There is a need for neonatal screening tools to improve the long-term clinical outcome of patients with primary immunodeficiency diseases (PID. Recently, a PCR-based screening method for both TRECs and KRECs using Guthrie card samples has been developed. However, the applicability of these excision circle assays is limited to patients with severe T or B cell lymphopenia (SCID, XLA and A-T, whereas the most common forms of PID are not detected. Absence of serum IgA is seen in a major fraction of patients with immunological defects. As serum IgA in newborns is considered to be of fetal origin, eluates from routinely collected dried blood spot samples might thus be suitable for identification of children with PID. To assess the applicability of such screening assays, stored Guthrie card samples were obtained from 47 patients with various forms of primary immunodeficiency diseases (SCID, XLA, A-T, HIGM and IgAD, 20 individuals with normal serum IgA levels born to IgA-deficient mothers and 51 matched healthy newborns. Surprisingly, normal serum IgA levels were found in all SCID, XLA, A-T and HIGM patients and, additionally, in all those IgAD patients born to IgA-sufficient mothers. Conversely, no serum IgA was found in any of the 16 IgAD patients born by IgA-deficient mothers. Moreover, half of the IgA-sufficient individuals born by IgA-deficient mothers also lacked IgA at birth whereas no IgA-deficient individuals were found among the controls. IgA in neonatal dried blood samples thus appears to be of both maternal and fetal origin and precludes its use as a reliable marker for neonatal screening of primary immunodeficiency diseases.

  11. Placental transfer of maternally-derived IgA precludes the use of guthrie card eluates as a screening tool for primary immunodeficiency diseases.

    Science.gov (United States)

    Borte, Stephan; Janzi, Magdalena; Pan-Hammarström, Qiang; von Döbeln, Ulrika; Nordvall, Lennart; Winiarski, Jacek; Fasth, Anders; Hammarström, Lennart

    2012-01-01

    There is a need for neonatal screening tools to improve the long-term clinical outcome of patients with primary immunodeficiency diseases (PID). Recently, a PCR-based screening method for both TRECs and KRECs using Guthrie card samples has been developed. However, the applicability of these excision circle assays is limited to patients with severe T or B cell lymphopenia (SCID, XLA and A-T), whereas the most common forms of PID are not detected. Absence of serum IgA is seen in a major fraction of patients with immunological defects. As serum IgA in newborns is considered to be of fetal origin, eluates from routinely collected dried blood spot samples might thus be suitable for identification of children with PID. To assess the applicability of such screening assays, stored Guthrie card samples were obtained from 47 patients with various forms of primary immunodeficiency diseases (SCID, XLA, A-T, HIGM and IgAD), 20 individuals with normal serum IgA levels born to IgA-deficient mothers and 51 matched healthy newborns. Surprisingly, normal serum IgA levels were found in all SCID, XLA, A-T and HIGM patients and, additionally, in all those IgAD patients born to IgA-sufficient mothers. Conversely, no serum IgA was found in any of the 16 IgAD patients born by IgA-deficient mothers. Moreover, half of the IgA-sufficient individuals born by IgA-deficient mothers also lacked IgA at birth whereas no IgA-deficient individuals were found among the controls. IgA in neonatal dried blood samples thus appears to be of both maternal and fetal origin and precludes its use as a reliable marker for neonatal screening of primary immunodeficiency diseases.

  12. Arginine Deficiency Causes Runting in the Suckling Period by Selectively Activating the Stress Kinase GCN2

    NARCIS (Netherlands)

    Marion, Vincent; Sankaranarayanan, Selvakumari; de Theije, Chiel; van Dijk, Paul; Lindsey, Patrick; Lamers, Marinus C.; Harding, Heather P.; Ron, David; Lamers, Wouter H.; Koehler, S. Eleonore

    2011-01-01

    Suckling "F/A2" mice, which overexpress arginase-I in their enterocytes, develop a syndrome (hypoargininemia, reduced hair and muscle growth, impaired B-cell maturation) that resembles IGF1 deficiency. The syndrome may result from an impaired function of the GH-IGF1 axis, activation of the

  13. Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?

    Directory of Open Access Journals (Sweden)

    Floriana Giorgio

    2015-09-01

    Full Text Available In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs count and gluten “challenge” are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG-targeted mucosal immunoglobulin A (IgA immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs’ range of 15–25/100 enterocytes, suggesting that there may be a “grey zone” of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID/IgA selective deficiency. CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD. We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD is rare (<300 cases and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association.

  14. Evaluating the relationship between dental caries number and salivary level of IgA in adults

    Science.gov (United States)

    Haeri-Araghi, Hesam; Safarzadeh-Khosroshahi, Shadab; Mirzadeh, Monirsadat

    2018-01-01

    Background Dental caries are the most common mouth infectious disease and also chronic disease of childhood. Saliva plays different roles in oral cavity; for example, salivary immunoglobulins play significant role in body and oral immunity. Various studies were conducted on the different effects of IgA on oral cavity, especially dental caries, and reported controversial results. The current study aimed to compare salivary IgA level at different stages of dental caries in adults. Material and Methods A total of 40 adults, aged 20 to 40 years, referred to the department of oral medicine at Qazvin Faculty of Dentistry, were selected voluntarily based on the number of decayed teeth. Their unstimulated saliva was collected by the spitting method. The cases were assigned to 4 groups each of 10, based on the number of decayed teeth, as follows: Group 1: Caries free, Group 2: With 1 or 2 decayed teeth, Group 3: With 3 or 4 decayed teeth, and Group 4: With 5 or more decayed teeth. None of the cases had systemic diseases or the history of using medicines which affect the quality or quantity of saliva. The salivary IgA level of the cases was measured immunoturbidometrically and analyzed by ANOVA and t test. Results Significant difference was observed between the groups 1 and 4, but there was no significant difference between the other groups. Conclusions According to the results of the current study, the salivary IgA can be considered as an index for the function of immune system, which may be increased by the number of decayed teeth. In fact, the increase of salivary IgA is just the response of immune system to the accumulation of microorganisms and may be the attempt of body to control them. Key words:Saliva, IgA, Dental caries. PMID:29670718

  15. A sparse version of IGA solvers

    KAUST Repository

    Beck, Joakim

    2017-07-30

    Isogeometric Analysis (IGA) typically adopts tensor-product splines and NURBS as a basis for the approximation of the solution of PDEs. In this work, we investigate to which extent IGA solvers can benefit from the so-called sparse-grids construction in its combination technique form, which was first introduced in the early 90s in the context of the approximation of high-dimensional PDEs. The tests that we report show that, in accordance to the literature, a sparse grids construction can indeed be useful if the solution of the PDE at hand is sufficiently smooth. Sparse grids can also be useful in the case of non-smooth solutions when some a-priori knowledge on the location of the singularities of the solution can be exploited to devise suitable non-equispaced meshes. Finally, we remark that sparse grids can be seen as a simple way to parallelize pre-existing serial IGA solvers in a straightforward fashion, which can be beneficial in many practical situations.

  16. A sparse version of IGA solvers

    KAUST Repository

    Beck, Joakim; Sangalli, Giancarlo; Tamellini, Lorenzo

    2017-01-01

    Isogeometric Analysis (IGA) typically adopts tensor-product splines and NURBS as a basis for the approximation of the solution of PDEs. In this work, we investigate to which extent IGA solvers can benefit from the so-called sparse-grids construction in its combination technique form, which was first introduced in the early 90s in the context of the approximation of high-dimensional PDEs. The tests that we report show that, in accordance to the literature, a sparse grids construction can indeed be useful if the solution of the PDE at hand is sufficiently smooth. Sparse grids can also be useful in the case of non-smooth solutions when some a-priori knowledge on the location of the singularities of the solution can be exploited to devise suitable non-equispaced meshes. Finally, we remark that sparse grids can be seen as a simple way to parallelize pre-existing serial IGA solvers in a straightforward fashion, which can be beneficial in many practical situations.

  17. Nefropatia por IgA nas espondiloartrites IgA nephropathy in spondyloarthritis

    Directory of Open Access Journals (Sweden)

    Daniela Castelo Azevedo

    2011-02-01

    Full Text Available Pacientes com espondiloartrites poderiam ser mais acometidos pela nefropatia por IgA do que a população geral, havendo, possivelmente, um mecanismo etiopatogênico comum. O seguinte artigo relaciona quatro casos que exemplificam essa possível associaçãoSpondyloarthritis patients can be more frequently affected by IgA nephropathy than the general population, and a common etiopathogenic mechanism can be involved. We report four cases that may exemplify that association

  18. Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion.

    Science.gov (United States)

    Carbonaro, Denise A; Jin, Xiangyang; Cotoi, Daniel; Mi, Tiejuan; Yu, Xiao-Jin; Skelton, Dianne C; Dorey, Frederick; Kellems, Rodney E; Blackburn, Michael R; Kohn, Donald B

    2008-06-15

    Adenosine deaminase (ADA)-deficient severe combined immune deficiency (SCID) may be treated by allogeneic hematopoietic stem cell transplantation without prior cytoreductive conditioning, although the mechanism of immune reconstitution is unclear. We studied this process in a murine gene knockout model of ADA-deficient SCID. Newborn ADA-deficient pups received transplants of intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, which resulted in long-term survival, multisystem correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses. Only 1% to 3% of lymphocytes and myeloid cells were of donor origin without a selective expansion of donor-derived lymphocytes; immune reconstitution was by endogenous, host-derived ADA-deficient lymphocytes. Preconditioning of neonates with 100 to 400 cGy of total body irradiation before normal donor marrow transplant increased the levels of engrafted donor cells in a radiation dose-dependent manner, but the chimerism levels were similar for lymphoid and myeloid cells. The absence of selective reconstitution by donor T lymphocytes in the ADA-deficient mice indicates that restoration of immune function occurred by rescue of endogenous ADA-deficient lymphocytes through cross-correction from the engrafted ADA-replete donor cells. Thus, ADA-deficient SCID is unique in its responses to nonmyeloablative bone marrow transplantation, which has implications for clinical bone marrow transplantation or gene therapy.

  19. The kinetics of glomerular deposition of nephritogenic IgA.

    Directory of Open Access Journals (Sweden)

    Kenji Yamaji

    Full Text Available Whether IgA nephropathy is attributable to mesangial IgA is unclear as there is no correlation between intensity of deposits and extent of glomerular injury and no clear mechanism explaining how these mesangial deposits induce hematuria and subsequent proteinuria. This hinders the development of a specific therapy. Thus, precise events during deposition still remain clinical challenge to clarify. Since no study assessed induction of IgA nephropathy by nephritogenic IgA, we analyzed sequential events involving nephritogenic IgA from IgA nephropathy-prone mice by real-time imaging systems. Immunofluorescence and electron microscopy showed that serum IgA from susceptible mice had strong affinity to mesangial, subepithelial, and subendothelial lesions, with effacement/actin aggregation in podocytes and arcade formation in endothelial cells. The deposits disappeared 24-h after single IgA injection. The data were supported by a fluorescence molecular tomography system and real-time and 3D in vivo imaging. In vivo imaging showed that IgA from the susceptible mice began depositing along the glomerular capillary from 1 min and accumulated until 2-h on the first stick in a focal and segmental manner. The findings indicate that glomerular IgA depositions in IgAN may be expressed under the balance between deposition and clearance. Since nephritogenic IgA showed mesangial as well as focal and segmental deposition along the capillary with acute cellular activation, all glomerular cellular elements are a plausible target for injury such as hematuria.

  20. Selective oxidation of n-butane to maleic anhydride under oxygen-deficient conditions over V-P-O mixed oxides

    NARCIS (Netherlands)

    Bosch, H.; Bruggink, A.A.; Ross, J.R.H.

    1987-01-01

    The selective oxidation of n-butane to maleic anhydride over V-P-O mixed oxides was studied under oxygen deficient conditions. The mixed oxides were prepared with P/V atomic ratios ranging from 0.7 to 1.0. Catalysts with P/V <1.0 did not show any selectivity to maleic anhydride formation, regardless

  1. Correlation of Serum Anti- Helicobacter pylori Immunoglobulin A (IGA)

    African Journals Online (AJOL)

    Background: The seroprevalence of anti-H. pylori IgA antibodies has been reported to vary among populations and in relation to strains of Helicobacter pylori bacterium. However, there has been conflicting reports on the association between IgA serological status and the histological variables of chronic gastritis. This study ...

  2. The mucosal adjuvant cholera toxin B instructs non-mucosal dendritic cells to promote IgA production via retinoic acid and TGF-β.

    Directory of Open Access Journals (Sweden)

    Anouk K Gloudemans

    Full Text Available It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA, and how T cell-dependent (TD or -independent (TI pathways might be involved. Mucosal dendritic cells (DCs are the primary antigen presenting cells driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL, B cell activating factor (BAFF, Retinoic Acid (RA, TGF-β or nitric oxide (NO. We hypothesized that the mucosal adjuvant Cholera Toxin subunit B (CTB could imprint non-mucosal DCs to induce IgA synthesis, and studied the mechanism of its induction. In vitro, CTB-treated bone marrow derived DCs primed for IgA production by B cells without the help of T cells, yet required co-signaling by different Toll-like receptor (TLR ligands acting via the MyD88 pathway. CTB-DC induced IgA production was blocked in vitro or in vivo when RA receptor antagonist, TGF-β signaling inhibitor or neutralizing anti-TGF-β was added, demonstrating the involvement of RA and TGF-β in promoting IgA responses. There was no major involvement for BAFF, APRIL or NO. This study highlights that synergism between CTB and MyD88-dependent TLR signals selectively imprints a TI IgA-inducing capacity in non-mucosal DCs, explaining how CTB acts as an IgA promoting adjuvant.

  3. The mucosal adjuvant cholera toxin B instructs non-mucosal dendritic cells to promote IgA production via retinoic acid and TGF-β.

    Science.gov (United States)

    Gloudemans, Anouk K; Plantinga, Maud; Guilliams, Martin; Willart, Monique A; Ozir-Fazalalikhan, Arifa; van der Ham, Alwin; Boon, Louis; Harris, Nicola L; Hammad, Hamida; Hoogsteden, Henk C; Yazdanbakhsh, Maria; Hendriks, Rudi W; Lambrecht, Bart N; Smits, Hermelijn H

    2013-01-01

    It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL), B cell activating factor (BAFF), Retinoic Acid (RA), TGF-β or nitric oxide (NO). We hypothesized that the mucosal adjuvant Cholera Toxin subunit B (CTB) could imprint non-mucosal DCs to induce IgA synthesis, and studied the mechanism of its induction. In vitro, CTB-treated bone marrow derived DCs primed for IgA production by B cells without the help of T cells, yet required co-signaling by different Toll-like receptor (TLR) ligands acting via the MyD88 pathway. CTB-DC induced IgA production was blocked in vitro or in vivo when RA receptor antagonist, TGF-β signaling inhibitor or neutralizing anti-TGF-β was added, demonstrating the involvement of RA and TGF-β in promoting IgA responses. There was no major involvement for BAFF, APRIL or NO. This study highlights that synergism between CTB and MyD88-dependent TLR signals selectively imprints a TI IgA-inducing capacity in non-mucosal DCs, explaining how CTB acts as an IgA promoting adjuvant.

  4. The first dose of a Haemophilus influenzae type b conjugate vaccine reactivates memory B cells: evidence for extensive clonal selection, intraclonal affinity maturation, and multiple isotype switches to IgA2

    DEFF Research Database (Denmark)

    Hougs, L; Juul, L; Ditzel, H J

    1999-01-01

    selected, and expanded population of cells existing before vaccination, i.e., memory B cells. The dominating heavy and light chains of the response were combined in a Fab that bound HibCP. It was shown that the shared heavy and light chain mutations increased the affinity for HibCP considerably, indicating...

  5. Phase Field Modeling Using PetIGA

    KAUST Repository

    Vignal, Philippe

    2013-06-01

    Phase field modeling has become a widely used framework in the computational material science community. Its ability to model different problems by defining appropriate phase field parameters and relating it to a free energy functional makes it highly versatile. Thermodynamically consistent partial differential equations can then be generated by assuming dissipative dynamics, and setting up the problem as one of minimizing this free energy. The equations are nonetheless challenging to solve, and having a highly efficient and parallel framework to solve them is necessary. In this work, a brief review on phase field models is given, followed by a short analysis of the Phase Field Crystal Model solved with Isogeometric Analysis us- ing PetIGA. We end with an introduction to a new modeling concept, where free energy functions are built with a periodic equilibrium structure in mind.

  6. Molecular Analysis of Activation-Induced Cytidine Deaminase Gene in Immunoglobulin-E Deficient Patients

    Directory of Open Access Journals (Sweden)

    Sergio Roa

    2008-01-01

    Full Text Available Understanding how class switch recombination (CSR is regulated to produce immunoglobulin E (IgE has become fundamental because of the dramatic increase in the prevalence of IgE-mediated hypersensitivity reactions. CSR requires the induction of the enzyme AICDA in B cells. Mutations in AICDA have been linked to Hyper-IgM syndrome (HIGM2, which shows absence of switching to IgE as well as to IgG and IgA. Although isolated IgE deficiency is a rare entity, here we show some individuals with normal serum IgM, IgG, and IgA levels that had undetectable total serum IgE levels. We have analyzed the AICDA gene in these individuals to determine if there are mutations in AICDA that could lead to selective IgE deficiency. Conformational sensitive gel electrophoresis (CSGE and sequencing analysis of AICDA coding sequences demonstrated sequence heterogeneity due to 5923A/G and 7888C/T polymorphisms, but did not reveal any novel mutation that might explain the selective IgE deficit.

  7. Treatment of IgA nephropathy.

    Science.gov (United States)

    Barratt, J; Feehally, J

    2006-06-01

    IgA nephropathy (IgAN) is an important cause of progressive kidney disease with 25-30% of patients developing end-stage renal disease within 20 years of diagnosis. There is still no treatment to modify mesangial IgA deposition and available treatments are those extrapolated from the management of other patterns of chronic glomerulonephritis. There remains no consensus on the use of immunosuppressive agents for treatment of progressive IgAN and this is compounded by the relative lack in IgAN of randomized controlled trials relevant to current clinical practice. Patients with recurrent macroscopic hematuria or isolated microscopic hematuria and proteinuria renal biopsy should be managed as for minimal change nephropathy. There is no evidence to support the use of corticosteroids for nephrotic IgAN outside this group of patients. Patients presenting with acute renal failure require evaluation to distinguish acute tubular necrosis, which requires supportive therapy only, from crescentic IgAN, for which treatment with cyclophosphamide and corticosteroids in a regimen similar to that for renal small vessel vasculitis is indicated in the absence of significant chronic histologic injury. Patients at greatest risk of progressive renal impairment are those with hypertension, proteinuria >1 g/24 h, and reduced glomerular filtration rate at diagnosis. All such patients should be treated to a blood pressure of 125/75 mm Hg with dual blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibition and angiotensin receptor blockade. At present, there is insufficient evidence for the additional use of immunosuppressive agents, antiplatelet agents, or anticoagulants.

  8. Selective muscle fiber loss and molecular compensation in mitochondrial myopathy due to TK2 deficiency.

    Science.gov (United States)

    Vilà, Maya R; Villarroya, Joan; García-Arumí, Elena; Castellote, Amparo; Meseguer, Anna; Hirano, Michio; Roig, Manuel

    2008-04-15

    A 12-year-old patient with mitochondrial DNA (mtDNA) depletion syndrome due to TK2 gene mutations has been evaluated serially over the last 10 years. We observed progressive muscle atrophy with selective loss of type 2 muscle fibers and, despite severe depletion of mtDNA, normal activities of respiratory chain (RC) complexes and levels of COX II mitochondrial protein in the remaining muscle fibers. These results indicate that compensatory mechanisms account for the slow progression of the disease. Identification of factors that ameliorate mtDNA depletion may reveal new therapeutic targets for these devastating disorders.

  9. Evaluation of salivary glucose, IgA and flow rate in diabetic patients: a case-control study.

    Science.gov (United States)

    Bakianian Vaziri, P; Vahedi, M; Mortazavi, H; Abdollahzadeh, Sh; Hajilooi, M

    2010-01-01

    An association between diabetes mellitus and alterations in the oral cavity has been noted. In this study, we evaluated differences between salivary IgA, glucose and flow rate in diabetic patients compared with healthy controls. Forty patients with type 1 diabetes, 40 patients with type 2 diabetes and 40 healthy controls were selected. Whole unstimulated saliva samples were collected by the standard method and the salivary flow rate was determined. Nephelometric and Pars method were used to measure salivary IgA and salivary glucose concentrations, respectively. Statistical analysis was performed by Chi-square and t test. There were no significant differences in salivary IgA and glucose concentrations between type 1 and type 2 diabetic patients and their matched control subjects (P>0.05). Salivary flow rate was significantly lower in diabetic patients (Pdiabetic patients than the controls. Determination of salivary constituents may be useful in the description and management of oral findings in diabetic patients.

  10. Selective deficiencies in descending inhibitory modulation in neuropathic rats: implications for enhancing noradrenergic tone.

    Science.gov (United States)

    Patel, Ryan; Qu, Chaoling; Xie, Jennifer Y; Porreca, Frank; Dickenson, Anthony H

    2018-05-31

    Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury. In vivo electrophysiology was performed in anaesthetised spinal nerve ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus (VPL). In sham rats, spinal block of α2-adrenoceptors with atipamezole resulted in enhanced stimulus-evoked and spontaneous firing in the VPL, and produced conditioned place avoidance. However, in SNL rats these conditioned avoidance behaviours were absent. Furthermore, inhibitory control of evoked neuronal responses was lost but spinal atipamezole markedly increased spontaneous firing. Augmenting spinal noradrenergic tone in neuropathic rats with reboxetine, a selective noradrenergic reuptake inhibitor, modestly reinstated inhibitory control of evoked responses in the VPL but had no effect on spontaneous firing. In contrast, clonidine, an α2 agonist, inhibited both evoked and spontaneous firing, and exhibited increased potency in SNL rats compared to sham controls. These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic system provide relief.

  11. Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD).

    Science.gov (United States)

    McCullagh, Brian N; Comellas, Alejandro P; Ballas, Zuhair K; Newell, John D; Zimmerman, M Bridget; Azar, Antoine E

    2017-01-01

    Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors. We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations. We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome. We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency. We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed. Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time. A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year. Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1). Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations. This case series identifies antibody deficiency as a

  12. Storage Pool Deficiencies

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  13. Selective killing of tumors deficient in methylthioadenosine phosphorylase: a novel strategy.

    Directory of Open Access Journals (Sweden)

    Martin Lubin

    2009-05-01

    .We describe a selective strategy to kill tumor cells lacking MTAP.

  14. IL-17A promotes protective IgA responses and expression of other potential effectors against the lumen-dwelling enteric parasite Giardia.

    Science.gov (United States)

    Dann, Sara M; Manthey, Carolin F; Le, Christine; Miyamoto, Yukiko; Gima, Lauren; Abrahim, Andrew; Cao, Anthony T; Hanson, Elaine M; Kolls, Jay K; Raz, Eyal; Cong, Yingzi; Eckmann, Lars

    2015-09-01

    Giardia lamblia is a leading protozoan cause of diarrheal disease worldwide. It colonizes the lumen and epithelial surface of the small intestine, but does not invade the mucosa. Acute infection causes only minimal mucosal inflammation. Effective immune defenses exist, yet their identity and mechanisms remain incompletely understood. Interleukin (IL)-17A has emerged as an important cytokine involved in inflammation and antimicrobial defense against bacterial pathogens at mucosal surfaces. In this study, we demonstrate that IL-17A has a crucial function in host defense against Giardia infection. Using murine infection models with G. muris and G. lamblia, we observed marked and selective induction of intestinal IL-17A with peak expression after 2 weeks. Th17 cells in the lamina propria and innate immune cells in the epithelial compartment of the small intestine were responsible for the IL-17A response. Experiments in gene-targeted mice revealed that the cytokine, and its cognate receptor IL-17RA, were required for eradication of the parasite. The actions of the cytokine were mediated by hematopoietic cells, and were required for the transport of IgA into the intestinal lumen, since IL-17A deficiency led to marked reduction of fecal IgA levels, as well as for increased intestinal expression of several other potential effectors, including β-defensin 1 and resistin-like molecule β. In contrast, intestinal hypermotility, another major antigiardial defense mechanism, was not impacted by IL-17A loss. Taken together, these findings demonstrate that IL-17A and IL-17 receptor signaling are essential for intestinal defense against the important lumen-dwelling intestinal parasite Giardia. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Borrelia burgdorferi-specific IgA in Lyme Disease

    Directory of Open Access Journals (Sweden)

    Christina D'Arco

    2017-05-01

    Full Text Available The laboratory diagnosis of Lyme disease is currently dependent on the detection of IgM and IgG antibodies against Borrelia burgdorferi, the causative agent of the disease. The significance of serum IgA against B. burgdorferi remains unclear. The production of intrathecal IgA has been noted in patients with the late Lyme disease manifestation, neuroborreliosis, but production of antigen-specific IgA during early disease has not been evaluated. In the current study, we assessed serum IgA binding to the B. burgdorferi peptide antigens, C6, the target of the FDA-cleared C6 EIA, and FlaB(211-223-modVlsE(275-291, a peptide containing a Borrelia flagellin epitope linked to a modified VlsE sequence, in patients with early and late Lyme disease. Specific IgA was detected in 59 of 152 serum samples (38.8% from early Lyme disease patients. Approximately 50% of early Lyme disease patients who were seropositive for peptide-specific IgM and/or IgG were also seropositive for peptide-specific IgA. In a subpopulation of patients, high peptide-specific IgA could be correlated with disseminated disease, defined as multiple erythema migrans lesions, and neurological disease complications. These results suggest that there may be an association between elevated levels of antigen-specific IgA and particular disease manifestations in some patients with early Lyme disease.

  16. Borrelia burgdorferi-specific IgA in Lyme Disease.

    Science.gov (United States)

    D'Arco, Christina; Dattwyler, Raymond J; Arnaboldi, Paul M

    2017-05-01

    The laboratory diagnosis of Lyme disease is currently dependent on the detection of IgM and IgG antibodies against Borrelia burgdorferi, the causative agent of the disease. The significance of serum IgA against B. burgdorferi remains unclear. The production of intrathecal IgA has been noted in patients with the late Lyme disease manifestation, neuroborreliosis, but production of antigen-specific IgA during early disease has not been evaluated. In the current study, we assessed serum IgA binding to the B. burgdorferi peptide antigens, C6, the target of the FDA-cleared C6 EIA, and FlaB(211-223)-modVlsE(275-291), a peptide containing a Borrelia flagellin epitope linked to a modified VlsE sequence, in patients with early and late Lyme disease. Specific IgA was detected in 59 of 152 serum samples (38.8%) from early Lyme disease patients. Approximately 50% of early Lyme disease patients who were seropositive for peptide-specific IgM and/or IgG were also seropositive for peptide-specific IgA. In a subpopulation of patients, high peptide-specific IgA could be correlated with disseminated disease, defined as multiple erythema migrans lesions, and neurological disease complications. These results suggest that there may be an association between elevated levels of antigen-specific IgA and particular disease manifestations in some patients with early Lyme disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. A synthetic interaction screen identifies factors selectively required for proliferation and TERT transcription in p53-deficient human cancer cells.

    Directory of Open Access Journals (Sweden)

    Li Xie

    Full Text Available Numerous genetic and epigenetic alterations render cancer cells selectively dependent on specific genes and regulatory pathways, and represent potential vulnerabilities that can be therapeutically exploited. Here we describe an RNA interference (RNAi-based synthetic interaction screen to identify genes preferentially required for proliferation of p53-deficient (p53- human cancer cells. We find that compared to p53-competent (p53+ human cancer cell lines, diverse p53- human cancer cell lines are preferentially sensitive to loss of the transcription factor ETV1 and the DNA damage kinase ATR. In p53- cells, RNAi-mediated knockdown of ETV1 or ATR results in decreased expression of the telomerase catalytic subunit TERT leading to growth arrest, which can be reversed by ectopic TERT expression. Chromatin immunoprecipitation analysis reveals that ETV1 binds to a region downstream of the TERT transcriptional start-site in p53- but not p53+ cells. We find that the role of ATR is to phosphorylate and thereby stabilize ETV1. Our collective results identify a regulatory pathway involving ETV1, ATR, and TERT that is preferentially important for proliferation of diverse p53- cancer cells.

  18. Interaction between the macrophage system and IgA immune complexes in IgA nephropathy.

    Science.gov (United States)

    Roccatello, D; Coppo, R; Basolo, B; Martina, G; Rollino, C; Cordonnier, D; Busquet, G; Picciotto, G; Sena, L M; Piccoli, G

    1983-01-01

    In nine patients with IgA nephropathy, the function of the mononuclear phagocyte system was assessed by measuring in vivo clearance of anti-D coated red blood cells (RBC) and in vitro phagocytosis of sensitised RBC by monocytes. A strict correlation was found between in vivo macrophage function and in vitro monocyte phagocytosis. Statistical correlations were also found between in vivo clearance values and IgAIC and C3d values. A defective macrophage and monocyte function affects patients with major signs of clinical activity, highest IgAIC values, signs of complement activation and the most unfavourable clinical course.

  19. Oral administration of Lactobacillus plantarum strain AYA enhances IgA secretion and provides survival protection against influenza virus infection in mice.

    Directory of Open Access Journals (Sweden)

    Yosuke Kikuchi

    Full Text Available The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer's patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer's patch dendritic cells, with this production promoting IgA(+ B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection.

  20. Pathophysiology of B-cell intrinsic immunoglobulin class switch recombination deficiencies.

    Science.gov (United States)

    Durandy, Anne; Taubenheim, Nadine; Peron, Sophie; Fischer, Alain

    2007-01-01

    B-cell intrinsic immunoglobulin class switch recombination (Ig-CSR) deficiencies, previously termed hyper-IgM syndromes, are genetically determined conditions characterized by normal or elevated serum IgM levels and an absence or very low levels of IgG, IgA, and IgE. As a function of the molecular mechanism, the defective CSR is variably associated to a defect in the generation of somatic hypermutations (SHMs) in the Ig variable region. The study of Ig-CSR deficiencies contributed to a better delineation of the mechanisms underlying CSR and SHM, the major events of antigen-triggered antibody maturation. Four Ig-CSR deficiency phenotypes have been so far reported: the description of the activation-induced cytidine deaminase (AID) deficiency (Ig-CSR deficiency 1), caused by recessive mutations of AICDA gene, characterized by a defect in CSR and SHM, clearly established the role of AID in the induction of the Ig gene rearrangements underlying CSR and SHM. A CSR-specific function of AID has, however, been detected by the observation of a selective CSR defect caused by mutations affecting the C-terminus of AID. Ig-CSR deficiency 2 is the consequence of uracil-N-glycosylase (UNG) deficiency. Because UNG, a molecule of the base excision repair machinery, removes uracils from DNA and AID deaminates cytosines into uracils, that observation indicates that the AID-UNG pathway directly targets DNA of switch regions from the Ig heavy-chain locus to induce the CSR process. Ig-CSR deficiencies 3 and 4 are characterized by a selective CSR defect resulting from blocks at distinct steps of CSR. A further understanding of the CSR machinery is expected from their molecular definition.

  1. Inhibition of GSK-3β Rescues the Impairments in Bone Formation and Mechanical Properties Associated with Fracture Healing in Osteoblast Selective Connexin 43 Deficient Mice

    Science.gov (United States)

    Loiselle, Alayna E.; Lloyd, Shane A. J.; Paul, Emmanuel M.; Lewis, Gregory S.; Donahue, Henry J.

    2013-01-01

    Connexin 43 (Cx43) is the most abundant gap junction protein in bone and is required for osteoblastic differentiation and bone homeostasis. During fracture healing, Cx43 is abundantly expressed in osteoblasts and osteocytes, while Cx43 deficiency impairs bone formation and healing. In the present study we selectively deleted Cx43 in the osteoblastic lineage from immature osteoblasts through osteocytes and tested the hypothesis that Cx43 deficiency results in delayed osteoblastic differentiation and impaired restoration of biomechanical properties due to attenuated β-catenin expression relative to wild type littermates. Here we show that Cx43 deficiency results in alterations in the mineralization and remodeling phases of healing. In Cx43 deficient fractures the mineralization phase is marked by delayed expression of osteogenic genes. Additionally, the decrease in the RankL/ Opg ratio, osteoclast number and osteoclast size suggest decreased osteoclast bone resorption and remodeling. These changes in healing result in functional deficits as shown by a decrease in ultimate torque at failure. Consistent with these impairments in healing, β-catenin expression is attenuated in Cx43 deficient fractures at 14 and 21 days, while Sclerostin (Sost) expression, a negative regulator of bone formation is increased in Cx43cKO fractures at 21 days, as is GSK-3β, a key component of the β-catenin proteasomal degradation complex. Furthermore, we show that alterations in healing in Cx43 deficient fractures can be rescued by inhibiting GSK-3β activity using Lithium Chloride (LiCl). Treatment of Cx43 deficient mice with LiCl restores both normal bone formation and mechanical properties relative to LiCl treated WT fractures. This study suggests that Cx43 is a potential therapeutic target to enhance fracture healing and identifies a previously unknown role for Cx43 in regulating β-catenin expression and thus bone formation during fracture repair. PMID:24260576

  2. Biomarkers for IgA nephropathy on the basis of multi-hit pathogenesis.

    Science.gov (United States)

    Suzuki, Hitoshi

    2018-05-08

    IgA nephropathy (IgAN) is the most prevalent glomerular disease worldwide and is associated with a poor prognosis. Development of curative treatment strategies and approaches for early diagnosis is necessary. Renal biopsy is the gold standard for the diagnosis and assessment of disease activity. However, reliable biomarkers are needed for the noninvasive diagnosis of this disease and to more fully delineate the risk of progression. With regard to the pathogenesis of IgAN, the multi-hit hypothesis, including production of galactose-deficient IgA1 (Gd-IgA1; Hit 1), IgG or IgA autoantibodies that recognize Gd-IgA1 (Hit 2), and their subsequent immune complexes formation (Hit 3) and glomerular deposition (Hit 4), has been widely supported by many studies. Although the prognostic values of several biomarkers have been discussed, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of Gd-IgA1 and Gd-IgA1-containing immune complexes. In addition, urinary Gd-IgA1 may represent a disease-specific biomarker for IgAN. We also confirmed that there is a significant correlation between serum levels of these effector molecules and disease activity, suggesting that each can be considered a practical surrogate marker of therapeutic response. Thus, these disease-oriented specific serum and urine biomarkers may be useful for screening of potential IgAN with isolated hematuria, earlier diagnosis, disease activity, and eventually, response to treatment. In this review, we discuss these concepts, with a focus on potential clinical applications of these biomarkers.

  3. Insights into Resistance to Fe Deficiency Stress from a Comparative Study of In Vitro-Selected Novel Fe-Efficient and Fe-Inefficient Potato Plants

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    Georgina A. Boamponsem

    2017-09-01

    Full Text Available Iron (Fe deficiency induces chlorosis (IDC in plants and can result in reduced plant productivity. Therefore, development of Fe-efficient plants is of great interest. To gain a better understanding of the physiology of Fe-efficient plants, putative novel plant variants were regenerated from potato (Solanum tubersosum L. var. ‘Iwa’ callus cultures selected under Fe deficient or low Fe supply (0–5 μM Fe. Based on visual chlorosis rating (VCR, 23% of callus-derived regenerants were classified as Fe-efficient (EF and 77% as Fe-inefficient (IFN plant lines when they were grown under Fe deficiency conditions. Stem height was found to be highly correlated with internodal distance, leaf and root lengths in the EF plant lines grown under Fe deficiency conditions. In addition, compared to the IFN plant lines and control parental biotype, the EF plants including the lines named A1, B2, and B9, exhibited enhanced formation of lateral roots and root hairs as well as increased expression of ferritin (fer3 in the leaf and iron-regulated transporter (irt1 in the root. These morphological adaptations and changes in expression the fer3 and irt1 genes of the selected EF potato lines suggest that they are associated with resistance to low Fe supply stress.

  4. Effect of dietary zinc deficiency on the accumulation of cadmium and metallothionein in selected tissues of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Waalkes, M.P.

    1986-01-01

    The effect of continuous dietary zinc deficiency on the metabolism of the toxic heavy metal cadmium has not been widely studied. This investigation was designed to assess the effects of subadequate dietary zinc intake on the accumulation of dietary cadmium and on metallothionein (MT) and zinc concentrations in target organs of cadmium toxicity. Adult male Wistar rats (180-200 g) were allowed, ad libitum, diets either adequate (60 ppm) or deficient (7 ppm) in zinc for a total of 9 wk. The zinc-deficient diet resulted in an approximately 40% reduction in plasma zinc (assessed at 3, 6, and 9 wk) in the absence of overt signs of zinc deficiency (i.e., reduced weight gain, alopecia, etc.). Separate groups of rats were also maintained on zinc-defined diets for a total of 9 wk, but cadmium was added to the diet (0, 12.5, 25, 50, 100, and 200 ppm) a the end of wk 3 and maintained at that level throughout the remaining 6 wk of the study, when the rats were killed. The feeding of the zinc-deficient diet markedly enhanced the accumulation of cadmium in the liver, kidney, and testes. Hepatic, renal, and testicular zinc concentrations were not affected by suboptimal zinc intake alone. However, marked reductions in renal and testicular zinc concentrations were caused by zinc deficiency in concert with cadmium exposure. MT levels, when related to tissue cadmium concentrations, were elevated to a significantly lesser extent in the kidneys of zinc-deficient animals. These results indicate that marginal zinc deficiency markedly increases cadmium accumulation in various organs and reduces zinc content and MT induction in some organs.

  5. Plasma Gelsolin Promotes Proliferation of Mesangial Cell in IgA Nephropathy

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    Lei Zhang

    2016-12-01

    Full Text Available Background/Aims: Plasma gelsolin (pGSN is an actin-binding protein that plays a critical role in the pathogenesis of rheumatoid arthritis. However, whether pGSN is involved in other immunological diseases remains unknown. This study focused on the relationship between pGSN and immunoglobulin A (IgA nephropathy (IgAN. Methods: Two hundred patients with IgAN, 200 patients each with several other types of nephropathy and healthy controls (HCs who underwent kidney biopsies between 2000 and 2014 were enrolled in the study. The Oxford classification system was used to predict the risk of disease progression. Serum and renal tissue were used to detect pGSN, and the correlations between pGSN and IgA, galactose-deficient IgA1 (Gd-IgA1, transforming growth factor beta1 (TGF-β1, fibronectin (FN content, clinical symptoms, and kidney function were analyzed. Results: We found that the pGSN levels were significantly decreased in sera from IgAN patients compared to sera from patients with other forms of glomerular nephritis and HCs. Furthermore, the serum pGSN levels were negatively correlated with the serum IgA1, FN, and TGF-β1 levels, and positively correlated with the estimated glomerular filtration rate. Conversely, the glomerular pGSN content was significantly elevated in the IgAN patients and was positively correlated with TGF-β1 and FN levels. In renal tissue, the pGSN levels were significantly higher in IgAN patients with M1 and S1 compared to patients with M0 and S0 (p in vitro. pGSN also promoted integrin α2β1 expression in HMCs and enhanced the integrin α2β1-pGSN interaction. Conclusion: Our study suggested that pGSN may play an important role in the development of IgAN by promoting the proliferation of mesangial cells and that serum and glomerular pGSN levels may be new markers for predicting IgAN progression and prognosis.

  6. A Study on Clinical and Pathologic Features in Lupus Nephritis with Mainly IgA Deposits and a Literature Review

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    Liu Hongyan

    2013-01-01

    Full Text Available Objective. To study the clinical and pathologic features of systemic lupus erythematosus (SLE that has atypical lupus nephritis (LN with mainly IgA deposits. Methods. We searched the SLE patients who had nephritis with mainly IgA deposits in our hospital and selected the information including clinical manifestations, laboratory tests, treatments, and prognosis. Results. From January 2009 to June 2012, 5 patients were definitely diagnosed as SLE according to both 1982 and 2009 ACR classification criteria. But renal biopsy showed that all cases had mainly IgA deposits and were free of IgG, C1q, and fibrinogen-related antigen deposits under immunofluorescent microscopy, which did not match with typical LN. There were 2 males and 3 females, aging from 31 to 64 years and with an average of years. The 5 cases had multiple-system involvements, mainly the renal system. Compared to primary IgAN, the atypical LN showed some differences: older than primary IgAN, more women than men, no previous infection history, lower incidence of serum IgA elevation, and ACL positive rate as high as 100%. Conclusion. Nephritis with mainly IgAN deposits, as an atypical LN, may be a special subtype of SLE.

  7. Salivary IgA and dental caries in HIV patients: A pilot study.

    Science.gov (United States)

    Acharya, Sonu; Mandal, Pradip Kumar

    2016-01-01

    The interrelationship of human immunodeficiency virus (HIV) infection and dental caries, as well as Salivary IgA (S-IgA) level, appear to remain underexplored while a manual and electronic search of the literature was made. Hence, this study was undertaken to assess the relationship of S-IgA and dental caries status in HIV +ve children. The aim of this study was to find out the relationship of S-IgA antibody with dental caries by measuring the concentration of IgA in saliva of HIV +ve and HIV -ve children and to determine the dental caries status in HIV +ve and HIV -ve children, which may help in treatment planning and prevention of the same. Twenty-eight HIV +ve children aged between 6 and 14 years and 28 age matched HIV -ve children were included in this study, and both samples were randomly selected from the same nongovernmental organization (NGO). The HIV status of both these samples was confirmed from their medical records provided by the NGO. 2 cc of unstimulated saliva was collected from both groups in special tubes coded numerically using the method described by Collins and Dawes, and the samples were analyzed to measure the concentration of IgA using commercially available ELISA kit (DRG Diagnostics, Germany). Examination of dental caries was carried out according to the WHO criteria (1997) using a flat mouth mirror and Community periodontal index (CPI) probe. In HIV +ve group, mean salivary IgA level was calculated as 81.61 ± 6.20 μg/ml, mean decayed, missing, filled teeth (DMFT) was 3.86 ± 3.37, mean decayed, extracted and filled teeth (deft) was 4.75 ± 2.86. In HIV -ve group, the mean salivary IgA level was calculated as 145.57 ±17.83 μg/ml, mean DMFT was 2.54 ± 0.69, mean deft was 2.43 ± 2.01. Strong -ve correlation between S-IgA and DMFT (r = -0.781, t = 6.38, P 0.05) between S-IgA and deft was found in HIV +ve group. Strong -ve correlation between S-IgA and DMFT (r = -0.655, t = 4.42, P caries than normal individuals.

  8. IgA Nephropathy and Thrombotic Microangiopathy

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    Graciela De Rosa

    2017-06-01

    Full Text Available Introduction: Although the association between thrombotic microangiopathy (TMA and IgA nephropathy (IgAN is a known fact, its prevalence, pathogenesis and progression are not clear yet. Methods: A descriptive, retrospective study involving 12 patients with IgAN and TMA (IgAN-TMA was carried out; patients were diagnosed by a renal biopsy performed in our hospital in order to analyze clinicopathologic features. All the biopsy samples were processed for light microscopy and immunofluorescence. Results: The prevalence of patients with IgAN-TMA was 4.4% (12/274. The mean age was 33 and 58.3% of the subjects were men, showing, during diagnosis, mean systolic and diastolic blood pressure values of 171.3±53 mmHg and 97.5±19.8 mmHg, respectively. The average amount of protein in urine was 5.3 ± 3.7g/24 h and 8 patients had nephrotic- range proteinuria. Impairment of renal function was found in 11 patients, with a mean serum creatinine level of 7.2±4.7 mg/dL. No clinical or laboratory findings suggested thrombotic microangiopathy in any of the patients. The renal biopsy showed acute TMA with arteriolar fibrin thrombi in 75% of the subjects and ‘onion-skin-like’ chronic lesions with concentric intimal hyperplasia in 83.3% of them, which were associated with a high percentage of global glomerulosclerosis (72%, moderate tubular atrophy (38.6% and/or interstitial fibrosis (31.3%. In 91.7% of the cases, TMA was related to histological grade 5. Conclusions: The prevalence and significance of the relationship between IgAN and TMA pose the question of whether TMA is the cause or consequence of advanced stage IgAN. Several clinicopathologic studies have proved that TMA plays a major role in IgAN progression. The connection of TMA with creatinine serum and proteinuria levels seems to support this conclusion. While systemic TMA usually affects multiple organs, in these cases, the kidney was the only one compromised. Endothelial injury and the

  9. Eosinophils may play regionally disparate roles in influencing IgA(+) plasma cell numbers during large and small intestinal inflammation.

    Science.gov (United States)

    Forman, Ruth; Bramhall, Michael; Logunova, Larisa; Svensson-Frej, Marcus; Cruickshank, Sheena M; Else, Kathryn J

    2016-05-31

    Eosinophils are innate immune cells present in the intestine during steady state conditions. An intestinal eosinophilia is a hallmark of many infections and an accumulation of eosinophils is also observed in the intestine during inflammatory disorders. Classically the function of eosinophils has been associated with tissue destruction, due to the release of cytotoxic granule contents. However, recent evidence has demonstrated that the eosinophil plays a more diverse role in the immune system than previously acknowledged, including shaping adaptive immune responses and providing plasma cell survival factors during the steady state. Importantly, it is known that there are regional differences in the underlying immunology of the small and large intestine, but whether there are differences in context of the intestinal eosinophil in the steady state or inflammation is not known. Our data demonstrates that there are fewer IgA(+) plasma cells in the small intestine of eosinophil-deficient ΔdblGATA-1 mice compared to eosinophil-sufficient wild-type mice, with the difference becoming significant post-infection with Toxoplasma gondii. Remarkably, and in complete contrast, the absence of eosinophils in the inflamed large intestine does not impact on IgA(+) cell numbers during steady state, and is associated with a significant increase in IgA(+) cells post-infection with Trichuris muris compared to wild-type mice. Thus, the intestinal eosinophil appears to be less important in sustaining the IgA(+) cell pool in the large intestine compared to the small intestine, and in fact, our data suggests eosinophils play an inhibitory role. The dichotomy in the influence of the eosinophil over small and large intestinal IgA(+) cells did not depend on differences in plasma cell growth factors, recruitment potential or proliferation within the different regions of the gastrointestinal tract (GIT). We demonstrate for the first time that there are regional differences in the requirement of

  10. Linear IgA bullous dermatosis in a neonate.

    Science.gov (United States)

    Hruza, L L; Mallory, S B; Fitzgibbons, J; Mallory, G B

    1993-06-01

    A newborn black boy had two facial blisters at birth that progressed to bullous lesions over the trunk, genitals, extremities, and oral and tracheal mucosa. A biopsy specimen demonstrated a subepidermal bulla with mixed eosinophilic and neutrophilic, inflammatory infiltrate. Direct immunofluorescence showed linear IgA, IgG, and C3 depositions along the basement membrane zone, consistent with a diagnosis of childhood linear IgA bullous dermatosis (chronic bullous dermatosis of childhood). The skin disease was controlled with combined prednisone and dapsone. This is the youngest reported patient with the disease. Linear IgA bullous dermatosis should be considered in the differential diagnosis of blistering diseases of the newborn, and immunofluorescence should be performed on a skin biopsy specimen.

  11. Uncoupling of glomerular IgA deposition and disease progression in alymphoplasia mice with IgA nephropathy.

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    Masashi Aizawa

    Full Text Available Previous clinical and experimental studies have indicated that cells responsible for IgA nephropathy (IgAN, at least in part, are localized in bone marrow (BM. Indeed, we have demonstrated that murine IgAN can be experimentally reconstituted by bone marrow transplantation (BMT from IgAN prone mice in not only normal mice, but also in alymphoplasia mice (aly/aly independent of IgA+ cells homing to mucosa or secondary lymphoid tissues. The objective of the present study was to further assess whether secondary lymph nodes (LN contribute to the progression of this disease. BM cells from the several lines of IgAN prone mice were transplanted into aly/aly and wild-type mice (B6. Although the transplanted aly/aly showed the same degree of mesangial IgA and IgG deposition and the same serum elevation levels of IgA and IgA-IgG immune-complexes (IC as B6, even in extent, the progression of glomerular injury was observed only in B6. This uncoupling in aly/aly was associated with a lack of CD4+ T cells and macrophage infiltration, although phlogogenic capacity to nephritogenic IC of renal resident cells was identical between both recipients. It is suggested that secondary LN may be required for the full progression of IgAN after nephritogenic IgA and IgA/IgG IC deposition.

  12. Gluten sensitivity in patients with IgA nephropathy.

    Science.gov (United States)

    Smerud, Hilde Kloster; Fellström, Bengt; Hällgren, Roger; Osagie, Sonia; Venge, Per; Kristjánsson, Gudjón

    2009-08-01

    Coeliac disease is more frequent in IgA nephropathy (IgAN) patients compared to the healthy population. Several hypotheses postulate that food antigens like gluten may be involved in the onset of IgAN. In this study, we used a recently developed mucosal patch technique to evaluate the rectal mucosal inflammatory reaction to gluten in patients with IgAN (n = 27) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analysed for IgA and IgG antigliadin antibodies (AGA), IgA antibodies against tissue transglutaminase and IgA endomysium antibodies. Gluten reactivity, defined as increase in MPO and/or NO after gluten exposure, was observed in 8 of 27 IgAN patients. The prevalence of HLA-DQ2 and DQ8 was not increased among gluten-sensitive patients, and the total prevalence among IgAN patients was the same as for the normal population. An elevated serum IgA AGA response was seen in 9 of 27 IgAN patients. The increase in IgA AGA did not correlate with the gluten sensitivity as measured by NO and/or MPO. A specific serum IgG AGA response was seen in one patient only. Antibodies against tissue transglutaminase and endomysium were not observed. It is concluded that approximately one-third of our IgAN patients have a rectal mucosal sensitivity to gluten, but without signs of coeliac disease, and we hypothesize that such sub-clinical inflammation to gluten might be involved in the pathogenesis of IgAN in a subgroup of patients.

  13. Hepatic tissue environment in NEMO-deficient mice critically regulates positive selection of donor cells after hepatocyte transplantation.

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    Michaela Kaldenbach

    Full Text Available BACKGROUND: Hepatocyte transplantation (HT is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. METHODS: Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa. RESULTS: Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. CONCLUSION: This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and

  14. MTH1 deficiency selectively increases non-cytotoxic oxidative DNA damage in lung cancer cells: more bad news than good?

    Science.gov (United States)

    Abbas, Hussein H K; Alhamoudi, Kheloud M H; Evans, Mark D; Jones, George D D; Foster, Steven S

    2018-04-16

    Targeted therapies are based on exploiting cancer-cell-specific genetic features or phenotypic traits to selectively kill cancer cells while leaving normal cells unaffected. Oxidative stress is a cancer hallmark phenotype. Given that free nucleotide pools are particularly vulnerable to oxidation, the nucleotide pool sanitising enzyme, MTH1, is potentially conditionally essential in cancer cells. However, findings from previous MTH1 studies have been contradictory, meaning the relevance of MTH1 in cancer is still to be determined. Here we ascertained the role of MTH1 specifically in lung cancer cell maintenance, and the potential of MTH1 inhibition as a targeted therapy strategy to improve lung cancer treatments. Using siRNA-mediated knockdown or small-molecule inhibition, we tested the genotoxic and cytotoxic effects of MTH1 deficiency on H23 (p53-mutated), H522 (p53-mutated) and A549 (wildtype p53) non-small cell lung cancer cell lines relative to normal MRC-5 lung fibroblasts. We also assessed if MTH1 inhibition augments current therapies. MTH1 knockdown increased levels of oxidatively damaged DNA and DNA damage signaling alterations in all lung cancer cell lines but not normal fibroblasts, despite no detectable differences in reactive oxygen species levels between any cell lines. Furthermore, MTH1 knockdown reduced H23 cell proliferation. However, unexpectedly, it did not induce apoptosis in any cell line or enhance the effects of gemcitabine, cisplatin or radiation in combination treatments. Contrastingly, TH287 and TH588 MTH1 inhibitors induced apoptosis in H23 and H522 cells, but only increased oxidative DNA damage levels in H23, indicating that they kill cells independently of DNA oxidation and seemingly via MTH1-distinct mechanisms. MTH1 has a NSCLC-specific p53-independent role for suppressing DNA oxidation and genomic instability, though surprisingly the basis of this may not be reactive-oxygen-species-associated oxidative stress. Despite this, overall

  15. Isogeometric Analysis of Hyperelastic Materials Using PetIGA

    KAUST Repository

    Bernal, L.M.

    2013-06-01

    In this work different nonlinear hyperelastic models for slightly compressible materials are implemented in an isogeometric finite element model. This is done within the recently developed computational framework called PetIGA, which uses isoge- ometric analysis and modern computational tools to solve systems of equations directly and iteratively. A flexible theoretical background is described to implement other hyperelastic models and possibly transient problems in future work. Results show quadratic convergence of the nonlinear solution consistent with the Newton-Raphson method that was used. Finally, PetIGA proves to be a powerful and versatile tool to solve these types of problems efficiently.

  16. Isogeometric Analysis of Hyperelastic Materials Using PetIGA

    KAUST Repository

    Bernal, L.M.; Calo, Victor M.; Collier, Nathan; Espinosa, G.A.; Fuentes, F.; Mahecha, J.C.

    2013-01-01

    In this work different nonlinear hyperelastic models for slightly compressible materials are implemented in an isogeometric finite element model. This is done within the recently developed computational framework called PetIGA, which uses isoge- ometric analysis and modern computational tools to solve systems of equations directly and iteratively. A flexible theoretical background is described to implement other hyperelastic models and possibly transient problems in future work. Results show quadratic convergence of the nonlinear solution consistent with the Newton-Raphson method that was used. Finally, PetIGA proves to be a powerful and versatile tool to solve these types of problems efficiently.

  17. Selective alteration of adult hippocampal neurogenesis and impaired spatial pattern separation performance in the RSK2-deficient mouse model of Coffin-Lowry syndrome.

    Science.gov (United States)

    Castillon, Charlotte; Lunion, Steeve; Desvignes, Nathalie; Hanauer, André; Laroche, Serge; Poirier, Roseline

    2018-07-01

    Adult neurogenesis is involved in certain hippocampus-dependent cognitive functions and is linked to psychiatric diseases including intellectual disabilities. The Coffin-Lowry syndrome (CLS) is a developmental disorder caused by mutations in the Rsk2 gene and characterized by intellectual disabilities associated with growth retardation. How RSK2-deficiency leads to cognitive dysfunctions in CLS is however poorly understood. Here, using Rsk2 Knock-Out mice, we characterized the impact of RSK2 deficiency on adult hippocampal neurogenesis in vivo. We report that the absence of RSK2 does not affect basal proliferation, differentiation and survival of dentate gyrus adult-born neurons but alters the maturation progression of young immature newborn neurons. Moreover, when RSK2-deficient mice were submitted to spatial learning, in contrast to wild-type mice, proliferation of adult generated neurons was decreased and no pro-survival effect of learning was observed. Thus, learning failed to recruit a selective population of young newborn neurons in association with deficient long-term memory recall. Given the proposed role of the dentate gyrus and of adult-generated newborn neurons in hippocampal-dependent pattern separation function, we explored this function in a delayed non-matching to place task and in an object-place pattern separation task and report severe deficits in spatial pattern separation in Rsk2-KO mice. Together, this study reveals a previously unknown role for RSK2 in the early stages of maturation and learning-dependent involvement of adult-born dentate gyrus neurons. These alterations associated with a deficit in the ability of RSK2-deficient mice to finely discriminate relatively similar spatial configurations, may contribute to cognitive dysfunction in CLS. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. DNA methylation in Cosmc promoter region and aberrantly glycosylated IgA1 associated with pediatric IgA nephropathy.

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    Qiang Sun

    Full Text Available IgA nephropathy (IgAN is one of the most common glomerular diseases leading to end-stage renal failure. Elevation of aberrantly glycosylated IgA1 is a key feature of it. The expression of the specific molecular chaperone of core1ß1, 3galactosyl transferase (Cosmc is known to be reduced in IgAN. We aimed to investigate whether the methylation of CpG islands of Cosmc gene promoter region could act as a possible mechanism responsible for down-regulation of Cosmc and related higher secretion of aberrantly glycosylated IgA1in lymphocytes from children with IgA nephropathy. Three groups were included: IgAN children (n = 26, other renal diseases (n = 11 and healthy children (n = 13. B-lymphocytes were isolated and cultured, treated or not with IL-4 or 5-Aza-2'-deoxycytidine (AZA. The levels of DNA methylation of Cosmc promotor region were not significantly different between the lymphocytes of the three children populations (P = 0.113, but there were significant differences between IgAN lymphocytes and lymphocytes of the other two children populations after IL-4 (P<0.0001 or AZA (P<0.0001. Cosmc mRNA expression was low in IgAN lymphocytes compared to the other two groups (P<0.0001. The level of aberrantly glycosylated IgA1 was markedly higher in IgAN group compared to the other groups (P<0.0001. After treatment with IL-4, the levels of Cosmc DNA methylation and aberrantly glycosylated IgA1 in IgAN lymphocytes were remarkably higher than the other two groups (P<0.0001 with more markedly decreased Cosmc mRNA content (P<0.0001. After treatment with AZA, the levels in IgAN lymphocytes were decreased, but was still remarkably higher than the other two groups (P<0.0001, while Cosmc mRNA content in IgAN lymphocytes were more markedly increased than the other two groups (P<0.0001. The alteration of DNA methylation by IL-4 or AZA specifically correlates in IgAN lymphocytes with alterations in Cosmc mRNA expression and with the level of aberrantly glycosylated

  19. Evaluation of Salivary Glucose, IgA and Flow Rate in Diabetic Patients: A Case-Control Study

    OpenAIRE

    Bakianian Vaziri, P.; Vahedi, M.; Mortazavi, H.; Abdollahzadeh, Sh.; Hajilooi, M.

    2010-01-01

    Objective: An association between diabetes mellitus and alterations in the oral cavity has been noted. In this study, we evaluated differences between salivary IgA, glucose and flow rate in diabetic patients compared with healthy controls. Materials and Methods: Forty patients with type 1 diabetes, 40 patients with type 2 diabetes and 40 healthy controls were selected. Whole unstimulated saliva samples were collected by the standard method and the salivary flow rate was determined. Nephelomet...

  20. Early pre-eclampsia unmasks underlying IgA nephropathy

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    Mona Singh

    2010-12-01

    Full Text Available Mona Singh, Akhenaton Pappoe, Burl R DonDivision of Nephrology, University of California Davis Medical Center, Sacramento, CA, USAAbstract: Pre-eclampsia is the most ominous complication of pregnancy, and primary glomerular diseases can mimic pre-eclampsia in presentation. A patient presented at 21 weeks gestation with signs and symptoms of both pre-eclampsia and primary glomerular nephropathy. A critical clinical decision whether to continue or terminate the pregnancy was dependent on results of a renal biopsy. The biopsy noted the presence of both pre-eclampsia and immunoglobulin A (IgA nephropathy. Thus, the onset of pre-eclampsia unmasked the presence of unrecognized IgA nephropathy, and the IgA nephropathy was a risk factor for this patient developing pre-eclampsia. The results of a renal biopsy are key in distinguishing pre-eclampsia from other kidney diseases and instituting appropriate clinical management.Keywords: proteinuria, IgA nephropathy, renal biopsy, pre-eclampsia

  1. CD44 expression in IgA nephropathy

    NARCIS (Netherlands)

    Florquin, Sandrine; Nunziata, Raffaele; Claessen, Nike; van den Berg, Frank M.; Pals, Steven T.; Weening, Jan J.

    2002-01-01

    Immunoglobulin A (IgA) nephropathy is a frequent, chronic renal disease characterized by a broad spectrum of clinical presentations and pathologic findings. CD44, a family of type I transmembrane glycoproteins: involved in cell-cell and cell-matrix interactions, may orchestrate partially the cascade

  2. Screening for C3 deficiency in newborns using microarrays.

    Directory of Open Access Journals (Sweden)

    Magdalena Janzi

    Full Text Available BACKGROUND: Dried blood spot samples (DBSS from newborns are widely used in neonatal screening for selected metabolic diseases and diagnostic possibilities for additional disorders are continuously being evaluated. Primary immunodeficiency disorders comprise a group of more than one hundred diseases, several of which are fatal early in life. Yet, a majority of the patients are not diagnosed due to lack of high-throughput screening methods. METHODOLOGY/PRINCIPAL FINDINGS: We have previously developed a system using reverse phase protein microarrays for analysis of IgA levels in serum samples. In this study, we extended the applicability of the method to include determination of complement component C3 levels in eluates from DBSS collected at birth. Normal levels of C3 were readily detected in 269 DBSS from healthy newborns, while no C3 was detected in sera and DBSS from C3 deficient patients. CONCLUSIONS/SIGNIFICANCE: The findings suggest that patients with deficiencies of specific serum proteins can be identified by analysis of DBSS using reverse phase protein microarrays.

  3. IgA attenuates anaphylaxis and subsequent immune responses in mice: possible application of IgA to vaccines.

    Science.gov (United States)

    Yamaki, Kouya; Nakashima, Takayuki; Miyatake, Kenji; Ishibashi, Yuki; Ito, Ayaka; Kuranishi, Ayu; Taguchi, Akihito; Morioka, Ayumi; Yamamoto, Midori; Yoshino, Shin

    2014-01-01

    Administration of the influenza vaccination to patients with an egg allergy is major health concern. Contaminating egg antigens occasionally induce severe anaphylactic shock in these patients following administration of the vaccination; therefore, the development of a safer vaccination is needed. In the present study, we investigated whether a mixture of four newly and previously generated anti-ovalbumin (OVA) IgA monoclonal antibodies (mAbs) could inhibit both anaphylactic shock upon a subcutaneous OVA challenge and subsequent further sensitization against OVA in passively anti-OVA IgE-sensitized mice and actively sensitized mice with an injection of OVA. The prevention of anaphylaxis by anti-OVA IgA mAbs was suggested to be mediated through the inhibition of OVA binding to allergenic antibodies such as anti-OVA IgE on mast cells and deceleration of the rate of OVA penetration from the injected site into the systemic circulation. Anti-OVA IgA mAbs inhibited further sensitization against OVA in mice actively sensitized with OVA, but did not affect sensitization against the unrelated antigen, phosphorylcholine-keyhole limpet hemocyanin co-injected with OVA. Our findings indicate that adding the anti-egg antigen IgA to the influenza vaccine should reduce not only the risk of inducing anaphylactic shock, but also undesired further sensitization against egg antigens following the vaccination without affecting the intended beneficial effect of the vaccine, namely the upregulation of immune responses to influenza viruses.

  4. Iodine Deficiency

    Science.gov (United States)

    ... Fax/Phone Home » Iodine Deficiency Leer en Español Iodine Deficiency Iodine is an element that is needed ... world’s population remains at risk for iodine deficiency. Iodine Deficiency FAQs WHAT IS THE THYROID GLAND? The ...

  5. Identification of distinct glycoforms of IgA1 in plasma from patients with IgA nephropathy and healthy individuals

    DEFF Research Database (Denmark)

    Lehoux, Sylvain; Mi, Rongjuan; Aryal, Rajindra P

    2014-01-01

    Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis worldwide and is histologically characterized by the deposition of IgA1 and consequent inflammation in the glomerular mesangium. Prior studies suggested that serum IgA1 from IgAN patients contains aberrant, undergal......Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis worldwide and is histologically characterized by the deposition of IgA1 and consequent inflammation in the glomerular mesangium. Prior studies suggested that serum IgA1 from IgAN patients contains aberrant...... there are different glycoforms of IgA1 in plasma from patients with IgAN and healthy individuals. While total plasma IgA in IgAN patients was elevated ~1.6-fold compared to that in healthy donors, IgA1 in all samples was unexpectedly separable into two distinct glycoforms: one with core 1 based O......-glycans, and the other exclusively containing Tn/STn structures. Importantly, Tn antigen present on IgA1 from IgAN patients and controls was convertible into the core 1 structure in vitro by recombinant T-synthase. Our results demonstrate that undergalactosylation of O-glycans in IgA1 is not restricted to Ig...

  6. Amino acid sequence requirements in the human IgA1 hinge for cleavage by streptococcal IgA1 proteases

    DEFF Research Database (Denmark)

    Senior, BW; Batten, MR; Kilian, Mogens

    2002-01-01

    All the IgA1 proteases of the different pathogenic species of Streptococcus cleave the hinge of the alpha chain of human IgA1 only at one proline-threonine peptide bond. In order to study the importance of these amino acids for cleavage, several hinge mutant recombinant IgA1 antibodies were const...... constructed. The mutations were found to be without major effect upon the structure or functional abilities of the antibodies. However, they had a major effect upon their sensitivity to cleavage by some of the IgA1 proteases....

  7. Amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by streptococcal IgA1 proteases

    DEFF Research Database (Denmark)

    Batten, MR; Senior, BW; Kilian, Mogens

    2003-01-01

    The amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by IgA1 proteases of different species of Streptococcus were investigated. Recombinant IgA1 antibodies were generated with point mutations at proline 227 and threonine 228, the residues lying on either...... side of the peptide bond at which all streptococcal IgA1 proteases cleave wild-type human IgA1. The amino acid substitutions produced no major effect upon the structure of the mutant IgA1 antibodies or their functional ability to bind to Fcalpha receptors. However, the substitutions had a substantial...... effect upon sensitivity to cleavage with some streptococcal IgA1 proteases, with, in some cases, a single point mutation rendering the antibody resistant to a particular IgA1 protease. This effect was least marked with the IgA1 protease from Streptococcus pneumoniae, which showed no absolute requirement...

  8. Working mechanism of immunoglobulin A1 (IgA1) protease: cleavage of IgA1 antibody to Neisseria meningitidis PorA requires de novo synthesis of IgA1 Protease

    NARCIS (Netherlands)

    Vidarsson, Gestur; Overbeeke, Natasja; Stemerding, Annette M.; van den Dobbelsteen, Germie; van Ulsen, Peter; van der Ley, Peter; Kilian, Mogens; van de Winkel, Jan G. J.

    2005-01-01

    Neisseria meningitidis secretes a protease that specifically cleaves the hinge region of immunoglobulin A1 (IgA1), releasing the effector (Fc) domain of IgA1 from the antigen binding (Fab) determinants. Theoretically, the remaining Fab fragments can block pathogen receptors or toxins and still

  9. Working mechanism of immunoglobulin A1 (IgA1) protease: cleavage of IgA1 antibody to Neisseria meningitidis PorA requires de novo synthesis of IgA1 Protease

    DEFF Research Database (Denmark)

    Vidarsson, G; Overbeeke, N; Stemerding, AM

    2005-01-01

    Neisseria meningitidis secretes a protease that specifically cleaves the hinge region of immunoglobulin A1 (IgA1), releasing the effector (Fc) domain of IgA1 from the antigen binding (Fab) determinants. Theoretically, the remaining Fab fragments can block pathogen receptors or toxins and still...

  10. Secretory IgA (SIgA: designed for antimicrobial defence

    Directory of Open Access Journals (Sweden)

    Per eBrandtzaeg

    2013-08-01

    Full Text Available Prevention of infections by vaccination remains a compelling goal to improve public health. Mucosal vaccines would make immunization procedures easier, be better suited for mass administration, and most efficiently induce immune exclusion -- a term coined for non-inflammatory antibody shielding of internal body surfaces, mediated principally by secretory immunoglobulin A (SIgA. The exported antibodies are polymeric, mainly IgA dimers (pIgA, produced by local plasma cells stimulated by antigens that target the mucosae. SIgA was early shown to be complexed with an epithelial glycoprotein -- the secretory component (SC. A common SC-dependent transport mechanism for pIgA and pentameric IgM was then proposed, implying that membrane SC acts as a receptor, now usually called the polymeric Ig receptor (pIgR. From the basolateral surface, pIg-pIgR complexes are taken up by endocytosis and then extruded into the lumen after apical cleavage of the receptor -- bound SC having stabilizing and innate functions in the secretory antibodies. Mice deficient for pIgR show that this is the only receptor responsible for epithelial export of IgA and IgM. These knockout mice show a variety of defects in their mucosal defensce and changes in their intestinal microbiota. In the gut, induction of B cells occurs in gut-associated lymphoid tissue (GALT, particularly the Peyer’s patches and isolated lymphoid follicles, but also in mesenteric lymph nodes. Plasma cell differentiation is accomplished in the lamina propria to which the activated memory/effector B cells home. The airways also receive such cells from nasopharynx-associated lymphoid tissue (NALT but by different homing receptors. This compartmentalization is a challenge for mucosal vaccination, as are the mechanisms used by the mucosal immune system to discriminate between commensal symbionts (mutualism, pathobionts and overt pathogens (elimination.

  11. IgA LINEAR BULLOUS DERMATOSIS IN CHILDHOOD.

    Directory of Open Access Journals (Sweden)

    Ivelina Yordanova

    2015-12-01

    Full Text Available IgA linear bullous dermatosis, also known as chronic bullous dermatosis of childhood, is an autoimmune disease which may be idiopathic or drug-induced. The disease affects children and adults. We present a 4 years old girl with itchy polymorphic eruptions. The skin rash was presented by bullous-erosive rosette-like lesions with reddish-brown crust in the center, distributed on the skin of the face, trunk and extremities. The vesicles were filled with serous and hemorrhagic content. Laboratory examinations were within normal values according the age. Histopathological examination of the lesional skin revealed sub epidermal blister. Direct immunofluorescence of perilesional skin demonstrated linear deposition of IgA in the basement membrane. Systemic treatment with Methylprednisolon and Claritromycin was applied with satisfactory effect. The patient is under observation.

  12. Razlikovnost kao pretpostavka za registraciju žiga

    OpenAIRE

    Matanovac Vučković, Romana

    2012-01-01

    U radu se obrazlaže stupnjevanje razlikovnosti u ispitivanju apsolutnih smetnji za registraciju nekog znaka kao žiga nakon harmonizacije žigovnoga prava u Europskoj uniji. Obrazlaže se i nerazdruživost između funkcije označivanja podrijetla i razlikovnosti žiga. S time u svezi obrađuju se Direktiva 2008/95/EZ Europskog parlamenta i Vijeća od 22. listopada 2008. za usklađivanje propisa država članica koji se odnose na žigove (kodificirani tekst), Uredba Vijeća (EZ) 207/2009 od 26. veljače 2009...

  13. Deficient attention is hard to find: applying the perceptual load model of selective attention to attention deficit hyperactivity disorder subtypes.

    Science.gov (United States)

    Huang-Pollock, Cynthia L; Nigg, Joel T; Carr, Thomas H

    2005-11-01

    Whether selective attention is a primary deficit in childhood Attention Deficit Hyperactivity Disorder (ADHD) remains in active debate. We used the perceptual load paradigm to examine both early and late selective attention in children with the Primarily Inattentive (ADHD-I) and Combined subtypes (ADHD-C) of ADHD. No evidence emerged for selective attention deficits in either of the subtypes, but sluggish cognitive tempo was associated with abnormal early selection. At least some, and possibly most, children with DSM-IV ADHD have normal selective attention. Results support the move away from theories of attention dysfunction as primary in ADHD-C. In ADHD-I, this was one of the first formal tests of posterior attention network dysfunction, and results did not support that theory. However, ADHD children with sluggish cognitive tempo (SCT) warrant more study for possible early selective attention deficits.

  14. Igaühele hea haridus!? / Olav Aarna

    Index Scriptorium Estoniae

    Aarna, Olav, 1942-

    2005-01-01

    Ilmunud ka: Järva Teataja 1. september lk. 2, Meie Maa 1. september lk. 2, Koit 1. september lk. 6, Severnoje Poberezhje 1. september lk. 2, Vali Uudised 2. september lk. 2, Sakala 2. september lk. 2, Hiiu Leht 2. september lk. 2, Kuulutaja 2. september lk. 4, Nädaline 8. september lk. 4. Riigikogu kultuurikomisjoni esimehe sõnul peaks igaüks sõnastama enda jaoks rahuldava vastuse küsimusele, mis on hea haridus

  15. Characterization of IgA response among women with incident HPV 16 infection

    International Nuclear Information System (INIS)

    Onda, Takashi; Carter, Joseph J.; Koutsky, Laura A.; Hughes, James P.; Lee, Shu-Kuang; Kuypers, Jane; Kiviat, Nancy; Galloway, Denise A.

    2003-01-01

    Previous studies have characterized the prevalence and duration of serum IgG antibodies to human papillomavirus type 16 (HPV 16) in a well-studied cohort of college women, using viruslike particle- (VLP) based ELISAs. In this study IgA antibodies in cervical secretions and sera were examined using a newly developed capsomer-based ELISA and the patterns observed for serum IgG, serum IgA, and cervical IgA antibodies were compared. The median time to antibody detection from the first detection of HPV 16 DNA was 10.5 months for IgA in cervical secretions and 19.1 months for serum IgA. Serum IgA antibody conversion was observed less frequently and occurred later than IgA conversion in cervical secretions (P = 0.011) or serum IgG conversion (P 0.051). The median time to antibody reversion, following seroconversion, was 12.0 months for IgA in cervical secretions and 13.6 months for serum IgA, whereas approximately 20% of women with serum IgG antibodies reverted within 36 months. Thus, the duration of IgA in cervical secretions and sera was shorter than the duration of serum IgG (P = 0.007 and 0.001)

  16. Deficient Attention Is Hard to Find: Applying the Perceptual Load Model of Selective Attention to Attention Deficit Hyperactivity Disorder Subtypes

    Science.gov (United States)

    Huang-Pollock, Cynthia L.; Nigg, Joel T.; Carr, Thomas H.

    2005-01-01

    Background: Whether selective attention is a primary deficit in childhood Attention Deficit Hyperactivity Disorder (ADHD) remains in active debate. Methods: We used the "perceptual load" paradigm to examine both early and late selective attention in children with the Primarily Inattentive (ADHD-I) and Combined subtypes (ADHD-C) of ADHD. Results:…

  17. Health Deficiencies

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of all health deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection date,...

  18. Evaluation of Salivary Glucose, IgA and Flow Rate in Diabetic Patients: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    P. Bakianian Vaziri

    2010-03-01

    Full Text Available Objective: An association between diabetes mellitus and alterations in the oral cavity has been noted. In this study, we evaluated differences between salivary IgA, glucose and flow rate in diabetic patients compared with healthy controls.Materials and Methods: Forty patients with type 1 diabetes, 40 patients with type 2 diabetes and 40 healthy controls were selected. Whole unstimulated saliva samples were collected by the standard method and the salivary flow rate was determined. Nephelometricand Pars method were used to measure salivary IgA and salivary glucose concentrations,respectively. Statistical analysis was performed by Chi-square and t test.Results: There were no significant differences in salivary IgA and glucose concentrations between type 1 and type 2 diabetic patients and their matched control subjects (P>0.05.Salivary flow rate was significantly lower in diabetic patients (P<0.05. In addition,DMFT was higher in diabetic patients than the controls.Conclusion: Determination of salivary constituents may be useful in the description and management of oral findings in diabetic patients.

  19. Active tuberculosis patients have high levels of IgA anti-alpha-crystallin and isocitrate lyase proteins.

    Science.gov (United States)

    Talavera-Paulín, M; García-Morales, L; Ruíz-Sánchez, B P; Caamal-Ley, Á D; Hernández-Solis, A; Ramírez-Casanova, E; Cicero-Sabido, R; Espitia, C; Helguera-Repetto, C; González-Y-Merchand, J A; Flores-Mejía, R; Estrada-Parra, S; Estrada-García, I; Chacón-Salinas, R; Wong-Baeza, I; Serafín-López, J

    2016-12-01

    Mexico City, Mexico. To identify proteins synthetised by Mycobacterium tuberculosis in hypoxic culture, which resemble more closely a granuloma environment than aerobic culture, and to determine if they are recognised by antibodies from patients with active pulmonary tuberculosis (PTB). Soluble extracts from M. tuberculosis H37Rv cultured under aerobic or hypoxic conditions were analysed using two-dimensional polyacrylamide gel electrophoresis, and proteins over-expressed under hypoxia were identified by mass spectrometry. The presence of immunoglobulin (Ig) G, IgA and IgM antibodies against these proteins was determined in the serum of 42 patients with active PTB and 42 healthy controls. We selected three M. tuberculosis H37Rv proteins (alpha-crystallin protein [Acr, Rv2031c], universal stress protein Rv2623 and isocitrate lyase [ICL, RV0467]) that were over-expressed under hypoxia. Titres of anti-Acr and anti-ICL IgA antibodies were higher in patients than in healthy controls, with an area under the receiver operating characteristic curve of 0.71 for anti-ICL IgA antibodies. ICL could be used in combination with other M. tuberculosis antigens to improve the sensitivity and specificity of current serological TB diagnostic methods.

  20. Dopamine receptor D5 deficiency results in a selective reduction of hippocampal NMDA receptor subunit NR2B expression and impaired memory.

    Science.gov (United States)

    Moraga-Amaro, Rodrigo; González, Hugo; Ugalde, Valentina; Donoso-Ramos, Juan Pablo; Quintana-Donoso, Daisy; Lara, Marcelo; Morales, Bernardo; Rojas, Patricio; Pacheco, Rodrigo; Stehberg, Jimmy

    2016-04-01

    Pharmacological evidence associates type I dopamine receptors, including subtypes D1 and D5, with learning and memory. Analyses using genetic approaches have determined the relative contribution of dopamine receptor D1 (D1R) in cognitive tasks. However, the lack of drugs that can discriminate between D1R and D5R has made the pharmacological distinction between the two receptors difficult. Here, we aimed to determine the role of D5R in learning and memory. In this study we tested D5R knockout mice and wild-type littermates in a battery of behavioral tests, including memory, attention, locomotion, anxiety and motivational evaluations. Our results show that genetic deficiency of D5R significantly impairs performance in the Morris water maze paradigm, object location and object recognition memory, indicating a relevant role for D5R in spatial memory and recognition memory. Moreover, the lack of D5R resulted in decreased exploration and locomotion. In contrast, D5R deficiency had no impact on working memory, anxiety and depressive-like behavior, measured using the spontaneous alternation, open-field, tail suspension test, and forced swimming test. Electrophysiological analyses performed on hippocampal slices showed impairment in long-term-potentiation in mice lacking D5R. Further analyses at the molecular level showed that genetic deficiency of D5R results in a strong and selective reduction in the expression of the NMDA receptor subunit NR2B in the hippocampus. These findings demonstrate the relevant contribution of D5R in memory and suggest a functional interaction of D5R with hippocampal glutamatergic pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. The selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen improve ANP levels and decrease nuclear translocation of NF-kB in estrogen-deficient rats.

    Science.gov (United States)

    Lamas, Aline Z; Nascimento, Andrews M; Medeiros, Ana Raquel S; Caliman, Izabela F; Dalpiaz, Polyana L M; Firmes, Luciana B; Sousa, Glauciene J; Oliveira, Phablo Wendell C; Andrade, Tadeu U; Reis, Adelina M; Gouvea, Sônia A; Bissoli, Nazaré S

    2017-08-01

    The selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen are used for the treatment of osteoporosis and cancer, respectively, in women. The impairment of both the Atrial Natriuretic Peptide (ANP) cell signaling system and the translocation of nuclear factor-kappa B (NF-kB) to the cell nucleus are associated with detrimental cardiovascular effects and inflammation. The effects of SERMs on these parameters in the cardiac tissue of estrogen-deficient rats has not been reported. We investigated the effects of raloxifene and tamoxifen on ANP signaling, p65 NF-kB nuclear translocation, cardiac histology and contractility. Female rats were divided into five groups: control (SHAM), ovariectomized (OVX), OVX-treated 17-β-estradiol (E), OVX-treated raloxifene (RLX) and OVX-treated tamoxifen (TAM). The treatments started 21days after ovariectomy and continued for 14days. Ovariectomy reduced ANP mRNA in the left atrium (LA), decreased the content of ANP protein in the LA and in plasma, and increased the level of p65 NF-kB nuclear translocation in the left ventricle. Both 17-β-estradiol and SERMs were able to reverse these alterations, which were induced by the estrogen deficient state. The hemodynamic and cardiac structural parameters analyzed in the present work were not modified by the interventions. Our study demonstrates, for the first time, the additional benefits of raloxifene and tamoxifen in an estrogen-deficient state. These include the normalization of plasmatic and cardiac ANP levels and cardiac p65 NF-kB translocation. Therefore, these treatments promote cardiovascular protection and may contribute to the prevention of cardiac dysfunction observed long-term in postmenopausal women. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  2. Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors

    Directory of Open Access Journals (Sweden)

    Frank Fornari

    2011-11-01

    Full Text Available Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS. RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic. Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]. Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms. Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015 more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32 and 47.8% of Family B subjects (11 of 23. No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific

  3. Chronic exposure to sublethal doses of radiation mimetic ZeocinTM selects for clones deficient in homologous recombination

    International Nuclear Information System (INIS)

    Delacote, Fabien; Deriano, Ludovic; Lambert, Sarah; Bertrand, Pascale; Saintigny, Yannick; Lopez, Bernard S.

    2007-01-01

    DNA double-strand breaks (DSBs) are highly toxic lesions leading to genome variability/instability. The balance between homologous recombination (HR) and non-homologous end-joining (NHEJ), two alternative DSB repair systems, is essential to ensure genome maintenance in mammalian cells. Here, we transfected CHO hamster cells with the pcDNA TM 3.1/Zeo plasmid, and selected transfectants with Zeocin TM , a bleomycin analog which produces DSBs. Despite the presence of a Zeocin TM resistance gene in pcDNA TM 3.1/Zeo, Zeocin TM induced 8-10 γ-H2AX foci per cell. This shows that the Zeocin TM resistance gene failed to fully detoxify cells treated with Zeocin TM , and that during selection cells were submitted to a chronic sublethal DSB stress. Selected clones show decreases in both spontaneous and induced intrachromosomal HR. In contrast, in an in vitro assay, these clones show an increase in NHEJ products specific to the KU86 pathway. We selected cells, in the absence of pcDNA TM 3.1/Zeo, with low and sublethal doses of Zeocin TM , producing a mean 8-10 γ-H2AX foci per cell. Newly selected clones exhibited similar phenotypes: HR decrease accompanied by an increase in KU86-dependent NHEJ efficiency. Thus chronic exposure to sublethal numbers of DSBs selects cells whose HR versus NHEJ balance is altered. This may well have implications for radio- and chemotherapy, and for management of environmental hazards

  4. Altered Ca2+ kinetics associated with α-actinin-3 deficiency may explain positive selection for ACTN3 null allele in human evolution.

    Directory of Open Access Journals (Sweden)

    Stewart I Head

    Full Text Available Over 1.5 billion people lack the skeletal muscle fast-twitch fibre protein α-actinin-3 due to homozygosity for a common null polymorphism (R577X in the ACTN3 gene. α-Actinin-3 deficiency is detrimental to sprint performance in elite athletes and beneficial to endurance activities. In the human genome, it is very difficult to find single-gene loss-of-function variants that bear signatures of positive selection, yet intriguingly, the ACTN3 null variant has undergone strong positive selection during recent evolution, appearing to provide a survival advantage where food resources are scarce and climate is cold. We have previously demonstrated that α-actinin-3 deficiency in the Actn3 KO mouse results in a shift in fast-twitch fibres towards oxidative metabolism, which would be more "energy efficient" in famine, and beneficial to endurance performance. Prolonged exposure to cold can also induce changes in skeletal muscle similar to those observed with endurance training, and changes in Ca2+ handling by the sarcoplasmic reticulum (SR are a key factor underlying these adaptations. On this basis, we explored the effects of α-actinin-3 deficiency on Ca2+ kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice, using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO mice showed: (i an increased rate of decay of the twitch transient; (ii a fourfold increase in the rate of SR Ca2+ leak; (iii a threefold increase in the rate of SR Ca2+ pumping; and (iv enhanced maintenance of tetanic Ca2+ during fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin and sarcalumenin, showed markedly increased expression in muscles of KO mice. Together, these changes in Ca2+ handling in the absence of α-actinin-3 are consistent with cold acclimatisation and thermogenesis, and offer an additional explanation for the positive selection of the ACTN3 577X null allele in populations living in cold environments

  5. A pyrazolyl-based thiolato single-source precursor for the selective synthesis of isotropic copper-deficient copper(I) sulfide nanocrystals: synthesis, optical and photocatalytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Mondal, Gopinath; Santra, Ananyakumari; Bera, Pradip; Acharjya, Moumita [Vidyasagar University, Post Graduate Department of Chemistry, Panskura Banamali College (India); Jana, Sumanta [Indian Institute of Engineering Science and Technology (IIEST), Department of Chemistry (India); Chattopadhyay, Dipankar [University of Calcutta, Department of Polymer Science and Technology (India); Mondal, Anup [Indian Institute of Engineering Science and Technology (IIEST), Department of Chemistry (India); Seok, Sang Il [Korea Research Institute of Chemical Technology, KRICT-EPFL Global Research Laboratory, Division of Advanced Materials (Korea, Republic of); Bera, Pulakesh, E-mail: pbera.pbc.chem@gmail.com [Vidyasagar University, Post Graduate Department of Chemistry, Panskura Banamali College (India)

    2016-10-15

    Hexagonal copper-deficient copper(I) sulfide (Cu{sub 2-x}S, x = 0.03, 0.2) nanocrystals (NCs) are synthesized from a newly prepared single-source precursor (SP), [Cu(bdpa){sub 2}][CuCl{sub 2}], where bdpa is benzyl 3,5-dimethyl-pyrazole-1-carbodithioate. The SP is crystallized with space group Pī and possesses a distorted tetrahedron structure with a CuN{sub 2}S{sub 2} chromophore where the central copper is in +1 oxidation state. Distortion in copper(I) structure and the low decomposition temperature of SP make it favorable for the low-temperature solvent-assisted selective growth of high-copper content sulfides. The nucleation and growth of Cu{sub 2-x}S (x = 0.03, 0.2) are effectively controlled by the SP and the solvent in the solvothermal decomposition process. During decomposition, fragment benzyl thiol (PhCH{sub 2}SH) from SP effectively passivates the nucleus leading to spherical nanocrystals. Further, solvent plays an important role in the selective thermochemical transformation of Cu{sup I}-complex to Cu{sub 2-x}S (x = 0.03, 0.2) NCs. The chelating binders (solvent) like ethylene diamine (EN) and ethylene glycol (EG) prefer to form spherical Cu{sub 1.97}S nanoparticles (djurleite), whereas nonchelating hydrazine hydrate (HH) shows the tendency to furnish hexagonal platelets of copper-deficient Cu{sub 1.8}S. The optical band gap values (2.25–2.50 eV) show quantum confinement effect in the structure. The synthesized NCs display excellent catalytic activity (~87 %) toward photodegradation of organic dyes like Congo Red (CR) and Methylene Blue (MB).Graphical abstractA pyrazolyl-based thiolato single-source precursor for the selective synthesis of isotropic copper-deficient copper(I) sulfide nanocrystals: Synthesis, optical and photocatalytic activity.Gopinath Mondal, Ananyakumari Santra, Pradip Bera, Moumita Acharjya, Sumanta Jana, Dipankar Chattopadhyay, Anup Mondal, Sang Il Seok, Pulakesh Bera.

  6. The Dual Origin Of The Nitrogen Deficiency In Comets: Selective Volatile Trapping In The Nebula And Postaccretion Radiogenic Heating

    Science.gov (United States)

    Mousis, Olivier; Guilbert-Lepoutre, A.; Lunine, J. I.; Cochran, A. L.; Waite, J. H.; Petit, J.; Rousselot, P.

    2012-10-01

    We propose a scenario that explains the apparent nitrogen deficiency in comets in a way consistent with the presence of this molecule in the atmospheres of Pluto and Triton. We use a statistical thermodynamic model to investigate the composition of the successive multiple guest clathrates that may have formed during the cooling of the primordial nebula from the most abundant volatiles present in the gas phase. These clathrates agglomerated with the other ices (pure condensates or stoechiometric hydrates) and formed the building blocks of comets. We report that molecular nitrogen is a poor clathrate former, when we consider a plausible gas phase composition of the primordial nebula. This implies that its trapping into cometesimals requires a low disk temperature (about 20 K) in order to allow the formation of its pure condensate. We find that it is possible to explain the lack of molecular nitrogen in comets as a consequence of their postformation internal heating engendered by the decay of radiogenic nuclides. This scenario is found to be consistent with the presence of nitrogen-rich atmospheres around Pluto and Triton. Our model predicts that comets should present xenon-to-water and krypton-to-water ratios close to solar xenon-to-oxygen and krypton-to-oxygen ratios, respectively. In contrast, the argon-to-water ratio is predicted to be depleted by a factor of about 300 in comets compared to solar argon-to-oxygen, as a consequence of the nitrogen outgassing.

  7. Vitamin A Deficiency Due to Selective Eating as a Cause of Blindness in a High-Income Setting.

    Science.gov (United States)

    Martini, Silvia; Rizzello, Angela; Corsini, Ilaria; Romanin, Benedetta; Fiorentino, Michelangelo; Grandi, Sara; Bergamaschi, Rosalba

    2018-04-01

    Vitamin A is a fat-soluble micronutrient involved in the regulation of several physiologic functions, such as visual acuity, epithelial tissue integrity, immune response, and gene expression, thus playing a crucial role in childhood growth and development. Although vitamin A deficiency (VAD) in resource-limited settings is still an actual issue and represents the leading cause of preventable childhood blindness, its occurrence in high-income countries is rare, although possibly underdiagnosed because of its nonspecific early manifestations. A good awareness of VAD symptoms and risk factors could aid its early diagnosis, which is fundamental to undertake a prompt treatment and to prevent ocular complications. Nevertheless, the role of restrictive dietary habits, increasingly common in developed countries, is often overlooked in infants and children. We present a case of VAD with permanent ocular sequelae in a 5-year-old girl from a high-income country. In the case described, VAD ensued from a highly restricted diet, mainly limited to oat milk, which had been followed for more than 2 years. This child presented with ocular symptoms, opportunistic infection, anemia, poor growth, and a diffuse squamous metaplasia of the bladder; after commencing retinol supplementation, a gradual healing of clinical VAD manifestations occurred, with the exception of the ocular sequelae, which resulted in irreversible visual loss. Copyright © 2018 by the American Academy of Pediatrics.

  8. A Method for Selective Depletion of Zn(II) Ions from Complex Biological Media and Evaluation of Cellular Consequences of Zn(II) Deficiency

    Science.gov (United States)

    Richardson, Christopher E. R.; Cunden, Lisa S.; Butty, Vincent L.; Nolan, Elizabeth M.; Lippard, Stephen J.; Shoulders, Matthew D.

    2018-01-01

    We describe the preparation, evaluation, and application of an S100A12 protein-conjugated solid support, hereafter the “A12-resin,” that can remove 99% of Zn(II) from complex biological solutions without significantly perturbing the concentrations of other metal ions. The A12-resin can be applied to selectively deplete Zn(II) from diverse tissue culture media and from other biological fluids, including human serum. To further demonstrate the utility of this approach, we investigated metabolic, transcriptomic, and metallomic responses of HEK293 cells cultured in medium depleted of Zn(II) using S100A12. The resulting data provide insight into how cells respond to acute Zn(II) deficiency. We expect that the A12-resin will facilitate interrogation of disrupted Zn(II) homeostasis in biological settings, uncovering novel roles for Zn(II) in biology. PMID:29334734

  9. Chlamydial serum IgG, IgA and local IgA antibodies in patients with genital-tract infections measured by solid-phase radioimmunoassay

    International Nuclear Information System (INIS)

    Terho, P.; Meurman, O.

    1981-01-01

    A solid-phase radioimmunoassay (RIA) for IgG and IgA class antibodies to Chlamydia trachomatis was developed with C. trachomatis serotype L2 as antigen. The assay was sensitive, reproducible and correlated well with an immunofluorescence test (r = 0.85). Serum IgG antibodies were detected in 79% of Chlamydia isolation-positive versus 43% of isolation-negative male patients with urethritis and serum IgA antibodies in 53% and 21%, respectively. Urethral IgA antibodies, measured from specimens taken for chlamydial isolation, could be detected in 94% and 38%, respectively. From 737 male urethral and 909 female cervical secretions screened for the presence of IgA antibodies, about half were isolation and IgA negative. Only 4% (6/151) of male and 5.4% (2/37) of female isolation-positive specimens were IgA negative. The determination of local IgA antibodies may be used as a screening test in chlamydial genital infections. (author)

  10. Purine salvage in the apicomplexan Sarcocystis neurona, and generation of hypoxanthine-xanthine-guanine phosphoribosyltransferase-deficient clones for positive-negative selection of transgenic parasites.

    Science.gov (United States)

    Dangoudoubiyam, Sriveny; Zhang, Zijing; Howe, Daniel K

    2014-09-01

    Sarcocystis neurona is an apicomplexan parasite that causes severe neurological disease in horses and marine mammals. The Apicomplexa are all obligate intracellular parasites that lack purine biosynthesis pathways and rely on the host cell for their purine requirements. Hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK) are key enzymes that function in two complementary purine salvage pathways in apicomplexans. Bioinformatic searches of the S. neurona genome revealed genes encoding HXGPRT, AK and all of the major purine salvage enzymes except purine nucleoside phosphorylase. Wild-type S. neurona were able to grow in the presence of mycophenolic acid (MPA) but were inhibited by 6-thioxanthine (6-TX), suggesting that the pathways involving either HXGPRT or AK are functional in this parasite. Prior work with Toxoplasma gondii demonstrated the utility of HXGPRT as a positive-negative selection marker. To enable the use of HXGPRT in S. neurona, the SnHXGPRT gene sequence was determined and a gene-targeting plasmid was transfected into S. neurona. SnHXGPRT-deficient mutants were selected with 6-TX, and single-cell clones were obtained. These Sn∆HXG parasites were susceptible to MPA and could be complemented using the heterologous T. gondii HXGPRT gene. In summary, S. neurona possesses both purine salvage pathways described in apicomplexans, thus allowing the use of HXGPRT as a positive-negative drug selection marker in this parasite.

  11. "Iga päev..." : [luuletused] / Doris Kareva

    Index Scriptorium Estoniae

    Kareva, Doris, 1958-

    2001-01-01

    Tekst eesti ja inglise k. D. Kareva lühibiograafia eesti ja inglise k. lk. 175. Sisu: "Iga päev..." = "Every day..." ; "Ma nägin unes - Saatan kõneles..." = "I dream that I heard Satan speak..." ; "Viib sünnieelsest unest surmaunne..." = "Rainbow-coloured confusion bears us..." ; "Vaadeldes vikerkaarlevat maailma..." = "Viewing the rainbowing world..." ; "Ei jõua kirjutada puhtandit..." = "No time to write the final draft..." ; "Põletatud luuletused..." = ""Burnt poems..." ; Fraktalia ; Müsteerium 1-5 = Enigma 1-5 ; "Jumal juhtub..." = "God happens..." ; Moira 1-7 = Wishing well 1-7 ; Concerto strumenti e voce

  12. IgA LINEAR BULLOUS DERMATOSIS IN CHILDHOOD.

    OpenAIRE

    Ivelina Yordanova; Valentin Valtchev; Dimitar Gospodinov; Snejina Vassileva

    2015-01-01

    IgA linear bullous dermatosis, also known as chronic bullous dermatosis of childhood, is an autoimmune disease which may be idiopathic or drug-induced. The disease affects children and adults. We present a 4 years old girl with itchy polymorphic eruptions. The skin rash was presented by bullous-erosive rosette-like lesions with reddish-brown crust in the center, distributed on the skin of the face, trunk and extremities. The vesicles were filled with serous and hemorrhagic content. Laboratory...

  13. The human intestinal IgA response; burning questions.

    Directory of Open Access Journals (Sweden)

    Jo eSpencer

    2012-05-01

    Full Text Available Understanding the cellular and molecular mechanisms that generate the human intestinal IgA response is fundamentally important if effective mucosal vaccination is to be successful and broadly applied. There have been several major advances in this field recently that have allowed us to feel optimistic that this will be achieved. However, there are still many unanswered questions. These questions have been used as a scaffold for this review that considers findings at the current leading edge alongside the many uncertainties in this field.

  14. Human Cell Line-Derived Monoclonal IgA Antibodies for Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Felix Hart

    2017-05-01

    Full Text Available IgA antibodies have great potential to improve the functional diversity of current IgG antibody-based cancer immunotherapy options. However, IgA production and purification is not well established, which can at least in part be attributed to the more complex glycosylation as compared to IgG antibodies. IgA antibodies possess up to five N-glycosylation sites within their constant region of the heavy chain as compared to one site for IgG antibodies. The human GlycoExpress expression system was developed to produce biotherapeutics with optimized glycosylation and used here to generate a panel of IgA isotype antibodies directed against targets for solid (TA-mucin 1, Her2, EGFR, Thomsen–Friedenreich and hematological (CD20 cancer indications. The feasibility of good manufacturing practice was shown by the production of 11 g IgA within 35 days in a one liter perfusion bioreactor, and IgA antibodies in high purity were obtained after purification. The monoclonal IgA antibodies possessed a high sialylation degree, and no non-human glycan structures were detected. Kinetic analysis revealed increased avidity antigen binding for IgA dimers as compared to monomeric antibodies. The IgA antibodies exhibited potent Fab- and Fc-mediated functionalities against cancer cell lines, whereby especially granulocytes are recruited. Therefore, for patients who do not sufficiently benefit from therapeutic IgG antibodies, IgA antibodies may complement current regiment options and represent a promising strategy for cancer immunotherapy. In conclusion, a panel of novel biofunctional IgA antibodies with human glycosylation was successfully generated.

  15. Gluten exacerbates IgA nephropathy in humanized mice through gliadin-CD89 interaction.

    Science.gov (United States)

    Papista, Christina; Lechner, Sebastian; Ben Mkaddem, Sanae; LeStang, Marie-Bénédicte; Abbad, Lilia; Bex-Coudrat, Julie; Pillebout, Evangéline; Chemouny, Jonathan M; Jablonski, Mathieu; Flamant, Martin; Daugas, Eric; Vrtovsnik, François; Yiangou, Minas; Berthelot, Laureline; Monteiro, Renato C

    2015-08-01

    IgA1 complexes containing deglycosylated IgA1, IgG autoantibodies, and a soluble form of the IgA receptor (sCD89), are hallmarks of IgA nephropathy (IgAN). Food antigens, notably gluten, are associated with increased mucosal response and IgAN onset, but their implication in the pathology remains unknown. Here, an IgAN mouse model expressing human IgA1 and CD89 was used to examine the role of gluten in IgAN. Mice were given a gluten-free diet for three generations to produce gluten sensitivity, and then challenged for 30 days with a gluten diet. A gluten-free diet resulted in a decrease of mesangial IgA1 deposits, transferrin 1 receptor, and transglutaminase 2 expression, as well as hematuria. Mice on a gluten-free diet lacked IgA1-sCD89 complexes in serum and kidney eluates. Disease severity depended on gluten and CD89, as shown by reappearance of IgAN features in mice on a gluten diet and by direct binding of the gluten-subcomponent gliadin to sCD89. A gluten diet exacerbated intestinal IgA1 secretion, inflammation, and villous atrophy, and increased serum IgA1 anti-gliadin antibodies, which correlated with proteinuria in mice and patients. Moreover, early treatment of humanized mice with a gluten-free diet prevented mesangial IgA1 deposits and hematuria. Thus, gliadin-CD89 interaction may aggravate IgAN development through induction of IgA1-sCD89 complex formation and a mucosal immune response. Hence, early-stage treatment with a gluten-free diet could be beneficial to prevent disease.

  16. Is Visual Selective Attention in Deaf Individuals Enhanced or Deficient? The Case of the Useful Field of View

    Science.gov (United States)

    Dye, Matthew W. G.; Hauser, Peter C.; Bavelier, Daphne

    2009-01-01

    Background Early deafness leads to enhanced attention in the visual periphery. Yet, whether this enhancement confers advantages in everyday life remains unknown, as deaf individuals have been shown to be more distracted by irrelevant information in the periphery than their hearing peers. Here, we show that, in a complex attentional task, a performance advantage results for deaf individuals. Methodology/Principal Findings We employed the Useful Field of View (UFOV) which requires central target identification concurrent with peripheral target localization in the presence of distractors – a divided, selective attention task. First, the comparison of deaf and hearing adults with or without sign language skills establishes that deafness and not sign language use drives UFOV enhancement. Second, UFOV performance was enhanced in deaf children, but only after 11 years of age. Conclusions/Significance This work demonstrates that, following early auditory deprivation, visual attention resources toward the periphery slowly get augmented to eventually result in a clear behavioral advantage by pre-adolescence on a selective visual attention task. PMID:19462009

  17. Selected Alkylating Agents Can Overcome Drug Tolerance of G0-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice.

    Science.gov (United States)

    Pajic, Marina; Blatter, Sohvi; Guyader, Charlotte; Gonggrijp, Maaike; Kersbergen, Ariena; Küçükosmanoğlu, Aslι; Sol, Wendy; Drost, Rinske; Jonkers, Jos; Borst, Piet; Rottenberg, Sven

    2017-11-15

    Purpose: We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse. Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53 -mutant breast cancer. Because of the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore, no BRCA1-dependent acquired resistance occurs. To characterize the cell-cycle stage from which Brca1 -/- ;p53 -/- mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell-cycle indicator (FUCCI) construct into the tumor cells. Results: Despite repeated sensitivity to the MTD of platinum drugs, the Brca1 -mutated mammary tumors are not eradicated, not even by a frequent dosing schedule. We show that relapse comes from single-nucleated cells delaying entry into the S-phase. Such slowly cycling cells, which are present within the drug-naïve tumors, are enriched in tumor remnants. Using the FUCCI construct, we identified nonfluorescent G 0 -like cells as the population most tolerant to platinum drugs. Intriguingly, these cells are more sensitive to the DNA-crosslinking agent nimustine, resulting in an increased number of multinucleated cells that lack clonogenicity. This is consistent with our in vivo finding that the nimustine MTD, among several alkylating agents, is the most effective in eradicating Brca1 -mutated mouse mammary tumors. Conclusions: Our data show that targeting G 0 -like cells is crucial for the eradication of BRCA1/p53-deficient tumor cells. This can be achieved with selected alkylating agents such as nimustine. Clin Cancer Res; 23(22); 7020-33. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Iodine Deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.

    2009-01-01

    Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected.

  19. Reactivities of N-acetylgalactosamine-specific lectins with human IgA1 proteins

    DEFF Research Database (Denmark)

    Moore, J.S.; Kulhavy, R.; Tomana, M.

    2007-01-01

    , VV reacted with sugars of both IgA subclasses and IgG, indicating that it also recognized N-linked glycans without GalNAc. Furthermore, HAA and HPA from several manufacturers differed in their ability to bind various IgA1 myeloma proteins and other GalNAc-containing glycoproteins in ELISA and Western...

  20. Linear IgA bullous dermatosis in a patient with renal cell carcinoma

    NARCIS (Netherlands)

    Van der Waal, RIF; Van de Scheur, MR; Pas, HH; Jonkman, MF; Van Groeningen, CJ; Nieboer, C; Starink, TM

    Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal bullous disease with heterogeneous clinical manifestations, characterized by linear deposition of IgA along the epidermal basement membrane zone. We report a patient with a metastasized renal cell carcinoma who developed an extensive

  1. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification

    NARCIS (Netherlands)

    Cattran, Daniel C.; Coppo, Rosanna; Cook, H. Terence; Feehally, John; Roberts, Ian S. D.; Troyanov, Stéphan; Alpers, Charles E.; Amore, Alessandro; Barratt, Jonathan; Berthoux, Francois; Bonsib, Stephen; Bruijn, Jan A.; D'Agati, Vivette; D'Amico, Giuseppe; Emancipator, Steven; Emma, Francesco; Ferrario, Franco; Fervenza, Fernando C.; Florquin, Sandrine; Fogo, Agnes; Geddes, Colin C.; Groene, Hermann-Josef; Haas, Mark; Herzenberg, Andrew M.; Hill, Prue A.; Hogg, Ronald J.; Hsu, Stephen I.; Jennette, J. Charles; Joh, Kensuke; Julian, Bruce A.; Kawamura, Tetsuya; Lai, Fernand M.; Leung, Chi Bon; Li, Lei-Shi; Li, Philip K. T.; Liu, Zhi-Hong; Mackinnon, Bruce; Mezzano, Sergio; Schena, F. Paolo; Tomino, Yasuhiko; Walker, Patrick D.; Wang, Haiyan; Weening, Jan J.; Yoshikawa, Nori; Zhang, Hong

    2009-01-01

    IgA nephropathy is the most common glomerular disease worldwide, yet there is no international consensus for its pathological or clinical classification. Here a new classification for IgA nephropathy is presented by an international consensus working group. The goal of this new system was to

  2. PetIGA: A framework for high-performance isogeometric analysis

    KAUST Repository

    Dalcin, Lisandro; Collier, N.; Vignal, Philippe; Cortes, Adriano Mauricio; Calo, Victor M.

    2016-01-01

    We present PetIGA, a code framework to approximate the solution of partial differential equations using isogeometric analysis. PetIGA can be used to assemble matrices and vectors which come from a Galerkin weak form, discretized with Non-Uniform Rational B-spline basis functions. We base our framework on PETSc, a high-performance library for the scalable solution of partial differential equations, which simplifies the development of large-scale scientific codes, provides a rich environment for prototyping, and separates parallelism from algorithm choice. We describe the implementation of PetIGA, and exemplify its use by solving a model nonlinear problem. To illustrate the robustness and flexibility of PetIGA, we solve some challenging nonlinear partial differential equations that include problems in both solid and fluid mechanics. We show strong scaling results on up to 40964096 cores, which confirm the suitability of PetIGA for large scale simulations.

  3. Serological Analysis of Immunogenic Properties of Recombinant Meningococcus IgA1 Protease-Based Proteins.

    Science.gov (United States)

    Kotelnikova, O V; Zinchenko, A A; Vikhrov, A A; Alliluev, A P; Serova, O V; Gordeeva, E A; Zhigis, L S; Zueva, V S; Razgulyaeva, O A; Melikhova, T D; Nokel, E A; Drozhzhina, E Yu; Rumsh, L D

    2016-07-01

    Using the genome sequence of IgA1 protease of N. meningitidis of serogroup B, four recombinant proteins of different structure and molecular weight were constructed. These proteins were equal in inducing the formation of specific antibodies to IgA1 protease and had protective properties against meningococci. In the sera of immunized mice, anti-IgA1 protease antibodies were detected by whole-cell ELISA, which indicated the presence of IgA1 protease on the surface of these bacteria. We hypothesized that the protective properties of IgA1 protease-based antigens and IgA1 protease analogs could be realized not only via impairment of bacterium adhesion to the mucosa, but also via suppression of this pathogen in the organism. The presented findings seem promising for using these proteins as the basis for anti-meningococcus vaccine.

  4. PetIGA: A framework for high-performance isogeometric analysis

    KAUST Repository

    Dalcin, L.

    2016-05-25

    We present PetIGA, a code framework to approximate the solution of partial differential equations using isogeometric analysis. PetIGA can be used to assemble matrices and vectors which come from a Galerkin weak form, discretized with Non-Uniform Rational B-spline basis functions. We base our framework on PETSc, a high-performance library for the scalable solution of partial differential equations, which simplifies the development of large-scale scientific codes, provides a rich environment for prototyping, and separates parallelism from algorithm choice. We describe the implementation of PetIGA, and exemplify its use by solving a model nonlinear problem. To illustrate the robustness and flexibility of PetIGA, we solve some challenging nonlinear partial differential equations that include problems in both solid and fluid mechanics. We show strong scaling results on up to 40964096 cores, which confirm the suitability of PetIGA for large scale simulations.

  5. A case of linear IgA bullous dermatosis with IgA anti-type VII collagen autoantibodies.

    Science.gov (United States)

    Hashimoto, T; Ishiko, A; Shimizu, H; Tanaka, T; Dodd, H J; Bhogal, B S; Black, M M; Nishikawa, T

    1996-02-01

    In this study we present a patient with the sublamina densa type of linear IgA bullous dermatosis (LABD), with IgA autoantibodies reactive with the 290-kDa type VII collagen (the epidermolysis bullosa acquisita (EBA) antigen) and with immunoblotting of normal human dermal extracts. The clinical and histological features of the present case were compatible with those of LABD but quite different from those of EBA. Although EBA sera reacted with the bacterial fusion protein of the N-terminal globular (NC1) domain of type VII collagen, this patient's serum did not show reactivity. Furthermore, ultrastructural localization of target epitopes on the anchoring fibrils in this patient was considerably different from EBA. These results indicate that, whereas EBA antibodies react with the NC1 domain of type VII collagen, the epitope in this case is different from that of EBA (and is most likely on the central triple helical domain). This difference may be responsible for the clinical presentation in this patient being distinct from that of EBA.

  6. PetIGA-MF: a multi-field high-performance toolbox for structure-preserving B-splines spaces

    KAUST Repository

    Sarmiento, Adel; Cô rtes, A.M.A.; Garcia, D.A.; Dalcin, Lisandro; Collier, N.; Calo, V.M.

    2016-01-01

    We describe a high-performance solution framework for isogeometric discrete differential forms based on B-splines: PetIGA-MF. Built on top of PetIGA, an open-source library we have built and developed over the last decade, PetIGA-MF is a general

  7. Elucidating heterogeneity of IgA1 hinge-region O-glycosylation by use of MALDI-TOF/TOF mass spectrometry: role of cysteine alkylation during sample processing.

    Science.gov (United States)

    Franc, Vojtěch; Řehulka, Pavel; Raus, Martin; Stulík, Jiří; Novak, Jan; Renfrow, Matthew B; Šebela, Marek

    2013-10-30

    Determining disease-associated changes in protein glycosylation provides a better understanding of pathogenesis. This work focuses on human immunoglobulin A1 (IgA1), where aberrant O-glycosylation plays a key role in the pathogenesis of IgA nephropathy (IgAN). Normal IgA1 hinge region carries 3 to 6 O-glycans consisting of N-acetylgalactosamine (GalNAc) and galactose (Gal); both sugars may be sialylated. In IgAN patients, some O-glycans on a fraction of IgA1 molecules are Gal-deficient. Here we describe a sample preparation protocol with optimized cysteine alkylation of a Gal-deficient polymeric IgA1 myeloma protein prior to in-gel digestion and analysis of the digest by MALDI-TOF/TOF mass spectrometry (MS). Following a novel strategy, IgA1 hinge-region O-glycopeptides were fractionated by reversed-phase liquid chromatography using a microgradient device and identified by MALDI-TOF/TOF tandem MS (MS/MS). The acquired MS/MS spectra were interpreted manually and by means of our own software. This allowed assigning up to six O-glycosylation sites and demonstration, for the first time, of the distribution of isomeric O-glycoforms having the same molecular mass, but a different glycosylation pattern. The most abundant Gal-deficient O-glycoforms were GalNAc4Gal3 and GalNAc5Gal4 with one Gal-deficient site and GalNAc5Gal3 and GalNAc4Gal2 with two Gal-deficient sites. The most frequent Gal-deficient sites were at Ser230 and/or Thr236. In this work, we studied the O-glycosylation in the hinge region of human immunoglobulin A1 (IgA1). Aberrant glycosylation of the protein plays a key role in the pathogenesis of IgA nephropathy. Thus identification of the O-glycan composition of IgA1 is important for a deeper understanding of the disease mechanism, biomarker discovery and validation, and implementation and monitoring of disease-specific therapies. We developed a new procedure for elucidating the heterogeneity of IgA1 O-glycosylation. After running a polyacrylamide gel

  8. Anti-actin IgA antibodies in severe coeliac disease.

    Science.gov (United States)

    Granito, A; Muratori, P; Cassani, F; Pappas, G; Muratori, L; Agostinelli, D; Veronesi, L; Bortolotti, R; Petrolini, N; Bianchi, F B; Volta, U

    2004-08-01

    Anti-actin IgA antibodies have been found in sera of coeliacs. Our aim was to define the prevalence and clinical significance of anti-actin IgA in coeliacs before and after gluten withdrawal. One hundred and two biopsy-proven coeliacs, 95 disease controls and 50 blood donors were studied. Anti-actin IgA were evaluated by different methods: (a) antimicrofilament positivity on HEp-2 cells and on cultured fibroblasts by immunofluorescence; (b) anti-actin positivity by enzyme-linked immuosorbent assay (ELISA); and (c) presence of the tubular/glomerular pattern of anti-smooth muscle antibodies on rat kidney sections by immunofluorescence. Antimicrofilament IgA were present in 27% of coeliacs and in none of the controls. Antimicrofilament antibodies were found in 25 of 54 (46%) coeliacs with severe villous atrophy and in three of 48 (6%) with mild damage (P < 0.0001). In the 20 patients tested, antimicrofilaments IgA disappeared after gluten withdrawal in accordance with histological recovery. Our study shows a significant correlation between antimicrofilament IgA and the severity of intestinal damage in untreated coeliacs. The disappearance of antimicrofilament IgA after gluten withdrawal predicts the normalization of intestinal mucosa and could be considered a useful tool in the follow-up of severe coeliac disease.

  9. Evaluation of Serum IgA level in nontreated and treated oral squamous cell carcinoma patients

    Directory of Open Access Journals (Sweden)

    Richa Mishra

    2018-01-01

    Full Text Available Introduction: Research in early cancer detection has led to discovery of many immunological tumor markers that contribute considerably to supplement the method of diagnosis. High serum immunoglobulin A (IgA values in patients with cancer have been used as tumor markers. Aims and Objectives: To evaluate and compare the serum IgA levels in nontreated, treated oral squamous cell carcinoma (SCC patients, and control group. Materials and Methods: A total of 60 patients were included in the study. 20 biopsy confirmed oral SCC patients, who have received no medical treatment, 20 oral SCC patients treated with surgery and/or radiotherapy and 20 normal healthy individuals. Venous blood samples were collected from anterior cubital vein and were delivered to the biochemistry laboratory for the estimation of serum IgA level by nephelometry method. Statistical Analysis Used: Statistical method employed were the Pearson's Chi-square test and One-way analysis of variance (Welch followed by Games-Howell post-hoc test. Results: We observed significant difference for serum IgA between study subjects in control, nontreated and treated oral SCC patients (P < 0.001. Serum IgA level in nontreated group was significantly higher than treated group and there was an approximately two-fold increase in serum IgA level in nontreated oral SCC patients when compared to that of the normal healthy individuals. Conclusion: Serum level of IgA might be employed as diagnostic and prognostic indicators in oral cancer.

  10. Gene Expression Analysis in Tubule Interstitial Compartments Reveals Candidate Agents for IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Jinling Wang

    2014-09-01

    Full Text Available Background/Aims: Our aim was to explore the molecular mechanism underlying development of IgA nephropathy and discover candidate agents for IgA nephropathy. Methods: The differentially expressed genes (DEGs between patients with IgA nephropathy and normal controls were identified by the data of GSE35488 downloaded from GEO (Gene Expression Omnibus database. The co-expressed gene pairs among DEGs were screened to construct the gene-gene interaction network. Gene Ontology (GO enrichment analysis was performed to analyze the functions of DEGs. The biologically active small molecules capable of targeting IgA nephropathy were identified using the Connectivity Map (cMap database. Results: A total of 55 genes involved in response to organic substance, transcription factor activity and response to steroid hormone stimulus were identified to be differentially expressed in IgA nephropathy patients compared to healthy individuals. A network with 45 co-expressed gene pairs was constructed. DEGs in the network were significantly enriched in response to organic substance. Additionally, a group of small molecules were identified, such as doxorubicin and thapsigargin. Conclusion: Our work provided a systematic insight in understanding the mechanism of IgA nephropathy. Small molecules such as thapsigargin might be potential candidate agents for the treatment of IgA nephropathy.

  11. Diagnosis and treatment of unexplained anemia with iron deficiency without overt bleeding

    DEFF Research Database (Denmark)

    Dahlerup, Jens Frederik; Eivindson, Martin; Jacobsen, Bent Ascanius

    2015-01-01

    A general overview is given of the causes of anemia with iron deficiency as well as the pathogenesis of anemia and the para-clinical diagnosis of anemia. Anemia with iron deficiency but without overt GI bleeding is associated with a risk of malignant disease of the gastrointestinal tract; upper...... gastrointestinal cancer is 1/7 as common as colon cancer. Benign gastrointestinal causes of anemia are iron malabsorption (atrophic gastritis, celiac disease, chronic inflammation, and bariatric surgery) and chronic blood loss due to gastrointestinal ulcerations. The following diagnostic strategy is recommended...... for unexplained anemia with iron deficiency: conduct serological celiac disease screening with transglutaminase antibody (IgA type) and IgA testing and perform bidirectional endoscopy (gastroscopy and colonoscopy). Bidirectional endoscopy is not required in premenopausal women

  12. Linear IgA dermatosis associated with ulcerative colitis: complete and sustained remission after total colectomy

    OpenAIRE

    Vargas,Thiago Jeunon de Sousa; Fialho,Mônica; Santos,Luiza Tavares dos; Rodrigues,Palmira Assis de Jesus Barreto; Vargas,Ana Luisa Bittencourt Sampaio Jeunon; Sousa,Maria Auxiliadora Jeunon

    2013-01-01

    Linear IgA dermatosis has been increasingly associated with inflammatory bowel diseases, particularly ulcerative colitis. A 13-year-old male patient with an 11-month history of ulcerative colitis developed vesicles, pustules and erosions on the skin of the face, trunk and buttocks and in the oral mucosa. The work-up revealed a neutrophil-rich sub-epidermal bullous disease and linear deposition of IgA along the dermoepidermal junction, establishing the diagnosis of linear IgA dermatosis. The p...

  13. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN)

    DEFF Research Database (Denmark)

    Fellström, Bengt C.; Barratt, Jonathan; Cook, Heather

    2017-01-01

    Background IgA nephropathy is thought to be associated with mucosal immune system dysfunction, which manifests as renal IgA deposition that leads to impairment and end-stage renal disease in 20–40% of patients within 10–20 years. In this trial (NEFIGAN) we aimed to assess safety and efficacy...... at 62 nephrology clinics across ten European countries. We recruited patients aged at least 18 years with biopsy-confirmed primary IgA nephropathy and persistent proteinuria despite optimised renin-angiotensin system (RAS) blockade. We randomly allocated patients with a computer algorithm, with a fixed...

  14. An oncolytic adenovirus enhances antiangiogenic and antitumoral effects of a replication-deficient adenovirus encoding endostatin by rescuing its selective replication in nasopharyngeal carcinoma cells

    International Nuclear Information System (INIS)

    Liu, Ran-yi; Zhou, Ling; Zhang, Yan-ling; Huang, Bi-jun; Ke, Miao-la; Chen, Jie-min; Li, Li-xia; Fu, Xiang; Wu, Jiang-xue; Huang, Wenlin

    2013-01-01

    Highlights: •H101 promotes endostatin expression by Ad-Endo via rescuing Ad-Endo replication. •H101 rescued Ad-Endo replication by supplying E1A and E1B19k proteins. •Ad-Endo enhanced the cytotoxicity of H101 in NPC cells. •Ad-Endo and oncolytic Ad H101 have synergistic antitumor effects on NPC. -- Abstract: A replication-deficient adenovirus (Ad) encoding secreted human endostatin (Ad-Endo) has been demonstrated to have promising antiangiogenic and antitumoral effects. The E1B55k-deleted Ad H101 can selectively lyse cancer cells. In this study, we explored the antitumor effects and cross-interactions of Ad-Endo and H101 on nasopharyngeal carcinoma (NPC). The results showed that H101 dramatically promoted endostatin expression by Ad-Endo via rescuing Ad-Endo replication in NPC cells, and the expressed endostatin proteins significantly inhibited the proliferation of human umbilical vein endothelial cells. E1A and E1B19k products are required for the rescuing of H101 to Ad-Endo replication in CNE-1 and CNE-2 cells, but not in C666-1 cells. On the other hand, Ad-Endo enhanced the cytotoxicity of H101 by enhancing Ad replication in NPC cells. The combination of H101 and Ad-Endo significantly inhibited CNE-2 xenografts growth through the increased endostatin expression and Ad replication. These findings indicate that the combination of Ad-Endo gene therapy and oncolytic Ad therapeutics could be promising in comprehensive treatment of NPC

  15. An oncolytic adenovirus enhances antiangiogenic and antitumoral effects of a replication-deficient adenovirus encoding endostatin by rescuing its selective replication in nasopharyngeal carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ran-yi, E-mail: liuranyi@mail.sysu.edu.cn [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); Zhou, Ling [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); Zhang, Yan-ling [School of Biotechnology, Southern Medical University, Guangzhou 510515 (China); Huang, Bi-jun; Ke, Miao-la; Chen, Jie-min [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); Li, Li-xia [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010 (China); Fu, Xiang; Wu, Jiang-xue [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); Huang, Wenlin, E-mail: hwenl@mail.sysu.edu.cn [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); Guangdong Provincial Key Laboratory of Tumor-Targeted Drug, Doublle Bioproducts Inc., Guangzhou 510663 (China)

    2013-12-13

    Highlights: •H101 promotes endostatin expression by Ad-Endo via rescuing Ad-Endo replication. •H101 rescued Ad-Endo replication by supplying E1A and E1B19k proteins. •Ad-Endo enhanced the cytotoxicity of H101 in NPC cells. •Ad-Endo and oncolytic Ad H101 have synergistic antitumor effects on NPC. -- Abstract: A replication-deficient adenovirus (Ad) encoding secreted human endostatin (Ad-Endo) has been demonstrated to have promising antiangiogenic and antitumoral effects. The E1B55k-deleted Ad H101 can selectively lyse cancer cells. In this study, we explored the antitumor effects and cross-interactions of Ad-Endo and H101 on nasopharyngeal carcinoma (NPC). The results showed that H101 dramatically promoted endostatin expression by Ad-Endo via rescuing Ad-Endo replication in NPC cells, and the expressed endostatin proteins significantly inhibited the proliferation of human umbilical vein endothelial cells. E1A and E1B19k products are required for the rescuing of H101 to Ad-Endo replication in CNE-1 and CNE-2 cells, but not in C666-1 cells. On the other hand, Ad-Endo enhanced the cytotoxicity of H101 by enhancing Ad replication in NPC cells. The combination of H101 and Ad-Endo significantly inhibited CNE-2 xenografts growth through the increased endostatin expression and Ad replication. These findings indicate that the combination of Ad-Endo gene therapy and oncolytic Ad therapeutics could be promising in comprehensive treatment of NPC.

  16. What Are Rare Clotting Factor Deficiencies?

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  17. Secretory IgA as a diagnostic tool for Pseudomonas aeruginosa respiratory colonization

    DEFF Research Database (Denmark)

    Aanaes, Kasper; Johansen, Helle Krogh; Poulsen, Steen Seier

    2012-01-01

    BACKGROUND: Pseudomonas aeruginosa sinusitis may be the focus for intermittent lung colonization in patients with cystic fibrosis (CF). The sinusitis may induce elevated IgA levels in nasal secretion and saliva against P. aeruginosa. METHODS: 120 CF patients chronically infected, intermittently...... colonized or without P. aeruginosa in the lungs participated in this cross-sectional study. IgA and IgG against P. aeruginosa sonicate and alginate were measured in nasal secretions, saliva, and in serum by ELISA. RESULTS: The intermittently colonized patients had significantly higher IgA levels in nasal...... secretions and saliva than those without P. aeruginosa in the lungs, indicating that P. aeruginosa sinusitis may precede intermittent colonization and chronic infection of the lungs. CONCLUSIONS: Specific IgA against P. aeruginosa in nasal secretions and saliva can contribute to differentiation between...

  18. Radioimmunoassay for the detection of virus-specific IgA antibodies in saliva

    International Nuclear Information System (INIS)

    Friedman, M.G.

    1982-01-01

    The use of a sensitive and versatile radioimmunoassay (RIA) for detection of mumps-specific IgA and measles-specific IgA in unconcentrated saliva samples is described. The samples were obtained either by expectoration or by swabbing of the oral cavity, with or without stimulation of secretion, and were inactivated and clarified before testing. Mumps-specific IgA antibodies were detected as early as one day after onset of illness and peaked at 1-2 weeks after onset. Measles-specific salivary IgA antibodies were detected in 15-month old children 2-3 weeks after immunization. These results suggest that the RIA technique may be useful for early diagnosis of viral infections and for confirmation of response to immunization without the need for a blood sample, as well as for the study of the secretory immune response in very young and older subjects. (Auth.)

  19. Linear IgA dermatosis associated with ulcerative colitis: complete and sustained remission after total colectomy.

    Science.gov (United States)

    Vargas, Thiago Jeunon de Sousa; Fialho, Mônica; Santos, Luiza Tavares dos; Rodrigues, Palmira Assis de Jesus Barreto; Vargas, Ana Luisa Bittencourt Sampaio Jeunon; Sousa, Maria Auxiliadora Jeunon

    2013-01-01

    Linear IgA dermatosis has been increasingly associated with inflammatory bowel diseases, particularly ulcerative colitis. A 13-year-old male patient with an 11-month history of ulcerative colitis developed vesicles, pustules and erosions on the skin of the face, trunk and buttocks and in the oral mucosa. The work-up revealed a neutrophil-rich sub-epidermal bullous disease and linear deposition of IgA along the dermoepidermal junction, establishing the diagnosis of linear IgA dermatosis. The patient experienced unsatisfactory partial control of skin and intestinal symptoms despite the use of adalimumab, mesalazine, prednisone and dapsone for some months. After total colectomy, he presented complete remission of skin lesions, with no need of medications during two years of follow-up. A review of previously reported cases of the association is provided here and the role of ulcerative colitis in triggering linear IgA dermatosis is discussed.

  20. Chronic myeloid leukemia in a child with IgA nephropathy.

    Science.gov (United States)

    Udani, Amish; Vijayakumar, Mahalingam; Prahlad, Nageswaran; Ekambaram, Sudha

    2012-08-01

    We report an 11 year old boy with IgA nephropathy developing chronic myeloid leukemia on follow-up. This association suggests that a B cell defect might be involved in the pathogenesis of these two conditions.

  1. The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults

    NARCIS (Netherlands)

    Coppo, Rosanna; Troyanov, Stéphan; Camilla, Roberta; Hogg, Ronald J.; Cattran, Daniel C.; Cook, H. Terence; Feehally, John; Roberts, Ian S. D.; Amore, Alessandro; Alpers, Charles E.; Barratt, Jonathan; Berthoux, Francois; Bonsib, Stephen; Bruijn, Jan A.; D'Agati, Vivette; D'Amico, Giuseppe; Emancipator, Steven N.; Emma, Francesco; Ferrario, Franco; Fervenza, Fernando C.; Florquin, Sandrine; Fogo, Agnes B.; Geddes, Colin C.; Groene, Hermann J.; Haas, Mark; Herzenberg, Andrew M.; Hill, Prue A.; Hsu, Stephen I.; Jennette, J. Charles; Joh, Kensuke; Julian, Bruce A.; Kawamura, Tetsuya; Lai, Fernand M.; Li, Lei S.; Li, Philip K.; Liu, Zhi H.; Mezzano, Sergio; Schena, F. Paolo; Tomino, Yasuhiko; Walker, Patrick D.; Wang, Haiyan; Weening, Jan J.; Yoshikawa, Norishige; Zhang, Hong

    2010-01-01

    To study the predictive value of biopsy lesions in IgA nephropathy in a range of patient ages we retrospectively analyzed the cohort that was used to derive a new classification system for IgA nephropathy. A total of 206 adults and 59 children with proteinuria over 0.5 g/24h/1.73 m(2) and an eGFR of

  2. Protein energy malnutrition alters mucosal IgA responses and reduces mucosal vaccine efficacy in mice.

    Science.gov (United States)

    Rho, Semi; Kim, Heejoo; Shim, Seung Hyun; Lee, Seung Young; Kim, Min Jung; Yang, Bo-Gie; Jang, Myoung Ho; Han, Byung Woo; Song, Man Ki; Czerkinsky, Cecil; Kim, Jae-Ouk

    2017-10-01

    Oral vaccine responsiveness is often lower in children from less developed countries. Childhood malnutrition may be associated with poor immune response to oral vaccines. The present study was designed to investigate whether protein energy malnutrition (PEM) impairs B cell immunity and ultimately reduces oral vaccine efficacy in a mouse model. Purified isocaloric diets containing low protein (1/10 the protein of the control diet) were used to determine the effect of PEM. PEM increased both nonspecific total IgA and oral antigen-specific IgA in serum without alteration of gut permeability. However, PEM decreased oral antigen-specific IgA in feces, which is consistent with decreased expression of polymeric Immunoglobulin receptor (pIgR) in the small intestine. Of note, polymeric IgA was predominant in serum under PEM. In addition, PEM altered B cell development status in the bone marrow and increased the frequency of IgA-secreting B cells, as well as IgA secretion by long-lived plasma cells in the small intestinal lamina propria. Moreover, PEM reduced the protective efficacy of the mucosally administered cholera vaccine and recombinant attenuated Salmonella enterica serovar Typhimurium vaccine in a mouse model. Our results suggest that PEM can impair mucosal immunity where IgA plays an important role in host protection and may partly explain the reduced efficacy of oral vaccines in malnourished subjects. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  3. Effect of the Various Steps in the Processing of Human Milk in the Concentrations of IgA, IgM, and Lactoferrin.

    Science.gov (United States)

    Arroyo, Gerardo; Ortiz Barrientos, Kevin Alexander; Lange, Karla; Nave, Federico; Miss Mas, Gabriela; Lam Aguilar, Pamela; Soto Galindo, Miguel Angel

    2017-09-01

    Human milk immune components are unique and important for the development of the newborn. Milk processing at the Human Milk Banks (HMB), however, causes partial destruction of immune proteins. The objective of this study was to determine the effects that heating during the milk processing procedure at the HMB had on the concentrations of IgA, IgM, and lactoferrin at three critical points in time. Fifty milk samples (150 mL) were collected from voluntary donors at the HMB at the Hospital Nacional Pedro de Bethancourt, located in Antigua Guatemala. Samples from three critical points in time during the milk processing procedure were selected for analysis: freezing/thawing I, freezing/thawing II, and pasteurization. IgA, IgM, and lactoferrin concentrations were determined during each critical point and compared with a baseline concentration. After milk processing, IgA, IgM, and lactoferrin mean concentrations were reduced by 30.0%, 36.0%, and 70.0%, respectively (p milk processing on the immune proteins that were evaluated in this study demonstrated a significant reduction.

  4. IgA class switch occurs in the organized nasopharynx- and gut-associated lymphoid tissue, but not in the diffuse lamina propria of airways and gut.

    Science.gov (United States)

    Shikina, Takashi; Hiroi, Takachika; Iwatani, Kohichi; Jang, Myoung Ho; Fukuyama, Satoshi; Tamura, Manabu; Kubo, Takeshi; Ishikawa, Hiromichi; Kiyono, Hiroshi

    2004-05-15

    Secretory IgA plays a crucial role in the host immune response as a first line of defense. A recent demonstration of in situ IgA class switching in intestinal lamina propria provided an opportunity to reconsider the model for the homing of IgA-committed B cells characterized by distinctive trafficking patterns to effector sites. Those effector sites depend on the organized mucosa-associated lymphoid tissues as their site of induction. In this report we show the preferential presence of IgM(+)B220(+) and IgA(+)B220(+) cells belonging to pre- and post-IgA isotype class-switched cells in the organized mucosa-associated lymphoid tissues, such as nasopharynx-associated lymphoid tissues, isolated lymphoid follicles, and Peyer's patches, and the defect of those populations in the diffuse effector tissues, such as the nasal passage and intestinal lamina propria. Consistent with these findings, the expressions of a series of IgA isotype class switch recombination-related molecules, including activation-induced cytidine deaminase, Ialpha-C micro circle transcripts, and Ialpha-C micro circle transcripts, were selectively detected in these organized mucosa-associated lymphoid structures, but not in the diffuse mucosal effector sites. Taken together, these findings suggest that IgA isotype class switching occurs only in the organized mucosa-associated lymphoid organs (e.g., nasopharynx-associated lymphoid tissues, isolated lymphoid follicles, and Peyer's patches), but not in the diffuse effector tissues of the upper respiratory and gastrointestinal tracts.

  5. HLA-A and -B alleles and haplotypes in 240 index patients with common variable immunodeficiency and selective IgG subclass deficiency in central Alabama

    Directory of Open Access Journals (Sweden)

    Barton James C

    2003-06-01

    Full Text Available Abstract Background We wanted to quantify HLA-A and -B phenotype and haplotype frequencies in Alabama index patients with common variable immunodeficiency (CVID and selective IgG subclass deficiency (IgGSD, and in control subjects. Methods Phenotypes were detected using DNA-based typing (index cases and microlymphocytotoxicity typing (controls. Results A and B phenotypes were determined in 240 index cases (114 CVID, 126 IgGSD and 1,321 controls and haplotypes in 195 index cases and 751 controls. Phenotyping revealed that the "uncorrected" frequencies of A*24, B*14, B*15, B*35, B*40, B*49, and B*50 were significantly greater in index cases, and frequencies of B*35, B*58, B*62 were significantly lower in index cases. After Bonferroni corrections, the frequencies of phenotypes A*24, B*14, and B*40 were significantly greater in index cases, and the frequency of B*62 was significantly lower in index cases. The most common haplotypes in index cases were A*02-B*44 (frequency 0.1385, A*01-B*08 (frequency 0.1308, and A*03-B*07 (frequency 0.1000, and the frequency of each was significantly greater in index cases than in control subjects ("uncorrected" values of p p p = 0.0166. Most phenotype and haplotype frequencies in CVID and IgGSD were similar. 26.7% of index patients were HLA-haploidentical with one or more other index patients. We diagnosed CVID or IgGSD in first-degree or other relatives of 26 of 195 index patients for whom HLA-A and -B haplotypes had been ascertained; A*01-B*08, A*02-B*44, and A*29-B*44 were most frequently associated with CVID or IgGSD in these families. We conservatively estimated the combined population frequency of CVID and IgGSD to be 0.0092 in adults, based on the occurrence of CVID and IgGSD in spouses of the index cases. Conclusions CVID and IgGSD in adults are significantly associated with several HLA haplotypes, many of which are also common in the Alabama Caucasian population. Immunoglobulin phenotype variability

  6. Urinary secretory IgA after nutritional rehabilitation

    Directory of Open Access Journals (Sweden)

    M.R. Teodósio

    1999-04-01

    Full Text Available We studied the secretory IgA (sIgA response of the mucosal urinary tract of malnourished children before and after nutritional rehabilitation. sIgA concentration (mg/l was determined by ELISA in 187 children aged 3 months to 5 years. The children, who frequented a day care center, were divided into four groups, according to nutritional status: 57 were eutrophic, 49 were undergrown, 57 were moderately malnourished and 24 were severely malnourished. In addition, dip slide (Urotube, Roche and dip-stick (Combur 9-Boehringer tests showed that children had no bacteriuria or any other urinary abnormalities. Plasma albumin concentration (g/dl was significantly lower (P<0.005 in the severely malnourished group (mean 3.0 ± 0.3 SD than in the eutrophic group (mean 4.0 ± 0.5 SD. When each nutritional state was analyzed, no significant differences in the sIgA were found between the 0 |-| 1 and 1 -| 5 year age range. In the moderately and severely malnourished groups, sIgA (0.36 and 0.45, respectively was significantly lower than in the eutrophic (0.69 and undergrown (0.75 groups. Ninety-five children were included in the 8-month follow-up study; 30 children were excluded from the follow-up because 4 had bacteriuria, 11 had leukocyturia, 8 had proteinuria and 7 had hematuria. Among the malnourished children, 40% showed nutritional improvement (P<0.05 and significantly increased sIgA as compared to reference values for the eutrophic and undergrown groups. These data suggest that malnourished children have a significantly lower urinary sIgA than eutrophic children. After nutritional rehabilitation, they develop local immunity with a significant increase in sIgA.

  7. Corticotherapy response in primary IgA nephropathy

    Directory of Open Access Journals (Sweden)

    Natália Novaretti

    2013-03-01

    Full Text Available INTRODUCTION: Some beneficial effects from long-term use of corticosteroids have been reported in patients with IgA nephropathy. OBJECTIVE: This retrospective study aimed to evaluate the outcome of proteinuria and renal function according to a protocol based on a 6-month course of steroid treatment. METHOD: Twelve patients were treated with 1 g/day intravenous methylprednisolone for 3 consecutive days at the beginning of months 1, 3, and 5 plus 0.5 mg/kg oral prednisone on alternate days for 6 months (treated group. The control group included 9 untreated patients. RESULTS: Proteinuria (median and 25th and 75th percentiles at baseline in the treated group was 1861 mg/24h (1518; 2417 mg/24h and was 703 mg/24h (245; 983 and 684 mg/24h (266; 1023 at the 6th (p < 0.05 vs. baseline and 12th months (p < 0.05 vs. baseline, respectively. In the control group the proteinuria was 1900 mg/24h (1620; 3197 at baseline and was 2290 mg/24h (1500; 2975 and 1600 mg/24h (1180; 2395 at the 6th and 12th months, respectively (not significant vs. baseline. When compared with the control group, the treated group showed lower proteinuria (p < 0.05 during the follow-up and a higher number of patients in remission (p < 0.05 at the 6th and 12th months. Renal function did not change during the follow-up and the adverse effects were mild in most of the patients. CONCLUSION: The 6-month course of steroid treatment was effective in reducing proteinuria during the 12 months of the follow-up, and was well-tolerated by most of the patients.

  8. Antibiotics with a selective aerobic or anaerobic spectrum have different therapeutic activities in various regions of the colon in interleukin 10 gene deficient mice

    NARCIS (Netherlands)

    Hoentjen, F; Harmsen, HJM; Braat, H; Torrice, CD; Mann, BA; Sartor, RB; Dieleman, LA

    2003-01-01

    Background and aims: Multiple rodent models implicate resident intestinal bacteria in the pathogenesis of chronic immune mediated intestinal inflammation. Specific pathogen free (SPF) interleukin 10 gene deficient (IL-10(-/-)) mice develop colitis, which does not occur in the germ free (GF) state.

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  10. S1P Signalling Differentially Affects Migration of Peritoneal B Cell Populations In Vitro and Influences the Production of Intestinal IgA In Vivo.

    Science.gov (United States)

    Kleinwort, Annabel; Lührs, Felix; Heidecke, Claus-Dieter; Lipp, Martin; Schulze, Tobias

    2018-01-29

    Introduction: Sphingosine-1-phosphate (S1P) regulates the migration of follicular B cells (B2 cells) and directs the positioning of Marginal zone B cells (MZ B cells) within the spleen. The function of S1P signalling in the third B cell lineage, B1 B cells, mainly present in the pleural and peritoneal cavity, has not yet been determined. Methods: S1P receptor expression was analysed in peritoneal B cells by real-time polymerase chain reaction (qPCR). The chemotactic response to S1P was studied in vitro. The role of S1P signalling was further explored in a s1p₄ -/- mouse strain. Results: Peritoneal B cells expressed considerable amounts of the S1P receptors 1 and 4 (S1P₁ and S1P₄, respectively). S1P₁ showed differential expression between the distinct peritoneal B cell lineages. While B2 cells showed no chemotactic response to S1P, B1 B cells showed a migration response to S1P. s1p₄ -/- mice displayed significant alterations in the composition of peritoneal B cell populations, as well as a significant reduction of mucosal immunoglobulin A (IgA) in the gut. Discussion: S1P signalling influences peritoneal B1 B cell migration. S1P₄ deficiency alters the composition of peritoneal B cell populations and reduces secretory IgA levels. These findings suggest that S1P signalling may be a target to modulate B cell function in inflammatory intestinal pathologies.

  11. Iron deficiency

    DEFF Research Database (Denmark)

    Schou, Morten; Bosselmann, Helle; Gaborit, Freja

    2015-01-01

    BACKGROUND: Both iron deficiency (ID) and cardiovascular biomarkers are associated with a poor outcome in heart failure (HF). The relationship between different cardiovascular biomarkers and ID is unknown, and the true prevalence of ID in an outpatient HF clinic is probably overlooked. OBJECTIVES.......043). CONCLUSION: ID is frequent in an outpatient HF clinic. ID is not associated with cardiovascular biomarkers after adjustment for traditional confounders. Inflammation, but not neurohormonal activation is associated with ID in systolic HF. Further studies are needed to understand iron metabolism in elderly HF...

  12. Influence of startup oxidizing transients of IGA/SCC in PWR steam generators

    International Nuclear Information System (INIS)

    Gorman, J.A.; McIlree, A.R.; Gaudreau, T.; Bjornkvist, L.; Andersson, P.-O.

    1998-01-01

    There is a considerable amount of evidence oxidizing conditions during and following startups are an important factor in the intergranular corrosion/stress corrosion cracking (IGA/SCC) of mill annealed alloy 600 steam generator tubes. This evidence includes plant data that indicate that the growth of IGA/SCC correlates better in some cases with numbers of startups than with time at power, laboratory tests in several plausible crevice environments that show that small amounts of copper oxides accelerate the rate of IGA/SCC, laboratory tests that show that elevating the electrochemical potential (ECP) increases the rates of IGA/SCC in many chemical environments, and laboratory tests that show that copper oxides, hematite, and other oxidized corrosion products can raise the ECP of several solution chemistries into aggressive ranges. Some preliminary data also exist that show that some amounts of oxidized species are produced during typical layup and startup conditions, but data for the subsequent reduction of these oxides are largely lacking. The purpose of this paper is to review the available evidence, to arrive at conclusions regarding the probable importance of oxidizing conditions during startup on occurrence of IGA/SCC, and to identify needed research to better quantify the situation. (author)

  13. Detection of H. Pylori infection on dyspepsia patients with IgA H. Pylori antibody

    Science.gov (United States)

    Loesnihari, R.

    2018-03-01

    Helicobacter pylori (H. pylori) has a big role in the relapse and pathogenesis of the upper gastrointestinal disease. Dyspepsia is characterized by uncomfortable feeling at the upper gastrointestinal area. IgA H. pylori antibody was in two-thirds of H. pylori infected patients, but about 7.2% of IgA H. Pylori antibody became the only positive result of the test between the two serology test (IgG and IgA). A cross-sectional study was conducted in 38 patients with dyspepsia. The IgA antibody test for H. pylori in the serum of dyspepsia patient conducted through the ELISA test. The hemoglobin levels, leukocytes, platelets number, and H. pylori infection via IgA antibody test on ulcer and non-ulcer dyspepsia patient had no significant difference. There was a relation between the number of platelets in the infected H. pylori patients compared to the non-infected patients. H. pylori infection in the ulcer and non-ulcer dyspepsia patient with serology method was 18%. H. pylori infection number on ulcer dyspepsia was not higher than the non-ulcer dyspepsia, all ulcer dyspepsia patients who were with H. pylori found with a lesion on the antrum.

  14. Minimal Change Disease and IgA Deposition: Separate Entities or Common Pathophysiology?

    Directory of Open Access Journals (Sweden)

    Brandon S. Oberweis

    2013-01-01

    Full Text Available Introduction. Minimal Change Disease (MCD is the most common cause of nephrotic syndrome in children, while IgA nephropathy is the most common cause of glomerulonephritis worldwide. MCD is responsive to glucocorticoids, while the role of steroids in IgA nephropathy remains unclear. We describe a case of two distinct clinical and pathological findings, raising the question of whether MCD and IgA nephropathy are separate entities or if there is a common pathophysiology. Case Report. A 19-year old man with no medical history presented to the Emergency Department with a 20-day history of anasarca and frothy urine, BUN 68 mg/dL, Cr 2.3 mg/dL, urinalysis 3+ RBCs, 3+ protein, and urine protein : creatinine ratio 6.4. Renal biopsy revealed hypertrophic podocytes on light microscopy, podocyte foot process effacement on electron microscopy, and immunofluorescent mesangial staining for IgA. The patient was started on prednisone and exhibited dramatic improvement. Discussion. MCD typically has an overwhelming improvement with glucocorticoids, while the resolution of IgA nephropathy is rare. Our patient presented with MCD with the uncharacteristic finding of hematuria. Given the improvement with glucocorticoids, we raise the question of whether there is a shared pathophysiologic component of these two distinct clinical diseases that represents a clinical variant.

  15. [A case of IgA2-lambda type M-protein that IgA concentration differs from the values of M-protein by serum protein electrophoresis].

    Science.gov (United States)

    Fukushima, M; Sugano, M; Ichikawa, T; Honda, T; Totsuka, M; Katsuyama, T; Fujita, K

    2001-07-01

    We report an IgA-lambda type M-protein in which the IgA concentration differed from the values of M-protein by serum protein electrophoresis found in a 53-year-old man with multiple myeloma. The M-protein value as determined by serum protein electrophoresis was 6,170 mg/dl. However, the serum IgA concentration was 3,052 mg/dl by turbidimetric immunoassay. Immuno-fixation electrophoresis using IgA subclass antisera revealed that this M-protein was the IgA2-lambda type. Western blotting analysis showed that the IgA2 molecules were composed of two approximately 68 kDa alpha 2 chains and two 28 kDa lambda chains. In addition the free lambda chain band was detected at the position of 28 kDa without 2-mercaptoethanol(2-ME) even though the patient IgA was purified. Since it is known that IgA2m(1) allotype easily release light chains from the IgA molecules in SDS-PAGE without 2-ME, we speculated that in this patient the IgA was the IgA2m(1) allotype. After peripheral blood stem cell transplantation(PBSCT), immunofixation electrophoresis of the patient serum revealed not only the bands of IgA2-lambda type M-protein, but also three bands of IgG1-kappa type M-protein in the gamma region.

  16. Detection of FMD virus type specific IgG1, IgG2 and IgA antibodies in milk and serum of buffaloes vaccinated with oil adjuvanted polyvalent FMD vaccine

    Directory of Open Access Journals (Sweden)

    R. Sharma

    2010-02-01

    Full Text Available The present investigation was carried out on 15 randomly selected milch buffaloes divided into three groups on the basis of lactation at an organized farm, to study the foot and mouth disease virus type specific antibodies in milk and serum following FMD vaccination. Milk and serum samples collected before vaccination i.e. 0 day and on 7, 14, 28, 42 and 56 days post vaccination, were analyzed for the detection of FMD virus specific IgG1, IgG2 and IgA antibody response by indirect double antibody sandwich ELISA. Significant FMD virus type specific antibody titres (IgG1, IgG2 and IgA were detected in milk and serum of buffaloes on different days post vaccination, though the levels of antibodies were lower in milk as compared to serum. FMD virus type specific IgG1 was found to be the predominant subclass as compared to IgG2 and IgA both in milk and serum of vaccinated buffaloes. Milk and serum IgG1, IgG2 and IgA antibody titres were positively correlated with values of regression coefficient (R as 0.506, 0.434 and 0.396, respectively.

  17. Systemic Scedosporium prolificans infection in an 11-month-old Border collie with cobalamin deficiency secondary to selective cobalamin malabsorption (canine Imerslund-Gräsbeck syndrome).

    Science.gov (United States)

    Erles, K; Mugford, A; Barfield, D; Leeb, T; Kook, P H

    2018-04-01

    An 11-month-old Border collie presented collapsed and continued to deteriorate rapidly despite supportive treatment. The dog had a history of failure to thrive and recurring respiratory infection. Laboratory abnormalities included neutrophilic leucocytosis, Heinz body anaemia, hyperammonaemia, hyperbilirubinaemia, proteinuria and hypocobalaminaemia. Post-mortem examination revealed multi-focal necrosis within the heart, kidneys, pancreas, liver, meninges and cerebral cortex. Fungal hyphae in lesions were identified as Scedosporium prolificans following culture. Subsequent genotyping confirmed that the dog carried the CUBN:c.8392delC mutation in a homozygous state, verifying hereditary cobalamin deficiency (a.k.a. Imerslund-Gräsbeck syndrome). Cobalamin deficiency may have been a predisposing factor for the development of systemic fungal infection in this dog. © 2017 British Small Animal Veterinary Association.

  18. Circulating IgA immune complexes in patients with psoriasis

    International Nuclear Information System (INIS)

    Hall, R.P.; Peck, G.L.; Lawley, T.J.

    1983-01-01

    The sera of 21 patients with psoriasis were examined for the presence of IgA-containing circulating immune complexes (CIC) using the Raji IgA radioimmunoassay. In addition, the Raji IgG radioimmunoassay and 125I-Clq binding assay were used to detect IgG- and IgM-containing CIC. Twenty-five patients with other hyperkeratotic skin disorders were studied as controls. Patients were studied before institution of systemic therapy with etretinate (20 patients) or 13-cis-retinoic acid (1 patient). In addition, sera of 15 of the patients treated with etretinate were studied before, during, and after therapy. The extent of pretreatment disease involvement as well as response to therapy were evaluated in a blinded fashion. Fourteen of 21 (67%) patients with psoriasis had evidence of IgA-containing CIC at some time during the course of their disease, as compared to only 1 of 25 patients with other hyperkeratotic skin disorders. In contrast, only 2 of 19 (11%) had evidence of IgG-containing CIC using the Raji IgG assay, and only 1 of 19 (5%) had evidence of IgG- or IgM-containing CIC using the 125I-Clq binding assay. A positive correlation was found between the extent of pretreatment disease involvement and the level of IgA-containing CIC by linear regression analysis (p . 0.01). There was, however, no correlation between clinical improvement and the presence or level of IgA-containing CIC in 15 patients followed during therapy. Sucrose density gradient analysis of the IgA-containing CIC found in 2 of these patients demonstrated IgA-containing CIC in the 9S to 13S region. The finding of IgA-containing CIC in a significant number of patients with psoriasis and the relative absence of IgG- or IgM-containing CIC suggest that IgA-containing CIC may play a role in psoriasis

  19. Cocoa and cocoa fibre differentially modulate IgA and IgM production at mucosal sites.

    Science.gov (United States)

    Massot-Cladera, Malen; Franch, Àngels; Pérez-Cano, Francisco J; Castell, Margarida

    2016-05-01

    Previous studies have shown that a 10 % cocoa (C10) diet, containing polyphenols and fibre among others, modifies intestinal and systemic Ig production. The present study aimed at evaluating the impact of C10 on IgA and IgM production in the intestinal and extra-intestinal mucosal compartments, establishing the involvement of cocoa fibre (CF) in such effects. Mechanisms by which C10 intake may affect IgA synthesis in the salivary glands were also studied. To this effect, rats were fed either a standard diet, a diet containing C10, CF or inulin. Intestinal (the gut wash (GW), Peyer's patches (PP) and mesenteric lymph nodes (MLN)) and extra-intestinal (salivary glands) mucosal tissues and blood samples were collected for IgA and IgM quantification. The gene expressions of IgA production- and homing-related molecules were studied in the salivary glands. The C10 diet decreased intestinal IgA and IgM production. Although the CF diet decreased the GW IgA concentration, it increased PP, MLN and serum IgA concentrations. Both the C10 and the CF diets produced a down-regulatory effect on IgA secretion in the extra-intestinal tissues. The C10 diet interacted with the mechanisms involved in IgA synthesis, whereas the CF showed particular effects on the homing and transcytosis of IgA across the salivary glands. Overall, CF was able to up-regulate IgA production in the intestinal-inductor compartments, whereas it down-regulated its production at the mucosal-effector ones. Further studies must be directed to ascertain the mechanisms involved in the effect of particular cocoa components on gut-associated lymphoid tissue.

  20. Lack of serologic evidence to link IgA nephropathy with celiac disease or immune reactivity to gluten.

    Directory of Open Access Journals (Sweden)

    Sina Moeller

    Full Text Available IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99, unaffected controls of similar age, gender, and race (n = 96, and patients with biopsy-proven celiac disease (n = 30. All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2. Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy.

  1. Lack of serologic evidence to link IgA nephropathy with celiac disease or immune reactivity to gluten.

    Science.gov (United States)

    Moeller, Sina; Canetta, Pietro A; Taylor, Annette K; Arguelles-Grande, Carolina; Snyder, Holly; Green, Peter H; Kiryluk, Krzysztof; Alaedini, Armin

    2014-01-01

    IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age, gender, and race (n = 96), and patients with biopsy-proven celiac disease (n = 30). All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy.

  2. Secretory IgA is Concentrated in the Outer Layer of Colonic Mucus along with Gut Bacteria

    Directory of Open Access Journals (Sweden)

    Eric W. Rogier

    2014-04-01

    Full Text Available Antibodies of the secretory IgA (SIgA class comprise the first line of antigen-specific immune defense, preventing access of commensal and pathogenic microorganisms and their secreted products into the body proper. In addition to preventing infection, SIgA shapes the composition of the gut microbiome. SIgA is transported across intestinal epithelial cells into gut secretions by the polymeric immunoglobulin receptor (pIgR. The epithelial surface is protected by a thick network of mucus, which is composed of a dense, sterile inner layer and a loose outer layer that is colonized by commensal bacteria. Immunofluorescence microscopy of mouse and human colon tissues demonstrated that the SIgA co-localizes with gut bacteria in the outer mucus layer. Using mice genetically deficient for pIgR and/or mucin-2 (Muc2, the major glycoprotein of intestinal mucus, we found that Muc2 but not SIgA was necessary for excluding gut bacteria from the inner mucus layer in the colon. Our findings support a model whereby SIgA is anchored in the outer layer of colonic mucus through combined interactions with mucin proteins and gut bacteria, thus providing immune protection against pathogens while maintaining a mutually beneficial relationship with commensals.

  3. Association of IgA multiple myeloma with pre-existing disease

    Energy Technology Data Exchange (ETDEWEB)

    Schafer, A.I.; Miller, J.B.

    1979-01-01

    A retrospective analysis of 153 patients with multiple myeloma was performed for evaluation of the possible significance of pre-existing disease. 37% of the group had no significant antecedent disorder. The most common prior illnesses were peptic ulcer disease and gallbladder disease. Of 12 patients in the group who had prior biliary tract disease and for whom immunoelectrophoretic studies were available, eight (66.7%) had IgA paraproteins. This figure is statistically higher than the 14.1% of prevalence of IgA paraproteins in those myeloma patients without biliary disease. We conclude that prior inflammatory gastrointestinal, pulmonary, and, particularly, biliary disease may be implicated in the pathogenesis of the IgA subset of multiple myeloma.

  4. Immunoglobulins in nasal secretions of healthy humans: structural integrity of secretory immunoglobulin A1 (IgA1) and occurrence of neutralizing antibodies to IgA1 proteases of nasal bacteria

    DEFF Research Database (Denmark)

    Kirkeby, L; Rasmussen, TT; Reinholdt, Jesper

    2000-01-01

    Certain bacteria, including overt pathogens as well as commensals, produce immunoglobulin A1 (IgA1) proteases. By cleaving IgA1, including secretory IgA1, in the hinge region, these enzymes may interfere with the barrier functions of mucosal IgA antibodies, as indicated by experiments in vitro....... Previous studies have suggested that cleavage of IgA1 in nasal secretions may be associated with the development and perpetuation of atopic disease. To clarify the potential effect of IgA1 protease-producing bacteria in the nasal cavity, we have analyzed immunoglobulin isotypes in nasal secretions of 11...... healthy humans, with a focus on IgA, and at the same time have characterized and quantified IgA1 protease-producing bacteria in the nasal flora of the subjects. Samples in the form of nasal wash were collected by using a washing liquid that contained lithium as an internal reference. Dilution factors and...

  5. Epidemiology of SHOX deficiency.

    Science.gov (United States)

    Nicolosi, A; Caruso-Nicoletti, M

    2010-06-01

    Deletion of short stature homeobox-containing (SHOX) gene, in the pseudoautosomal region (PAR1) of X and Y chromosomes, is an important cause of short stature. Homozygous loss of SHOX results in the more severe Langer mesomelic dysplasia, while SHOX haploinsufficiency cause a wide spectrum of short stature phenotypes, including patients with Turner syndrome, Leri Weill dyschondrosteosis (LWD), and idiopathic short stature (ISS). In Turner syndrome, haploinsufficiency of SHOX gene, as well as short stature, are present in 100%; nevertheless, SHOX deficiency accounts for only two-thirds of Turner patients' short stature. In LWD the prevalence of SHOX gene anomalies varies from 56% to 100%. This wide range might be due to different factors such as selection criteria of patients, sample size, and method used for screening SHOX mutations. The real challenge is to establish the prevalence of SHOX deficiency in ISS children given that published studies have reported this association with a very broad frequency range varying from 1.5% to 15%. An important variable in these studies is represented by the method used for screening SHOX mutations and sometimes by differences in patient selection. Short stature is present by definition in 3 out of 100 subjects; if we consider a frequency of SHOX defects of 3% among ISS, we should expect a population prevalence of 1 in 1000. This prevalence would be higher than that of GH deficiency (1:3,500) and of Turner syndrome (1:2,500 females), suggesting that SHOX deficiency could be one of the most frequent monogenetic causes of short stature.

  6. Urinary uromodulin excretion predicts progression of chronic kidney disease resulting from IgA nephropathy.

    Directory of Open Access Journals (Sweden)

    Jingjing Zhou

    Full Text Available BACKGROUND: Uromodulin, or Tamm-Horsfall protein, is the most abundant urinary protein in healthy individuals. Recent studies have suggested that uromodulin may play a role in chronic kidney diseases. We examined an IgA nephropathy cohort to determine whether uromodulin plays a role in the progression of IgA nephropathy. METHODS: A total of 344 IgA nephropathy patients were involved in this study. Morphological changes were evaluated with the Oxford classification of IgA nephropathy. Enzyme Linked Immunosorbent Assay (ELISA measured the urinary uromodulin level on the renal biopsy day. Follow up was done regularly on 185 patients. Time-average blood pressure, time-average proteinuria, estimated glomerular filtration rate (eGFR and eGFR decline rate were caculated. Association between the urinary uromodulin level and the eGFR decline rate was analyzed with SPSS 13.0. RESULTS: We found that lower baseline urinary uromodulin levels (P = 0.03 and higher time-average proteinuria (P = 0.04 were risk factors for rapid eGFR decline in a follow-up subgroup of the IgA nephropathy cohort. Urinary uromodulin level was correlated with tubulointerstitial lesions (P = 0.016. Patients that had more tubular atrophy/interstitial fibrosis on the surface had lower urinary uromodulin levels (P = 0.02. CONCLUSIONS: Urinary uromodulin level is associated with interstitial fibrosis/tubular atrophy and contributes to eGFR decline in IgA nephropathy.

  7. Salivary IgA concentration in diabetic patients compared to healthy controls

    Directory of Open Access Journals (Sweden)

    Farimah Sardari

    2015-01-01

    Full Text Available Introduction: The alterations in salivary flow rate and its compositions could affect the development, symptoms, and severity of oral changes in diabetic patients. The aim of this study was to assess the concentration of salivary IgA in type I in comparison with type II diabetic patients and healthy controls. Materials and Methods: In this cross-sectional study, 25 patients with type I diabetes, 25 patients with type II diabetes, and 25 control subjects (12 subjects for the type I and 13 subjects for the type II were enrolled. Unstimulated saliva samples were collected by spitting method and the concentration of salivary IgA was measured byenzyme-linked immunosorbent assay (ELISA method. Results: The mean of salivary IgA in type I diabetic patients was 148.3 ± 38.7 μg/ml and in their controls was 65.8 ± 17.4 μg/ml (P < 0.001. In type II diabetic patients the mean of salivary IgA was 67.3 ± 20.6 μg/ml and in their controls was 63.3 ± 15.2 μg/ml. There was no significant difference between patients with type II diabetes and controls (P = 0.54. The mean of salivary IgA in patients with type I diabetes was significantly higher than in patients with type II diabetes (148.3 ± 38.7 versus 67.3 ± 20.6 μg/ml, respectively, P < 0.001. Conclusions: Level of salivary IgA in type II diabetic patients in comparison with their healthy control did not show any significant difference, but in type I diabetic patients was higher than that of healthy controls and type II diabetic patients.

  8. Metabolic changes during B cell differentiation for the production of intestinal IgA antibody.

    Science.gov (United States)

    Kunisawa, Jun

    2017-04-01

    To sustain the bio-energetic demands of growth, proliferation, and effector functions, the metabolism of immune cells changes dramatically in response to immunologic stimuli. In this review, I focus on B cell metabolism, especially regarding the production of intestinal IgA antibody. Accumulating evidence has implicated not only host-derived factors (e.g., cytokines) but also gut environmental factors, including the possible involvement of commensal bacteria and diet, in the control of B cell metabolism during intestinal IgA antibody production. These findings yield new insights into the regulation of immunosurveillance and homeostasis in the gut.

  9. Anti Helicobacter pylori IgG and IgA response in patients with gastric cancer and chronic gastritis.

    Science.gov (United States)

    Manojlovic, Nebojsa; Babic, Dragana; Filipovic-Ljeshovic, Ivana; Pilcevic, Dijana

    2008-01-01

    Immune response against Helicobacter pylori is important for the course and outcome of infection. We conducted study looking for the difference in anti H. pylori IgG and IgA between patients with intestinal type of gastric cancer, superficial and atrophic gastritis. For this study, 133 patients infected with H. pylori were enrolled: 50 with superficial gastritis, 42 with atrophic gastritis and 41 with gastric cancer. Anti H. pylori IgG and IgA ELISA tests were performed. The difference in antibody titers of IgG and IgA, frequency of IgA > IgG ratio and combination of low IgG and IgA > IgG ratio were analyzed. The patients with gastritis had higher titer of IgG that the patients with gastric cancer (p gastritis had higher titer of IgA than the patients with gastric cancer (p IgG ratio is more frequent in patients with gastric cancer than in the patients with superficial gastritis (p IgG is more frequent in the patients with gastric cancer than in the patients with gastritis (p cancer elicit different anti H. pylori IgG and IgA response than the patients with superficial and atrophic gastritis. Low IgG and IgA predominance seems characteristic for gastric cancer.

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  11. Iron-Deficiency Anemia

    Science.gov (United States)

    ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  12. The ABC of Vitamin D: A Qualitative Study of the Knowledge and Attitudes Regarding Vitamin D Deficiency amongst Selected Population Groups

    OpenAIRE

    Bonevski, Billie; Bryant, Jamie; Lambert, Sylvie; Brozek, Irena; Rock, Vanessa

    2013-01-01

    Objective: In Australia, vitamin D supply in food is limited, and sun exposure is the main source of vitamin D. However skin cancer risk is high, and the need to gain some sun exposure for adequate vitamin D is challenging public health messages to use protection in the sun. The complex vitamin D public health message may be confusing the public and, in particular, those at highest risk for vitamin D deficiency. This study explored vitamin D and sun exposure attitudes, knowledge and practices...

  13. Presence of Lactobacillus reuteri in saliva coincide with higher salivary IgA in young adults after intake of probiotic lozenges.

    Science.gov (United States)

    Braathen, G; Ingildsen, V; Twetman, S; Ericson, D; Jørgensen, M R

    2017-02-07

    The aim of this study was to compare the concentration of salivary immunoglobulin A (IgA) and the selected interleukins (IL)-1β, IL-6, IL-8 and IL-10 in young individuals with presence and non-presence of Lactobacillus reuteri in saliva after a three-week intervention with probiotic lozenges. The study group consisted of 47 healthy individuals aged 18-32 years with no clinical signs of oral inflammation. In a randomised, double-blind, placebo-controlled, cross-over trial participants ingested two lozenges per day containing two strains of the probiotic bacterium L. reuteri or placebo lozenges. The intervention and wash-out periods were three weeks. Stimulated and unstimulated whole saliva was collected at baseline and immediately after termination of the intervention periods. The samples were analysed for total protein, salivary IgA and selected cytokines. In this extended analysis, data were collected by analysing baseline and follow-up saliva samples related to ingestion of the probiotic lozenges for the presence of L. reuteri through DNA-extraction, PCR-amplification and gel-electrophoresis. At baseline, 27% of the individuals displayed presence of L. reuteri and 42% were positive immediately after the three-week probiotic intervention. Individuals with presence of L. reuteri in saliva had significantly higher (Preuteri in saliva coincided with higher concentrations of salivary IgA and %IgA/protein in stimulated whole saliva after the three-week daily intake of probiotic lozenges. Our findings suggest that monitoring the presence of probiotic candidates in the oral environment is important to interpret and understand their possible immune-modulating role in maintaining oral health.

  14. Digital gene expression analysis of corky split vein caused by boron deficiency in 'Newhall' Navel Orange (Citrus sinensis Osbeck for selecting differentially expressed genes related to vascular hypertrophy.

    Directory of Open Access Journals (Sweden)

    Cheng-Quan Yang

    Full Text Available Corky split vein caused by boron (B deficiency in 'Newhall' Navel Orange was studied in the present research. The boron-deficient citrus exhibited a symptom of corky split vein in mature leaves. Morphologic and anatomical surveys at four representative phases of corky split veins showed that the symptom was the result of vascular hypertrophy. Digital gene expression (DGE analysis was performed based on the Illumina HiSeq™ 2000 platform, which was applied to analyze the gene expression profilings of corky split veins at four morphologic phases. Over 5.3 million clean reads per library were successfully mapped to the reference database and more than 22897 mapped genes per library were simultaneously obtained. Analysis of the differentially expressed genes (DEGs revealed that the expressions of genes associated with cytokinin signal transduction, cell division, vascular development, lignin biosynthesis and photosynthesis in corky split veins were all affected. The expressions of WOL and ARR12 involved in the cytokinin signal transduction pathway were up-regulated at 1(st phase of corky split vein development. Furthermore, the expressions of some cell cycle genes, CYCs and CDKB, and vascular development genes, WOX4 and VND7, were up-regulated at the following 2(nd and 3(rd phases. These findings indicated that the cytokinin signal transduction pathway may play a role in initiating symptom observed in our study.

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron- ... iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... to moderate iron-deficiency anemia, or red blood cell transfusion for severe iron-deficiency anemia. You may ... body needs iron to make healthy red blood cells. Iron-deficiency anemia usually develops over time because ...

  17. Vitamin Deficiency Anemia

    Science.gov (United States)

    ... are unique to specific vitamin deficiencies. Folate-deficiency anemia risk factors include: Undergoing hemodialysis for kidney failure. ... the metabolism of folate. Vitamin B-12 deficiency anemia risk factors include: Lack of intrinsic factor. Most ...

  18. Structural differences among serum IgA proteins of chimpanzee, rhesus monkey and rat origin

    NARCIS (Netherlands)

    Endo, T.; Radl, J.; Mestecky, J.

    1997-01-01

    Asparagine-linked sugar chains were quantitatively released from chimpanzee, Rhesus monkey and rat IgA proteins as oligosaccharides by hydrazinolysis, converted to radioactive oligosaccharides by reduction with NaB3H4, and separated into neutral and two acidic fractions by paper electrophoresis. The

  19. Inducement of IGA/SCC in Inconel 600 steam generator tubing during unit outages

    Energy Technology Data Exchange (ETDEWEB)

    Durance, D.; Sedman, K. [Bruce Power, Tiverton, Ontario (Canada); Roberts, J. [CANTECH Associates Ltd., Burlington, Ontario (Canada); King, P. [Babcock and Wilcox Canada, Cambridge, Ontario (Canada); Gorman, J. [Dominion Engineering, Reston, VA (United States); Allen, R. [Kinectrics, Inc., Toronto, Ontario (Canada)

    2008-07-01

    The degradation of Unit 4 SG tubing by IGA/SCC has limited both the operating period and end of life predictions for Unit 4 since restart in late 2003. The circumferential IGA/SCC has been most significant in SG4 with substantial increases in both initiation and growth rates from 2005 through the spring of 2007. A detailed review of the occurrence of circumferential OD IGA/SCC at the RTZ in the HL TTS region of Bruce 4 steam generator tubes has led a conclusion that it is probable that the IGA/SCC has been the result of attack by partially reduced sulfur species such as tetrathionates and thiosulfates during periods of low temperature exposure. It is believed that attack of this type has mostly likely occurred during startup evolutions following outages as the result the development of aggressive reduced sulfur species in the TTS region during periods when the boilers were fully drained for maintenance activities. The modification of outage practices to limit secondary side oxygen ingress in the spring of 2007 has apparently arrested the degradation and has had significant affects on the allowable operating interval and end of life predictions for the entire unit. (author)

  20. Inducement of IGA/SCC in Inconel 600 steam generator tubing during unit outages

    International Nuclear Information System (INIS)

    Durance, D.; Sedman, K.; Roberts, J.; King, P.; Gorman, J.; Allen, R.

    2008-01-01

    The degradation of Unit 4 SG tubing by IGA/SCC has limited both the operating period and end of life predictions for Unit 4 since restart in late 2003. The circumferential IGA/SCC has been most significant in SG4 with substantial increases in both initiation and growth rates from 2005 through the spring of 2007. A detailed review of the occurrence of circumferential OD IGA/SCC at the RTZ in the HL TTS region of Bruce 4 steam generator tubes has led a conclusion that it is probable that the IGA/SCC has been the result of attack by partially reduced sulfur species such as tetrathionates and thiosulfates during periods of low temperature exposure. It is believed that attack of this type has mostly likely occurred during startup evolutions following outages as the result the development of aggressive reduced sulfur species in the TTS region during periods when the boilers were fully drained for maintenance activities. The modification of outage practices to limit secondary side oxygen ingress in the spring of 2007 has apparently arrested the degradation and has had significant affects on the allowable operating interval and end of life predictions for the entire unit. (author)

  1. Primary breast cancer tumours contain high amounts of IgA1 immunoglobulin

    DEFF Research Database (Denmark)

    Welinder, Charlotte; Baldetorp, Bo; Blixt, Klas Ola

    2013-01-01

    seen in the percentage of stained cells and in the staining pattern in the different breast cancers analysed. Anti-Tn antibody and HPA were also shown to specifically bind to a number of possible constellations of the Tn antigen in the hinge region of IgA1. Both reagents could also detect the presence....... The short O-glycan that forms the antigen is carried by a number of different proteins. One potential carrier of the Tn antigen is immunoglobulin A1 (IgA1), which we surprisingly found in tumour cells of the invasive parts of primary breast carcinoma. Conventional immunohistochemical analysis of paraffin......-embedded sections from primary breast cancers showed IgA1 to be present in the cytoplasm and plasma membrane of 35 out of 36 individual primary tumours. The immunohistochemical staining of HPA and anti-Tn antibody (GOD3-2C4) did to some extent overlap with the presence of IgA1 in the tumours, but differences were...

  2. Bacteria as a target of human milk and myeloma IgA

    Czech Academy of Sciences Publication Activity Database

    Přibylová, Jaroslava; Moldoveanu, Z.; Mestecky, J.; Tlaskalová, Helena

    2009-01-01

    Roč. 39, - (2009), s. 760-760 ISSN 0014-2980. [European Congress of Immunology /2./. 13.09.2009-16.09.2009, Berlin] Institutional research plan: CEZ:AV0Z50200510 Keywords : human milk * myeloma IgA Subject RIV: EC - Immunology

  3. Circulating immune complexes, immunoglobulin classes (IgG, IgA ...

    African Journals Online (AJOL)

    Objective:- To evaluate serum levels of circulating immune complexes (CICs), immunoglobulin classes (IgG, IgA and IgM) and Complement Components (C3c, C4 and Factor B) in Nigerians with Type 1 or Type 2 diabetes mellitus. Design:- Case control study. Setting:- University College Hospital, Ibadan, Oyo State, Nigeria.

  4. Intranasal IFNγ extends passive IgA antibody protection of mice against Mycobacterium tuberculosis lung infection

    Science.gov (United States)

    Reljic, R; Clark, S O; Williams, A; Falero-Diaz, G; Singh, M; Challacombe, S; Marsh, P D; Ivanyi, J

    2006-01-01

    Intranasal inoculation of mice with monoclonal IgA against the α-crystallin (acr1) antigen can diminish the tuberculous infection in the lungs. As this effect has been observed only over a short-term, we investigated if it could be extended by inoculation of IFNγ 3 days before infection, and further coinoculations with IgA, at 2 h before and 2 and 7 days after aerosol infection with Mycobacterium tuberculosis H37Rv. This treatment reduced the lung infection at 4 weeks more than either IgA or IFNγ alone (i.e. 17-fold, from 4·2 × 107 to 2·5 × 106 CFU, P = 0·006), accompanied also by lower granulomatous infiltration of the lungs. IFNγ added prior to infection of mouse peritoneal macrophages with IgA-opsonized bacilli resulted in a synergistic increase of nitric oxide and TNFα production and a 2–3 fold decrease in bacterial counts. Our improved results suggest, that combined treatment with IFNγ and IgA could be developed towards prophylactic treatment of AIDS patients, or as an adjunct to chemotherapy. PMID:16487246

  5. Giardia muris trophozoite antigenic targets for mouse intestinal IgA antibody.

    Science.gov (United States)

    Heyworth, M F; Vergara, J A

    1994-02-01

    The aim of this work was to characterize Giardia muris trophozoite proteins that are targets for intestinal anti-trophozoite IgA in G. muris-infected mice. Intestinal secretions were obtained from immunocompetent BALB/c mice that had been infected with G. muris cysts 4-5 weeks previously and from control uninfected BALB/c mice. Flow cytometry of G. muris trophozoites that had been incubated with intestinal secretions and with fluorescein isothiocyanate-conjugated anti-mouse IgA showed that anti-trophozoite IgA was present in intestinal secretions obtained from infected BALB/c mice. By immunoblotting on G. muris trophozoite proteins separated by one-dimensional gel electrophoresis, this IgA recognized at least one trophozoite protein of molecular mass of approximately 80 kDa. The 80-kDa G. muris protein(s) has a molecular mass similar to that described for cysteine-rich surface proteins of the human parasite Giardia lamblia.

  6. Immunoglobulin classes (IgG, IgA and IgM) and acute phase ...

    African Journals Online (AJOL)

    The results indicate that USS or pregnancy changes different aspects of humoral immunity, thus the co-existence of pregnancy and S. haematobium infection may ... Résultats et conclusions: IgG, IgA et IgM étaient remarquablement élevés chez les femmes enceintes atteintes de la schistose urinaire par rapport aux femmes ...

  7. Gastrointestinal sensitivity to soy and milk proteins in patients with IgA nephropathy.

    Science.gov (United States)

    Kloster Smerud, H; Fellström, B; Hällgren, R; Osagie, S; Venge, P; Kristjánsson, G

    2010-11-01

    sensitivity to food antigens has been postulated as a contributing factor to the pathogenesis of IgA nephropathy (IgAN). in this study we used a recently developed mucosal patch technique to evaluate rectal mucosal sensitivity to soy and cow's milk (CM) proteins in IgAN patients (n = 28) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analyzed for IgA and IgG antibodies to alpha-lactalbumin, beta-lactoglobulin, casein and soy. 14 of 28 (14/28) patients experienced a rectal mucosal reaction, measured by increased NO and/or MPO levels, upon rectal challenge with soy and/or cow's milk proteins. The levels of IgG antibodies to alpha-lactalbumin, beta-lactoglobulin and casein were significantly higher in CM sensitive as compared with non-sensitive IgAN patients, whereas the mean serum levels of IgA antibodies were similar. No differences were seen in serum levels of IgA or IgG antibodies to soy. it is concluded that approximately half of our IgAN patients have a rectal mucosal sensitivity to soy or CM, and that an immune reactivity against antigens may be involved in the pathogenesis of IgAN in this subgroup of patients.

  8. Primary vs. secondary antibody deficiency: clinical features and infection outcomes of immunoglobulin replacement.

    Directory of Open Access Journals (Sweden)

    Sai S Duraisingham

    Full Text Available Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment.

  9. Primary vs. Secondary Antibody Deficiency: Clinical Features and Infection Outcomes of Immunoglobulin Replacement

    Science.gov (United States)

    Duraisingham, Sai S.; Buckland, Matthew; Dempster, John; Lorenzo, Lorena; Grigoriadou, Sofia; Longhurst, Hilary J.

    2014-01-01

    Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig)-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment. PMID:24971644

  10. Omega-3 fatty acid deficiency selectively up-regulates delta6-desaturase expression and activity indices in rat liver: prevention by normalization of omega-3 fatty acid status.

    Science.gov (United States)

    Hofacer, Rylon; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Magrisso, I Jack; Benoit, Stephen C; McNamara, Robert K

    2011-09-01

    This study investigated the effects of perinatal dietary omega-3 (n-3) fatty acid depletion and subsequent repletion on the expression of genes that regulate long-chain (LC) polyunsaturated fatty acid biosynthesis in rat liver and brain. It was hypothesized that chronic n-3 fatty acid deficiency would increase liver Fads1 and Fads2 messenger RNA (mRNA) expression/activity and that n-3 fatty acid repletion would normalize this response. Adult rats fed the n-3-free diet during perinatal development exhibited significantly lower erythrocyte, liver, and frontal cortex LCn-3 fatty acid composition and reciprocal elevations in LC omega-6 (n-6) fatty acid composition compared with controls (CONs) and repleted rats. Liver Fads2, but not Fads1, Elovl2, or Elovl5, mRNA expression was significantly greater in n-3-deficient (DEF) rats compared with CONs and was partially normalized in repleted rats. The liver 18:3n-6/18:2n-6 ratio, an index of delta6-desturase activity, was significantly greater in DEF rats compared with CON and repleted rats and was positively correlated with Fads2 mRNA expression among all rats. The liver 18:3n-6/18:2n-6 ratio, but not Fads2 mRNA expression, was also positively correlated with erythrocyte and frontal cortex LCn-6 fatty acid compositions. Neither Fads1 or Fads2 mRNA expression was altered in brain cortex of DEF rats. These results confirm previous findings that liver, but not brain, delta6-desaturase expression and activity indices are negatively regulated by dietary n-3 fatty acids. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Recombinant IgA Is Sufficient To Prevent Influenza Virus Transmission in Guinea Pigs

    Science.gov (United States)

    Seibert, Christopher W.; Rahmat, Saad; Krause, Jens C.; Eggink, Dirk; Albrecht, Randy A.; Goff, Peter H.; Krammer, Florian; Duty, J. Andrew; Bouvier, Nicole M.; García-Sastre, Adolfo

    2013-01-01

    A serum hemagglutination inhibition (HAI) titer of 40 or greater is thought to be associated with reduced influenza virus pathogenesis in humans and is often used as a correlate of protection in influenza vaccine studies. We have previously demonstrated that intramuscular vaccination of guinea pigs with inactivated influenza virus generates HAI titers greater than 300 but does not protect vaccinated animals from becoming infected with influenza virus by transmission from an infected cage mate. Only guinea pigs intranasally inoculated with a live influenza virus or a live attenuated virus vaccine, prior to challenge, were protected from transmission (A. C. Lowen et al., J. Virol. 83:2803–2818, 2009.). Because the serum HAI titer is mostly determined by IgG content, these results led us to speculate that prevention of viral transmission may require IgA antibodies or cellular immune responses. To evaluate this hypothesis, guinea pigs and ferrets were administered a potent, neutralizing mouse IgG monoclonal antibody, 30D1 (Ms 30D1 IgG), against the A/California/04/2009 (H1N1) virus hemagglutinin and exposed to respiratory droplets from animals infected with this virus. Even though HAI titers were greater than 160 1 day postadministration, Ms 30D1 IgG did not prevent airborne transmission to passively immunized recipient animals. In contrast, intramuscular administration of recombinant 30D1 IgA (Ms 30D1 IgA) prevented transmission to 88% of recipient guinea pigs, and Ms 30D1 IgA was detected in animal nasal washes. Ms 30D1 IgG administered intranasally also prevented transmission, suggesting the importance of mucosal immunity in preventing influenza virus transmission. Collectively, our data indicate that IgG antibodies may prevent pathogenesis associated with influenza virus infection but do not protect from virus infection by airborne transmission, while IgA antibodies are more important for preventing transmission of influenza viruses. PMID:23698296

  12. Levels and complexity of IgA antibody against oral bacteria in samples of human colostrum.

    Science.gov (United States)

    Petrechen, L N; Zago, F H; Sesso, M L T; Bertoldo, B B; Silva, C B; Azevedo, K P; de Lima Pereira, S A; Geraldo-Martins, V R; Ferriani, V P L; Nogueira, R D

    2015-01-01

    Streptococcus mutans (SM) have three main virulence antigens: glucan binding protein B (gbpB), glucosyltransferase (Gtf) and antigens I/II (Ag I/II) envolved in the capacity of those bacteria to adhere and accumulate in the dental biofilm. Also, the glycosyltransferases 153 kDa of Streptococcus gordonii (SGO) and 170kDa of Streptococcus sanguinis (SSA) were important antigens associated with the accumulation of those bacterias. Streptococcus mitis (SMI) present IgA1 protease of 202 kDa. We investigated the specificity and levels IgA against those antigens of virulence in samples of human colostrum. This study involved 77 samples of colostrum that were analyzed for levels of immunoglobulian A, M and G by Elisa. The specificity of IgA against extracts of SM and initials colonizators (SSA, SMI, SGO) were analyzed by the Western blot. The mean concentration of IgA was 2850.2 (±2567.2) mg/100 mL followed by IgM and IgG (respectively 321.8±90.3 and 88.3±51.5), statistically different (pbacteria antigens and theirs virulence antigens. To SM, the GbpB was significantly lower detected than others antigens of SM (p0.4). So, the breast milk from first hours after birth presented significant levels of IgA specific against important virulence of antigens those oral streptococci, which can disrupt the installation and accumulation process of these microorganisms in the oral cavity. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. The Evaluation of Psychological Factor and Salivary Cortisol and IgA Levels in

    Directory of Open Access Journals (Sweden)

    Fateme Arbabi-Kalati

    2014-07-01

    Full Text Available Background: Oral lichen planus (OLP is a chronic immunological disorder with unknown etiology. The aim of this study was to determine psychological factors and salivary cortisol, IgA level in patients with oral lichen planus. Materials and Methods: In this experimental study 20 patients with OLP and healthy person were admitted to this study. Saliva samples were collected between - Am. saliva cortisol, IgA level was detected by ELIZA method. In this study, patients with anxiety and depression were measured using the SCL-90 questionnaire. Data analyzed by t-test. Results: The mean salivary cortisol level in patients with OLP was 3.2±1.9 ng/mL and the mean saliva cortisol level in healthy person was 3.5±1.9 ng/mL. Significant difference was observed in the salivary cortisol levels in the 2 study groups (p=0.04. The mean salivary IgA level in patients with OLP was 0.69±0.29 ng/mL and the mean saliva IgA level in healthy person was 0.9±0.43 ng/mL but no significant difference was observed in the salivary cortisol levels in the 2 study groups. Results showed that anxiety levels in patients with oral lichen planus were slightly higher than controls but there was no significant difference between healthy subjects. Conclusion: Finding revealed the mean salivary cortisol level in patient with OLP less than healthy persons. Significant difference was observed in the salivary cortisol levels in the 2 study groups. Based on the t-student test, no significant difference was observed in the salivary IgA levels in the 2 study groups. Anxiety levels in patients with oral lichen planus were slightly higher than controls.

  14. Changes in IgA protease expression are conferred by changes in genomes during persistent infection by nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Gallo, Mary C; Kirkham, Charmaine; Eng, Samantha; Bebawee, Remon S; Kong, Yong; Pettigrew, Melinda M; Tettelin, Hervé; Murphy, Timothy F

    2018-05-14

    Nontypeable Haemophilus influenzae (NTHi) is an exclusively human pathobiont that plays a critical role in the course and pathogenesis of chronic obstructive pulmonary disease (COPD). NTHi causes acute exacerbations of COPD and also causes persistent infection of the lower airways. NTHi expresses four IgA protease variants (A1, A2, B1, and B2) that play different roles in virulence. Expression of IgA proteases varies among NTHi strains, but little is known about the frequency and mechanisms by which NTHi modulates IgA protease expression during infection in COPD. To assess expression of IgA protease during natural infection in COPD, we studied IgA protease expression of 101 persistent strains (median duration of persistence 161 days, range 2 to 1422) collected longitudinally from patients enrolled in a 20-year study of COPD upon initial acquisition and immediately before clearance from the host. Upon acquisition, 89 (88%) expressed IgA protease. A total of 16 of 101 (16%) strains of NTHi altered expression of IgA protease during persistence. Indels and slipped-strand mispairing of mononucleotide repeats conferred changes in expression of igaA1, igaA2, and igaB1 Strains with igaB2 underwent frequent changes in expression of IgA protease B2 during persistence, mediated by slipped-strand mispairing of a 7-nucleotide repeat, TCAAAAT, within the open reading frame of igaB2 We conclude that changes in iga gene sequences result in changes in expression of IgA proteases by NTHi during persistent infection in the respiratory tract of patients with COPD. Copyright © 2018 American Society for Microbiology.

  15. Intra-tumour IgA1 is common in cancer and is correlated with poor prognosis in bladder cancer.

    Directory of Open Access Journals (Sweden)

    Charlotte Welinder

    2016-08-01

    Full Text Available A high frequency of IgA1-positive tumour cells was found in tissue micro-arrays of oesophagus, colon, testis, lung, breast, bladder and ovarian cancer. IgA1 was observed in the cytoplasm and the plasma membrane. A correlation was found between intra-tumour IgA1 and poor overall survival in a large cohort of bladder cancer patients (n = 99, p = 0.011, log-rank test. The number of IgA1-positive tumour cells was also found to be higher in female than male bladder cancer patients. The presence of IgA1 was confirmed in formalin-fixed paraffin-embedded ovarian carcinoma samples using LC-MS/MS analysis. Uptake of IgA1 was also observed in breast cancer and melanoma cell lines when cultivated in the presence of serum from healthy individuals, indicating a possible origin of the IgA1 antibodies in cancer cells.

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency anemia is a ... address the cause of your iron deficiency, such as any underlying bleeding. If undiagnosed or untreated, iron- ...

  17. Vitamin C deficiency in weanling guinea pigs

    DEFF Research Database (Denmark)

    Lykkesfeldt, Jens; Trueba, Gilberto Perez; Poulsen, Henrik E.

    2007-01-01

    Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency...... increased, while protein oxidation decreased (P¼0003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during...

  18. HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis

    Science.gov (United States)

    2018-01-01

    ABSTRACT Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and its capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelope-specific IgA monoclonal antibodies (MAbs) by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, nonrecombinant IgA MAbs. The HG129 and HG130 MAbs mediated phagocytosis by monocytes, and HG129 blocked HIV-1 Env glycoprotein binding to galactosylceramide, an alternative HIV-1 receptor. These findings elucidate potential antiviral functions of vaccine-elicited HIV-1 envelope-specific IgA that may act to block HIV-1 acquisition at the portal of entry by preventing HIV-1 binding to galactosylceramide and mediating antibody Fc receptor-mediated virion phagocytosis. Furthermore, these findings highlight the complex and diverse interactions of vaccine-elicited IgA with pathogens that depend on IgA fine specificity and form (e.g., multimeric or monomeric) in the systemic circulation and mucosal compartments. IMPORTANCE Host-pathogen interactions in vivo involve numerous immune mechanisms that can lead to pathogen clearance. Understanding the nature of antiviral immune mechanisms can inform the design of efficacious HIV-1 vaccine strategies. Evidence suggests that both neutralizing and nonneutralizing antibodies can mediate some protection against HIV in animal models. Although numerous studies have characterized the

  19. PetIGA-MF: a multi-field high-performance toolbox for structure-preserving B-splines spaces

    KAUST Repository

    Sarmiento, Adel

    2016-10-01

    We describe a high-performance solution framework for isogeometric discrete differential forms based on B-splines: PetIGA-MF. Built on top of PetIGA, an open-source library we have built and developed over the last decade, PetIGA-MF is a general multi-field discretization tool. To test the capabilities of our implementation, we solve different viscous flow problems such as Darcy, Stokes, Brinkman, and Navier-Stokes equations. Several convergence benchmarks based on manufactured solutions are presented assuring optimal convergence rates of the approximations, showing the accuracy and robustness of our solver.

  20. Diagnosis and follow-up of genital chlamydial infection by direct methods and by detection of serum IgG, IgA and secretory IgA

    Directory of Open Access Journals (Sweden)

    Fresse A

    2010-01-01

    Full Text Available Purpose: To determine the prevalence of Chlamydia trachomatis infection in a high-risk population by direct and indirect methods and to evaluate the diagnosis of secretory immunoglobulin A (sIgA. Patients and Methods: Urethral or endocervical specimens from 78 patients (48 females and 30 males were examined by cell culture, direct fluorescence assay, PCR Cobas Amplicor (Roche Molecular Diagnostics, and sIgA was detected by the recombinant lipopolysaccharide (LPS-enzyme-linked immunoassay (rELISA. Serum from each patient was also obtained and analysed for the presence of IgG and IgA antibody by in-house microimmunofluorescence (MIF and by the rELISA method (Medac, Hamburg, Germany. Results: The overall C. trachomatis prevalence determined by direct methods was 28%. The detection of sIgA antibodies was significantly higher in the group of patients with a positive direct detection (50% than in the group of negative direct detection (10.7%. The Chlamydia-specific IgA antibodies were detected by the rELISA in 40.9 and 53.6% of group I (positive direct detection and group II patients (negative direct detection, respectively. The species-specific IgA antibodies were detected by the MIF method in 18.2 and 16.1% of group I and II patients, respectively. Chlamydia genus-specific IgG antibodies were detected by the rELISA in 86.4 and 83.9% of group I and group II patients and, C. trachomatis specific IgG were present in 81.8 and 73.2% of group I and group II patients, respectively, as assessed by the MIF test. Conclusion: Combining the positive direct methods and/or positive sIgA antibody results from cervical or urethral specimens had an indication of current C. trachomatis infection.

  1. Chronic Giardia muris infection in anti-IgM-treated mice. I. Analysis of immunoglobulin and parasite-specific antibody in normal and immunoglobulin-deficient animals.

    Science.gov (United States)

    Snider, D P; Gordon, J; McDermott, M R; Underdown, B J

    1985-06-01

    To investigate the role of B cells and antibody in the immune response of mice to the murine intestinal parasite Giardia muris, we used mice treated from birth with rabbit anti-IgM antisera (aIgM). Such mice developed in serum and in gut secretions extreme Ig deficiency (IgM, IgA, and IgG) relative to control animals. The aIgM-treated mice showed no anti-G. muris antibody in serum or in gut wash material. Infections of G. muris in these mice were chronic, with a high load of parasite present in the small bowel, as reflected by prolonged cyst excretion (greater than 11 wk) and high trophozoite counts. In contrast, normal, untreated mice or NRS-treated animals developed anti-parasite IgA and IgG antibody in serum, demonstrated IgA antibody against the parasite in gut washings, and expelled the parasite within 9 wk. These effects of aIgM treatment on the murine response to primary infection with G. muris were demonstrated in two strains of mice: BALB/c and (C57BL/6 X C3H/He) F1. It was also observed that the response to G. muris infection in untreated animals was characterized by higher than normal total secretion of IgA into the gut and a concomitant increase in the serum polymeric IgA level. Mice treated with aIgM had a marked decrease of both monomeric and polymeric IgA in serum, and little detectable IgA in the intestinal lumen. These experiments provide the first demonstration that anti-IgM treatment suppresses a specific intestinal antibody response to antigen, and provide evidence that B cells and antibody play a role in the development of an effective response to a primary infection with G. muris in mice.

  2. Imunocitoma IgA: A propósito de um caso clínico Immunocytoma IgA: Case report

    Directory of Open Access Journals (Sweden)

    Bebiana Conde

    2009-01-01

    Full Text Available O imunocitoma é um linfoma não Hodgkin (LNHde células B, com evolução habitualmente indolente. Representa aproximadamente 1 -3% dos LNH e atinge habitualmente adultos com mais de 50 anos, podendo manifestar-se por adenomegalias, hepatomegalia, esplenomegalia e linfocitose em 15 a 30% dos casos. Raramente tem envolvimento pulmonar. Com frequência ocorrendo picos monoclonais de imunoglobulinas, sericos, frequentemente IgM e raramente IgA. Como exemplo desta patologia apresentamos o caso clinico de um doente do sexo masculino, 52 anos, com clinica de infecções respiratórias bacterianas de repetição, com necessidade de internamentos sucessivos, cuja investigação identificou um imunocitoma IgA, estádio IV. Assumindo-se o diagnóstico de um linfoma indolente, decidiu-se iniciar terapêutica profiláctica com imunoglobulinas humanas poliespecÍficas, tendo havido diminuição das infecçoes respiratórias. Posteriormente, a evidência de progressão do linfoma condicionou o inicio de poliquimioterapia, com o esquema ciclofosfamida, vincristina, prednisolona (CVP e rituximabR, tendo-se alcançado uma resposta parcial, que se manteve durante dois anos.Immunocytoma is a non-Hodgkin’s indolent evolution B cell lymphoma. It accounts for approximately 1-3% of non-Hodgkin's limphomas and usually onsets in adults aged over 50 years old. It manifests as lymphadenopathy, splenomegaly, hepatomegaly and lymphcytosis in 15 -30% of cases and is rarely seen with pulmonary involvement. Monocloncal peaks of serum immunoglobulin often occur. These are IgM and rarely IgA. We present as an example a male patient aged 52 years old, with recurrent respiratory infections. Clinical work -up identified an immunocytoma IgA stage IV. Diagnosing an indolent lymphoma, we prophylactic polyspecific human immunoglobulin to treat the respiratory infection. Evidence of lymphoma progression leads us to prescribe combined cyclophosphamide (C, vincristine (V, prednisone (P

  3. S1P Signalling Differentially Affects Migration of Peritoneal B Cell Populations In Vitro and Influences the Production of Intestinal IgA In Vivo

    Directory of Open Access Journals (Sweden)

    Annabel Kleinwort

    2018-01-01

    Full Text Available Introduction: Sphingosine-1-phosphate (S1P regulates the migration of follicular B cells (B2 cells and directs the positioning of Marginal zone B cells (MZ B cells within the spleen. The function of S1P signalling in the third B cell lineage, B1 B cells, mainly present in the pleural and peritoneal cavity, has not yet been determined. Methods: S1P receptor expression was analysed in peritoneal B cells by real-time polymerase chain reaction (qPCR. The chemotactic response to S1P was studied in vitro. The role of S1P signalling was further explored in a s1p4−/− mouse strain. Results: Peritoneal B cells expressed considerable amounts of the S1P receptors 1 and 4 (S1P1 and S1P4, respectively. S1P1 showed differential expression between the distinct peritoneal B cell lineages. While B2 cells showed no chemotactic response to S1P, B1 B cells showed a migration response to S1P. s1p4−/− mice displayed significant alterations in the composition of peritoneal B cell populations, as well as a significant reduction of mucosal immunoglobulin A (IgA in the gut. Discussion: S1P signalling influences peritoneal B1 B cell migration. S1P4 deficiency alters the composition of peritoneal B cell populations and reduces secretory IgA levels. These findings suggest that S1P signalling may be a target to modulate B cell function in inflammatory intestinal pathologies.

  4. Variants in Complement Factor H and Complement Factor H-Related Protein Genes, CFHR3 and CFHR1, Affect Complement Activation in IgA Nephropathy.

    Science.gov (United States)

    Zhu, Li; Zhai, Ya-Ling; Wang, Feng-Mei; Hou, Ping; Lv, Ji-Cheng; Xu, Da-Min; Shi, Su-Fang; Liu, Li-Jun; Yu, Feng; Zhao, Ming-Hui; Novak, Jan; Gharavi, Ali G; Zhang, Hong

    2015-05-01

    Complement activation is common in patients with IgA nephropathy (IgAN) and associated with disease severity. Our recent genome-wide association study of IgAN identified susceptibility loci on 1q32 containing the complement regulatory protein-encoding genes CFH and CFHR1-5, with rs6677604 in CFH as the top single-nucleotide polymorphism and CFHR3-1 deletion (CFHR3-1∆) as the top signal for copy number variation. In this study, to explore the clinical effects of variation in CFH, CFHR3, and CFHR1 on IgAN susceptibility and progression, we enrolled two populations. Group 1 included 1178 subjects with IgAN and available genome-wide association study data. Group 2 included 365 subjects with IgAN and available clinical follow-up data. In group 1, rs6677604 was associated with mesangial C3 deposition by genotype-phenotype correlation analysis. In group 2, we detected a linkage between the rs6677604-A allele and CFHR3-1∆ and found that the rs6677604-A allele was associated with higher serum levels of CFH and lower levels of the complement activation split product C3a. Furthermore, CFH levels were positively associated with circulating C3 levels and negatively associated with mesangial C3 deposition. Moreover, serum levels of the pathogenic galactose-deficient glycoform of IgA1 were also associated with the degree of mesangial C3 deposition in patients with IgAN. Our findings suggest that genetic variants in CFH, CFHR3, and CFHR1 affect complement activation and thereby, predispose patients to develop IgAN. Copyright © 2015 by the American Society of Nephrology.

  5. Toxicological Effects of Nickel Chloride on IgA+ B Cells and sIgA, IgA, IgG, IgM in the Intestinal Mucosal Immunity in Broilers

    Directory of Open Access Journals (Sweden)

    Bangyuan Wu

    2014-08-01

    Full Text Available The objective of this study was to investigate the toxicological effects of dietary NiCl2 on IgA+ B cells and the immunoglobulins including sIgA, IgA, IgG and IgM in the small intestine and cecal tonsil of broilers by the methods of immunohistochemistry and enzyme-linked immunosorbent assay (ELISA. Two hundred and forty one-day-old avian broilers were randomly divided into four groups and fed on a control diet and three experimental diets supplemented with 300, 600, and 900 mg/kg NiCl2 for 42 days. Compared with the control group, the IgA+ B cell number and the sIgA, IgA, IgG, and IgM contents in the NiCl2-treated groups were significantly decreased (p < 0.05 or p < 0.01. It was concluded that dietary NiCl2 in the excess of 300 mg/kg had negative effects on the IgA+ B cell number and the abovementioned immunoglobulin contents in the small intestine and the cecal tonsil. NiCl2-reduced sIgA, IgA, IgG and IgM contents is due to decrease in the population and/or the activation of B cell. The results suggest that NiCl2 at high levels has intestinal mucosal humoral immunotoxicity in animals.

  6. Presence of Lactobacillus reuteri in saliva coincide with higher salivary IgA in young adults after intake of probiotic lozenges

    DEFF Research Database (Denmark)

    Braathen, G; Ingildsen, V; Twetman, S

    2017-01-01

    The aim of this study was to compare the concentration of salivary immunoglobulin A (IgA) and the selected interleukins (IL)-1β, IL-6, IL-8 and IL-10 in young individuals with presence and non-presence of Lactobacillus reuteri in saliva after a three-week intervention with probiotic lozenges. The...... to interpret and understand their possible immune-modulating role in maintaining oral health........ The study group consisted of 47 healthy individuals aged 18-32 years with no clinical signs of oral inflammation. In a randomised, double-blind, placebo-controlled, cross-over trial participants ingested two lozenges per day containing two strains of the probiotic bacterium L. reuteri or placebo lozenges......, detectable levels of L. reuteri in saliva coincided with higher concentrations of salivary IgA and %IgA/protein in stimulated whole saliva after the three-week daily intake of probiotic lozenges. Our findings suggest that monitoring the presence of probiotic candidates in the oral environment is important...

  7. IGA resistance of TT Alloy 690 and concentration behavior of Broached Egg Crate tube support configuration

    International Nuclear Information System (INIS)

    Suzuki, S.; Kusakabe, T.; Yamamoto, H.; Arioka, K.; Ochi, T.

    1992-01-01

    In order to improve the reliability of the Steam Generator (SG), TT Alloy 690 and BEC (Broached Egg Crate) type tube support plate has been developed. Some tests are carried out to heighten the reliability for these improvements all the more and the following results are obtained. (1) SERT test (Slow Extension Rate Test) made clear that TT690 has less IGA susceptibility in comparison with MA600. (2) The alkaline susceptibility on the occurrence of IGA/SCC on TT690 and MA600 obtained by SERT corresponds to that obtained by Model Boiler test. (3) By model boiler test, superior concentration behaviors for BEC type tube support plate configuration have been recognized in comparison with Drill type. This result is obtained by the joint research of the five utilities (Kansai Epco, Hokkaido Epco, Shikoku Epco, Kyushu Epco, JAPCO) and MHI

  8. Physical exercise, salivary IgA and mood states of elderly people

    Directory of Open Access Journals (Sweden)

    R. Martins

    2008-01-01

    Full Text Available It is generally accepted that the aging process is associated with immunosenescence. On the other hand, physical activity has been consistently associated with positive states of affection and mood which also implies gains on psychological well-being. However, more studies are needed to support the benefit effect of exercise on specific population groups like the elderly. The purpose of the present work is to study the functional fitness, mood states and salivary IgA chronic adaptations after a physical exercise program. 28 subjects aged between 65 and 95 years old participated in this study. The experimental group exercised during 16 weeks, 3 times per week. The Wilcoxon test was used to compare the data. The results showed positive changes on the functional fitness that reinforce the trainability principle of the older person. The data shows also an improvement in mood states and chronic positive effects on salivary IgA after the exercise program.

  9. Thioredoxin is involved in endothelial cell extracellular transglutaminase 2 activation mediated by celiac disease patient IgA.

    Directory of Open Access Journals (Sweden)

    Cristina Antonella Nadalutti

    Full Text Available PURPOSE: To investigate the role of thioredoxin (TRX, a novel regulator of extracellular transglutaminase 2 (TG2, in celiac patients IgA (CD IgA mediated TG2 enzymatic activation. METHODS: TG2 enzymatic activity was evaluated in endothelial cells (HUVECs under different experimental conditions by ELISA and Western blotting. Extracellular TG2 expression was studied by ELISA and immunofluorescence. TRX was analysed by Western blotting and ELISA. Serum immunoglobulins class A from healthy subjects (H IgA were used as controls. Extracellular TG2 enzymatic activity was inhibited by R281. PX12, a TRX inhibitor, was also employed in the present study. RESULTS: We have found that in HUVECs CD IgA is able to induce the activation of extracellular TG2 in a dose-dependent manner. Particularly, we noted that the extracellular modulation of TG2 activity mediated by CD IgA occurred only under reducing conditions, also needed to maintain antibody binding. Furthermore, CD IgA-treated HUVECs were characterized by a slightly augmented TG2 surface expression which was independent from extracellular TG2 activation. We also observed that HUVECs cultured in the presence of CD IgA evinced decreased TRX surface expression, coupled with increased secretion of the protein into the culture medium. Intriguingly, inhibition of TRX after CD IgA treatment was able to overcome most of the CD IgA-mediated effects including the TG2 extracellular transamidase activity. CONCLUSIONS: Altogether our findings suggest that in endothelial cells CD IgA mediate the constitutive activation of extracellular TG2 by a mechanism involving the redox sensor protein TRX.

  10. Physical exercise, salivary IgA and mood states of elderly people

    OpenAIRE

    R. Martins; F. Rosado; M.R. Cunha; M. Martins; A.M. Teixeira

    2008-01-01

    It is generally accepted that the aging process is associated with immunosenescence. On the other hand, physical activity has been consistently associated with positive states of affection and mood which also implies gains on psychological well-being. However, more studies are needed to support the benefit effect of exercise on specific population groups like the elderly. The purpose of the present work is to study the functional fitness, mood states and salivary IgA chronic adaptations after...

  11. Linear IgA Bullous Dermatosis:A Retrospective Study of 23 Patients in Denmark

    OpenAIRE

    Lings, Kristina; Bygum, Anette

    2015-01-01

    Linear IgA bullous dermatosis (LAD) is an autoimmune, chronic bullous disease affecting primarily young children and adults. Studies on LAD are relatively sparse and from Scandinavia we could only find a few case reports. Therefore we decided to conduct a retrospective investigation of patients seen at our department since 1972. The objective is to give a description of the different subgroups of patients with LAD with regard to precipitating factors, demographics, treatments, course of disea...

  12. AVIDITY EVALUATION OF LOCAL IgA ANTIBODIES IN PERSONS IMMUNIZED WITH LIVE INFLUENZA VACCINE

    Directory of Open Access Journals (Sweden)

    S. A. Donina

    2008-01-01

    Full Text Available Abstract. At present, immunogenicity evaluation of influenza vaccines is performed by quantitative assessment of increased serum antibodies. It was, however, shown that the degree of human defense against influenza is mostly related to their qualitative characteristics, i.e., avidity (functional activity. Leading role of local immunity is demonstrated in protection against influenza. Such immunity is mediated by IgA antibodies from mucosal airways. Meanwhile, the avidity issues for local antibodies still remain open.In present study, an attempt was undertaken to evaluate post-vaccination local immunological memory for influenza A virus, according to IgA antibodies from upper respiratory secretions. Two techniques were used to evaluate antibody avidity, that were previously applied for studying this phenomenon with serum imunoglobulins, i.e., a dynamic test (measurement of antigen-antibody reaction rates, and a test with urea, a chaotropic agent (avidity is determined as a strength of antigen-antibody complex. A total of 202 persons (18 to 20 years old were enrolled into the study.With both tests, a broad range of individual avidity values was observed for the antibodies. A significant cohort (up to 30 per cent of persons immunized with live influenza vaccine, showed sharply increased avidity of secretory IgA antibodies by both methods, along with accumulation of these immunoglobulins after vaccination. A reverse relationship is revealed between avidity levels of these antibodies before vaccination, and increase of this parameter post-immunization. The data present convincing arguments for specific renewal of local humoral immunological memory, as induced by live influenza vaccine. The study substantiates a necessity for application of the both tests in parallel, when determining avidity of secretory IgA antibodies. (Med. Immunol., vol. 10, N 4-5, pp 423-430.

  13. Role of macrophages and oxygen radicals in IgA induced lung injury in the rat

    International Nuclear Information System (INIS)

    Johnson, K.J.; Ward, P.A.; Kunkel, R.G.; Wilson, B.S.

    1986-01-01

    Acute lung injury in the rat has been induced by the instillation of affinity-purified mouse monoclonal IgA antibody with specific reactivity to dinitrophenol (DNP) coupled to albumin. This model of lung injury requires an intact complement system but not neutrophils, and evidence suggests that pulmonary macrophages are the critical effector cell. Macrophages retrievable from the lungs of the IgA immune complex treated rats are considerably increased in number as compared to control animals which received only the antibody. In addition these cells show evidence of activation in vivo with greater spontaneous generation of the superoxide anion (O 2 - ) as well as significantly enhanced O 2 - response in the presence of a second stimulus. Inhibition studies in vivo suggest that the lung injury is mediated by oxygen radical generation by the pulmonary macrophages. Pretreatment of rats with superoxide dismutase (SOD), catalase, the iron chelator deferoxamine or the hydroxyl radical scavenger dimethyl sulfoxide (DMSO) all markedly suppressed the development of the lung injury. In summary, these studies suggest that IgA immune complex injury in the rat lung is mediated by oxygen radical formation from pulmonary macrophages

  14. [Acute pancreatitis as the presenting feature of an IgA vasculitis: An unusual presentation].

    Science.gov (United States)

    Fertitta, L; Noel, N; Ackermann, F; Lerolle, N; Benoist, S; Rocher, L; Lambotte, O

    2017-10-01

    IgA vasculitis is a systemic small vessel leukocytoclastic vasculitis characterized by skin purpura, arthritis, abdominal pain and nephritis. Most of the abdominal complications are due to edema and hemorrhage in the small bowel wall, but rarely to acute secondary pancreatitis. Here, we report a 53-year-old woman who presented with acute pancreatitis and, secondarily, developed skin purpura and arthritis at the seventh day of the clinical onset. Biological tests and computed tomographic scan allowed to rule out another cause of pancreatitis and IgA vasculitis was diagnosed as its etiology. The outcome was favorable without any relapse on glucocorticoids. Despite its rarity, pancreatitis is a potential life-threatening complication of IgA vasculitis in which the role of glucocorticoids and immunosuppressive drugs remains uncertain. A prompt elimination of other usual pancreatitis etiologies is mandatory to improve the management of the patients. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  15. Saliva and sera IgA and IgG in Egyptian Giardia-infected children.

    Science.gov (United States)

    El-Gebaly, Naglaa Saad M; Halawa, Eman Fawzy; Moussa, Hanaa M Ezzat; Rabia, Ibrahim; Abu-Zekry, Maha

    2012-08-01

    Giardiasis is a gastrointestinal infection of wide distribution that is more prevalent in childhood. Easy and rapid diagnosis of giardiasis is essential for reduction of this infection. This cross-sectional study included 62 children in which collection of saliva, stool and serum samples was performed. An enzyme-linked immunosorbent assay (ELISA) technique was evaluated to detect IgA and IgG responses in both saliva and serum samples. Twenty-two children were positive for Giardia duodenalis infection by direct examination of faecal specimens, 20 non-infected and 20 infected with other parasites. Salivary and serum IgA and IgG responses against G. duodenalis infection were significantly higher in Giardia parasitized than non-Giardia parasitized children (p < 0.001). This concludes that specific salivary IgA may serve as a diagnostic tool and specific salivary IgG as a screening tool in monitoring the exposure of various populations to Giardia duodenalis. The advantage of salivary assays over serum immunoglobulin assay is being easy and non-invasive in sampling technique which is important especially for young children.

  16. Flame figures in linear IgA bullous dermatosis: a novel histopathologic finding.

    Science.gov (United States)

    Fulton, E; Jan, F; Zimarowski, M J

    2017-11-15

    Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal blistering disease usually with a neutrophil rich inflammatory infiltrate, and characterized by linear IgA deposition at the basement membrane zone (BMZ), and neutrophil predominant dermal inflammation. We report a case of LABD with numerous eosinophils and flame figure formation, a unique histopathologic finding not previously reported. A 69-year-old woman presented with a rapidly progressive, intensely pruritic rash over forearms, breasts, axillae, hips, and thighs. Thelesions were comprised of annular vesicles and bullae with hemorrhagic crusts and erosions. The clinical differential diagnosis included bullous pemphigoid(BP), LABD, and epidermolysis bullosa aquisita (EBA). A biopsy from a bullous plaque on the wrist revealed a subepidermal blister with neutrophils and numerous eosinophils with flame figure formation.Direct immunofluorescent (DIF) microscopy revealed linear deposition of IgA at the BMZ. Although unusual, the combined findings supported a diagnosis of LABD. Increased eosinophils may be associated with drug-induced LABD and may explain the numerous eosinophils in our case. It is important to be aware of this finding as the pathology may easily be misdiagnosed as BP, or possibly bullousWells syndrome. This case emphasizes that combined clinical, pathologic, and DIF findings are essential in the diagnosis of bullous dermatoses.

  17. Pathological Role of Tonsillar B Cells in IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Yusuke Suzuki

    2011-01-01

    Full Text Available Although impaired immune regulation along the mucosa-bone marrow axis has been postulated to play an important role, the pathogenesis of IgA nephropathy (IgAN is unknown; thus, no disease-specific therapy for this disease exists. The therapeutic efficacy of tonsillectomy or tonsillectomy in combination with steroid pulse therapy for IgAN has been discussed. Although randomized control trials for these therapies are ongoing in Japan, the scientific rationale for these therapies remains obscure. It is now widely accepted that abnormally glycosylated IgA1 and its related immune complex (IC are probably key molecules for the pathogenesis, and are thus considered possible noninvasive biomarkers for this disease. Emerging evidence indicates that B cells in mucosal infections, particularly in tonsillitis, may produce the nephritogenic IgA. In this paper, we briefly summarize characteristics of the nephritogenic IgA/IgA IC, responsible B cells, and underlying mechanisms. This clinical and experimental information may provide important clues for a therapeutic rationale.

  18. Clinical and pathological analysis of IgA nephropathy with chronic renal failure.

    Science.gov (United States)

    Liu, Yuyuan; Hu, Qinfeng; Shen, Ping; Tang, Li; Yuan, Gang; Zhou, Yongmei; Chai, Huaqi

    2016-10-01

    To investigative clinical and pathological characteristics of IgA nephropathy with chronic renal failure. Clinical and pathological findings from 65 cases of IgA nephropathy with chronic renal failure were reviewed. Pathological characteristics of all the cases were analyzed according to WHO definition and Oxford Classification. Evaluating the severity of pathological lesions by the Katafuchi R semiquantitative scoring system, and analyzing their relationship with clinical indexes of renal function. Of all 65 cases the male and female ratio was 1.4, and the mean age was 37 ± 13 years old. Levels of systolic pressure, mean arterial pressure (MAP), blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), album (Alb), serum IgG and 24 h urinary protein were related with eGRF level (p  0.05). IgA nephropathy with chronic renal failure usually occurred in young adults, and it had severe clinical condition and pathological changes, while there was no significant relationship between them.

  19. IGA/SCC propagation rate measurements on alloy 600 steam generator tubing using a side stream model boiler

    International Nuclear Information System (INIS)

    Takamatsu, H.; Matsueda, K.; Matsunaga, T.; Kitera, T.; Arioka, K.; Tsuruta, T.; Okamoto, S.

    1993-01-01

    IGA/SCC crack propagation rate measurements using various types of IGA/SCC predefected ALloy 600 tubing were tested in model boilers, a side stream model boiler at Ohi Unit 1 and similar model boilers in the laboratory. Types of IGA/SCC predefects introduced from the outside of the tubing were as follows. (1) Actual IGA/SCC predefect introduced by high temperature caustic environments; (2) Longitudinal predefect by electrodischarge machining (EDM) method, and then crack tip fatigue was introduced to serve as the marker on the fractured surface (EDM slit + fatigue). IGA/SCC crack propagation rate was measured after the destructive examination by Cr concentration profile on fracture surface for (1), and observation of intergranular fractured surface propagated from the marked fatigue was employed for (2) and (3) after the model boiler tests. As for the water chemistry conditions, mainly AVT (high N 2 H 4 ) + boric acid (5-10ppm as B in SGs) treatment for both model boilers, and some of the tests for the model boiler in the laboratory employed AVT (high N 2 H 4 ) without boric acid. The results of IGA/SCC crack propagation rate measurements were compared with each other, and the three methods employed showed a good coincidence with the rate of ca. 1 x 10 -5 mm/Hr for AVT (high N 2 H 4 ) + boric acid treatment condition, in the case that crack tip boron intensity (B/O value by IMMA analysis) of more than 1 was observed

  20. A Disulfide Bond in the Membrane Protein IgaA Is Essential for Repression of the RcsCDB System

    Directory of Open Access Journals (Sweden)

    M. Graciela Pucciarelli

    2017-12-01

    Full Text Available IgaA is an integral inner membrane protein that was discovered as repressor of the RcsCDB phosphorelay system in the intracellular pathogen Salmonella enterica serovar Typhimurium. The RcsCDB system, conserved in many members of the family Enterobacteriaceae, regulates expression of varied processes including motility, biofilm formation, virulence and response to envelope stress. IgaA is an essential protein to which, in response to envelope perturbation, the outer membrane lipoprotein RcsF has been proposed to bind in order to activate the RcsCDB phosphorelay. Envelope stress has also been reported to be sensed by a surface exposed domain of RcsF. These observations support a tight control of the RcsCDB system by RcsF and IgaA via mechanisms that, however, remain unknown. Interestingly, RcsF and IgaA have four conserved cysteine residues in loops exposed to the periplasmic space. Two non-consecutive disulfide bonds were shown to be required for RcsF function. Here, we report mutagenesis studies supporting the presence of one disulfide bond (C404-C425 in the major periplasmic loop of IgaA that is essential for repression of the RcsCDB phosphorelay. Our data therefore suggest that the redox state of the periplasm may be critical for the control of the RcsCDB system by its two upstream regulators, RcsF and IgaA.

  1. Intestinal IgA responses to Giardia muris in mice depleted of helper T lymphocytes and in immunocompetent mice.

    Science.gov (United States)

    Heyworth, M F

    1989-04-01

    Immunocompetent mice infected with Giardia muris generate an intestinal antibody response to this parasite and clear G. muris infection. Previous work has shown that G. muris infection is prolonged in mice that have been depleted of helper (CD4+) T lymphocytes by treatment with a monoclonal antibody (mAb) directed against the murine CD4 antigen. The aim of the present study was to compare the intestinal anti-Giardia antibody response in immunocompetent mice and in mice depleted of helper T (Th) lymphocytes by treatment with anti-CD4 mAb. Immunocompetent mice generated an IgA response to G. muris, as judged by the presence of IgA on Giardia trophozoites harvested from the intestine of these animals more than 10 days after the start of the infection. The anti-Giardia IgA response was impaired in mice depleted of Th lymphocytes, as judged by virtual absence of immunofluorescent staining of trophozoites from these animals for surface-bound IgA. Clearance of G. muris infection was impaired by treatment of mice with anti-CD4 mAb. The results suggest that Th (CD4+) lymphocytes are important for the generation of a local IgA response against G. muris trophozoites in the mouse intestine and that IgA anti-trophozoite antibody may contribute to the clearance of G. muris from the intestine of immunocompetent mice.

  2. Prevalence of latent and manifest hyperthyroidism in an iodine-deficient area: non-selected patient population admitted for CT studies with iodine-containing contrast agents

    International Nuclear Information System (INIS)

    Saam, T.; Hess, T.; Kasperk, C.; Kauffmann, G.W.; Duex, M.

    2005-01-01

    Purpose: to evaluate the prevalence of latent and manifest hyperthyroidism in a non-selected group of patients admitted for contrast enhanced CT studies blood samples were tested for the levels of thyroid-stimulating hormone (TSH). Material and methods: TSH blood levels were obtained in 548 consecutive patients who were scheduled for contrast-enhanced (Iopromide; 300 mg iodine/ml) CT scanning. In case of TSH levels registered (sodium perchlorate) was commenced before scanning. In case of TSH levels < 0.1 mU/l, CT scanning was not performed but further evaluation of the thyroid function was initiated. Results: TSH blood levels ranged from 0.4 to 7.5 mU/l in 512 patients, and 36 patients (6.6%) had TSH blood levels < 0.4 mU/l and 9 patients blood levels < 0.1 mU/l, with 32 of those patients (5.8%) having regular T3 and T4 blood levels consistent with latent hyperthyroidism. In 4 patients (0.8%), T3 or T4 blood levels were increased consistent with manifest hyperthyroidism. Conclusion: in South Germany, the prevalence of latent or manifest hyperthyroidism in a non-selected patient group is high. Therefore TSH blood levels should be obtained prior to contrast-enhanced CT studies. (orig.)

  3. Iron-Deficiency Anemia

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    Full Text Available ... fatigue or tiredness, shortness of breath, or chest pain. If your doctor diagnoses you with iron-deficiency ... Common symptoms of iron-deficiency anemia include: Chest pain Coldness in the hands and feet Difficulty concentrating ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, such as ... for iron-deficiency anemia. Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. ...

  5. Factor VII deficiency

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    ... this page: //medlineplus.gov/ency/article/000548.htm Factor VII deficiency To use the sharing features on this page, please enable JavaScript. Factor VII (seven) deficiency is a disorder caused by a ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... lead to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. People ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... view the colon directly. What if my doctor thinks something else is causing my iron-deficiency anemia? ... deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... mg and women need 18 mg. After age 51, both men and women need 8 mg. Pregnant ... for iron-deficiency anemia. Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. ...

  11. Iron-Deficiency Anemia

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  12. Iron-Deficiency Anemia

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  13. Iron-Deficiency Anemia

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    Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, lean red meat, ... signs of iron-deficiency anemia include: Brittle nails ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ...

  15. Fire Safety Deficiencies

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    U.S. Department of Health & Human Services — A list of all fire safety deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection...

  16. Iron-Deficiency Anemia

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    Full Text Available ... learning how having iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ... Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in a clinical trial . ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... leaving cells where it is stored or from being absorbed in the duodenum, the first part of ... treatments for iron-deficiency anemia. Living With After being diagnosed with iron-deficiency anemia, it is important ...

  19. A Novel Leu92 Mutant of HIV-1 Reverse Transcriptase with a Selective Deficiency in Strand Transfer Causes a Loss of Viral Replication.

    Science.gov (United States)

    Herzig, Eytan; Voronin, Nickolay; Kucherenko, Nataly; Hizi, Amnon

    2015-08-01

    The process of reverse transcription (RTN) in retroviruses is essential to the viral life cycle. This key process is catalyzed exclusively by the viral reverse transcriptase (RT) that copies the viral RNA into DNA by its DNA polymerase activity, while concomitantly removing the original RNA template by its RNase H activity. During RTN, the combination between DNA synthesis and RNA hydrolysis leads to strand transfers (or template switches) that are critical for the completion of RTN. The balance between these RT-driven activities was considered to be the sole reason for strand transfers. Nevertheless, we show here that a specific mutation in HIV-1 RT (L92P) that does not affect the DNA polymerase and RNase H activities abolishes strand transfer. There is also a good correlation between this complete loss of the RT's strand transfer to the loss of the DNA clamp activity of the RT, discovered recently by us. This finding indicates a mechanistic linkage between these two functions and that they are both direct and unique functions of the RT (apart from DNA synthesis and RNA degradation). Furthermore, when the RT's L92P mutant was introduced into an infectious HIV-1 clone, it lost viral replication, due to inefficient intracellular strand transfers during RTN, thus supporting the in vitro data. As far as we know, this is the first report on RT mutants that specifically and directly impair RT-associated strand transfers. Therefore, targeting residue Leu92 may be helpful in selectively blocking this RT activity and consequently HIV-1 infectivity and pathogenesis. Reverse transcription in retroviruses is essential for the viral life cycle. This multistep process is catalyzed by viral reverse transcriptase, which copies the viral RNA into DNA by its DNA polymerase activity (while concomitantly removing the RNA template by its RNase H activity). The combination and balance between synthesis and hydrolysis lead to strand transfers that are critical for reverse transcription

  20. Comparative innate immune interactions of human and bovine secretory IgA with pathogenic and non-pathogenic bacteria.

    Science.gov (United States)

    Hodgkinson, Alison J; Cakebread, Julie; Callaghan, Megan; Harris, Paul; Brunt, Rachel; Anderson, Rachel C; Armstrong, Kelly M; Haigh, Brendan

    2017-03-01

    Secretory IgA (SIgA) from milk contributes to early colonization and maintenance of commensal/symbiotic bacteria in the gut, as well as providing defence against pathogens. SIgA binds bacteria using specific antigenic sites or non-specifically via its glycans attached to α-heavy-chain and secretory component. In our study, we tested the hypothesis that human and bovine SIgA have similar innate-binding activity for bacteria. SIgAs, isolated from human and bovine milk, were incubated with a selection of commensal, pathogenic and probiotic bacteria. Using flow cytometry, we measured numbers of bacteria binding SIgA and their level of SIgA binding. The percentage of bacteria bound by human and bovine SIgA varied from 30 to 90% depending on bacterial species and strains, but was remarkably consistent between human and bovine SIgA. The level of SIgA binding per bacterial cell was lower for those bacteria that had a higher percentage of SIgA-bound bacteria, and higher for those bacteria that had lower percentage of SIgA-bound bacteria. Overall, human and bovine SIgA interacted with bacteria in a comparable way. This contributes to longer term research about the potential benefits of bovine SIgA for human consumers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Iron-Deficiency Anemia

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    Full Text Available ... if you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron-deficiency anemia because of your age, ... or sex. Age You may be at increased risk for iron deficiency at certain ages: Infants between ...

  2. Iron-Deficiency Anemia

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    Full Text Available ... Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español ... bleeding Consuming less than recommended daily amounts of iron Iron-deficiency anemia can be caused by getting ...

  3. Iron-Deficiency Anemia

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  4. Iron-Deficiency Anemia

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  5. Iron-Deficiency Anemia

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    Full Text Available ... for iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ...

  6. Decreased Taxon-Specific IgA Response in Relation to the Changes of Gut Microbiota Composition in the Elderly

    Directory of Open Access Journals (Sweden)

    Hirosuke Sugahara

    2017-09-01

    Full Text Available Gut microbiota is known to change with aging; however, the underlying mechanisms have not been well elucidated. Immunoglobulin A (IgA is the dominant class of antibody secreted by the intestinal mucosa, and are thought to play a key role in the regulation of the gut microbiota. T cells regulate the magnitude and nature of microbiota-specific IgA responses. However, it is also known that T cells become senescent in elderly people. Therefore, we speculated that the age-related changes of IgA response against the gut microbiota might be one of the mechanisms causing the age-associated changes of gut microbiota composition. To prove our hypothesis, fecal samples from 40 healthy subjects (adult group: n = 20, an average of 35 years old; elderly group: n = 20, an average of 76 years old were collected, and the gut microbiota composition and the response of IgA to gut microbiota were investigated. The relative abundance of Bifidobacteriaceae was significantly lower, whereas those of Clostridiaceae, Clostridiales;f__ and Enterobacteriaceae were significantly higher in the elderly group than in the adult group. There was no significant difference in the fecal IgA concentration between the adult and elderly groups. However, the taxon-specific IgA response to some bacterial taxa was different between the adult and elderly groups. To evaluate inter-group differences in the taxon-specific IgA response to each bacterial taxon, the IgA-indices were calculated, and the IgA-indices of Clostridiaceae and Enterobacteriaceae were found to be significantly lower in the elderly group than the adult group. In addition, Clostridiales;f__ and Enterobacteriaceae were significantly enriched in the IgA+ fraction in the adult group but not in the elderly group, whereas Clostridiaceae was significantly enriched in the IgA- fraction in the elderly group but not in the adult group. Some species assigned to Clostridiaceae or Enterobacteriaceae are known to be pathogenic

  7. Evolution of IgA nephropathy into anaphylactoid purpura in six cases--further evidence that IgA nephropathy and Henoch-Schonlein purpura nephritis share common pathogenesis.

    Science.gov (United States)

    Kamei, Koichi; Ogura, Masao; Sato, Mai; Ito, Shuichi; Ishikura, Kenji

    2016-05-01

    As the morphological and immunohistochemical manifestations of immunoglobulin A (IgA) nephropathy and Henoch-Schonlein purpura nephritis (HSPN) are very similar, they are considered to share a common pathogenesis. Although HSPN usually develops after the appearance of anaphylactoid purpura, we have encountered patients whose renal symptoms preceded purpura. We reviewed the clinical courses of patients who were first diagnosed with IgA nephropathy, but developed purpura later, at the National Center for Child Health and Development in Tokyo, Japan. Of the 53 patients who were diagnosed with primary IgA nephropathy at our institute during the study period (March 2002 to July 2015), six (11 %) developed anaphylactoid purpura after the diagnosis of primary IgA nephropathy and therefore met the inclusion criteria. Duration between the onset of nephritis and subsequent appearance of purpura ranged from 5 months to 14 years. One patient reached end-stage renal failure due to IgA nephropathy and developed purpura after renal transplantation. All renal biopsies performed before the appearance of purpura showed mesangial proliferation with predominant IgA deposits. Urinary findings deteriorated in three patients after the appearance of purpura, including one patient who developed rapidly progressive glomerulonephritis. Renal biopsy findings worsened in two patients. At the last observation, two patients showed mild renal insufficiency. Our clinical experience and previous reports support the argument that IgA nephropathy and HSPN are different manifestations of a single disease. Hence, it is acceptable to consider that they are variants of a single disease.

  8. IGA-ADS: Isogeometric analysis FEM using ADS solver

    Science.gov (United States)

    Łoś, Marcin M.; Woźniak, Maciej; Paszyński, Maciej; Lenharth, Andrew; Hassaan, Muhamm Amber; Pingali, Keshav

    2017-08-01

    In this paper we present a fast explicit solver for solution of non-stationary problems using L2 projections with isogeometric finite element method. The solver has been implemented within GALOIS framework. It enables parallel multi-core simulations of different time-dependent problems, in 1D, 2D, or 3D. We have prepared the solver framework in a way that enables direct implementation of the selected PDE and corresponding boundary conditions. In this paper we describe the installation, implementation of exemplary three PDEs, and execution of the simulations on multi-core Linux cluster nodes. We consider three case studies, including heat transfer, linear elasticity, as well as non-linear flow in heterogeneous media. The presented package generates output suitable for interfacing with Gnuplot and ParaView visualization software. The exemplary simulations show near perfect scalability on Gilbert shared-memory node with four Intel® Xeon® CPU E7-4860 processors, each possessing 10 physical cores (for a total of 40 cores).

  9. Carnitine Deficiency and Pregnancy

    Directory of Open Access Journals (Sweden)

    Anouk de Bruyn

    2015-01-01

    Full Text Available We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, supplementation with carnitine is advised. This supplementation should be continued throughout pregnancy according to plasma concentrations.

  10. Pre- and Posttransplant IgA Anti-Fab Antibodies to Predict Long-term Kidney Graft Survival.

    Science.gov (United States)

    Amirzargar, M A; Amirzargar, A; Basiri, A; Hajilooi, M; Roshanaei, G; Rajabi, G; Solgi, G

    2015-05-01

    Immunologic factors are reliable markers for allograft monitoring, because of their seminal role in rejection process. One of these factors is the immunoglobulin (Ig)A anti-Fab of the IgG antibody. This study aimed to evaluate the predictive value of pre- and posttransplant levels of this marker for kidney allograft function and survival. Sera samples of 59 living unrelated donor kidney recipients were collected before and after transplantation (days 7, 14, and 30) and investigated for IgA anti-Fab of IgG antibody levels using enzyme-linked immunosorbent assay in relation with allograft outcome. Among 59 patients, 15 cases (25%) including 10 with acute rejection and 5 with chronic rejection episodes showed graft failure during a mean of 5 years of follow-up. High posttransplant levels of IgA anti-Fab antibodies were observed more frequently in patients with stable graft function (SGF) compared with patients with graft failure (P = 2 × 10(-6)). None of patients with acute or chronic rejection episodes had high levels of IgA anti-Fab antibodies at day 30 posttransplant compared with the SGF group (P = 10(-6) and P = .01, respectively). In addition, high levels of IgA anti-Fab antibody correlated with lesser concentration of serum creatinine at 1 month posttransplantation (P = .01). Five-year graft survival was associated with high levels of pre- and posttransplant IgA anti-Fab antibodies (P = .02 and P = .003, respectively). Our findings indicate the protective effect of higher levels of IgA anti-Fab antibodies regarding to kidney allograft outcomes and long-term graft survival. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Dendritic cells support production of IgA and other non-IgM isotypes in clonal microculture.

    Science.gov (United States)

    Schrader, C E; George, A; Kerlin, R L; Cebra, J J

    1990-01-01

    Microcultures of helper T (Th) cells and a few appropriately primed murine B cells can be used to detect cognate T-B interactions which lead to clonal production of IgM, IgG1, and IgE. However, IgG2, IgG3, and IgA are very rarely expressed. We have found that the addition of dendritic cells to such cultures creates an extremely supportive environment for clones expressing IgA with other isotypes, as well as clones expressing only detectable IgA. Typically, 400 dendritic cells were added to 3000 conalbumin-specific Th cells (D10.G4.1) and 30 hapten-specific Peyer's patch (PP) B cells with antigen in 15 microliters. The response was antigen dependent and clonal. Almost half of the clones expressed only non-IgM isotypes, 43% expressed some IgA, and 14% expressed some IgG3; isotype diversity increased over time. Dendritic cells from PP and spleen were found to be equally supportive, and allowed the number of T cells required in microculture to be decreased from 3000 to 400. However, T cell proliferation was not required for the supportive effect of dendritic cells. Surface IgD-bearing cells were also found to switch to IgA production in microculture as judged by their generating clones expressing IgM along with IgA and other isotypes. Again, IgA was usually expressed only in the presence of dendritic cells. The mechanism may involve dendritic cell-induced T cell activation and/or dendritic cell factors, and is under investigation.

  12. IgA response in serum and gut secretion in sensitized mice fed with the dust mite Dermatophagoides pteronyssinus extract

    Directory of Open Access Journals (Sweden)

    Maciel M.

    2004-01-01

    Full Text Available Induced oral tolerance to mucosal-exposed antigens in immunized animals is of particular interest for the development of immunotherapeutic approaches to human allergic diseases. This is a unique feature of mucosal surfaces which represent the main contact interface with the external environment. However, the influence of oral tolerance on specific and natural polyreactive IgA antibodies, the major defense mechanism of the mucosa, is unknown. We have shown that oral administration of an extract of the dust mite Dermatophagoides pteronyssinus (Dp to primed mice caused down-regulation of IgE responses and an increase in tumor growth factor-ß secretion. In the present study, we observed that primed inbred female A/Sn mice (8 to 10 weeks old fed by gavage a total weight of 1.0-mg Dp extract on the 6th, 7th and 8th days post-immunization presented normal secretion of IL-4 and IL-10 in gut-associated lymphoid tissue and a decreased production of interferon gamma induced by Dp in the draining lymph nodes (13,340 ± 3,519 vs 29,280 ± 2,971 pg/ml. Mice fed the Dp extract also showed higher levels of serum anti-Dp IgA antibodies and an increase of IgA-secreting cells in mesenteric lymph nodes (N = 10, reflecting an increase in total fecal IgA antibodies (N = 10. The levels of secretory anti-Dp IgA antibodies increased after re-immunization regardless of Dp extract feeding. Oral tolerance did not interfere with serum or secretory IgA antibody reactivity related to self and non-self antigens. These results suggest that induction of oral tolerance to a Dp extract in sensitized mice triggered different regulatory mechanisms which inhibited the IgE response and stimulated systemic and secretory IgA responses, preserving the natural polyreactive IgA antibody production.

  13. Correlation between saliva IgA level and T cell CD4+ in HIV/AIDS patients

    Directory of Open Access Journals (Sweden)

    Irna Sufiawati

    2007-07-01

    Full Text Available Background: HIV infection appears to have direct effects on oral mucosal immunity, cellular and humoral. Antibody secretion, especially salivary immunoglobulin A (IgA, is a useful indicator of mucosal immune function. This immune system component is recognized as an important first-line of defence against pathogens which colonize and invade mucosal surfaces in the oral cavity. Objectives: The purpose of this study was to investigate salivary IgA levels and to determine its correlation with CD4+ T-cell counts among HIV-infected patients in Pokdisus AIDS Cipto Mangunkusomo Hospital Jakarta. Methods: The design study was using a cross-sectional study. Whole paraffin-wax-stimulated saliva was collected from 103 HIV-infected patients and 30 healthy individuals. Saliva was collected using the spitting method. Salivary IgA levels were determined by the immunoturbidimetry method using the Behring Turbitimer Analyser. CD4+ T-cell counts were analyzed by flow cytometry. Results: Salivary IgA levels were 141.55 ± 83.23 (HIV group and 97.24 ± 38.25 (healthy individuals. The Mann-Whitney U test showed salivary IgA levels were significantly higher in HIV/AIDS subjects compared with healthy individuals (p0.1. Conclusion: This study indicates that total salivary IgA levels were significantly higher in the HIV-infected patients compared to control, and salivary IgA level seems not to be related significantly to CD4+ T-cell counts.

  14. Transient glyco-engineering to produce recombinant IgA1 with defined N- and O-glycans in plants

    Directory of Open Access Journals (Sweden)

    Martina eDicker

    2016-01-01

    Full Text Available The production of therapeutic antibodies to combat pathogens and treat diseases such as cancer is of great interest for the biotechnology industry. The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. Compared to immunoglobulin G (IgG, less effort has been undertaken to express immunoglobulin A (IgA, which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumour activity. Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco-engineered deltaXT/FT Nicotiana benthamiana plants. Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. Our data demonstrate that deltaXT/FT Nicotiana benthamiana plants can be engineered towards the production of recombinant IgA1 with defined human-type N- and O-linked glycans.

  15. Binding and transepithelial transport of immunoglobulins by intestinal M cells: demonstration using monoclonal IgA antibodies against enteric viral proteins

    OpenAIRE

    1989-01-01

    M cells of intestinal epithelia overlying lymphoid follicles endocytose luminal macromolecules and microorganisms and deliver them to underlying lymphoid tissue. The effect of luminal secretory IgA antibodies on adherence and transepithelial transport of antigens and microorganisms by M cells is unknown. We have studied the interaction of monoclonal IgA antibodies directed against specific enteric viruses, or the hapten trinitrophenyl (TNP), with M cells. To produce monospecific IgA antibodie...

  16. Anxiety and depression with neurogenesis defects in exchange protein directly activated by cAMP 2-deficient mice are ameliorated by a selective serotonin reuptake inhibitor, Prozac

    Science.gov (United States)

    Zhou, L; Ma, S L; Yeung, P K K; Wong, Y H; Tsim, K W K; So, K F; Lam, L C W; Chung, S K

    2016-01-01

    Intracellular cAMP and serotonin are important modulators of anxiety and depression. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) also known as Prozac, is widely used against depression, potentially by activating cAMP response element-binding protein (CREB) and increasing brain-derived neurotrophic factor (BDNF) through protein kinase A (PKA). However, the role of Epac1 and Epac2 (Rap guanine nucleotide exchange factors, RAPGEF3 and RAPGEF4, respectively) as potential downstream targets of SSRI/cAMP in mood regulations is not yet clear. Here, we investigated the phenotypes of Epac1 (Epac1−/−) or Epac2 (Epac2−/−) knockout mice by comparing them with their wild-type counterparts. Surprisingly, Epac2−/− mice exhibited a wide range of mood disorders, including anxiety and depression with learning and memory deficits in contextual and cued fear-conditioning tests without affecting Epac1 expression or PKA activity. Interestingly, rs17746510, one of the three single-nucleotide polymorphisms (SNPs) in RAPGEF4 associated with cognitive decline in Chinese Alzheimer's disease (AD) patients, was significantly correlated with apathy and mood disturbance, whereas no significant association was observed between RAPGEF3 SNPs and the risk of AD or neuropsychiatric inventory scores. To further determine the detailed role of Epac2 in SSRI/serotonin/cAMP-involved mood disorders, we treated Epac2−/− mice with a SSRI, Prozac. The alteration in open field behavior and impaired hippocampal cell proliferation in Epac2−/− mice were alleviated by Prozac. Taken together, Epac2 gene polymorphism is a putative risk factor for mood disorders in AD patients in part by affecting the hippocampal neurogenesis. PMID:27598965

  17. Differences in serum IgA responses to HIV-1 gp41 in elite controllers compared to viral suppressors on highly active antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Rafiq Nabi

    Full Text Available Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV replication in elite controllers (EC remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC and viremic noncontrollers (HN on highly active antiretroviral therapy (HAART. Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays. Measurements for IgG were performed in parallel. EC were found to have stronger p24- and V1V2-specific IgG responses than HN, but there were no IgG differences for EC and HC. In contrast, IgA in EC serum bound more frequently to gp160 and gag proteins than IgA in HC or HN. The avidity of anti-gp41 IgA was also greater in EC, and these subjects had stronger IgA responses to the gp41 heptad repeat region 1 (HR1, a reported target of anti-bacterial RNA polymerase antibodies that cross react with gp41. However, EC did not demonstrate greater IgA responses to E. coli RNA polymerase or to peptides containing the shared LRAI sequence, suggesting that most of their HR1-specific IgA antibodies were not induced by intestinal microbiota. In both EC and HAART recipients, the concentrations of HIV-specific IgG were greater than HIV-specific IgA, but their avidities were comparable, implying that they could compete for antigen. Exceptions were C1 peptides and V1V2 loops. IgG and IgA responses to these antigens were discordant, with IgG reacting to V1V2, and IgA reacting to C1, especially in EC. Interestingly, EC with IgG hypergammaglobulinemia had greater HIV-specific IgA and IgG responses than EC with normal total IgG levels. Heterogeneity in EC antibody responses may therefore be due to a more focused HIV-specific B cell response in some of these individuals. Overall, these data suggest that development of

  18. A systematic review of anti-rotavirus serum IgA antibody titer as a potential correlate of rotavirus vaccine efficacy.

    Science.gov (United States)

    Patel, Manish; Glass, Roger I; Jiang, Baoming; Santosham, Mathuram; Lopman, Ben; Parashar, Umesh

    2013-07-15

    Identifying an immunological correlate of protection for rotavirus vaccines (Rotarix [RV1] and RotaTeq [RV5]) would substantially facilitate testing of interventions for improving efficacy in developing countries and evaluating additional candidate rotavirus vaccines. We accessed PubMed and ClinicalTrials.gov to identify immunogenicity and efficacy trials for RV1 and RV5 to correlate anti-rotavirus serum immunoglobulin A (IgA) antibody titers vs efficacy in regions stratified by all-cause under-5 mortality rates (u5MR). We established a cutoff point for IgA geometric mean concentration or titer (GMC) that predicted lower efficacy and calculated pooled vaccine efficacy among countries with high vs low IgA titers. We observed an inverse correlation between u5MR and IgA titers for RV1 (r(2) = 0.72; P efficacy and IgA titers for both vaccines (r(2) = 0.56; P = .005). Postimmunization anti-rotavirus IgA GMC vaccine efficacy. Efficacy during first 2 years of life was significantly lower among countries with IgA GMC 90 (85%; 95% CI, 82-88). We observed a significant correlation between IgA titers and rotavirus vaccine efficacy and hypothesize that a critical level of IgA antibody titer is associated with a sufficient level of sustained protection after rotavirus vaccination.

  19. Influência da seletividade de atenção no desenvolvimento da percepção corporal de crianças com deficiência motora Influence of selectivity of attention on the development of body awareness in children with motor deficiencies

    Directory of Open Access Journals (Sweden)

    ALS Bertoldi

    2007-08-01

    Full Text Available OBJETIVO: Verificar a influência do uso de estratégias cognitivas de direcionamento de atenção (dicas de aprendizagem no desenvolvimento de variáveis da percepção corporal de crianças com deficiência motora. MÉTODO: 22 sujeitos de 7 a 10 anos, de ambos os sexos, foram selecionados por similaridade de características funcionais e divididos aleatoriamente em dois grupos: CD (com dicas n= 11 e SD (sem dicas n= 11. Os grupos CD e SD desenvolveram os procedimentos metodológicos 1 (PM1 com direcionamento de atenção através do uso de dicas de aprendizagem e 2 (PM2 sem direcionamento de atenção respectivamente, durante 2 semanas com freqüência de 2 sessões semanais e duração de 50 minutos cada. Foram realizados pré-testes, pós-testes e testes de retenção com os seguintes instrumentos: teste de identificação das partes do corpo, teste de percepção cinética e teste de percepção crítica das partes do corpo. Foram utilizados a análise de variância multivariada MANOVA e o teste de comparações múltiplas de Tukey para analisar possíveis diferenças significativas. RESULTADOS: Os resultados indicaram diferenças significativas (pOBJECTIVE: To investigate the influence of using cognitive strategies for directing attention (learning cues on the development of body awareness in children with motor deficiencies. METHOD: Twenty-two children of both sexes, aged 7 to 10 years, were selected based on their similar functional characteristics and were divided randomly into two groups: cue group (n= 11 and no cue group (n= 11. The cue group followed a methodological sequence in which attention was directed using learning cues, while the no cue group followed a different sequence, in which there was no directing of attention. These programs were followed for two weeks, with two sessions of 50 minutes each per week. Pre, post and retention tests were applied using the following instruments: body part identification test, kinetic

  20. Major histocompatibility complex class III genes and susceptibility to immunoglobulin A deficiency and common variable immunodeficiency.

    OpenAIRE

    Volanakis, J E; Zhu, Z B; Schaffer, F M; Macon, K J; Palermos, J; Barger, B O; Go, R; Campbell, R D; Schroeder, H W; Cooper, M D

    1992-01-01

    We have proposed that significant subsets of individuals with IgA deficiency (IgA-D) and common variable immunodeficiency (CVID) may represent polar ends of a clinical spectrum reflecting a single underlying genetic defect. This proposal was supported by our finding that individuals with these immunodeficiencies have in common a high incidence of C4A gene deletions and C2 rare gene alleles. Here we present our analysis of the MHC haplotypes of 12 IgA-D and 19 CVID individuals from 21 families...

  1. Higher HOMA-IR index and correlated factors of insulin resistance in patients with IgA nephropathy.

    Science.gov (United States)

    Yang, Yue; Wei, Ri-Bao; Wang, Yuan-da; Zhang, Xue-Guang; Rong, Na; Tang, Li; Chen, Xiang-Mei

    2012-11-01

    To investigate the index of homeostasis model of insulin resistance (HOMA-IR) in IgA nephropathy (IgAN) patients, and to explore the possible correlated factors contributing to insulin resistance (IR) within these patients. There were 255 IgAN patients and 45 membranous nephropathy (MN) patients in our database. We identified 89 IgAN subjects and 21 MN subjects without diabetes and undergoing glucocorticoid therapy for at least 6 months. Data regarding physical examination, blood chemistry and renal pathology were collected from 89 IgAN subjects and 21 MN subjects. Then 62 IgAN patients and 19 MN patients with chronic kidney disease (CKD) Stage 1 - 2 were selected for the comparison of HOMA-IR index, 89 IgAN patients were selected for multiple regression analysis to test for correlated factors of HOMA-IR index with IgAN patients. Comparison between IgAN and MN show that HOMA-IR index was significantly higher in IgAN patients with CKD Stage 1 - 2. After logarithmic transformation with urine protein (UPr), Ln(UPr) (b = 0.186, p = 0.008), eGFR (b = -0.005, p = 0.014), > 50% of glomeruli with mesangial hypercellularity (b = 0.285, p = 0.027) and body mass index (BMI) (b = 0.039, p = 0.008) were correlated factors of HOMA-IR index in the multiple regression analysis. IgAN patients had higher HOMA-IR index compared with MN in the stages of CKD 1 - 2. For IgAN patients, more UPr, lower eGFR, > 50% of glomeruli with mesangial hypercellularity and higher BMI were correlated with IR.

  2. The need for direct immunofluorescence in the diagnosis of IgA bullous dermatosis

    OpenAIRE

    Chang, Daniel

    2012-01-01

    A dermatose bolhosa por imunoglobulina da classe A linear (DbIgA) do adulto é uma doença autoimune rara caracterizada por formação de bolhas subepidérmicas e depósito linear de imunoglobulina da classe A (IgA) na zona da membrana basal (ZMB). Por possuir aspectos clínicos e histológicos semelhantes a outras dermatoses bolhosas, principalmente a dermatite herpetiforme e o penfigoide bolhoso, faz-se necessária a realização de imunofluorescência direta para confirmação diagnóstica. Apresenta-se ...

  3. Pyoderma gangrenosum associated with subcorneal pustular dermatosis and IgA myeloma.

    LENUS (Irish Health Repository)

    Ahmad, K

    2012-01-31

    We report a 57-year-old woman with a 12-year history of ulcerative pyoderma gangrenosum (PG). Five years after the onset of PG, she developed subcorneal pustular dermatosis (SPD) and biclonal IgA and IgG gammopathy. She developed PG at two bone-marrow biopsy sites, showing pathergy. Finally, she developed multiple myeloma. Although PG and SPD may occur without associated underlying malignancy, these patients should be followed up for any prospective malignancy because of the association between these disorders.

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... increased need for iron during growth spurts. Older adults, especially those over age ... athletes. Athletes, especially young females, are at risk for iron deficiency. Endurance ...

  5. Iodine deficiency disorders

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S M [Pakistan Council for Science and Technology, Islamabad (Pakistan)

    1994-12-31

    Iodine deficiency (IDD) is one of the common problem in the diet. Iodine deficiency as prevalence of goiter in population occurs in the mountainous areas. There is consensus that 800 million people are at risk of IDD from living in iodine deficient area and 190 million from goiter. Very high prevalence of IDD in different parts of the world are striking. It has generally observed that in iodine-deficient areas about 50% are affected with goiter, 1-5% from cretinsim and 20% from impaired mental and/or mortor function. (A.B.).

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our ... more information about Donor Iron Deficiency Study - Red Blood Cells ...

  7. Potent neutralizing serum immunoglobulin A (IgA) in human immunodeficiency virus type 2-exposed IgG-seronegative individuals

    DEFF Research Database (Denmark)

    Lizeng, Q; Nilsson, C; Sourial, S

    2004-01-01

    Links Potent neutralizing serum immunoglobulin A (IgA) in human immunodeficiency virus type 2-exposed IgG-seronegative individuals.Lizeng Q, Nilsson C, Sourial S, Andersson S, Larsen O, Aaby P, Ehnlund M, Bjorling E. Research Center, South Hospital, Stockholm, Sweden. The mechanisms behind...... the resistance to human immunodeficiency virus type 2 (HIV-2) infection are still not fully understood. In the present study, we explored the HIV-2-specific humoral serum immunoglobulin A (IgA) immune response in HIV-2-exposed IgG-seronegative (EGSN) individuals. Serum samples from heterosexual EGSN individuals...... and their known HIV-2-infected partners, as well as controls originating from Guinea-Bissau in Africa, were studied. Antibody reactivity to native and recombinant envelope glycoproteins was investigated, and the capacity of purified serum IgA to neutralize HIV-2(SBL6669) was tested. Our results showed that 16...

  8. Intermittent fasting promotes bacterial clearance and intestinal IgA production in Salmonella typhimurium-infected mice.

    Science.gov (United States)

    Godínez-Victoria, M; Campos-Rodriguez, R; Rivera-Aguilar, V; Lara-Padilla, E; Pacheco-Yepez, J; Jarillo-Luna, R A; Drago-Serrano, M E

    2014-05-01

    The impact of intermittent fasting versus ad libitum feeding during Salmonella typhimurium infection was evaluated in terms of duodenum IgA levels, bacterial clearance and intestinal and extra-intestinal infection susceptibility. Mice that were intermittently fasted for 12 weeks or fed ad libitum were infected with S. typhimurium and assessed at 7 and 14 days post-infection. Next, we evaluated bacterial load in the faeces, Peyer's patches, spleen and liver by plate counting, as well as total and specific intestinal IgA and plasmatic corticosterone levels (by immunoenzymatic assay) and lamina propria IgA levels in plasma cells (by cytofluorometry). Polymeric immunoglobulin receptor, α- and J-chains, Pax-5 factor, pro-inflammatory cytokine (tumour necrosis factor-α and interferon-γ) and anti-inflammatory cytokine (transforming growth factor-β) mRNA levels were assessed in mucosal and liver samples (by real-time PCR). Compared with the infected ad libitum mice, the intermittently fasted infected animals had (1) lower intestinal and systemic bacterial loads; (2) higher SIgA and IgA plasma cell levels; (3) higher mRNA expression of most intestinal parameters; and (4) increased or decreased corticosterone levels on day 7 and 14 post-infection, respectively. No contribution of liver IgA was observed at the intestinal level. Apparently, the changes following metabolic stress induced by intermittent fasting during food deprivation days increased the resistance to S. typhimurium infection by triggering intestinal IgA production and presumably, pathogen elimination by phagocytic inflammatory cells. © 2014 John Wiley & Sons Ltd.

  9. Extracapillary proliferation in IgA nephropathy; recent findings and new ideas.

    Science.gov (United States)

    Nasri, Hamid; Mubarak, Muhammed

    2015-01-01

    IgA nephropathy (IgAN) is an autoimmune disorder and is the most common form of primary glomerulonephritis (GN) worldwide. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. It is a slowly progressing disorder that leads to end-stage renal disease (ESRD) in up to 50% of the patients within 25 years of the onset of the disease. IgAN is defined by predominant IgA deposition in the mesangial area on immunofluorescence (IF) microscopy. Its histology varies from mild focal segmental proliferation of mesangial cells to severe diffuse global proliferation with extracapillary proliferation (crescent formation). The Oxford classification, designed in 2009, is a new classification for the evaluation of morphologic lesions of IgAN. This classification, containing four pathology variables, was found to have prognostic implications. The variables included are mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S) and the proportion of interstitial fibrosis and tubular atrophy (T). However, crescents were not included in the Oxford classification. In this mini-review, we describe the recent publications about the significance of extracapillary proliferation in IgAN and we conclude that, there is much controversy about the role of extracapillary proliferation as a significant prognostic factor in IgAN. Hence, it is important to re-consider crescents in IgAN patients. Therefore, we suggest further investigations on this aspect of IgAN disease.

  10. Bilateral Testicular Infarction from IgA Vasculitis of the Spermatic Cords

    Directory of Open Access Journals (Sweden)

    Mazen Toushan

    2017-01-01

    Full Text Available A 51-year-old man with type 2 diabetes mellitus and chronic obstructive pulmonary disease presented to the emergency room with increasing bilateral leg pain, rash, and scrotal swelling with pain. Skin biopsy from his thigh revealed IgA-associated vasculitis. Due to hematuria, a renal biopsy was performed and showed an IgA glomerulonephritis with focal fibrinoid necrosis and neutrophil accumulation. Bilateral orchiectomies were performed in two separate procedures ten and thirteen days after the renal biopsy, as a result of uncontrolled abscess formation in testicles. Microscopically, both testicles revealed large abscess formation destroying almost the entire testicular parenchyma without tumor cells. Spermatic cord margins were further scrutinized microscopically to show bilateral vasculitis in many small size vessels, confirmed by positive endothelial staining for IgA. Some of the affected arteries revealed central organizing thrombi with recanalization features, highly suggestive of vasculitis-associated thrombi formation, resulting in testicular ischemic infarction and abscess formation. We conclude that this adult patient developed a severe form of Henoch-Schönlein purpura, with vasculitis affecting multiple organs, including the most serious and unusual complication of bilateral testicular infarction.

  11. IgA nephropathy: A clinicopathologic study from two centers in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Khawajah Azhar

    2010-01-01

    Full Text Available A total of 42 patients, who were diagnosed to have primary Immunoglobulin A neph-ropathy (IgAN at the King Abdul Aziz University Hospital and King Faisal Hospital, Jeddah over the last seven years, were studied. The objective was to analyze their clinical and pathological fea-tures and to classify them according to Hass Classification by using light, immunofluorescence and electron microscopy. Majority of the study cases were males in the second, third and fourth decades of life. Hematuria was the most common clinical complaint followed by proteinuria. There were varying degrees of mesangial proliferation. Majority of the cases presented with class-2 followed by class-3. Immunofluorescence demonstrated diffuse granular deposition of IgA in the glomerular mesangium in majority of the cases. Ultrastructural analysis showed electron dense deposits within the matrix of the mesangium and paramesangium in majority of the cases. Sub-endothelial deposits and mesangial interposition were demonstrated in few cases. Extensive effacement with fusion of the visceral epithelial foot processes was detected in only few patients while focal effacement was demonstrated in many cases. Irregularities of the glomerular basement membrane were seen in some cases. We conclude that IgA nephropathy is an immune-complex glomerular disease, which occurs at all ages and with higher frequency in males and presents mostly with hematuria and proteinuria. Public health awareness is seriously needed to perform the investigations at an early stage.

  12. Radioimmunoassay of IgM, IgG, and IgA brucella antibodies

    International Nuclear Information System (INIS)

    Parrett, D.; Nielson, K.H.; White, R.G.; Payne, D.J.H.

    1977-01-01

    A radioimmunoassay (R.I.A.) has been devised to measure the serum antibody against Brucella abortus in each of the immunoglobulin classes IgM, IgG, and IgA. This test was applied to 46 sera from individuals with various clinical types of brucellosis, and the results were compared with the results of conventional direct and indirect agglutination and complement-fixation tests. The R.I.A. provided a highly sensitive primary-type assay which avoided the difficulties with blocking or non-agglutinating antibody, and thus has many advantages in the diagnosis of acute and chronic stages of brucella infection in man. The R.I.A. was successful in detection of antibody in many instances in which conventional serological tests were negative, and such antibody could (if IgM) be associated with acute or (if IgG or IgA) with chronic cases of brucellosis. One case in which B.abortus was isolated by blood culture but which failed to yield antibody by conventional tests, nevertheless showed substantial levels of IgM and IgG antibody by R.I.A. In other cases the R.I.A. test helped to eliminate the diagnosis of brucellosis by revealing absent or low antibody levels. (author)

  13. Prevalence of IgA Antibodies to Endomysium and Tissue Transglutaminase in Primary Biliary Cirrhosis

    Directory of Open Access Journals (Sweden)

    Helen R Gillett

    2000-01-01

    Full Text Available The association between celiac disease and primary biliary cirrhosis has been described in several case reports and small screening studies, with varying prevalence rates. Stored sera from 378 patients with primary biliary cirrhosis were tested for immunoglobulin (Ig A endomysium and tissue transglutaminase antibodies. Ten patients were positive for both antibodies (2.6%; five of these patients had had small bowel biopsies confirming celiac disease. A further 44 patients (11.6% had raised titres of IgA tissue transglutaminase antibody but were negative for IgA endomysium antibody. The increased prevalence of celiac-related antibodies in patients with primary biliary cirrhosis suggests that the two conditions are associated, although the reason for the association remains unclear. Patients with primary biliary cirrhosis should be considered to be at high risk for celiac disease. Although liver biochemistry does not improve when these patients are fed a gluten-free diet, the complications of untreated celiac disease warrant the identification and treatment of the condition in this population.

  14. IgA nephropathy in systemic lupus erythematosus patients: case report and literature review

    Directory of Open Access Journals (Sweden)

    Leonardo Sales da Silva

    2016-06-01

    Full Text Available Abstract Systemic erythematosus lupus (SLE is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non‐lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN, the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1,280, nuclear fine speckled pattern, and anticardiolipin IgM and 280 U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non‐SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in the short and long term.

  15. Lacrimal secretory IgA in active posterior uveitis induced by Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Maria Isabel Lynch

    2004-12-01

    Full Text Available It is quite difficult to diagnose active toxoplasmosis in patients with ocular toxoplasmosis. Active posterior uveitis presumably due to Toxoplasma gondii infection (APUPT is seldom produced during a prime-infection; hence most patients do not show high IgM antibodies. High levels of IgA have been described in active toxoplasmosis. The purpose of this study was to investigate possible association between APUPT and the specific anti-parasite sIgA in tears. The study was carried out as case-control. Tears of 25 clinically confirmed APUPT patients and 50 healthy control subjects were analyzed. All were IgG seropositive. Specific sIgA was determined by ELISA assay using T. gondii RH strain crude extract. Anti-T. gondii sIgA was found in 84% of the cases and in 22% of the control subjects. The intensity of the reaction was higher in APUPT cases (P = 0.007. There was strong association between APUPT patients and lacrimal sIgA (odds-ratio 18.61, P = 0.0001. ELISA test sensitivity was 84% and specificity 78% . Our data suggest that anti-T.gondii secretory IgA found in tears may become an important marker for active ocular toxoplasmosis.

  16. Quantitation of sperm bindable IgA and IgG in seminal fluid.

    Science.gov (United States)

    Howe, S E; Lynch, D M

    1986-05-01

    Seminal fluid and serum from 95 infertile males were assayed for sperm bindable immunoglobulins using an indirect ELISA with whole target sperm. The ELISA method was compared to seminal fluid and serum immobilization and agglutination assays (functional assays). In this infertile group, the ELISA assay was positive in 22% of seminal fluids (greater than 1.2 fg IgA/sperm and greater than 0.3 fg IgG/sperm). The seminal fluid antibodies were IgA and had an accompanying elevated IgG component in 78% of patients. There was a 96% correlation between negative seminal fluid functional assays and negative ELISA, and a 95% correlation between positive seminal fluid functional assays and positive ELISA. Positive serum sperm antibody tests were found in 71% of the infertile males with positive seminal fluid sperm antibodies, but 29% of the infertile males with strongly positive IgA seminal fluid sperm antibodies showed normal levels of serum sperm antibodies by either ELISA or functional assays. The ELISA method gives reproducible quantitation of sperm antibodies in seminal fluid and correlates well with accepted functional assays. Comparisons with serum sperm antibody assays suggests that seminal fluid sperm antibody analysis complements the serum analysis of sperm antibodies.

  17. Lacrimal secretory IgA in active posterior uveitis induced by Toxoplasma gondii.

    Science.gov (United States)

    Lynch, Maria Isabel; Cordeiro, Francisco; Ferreira, Silvana; Ximenes, Ricardo; Oréfice, Fernando; Malagueño, Elizabeth

    2004-12-01

    It is quite difficult to diagnose active toxoplasmosis in patients with ocular toxoplasmosis. Active posterior uveitis presumably due to Toxoplasma gondii infection (APUPT) is seldom produced during a prime-infection; hence most patients do not show high IgM antibodies. High levels of IgA have been described in active toxoplasmosis. The purpose of this study was to investigate possible association between APUPT and the specific anti-parasite sIgA in tears. The study was carried out as case-control. Tears of 25 clinically confirmed APUPT patients and 50 healthy control subjects were analyzed. All were IgG seropositive. Specific sIgA was determined by ELISA assay using T. gondii RH strain crude extract. Anti-T. gondii sIgA was found in 84% of the cases and in 22% of the control subjects. The intensity of the reaction was higher in APUPT cases (P = 0.007). There was strong association between APUPT patients and lacrimal sIgA (odds-ratio 18.61, P = 0.0001). ELISA test sensitivity was 84% and specificity 78%. Our data suggest that anti-T.gondii secretory IgA found in tears may become an important marker for active ocular toxoplasmosis.

  18. Complement factor H-related proteins in IgA nephropathy-sometimes a gentle nudge does the trick.

    Science.gov (United States)

    Thurman, Joshua M; Laskowski, Jennifer

    2017-10-01

    Complement activation probably contributes to glomerular inflammation and damage in IgA nephropathy. In this issue, 2 groups report that levels of factor H-related protein 1 are elevated in patients with IgA nephropathy and correlate with disease progression. These studies provide new evidence that the complement cascade is important to the pathogenesis of this disease. These results also suggest that factor H-related protein 1 levels may be useful for identifying those patients at high risk of disease progression. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  19. The Mucosal Adjuvant Cholera Toxin B Instructs Non-Mucosal Dendritic Cells to Promote IgA Production Via Retinoic Acid and TGF-β

    NARCIS (Netherlands)

    A.K. Gloudemans (Anouk); M. Plantinga (Maud); M. Guilliams (Martin); M.A. Willart (Monique); A. Ozir-Fazalalikhan (Arifa); A. van der Ham (Alwin); L. Boon (Louis); N.L. Harris (Nicola); H. Hammad (Hamida); H.C. Hoogsteden (Henk); M. Yazdanbakhsh (Maria); R.W. Hendriks (Rudi); B.N.M. Lambrecht (Bart); H.H. Smits (Hermelijn)

    2013-01-01

    textabstractIt is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... exploring about iron-deficiency anemia. Read more New treatments for disorders that lead to iron-deficiency anemia. We are ... and other pathways. This could help develop new therapies for conditions that ... behavior, thinking, and mood during adolescence. Treating anemia in ...

  1. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... loss and lead to iron-deficiency anemia. Common causes of blood loss that lead to iron-deficiency anemia include: Bleeding in your GI tract, from an ulcer, colon cancer, or regular use of medicines such as aspirin ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia. Search the NIH Research Portfolio Online Reporting Tools (RePORT) to learn about research that ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... blocks the intestine from taking up iron. Other medical conditions Other medical conditions that may lead to iron-deficiency anemia ... daily amount of iron. If you have other medical conditions that cause iron-deficiency anemia , such as ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. Blood tests to screen for ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Are you curious about how inflammation from chronic diseases can cause iron-deficiency anemia? Read more When there is ... DBDR) is a leader in research on the causes, prevention, and treatment of blood diseases, including iron-deficiency anemia. Search the NIH Research ...

  7. Nutritional iron deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.; Hurrell, R.F.

    2007-01-01

    Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Topics section only, or the News and Resources section. NHLBI Entire Site NHLBI Entire Site Health ... español Iron-deficiency anemia is a common type of anemia that occurs if you do not have enough iron in your body. People with mild or moderate iron-deficiency anemia ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron is too ... clamping of your newborn’s umbilical cord at the time of delivery. This may help prevent iron-deficiency ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ... check the size of your liver and spleen. Blood tests Based on results from blood tests to screen ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children who do not consume the daily recommended amount of iron. Read less Participate in NHLBI Clinical Trials We lead or sponsor many studies related to iron-deficiency anemia. See if you ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... en español Iron-deficiency anemia is a common type of anemia that occurs if you do not ... iron-deficiency anemia and help rule out other types of anemia. Treatment will explain treatment-related complications ...

  14. Iron deficiency in childhood

    NARCIS (Netherlands)

    Uijterschout, L.

    2015-01-01

    Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia. Return to Signs, Symptoms, and Complications to review signs and symptoms as well as complications from iron-deficiency ... NIH]) Heavy Menstrual Bleeding (Centers for Disease Control and ... Dietary Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library ...

  16. Iron deficiency anemia

    Science.gov (United States)

    Anemia - iron deficiency ... iron from old red blood cells. Iron deficiency anemia develops when your body's iron stores run low. ... You may have no symptoms if the anemia is mild. Most of the time, ... slowly. Symptoms may include: Feeling weak or tired more often ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, ... you are experiencing side effects such as a bad metallic taste, vomiting, diarrhea, constipation, or upset stomach. ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... how we are using current research and advancing research to prevent iron-deficiency anemia. Participate in NHLBI Clinical Trials will explain our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and Complications ...

  19. Clinicopathological Features to Predict Progression of IgA Nephropathy with Mild Proteinuria.

    Science.gov (United States)

    Chen, Ding; Liu, Jian; Duan, Shuwei; Chen, Pu; Tang, Li; Zhang, Li; Feng, Zhe; Cai, Guangyan; Wu, Jie; Chen, Xiangmei

    2018-03-06

    In the past, little attention has been paid to patients with IgA nephropathy (IgAN) who had minimal proteinuria upon the onset. The aim of this study was to analyze the clinicopathological features and the prognostic factors in patients with IgA nephropathy. Data of patients that had their first renal biopsy in our hospital and were diagnosed with primary IgAN with proteinuria 1995 to December 2014 were retrospectively examined. Clinical records of the clinicopathological features, renal function, and proteinuria were collected and investigated. The factors affecting the renal function and proteinuria were analyzed by Cox regression. The predictive efficiencies of clinical and pathological models were evaluated by Harrell concordance index (C-index). A total of 506 patients with IgA nephropathy were included in this study. (1) Baseline proteinuria greater than 0.5 g/d was positively associated with Oxford M, S, and T lesions. eGFR less than 90 mL/min/1.73 m2 were positively associated with Oxford T. (2) In the follow-up with a median of 50 months, 82 patients (16.2%) achieved complete clinical remission (CCR), whereas 54 patients (10.6%) showed an increase in creatinine by more than 50% (not progressing to end-stage renal disease). The cumulative proportion of creatinine increased >50%, and the values obtained by life-table analysis in 10, 15, and 20 years were 15%, 21%, and 22%, respectively. Significant differences were found in baseline age, proteinuria, and Oxford T between the group of creatinine increase >50% and the CCR group. (4) Multivariate COX regression showed that baseline age and proteinuria > 0.5 g/d were independent risk factors of adverse outcome. C-index suggested that the clinical model was more effective than the pathological models in predicting endpoint events. (5) Effect of the mean value during the follow-up on adverse endpoint events: Multivariate COX regression found that the mean proteinuria during follow-up was an independent influencing

  20. Clinicopathological Features to Predict Progression of IgA Nephropathy with Mild Proteinuria

    Directory of Open Access Journals (Sweden)

    Ding Chen

    2018-03-01

    Full Text Available Background/Aims: In the past, little attention has been paid to patients with IgA nephropathy (IgAN who had minimal proteinuria upon the onset. The aim of this study was to analyze the clinicopathological features and the prognostic factors in patients with IgA nephropathy. Methods: Data of patients that had their first renal biopsy in our hospital and were diagnosed with primary IgAN with proteinuria <1 g/d from January 1995 to December 2014 were retrospectively examined. Clinical records of the clinicopathological features, renal function, and proteinuria were collected and investigated. The factors affecting the renal function and proteinuria were analyzed by Cox regression. The predictive efficiencies of clinical and pathological models were evaluated by Harrell concordance index (C-index. Results: A total of 506 patients with IgA nephropathy were included in this study. (1 Baseline proteinuria greater than 0.5 g/d was positively associated with Oxford M, S, and T lesions. eGFR less than 90 mL/min/1.73 m2 were positively associated with Oxford T. (2 In the follow-up with a median of 50 months, 82 patients (16.2% achieved complete clinical remission (CCR, whereas 54 patients (10.6% showed an increase in creatinine by more than 50% (not progressing to end-stage renal disease. The cumulative proportion of creatinine increased >50%, and the values obtained by life-table analysis in 10, 15, and 20 years were 15%, 21%, and 22%, respectively. Significant differences were found in baseline age, proteinuria, and Oxford T between the group of creatinine increase >50% and the CCR group. (4 Multivariate COX regression showed that baseline age and proteinuria > 0.5 g/d were independent risk factors of adverse outcome. C-index suggested that the clinical model was more effective than the pathological models in predicting endpoint events. (5 Effect of the mean value during the follow-up on adverse endpoint events: Multivariate COX regression found that the

  1. Decreased IgA+ B Cells Population and IgA, IgG, IgM Contents of the Cecal Tonsil Induced by Dietary High Fluorine in Broilers

    Directory of Open Access Journals (Sweden)

    Kangping Wang

    2013-05-01

    Full Text Available Fluoride is an environmental and industrial pollutant that affects various organs in humans and animals. The cecal tonsil is an important component of the mucosal immune system and performs important and unique immune functions. In the present study, we investigated the effects of dietary high fluorine on the quantities of IgA+ B cells in the cecal tonsil by immunohistochemistry, and the immunoglobulin A (IgA, immunoglobulin G (IgG and immunoglobulin M (IgM contents in the cecal tonsil by ELISA. A total of 280 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet (fluorine 22.6 mg/kg or the same diet supplemented with 400, 800 and 1,200 mg/kg fluorine (high fluorine groups I, II and III in the form of sodium fluoride, respectively, throughout a 42-day experimental period. The results showed that the quantities of IgA+ B cells were lower (p < 0.05 or p < 0.01 and the IgA, IgG, and IgM contents were decreased (p < 0.05 or p < 0.01 in high fluorine groups II and III in comparison with those of control group. It was concluded that dietary fluorine, in the 800–1,200 mg/kg range, could reduce the numbers of the IgA+ B cells and immunoglobulin contents in the cecal tonsil, implying the local mucosal immune function was ultimately impacted in broilers.

  2. Eesti välisminister jätab ELis ainsana Rice'iga kohtumata / Toomas Sildam

    Index Scriptorium Estoniae

    Sildam, Toomas, 1961-

    2005-01-01

    Seoses Rein Langi ametisse astumisega 22. veebr., ei jõua ta EL-i välisministrite kohtumisele USA välisministri Condoleezza Rice'iga ega NATO Nõukogu istungile. Lisa: Kaks nädalat välisministrita

  3. Label Free QCM Immunobiosensor for AFB1 Detection Using Monoclonal IgA Antibody as Recognition Element

    Directory of Open Access Journals (Sweden)

    Özlem Ertekin

    2016-08-01

    Full Text Available This study introduces the use of an IgA isotype aflatoxin (AF specific monoclonal antibody for the development of a highly sensitive Quartz Crystal Microbalance (QCM immunobiosensor for the detection of AF in inhibitory immunoassay format. The higher molecular weight of IgA antibodies proved an advantage over commonly used IgG antibodies in label free immunobiosensor measurements. IgA and IgG antibodies with similar affinity for AF were used in the comparative studies. Sensor surface was prepared by covalent immobilization of AFB1, using self assembled monolayer (SAM formed on gold coated Quartz Crystal, with 1-Ethyl-3-(3-dimethylaminopropyl carbodiimide/N-hydroxy succinimide (EDC/NHS method using a diamine linker. Nonspecific binding to the surface was decreased by minimizing the duration of EDC/NHS activation. Sensor surface was chemically blocked after AF immobilization without any need for protein blocking. This protein free sensor chip endured harsh solutions with strong ionic detergent at high pH, which is required for the regeneration of the high affinity antibody-antigen interaction. According to the obtained results, the detection range with IgA antibodies was higher than IgG antibodies in QCM immunosensor developed for AFB1.

  4. Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis

    NARCIS (Netherlands)

    Kiryluk, Krzysztof; Li, Yifu; Sanna-Cherchi, Simone; Rohanizadegan, Mersedeh; Suzuki, Hitoshi; Eitner, Frank; Snyder, Holly J.; Choi, Murim; Hou, Ping; Scolari, Francesco; Izzi, Claudia; Gigante, Maddalena; Gesualdo, Loreto; Savoldi, Silvana; Amoroso, Antonio; Cusi, Daniele; Zamboli, Pasquale; Julian, Bruce A.; Novak, Jan; Wyatt, Robert J.; Mucha, Krzysztof; Perola, Markus; Kristiansson, Kati; Viktorin, Alexander; Magnusson, Patrik K.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari; Boland, Anne; Metzger, Marie; Thibaudin, Lise; Wanner, Christoph; Jager, Kitty J.; Goto, Shin; Maixnerova, Dita; Karnib, Hussein H.; Nagy, Judit; Panzer, Ulf; Xie, Jingyuan; Chen, Nan; Tesar, Vladimir; Narita, Ichiei; Berthoux, Francois; Floege, Jürgen; Stengel, Benedicte; Zhang, Hong; Lifton, Richard P.; Gharavi, Ali G.

    2012-01-01

    IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility

  5. Intramuscular Priming and Intranasal Boosting Induce Strong Genital Immunity Through Secretory IgA in Minipigs Infected with Chlamydia trachomatis

    Science.gov (United States)

    Lorenzen, Emma; Follmann, Frank; Bøje, Sarah; Erneholm, Karin; Olsen, Anja Weinreich; Agerholm, Jørgen Steen; Jungersen, Gregers; Andersen, Peter

    2015-01-01

    International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular (IM) prime/intranasal boost vaccination strategy in a Göttingen Minipig model with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital IgA was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggests that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity and future vaccination strategies against C. trachomatis and genital pathogens in general. PMID:26734002

  6. HIV-i võib nakatunud olla iga sajas täiskasvanud eestlane / Marika Raiski

    Index Scriptorium Estoniae

    Raiski, Marika

    2005-01-01

    Vt. ka Nädaline 27. sept., lk. 7. Vastavalt Maailma Terviseorganisatsiooni (WHO) ja UNAIDS-i hinnangule on Eestis hulgaliselt registreerimata HIV-juhte ning tegelikult võib HIV-nakatunuid olla juba iga sajas täiskasvanud Eesti elanik

  7. Ganglioside-specific IgG and IgA recruit leukocyte effector functions in Guillain-Barre syndrome

    NARCIS (Netherlands)

    Sorge, N.M. van; Yuki, N.; Koga, M.; Susuki, K.; Jansen, M.D.; Kooten, C. van; Wokke, J.H.; Winkel, J.G.J. van de; Pol, W.L. van der; Berg, L.H. van den

    2007-01-01

    The capacity of ganglioside-specific autoantibodies to recruit leukocyte effector functions was studied. Serum samples from 87 patients with Guillain–Barré (GBS) or Miller Fisher syndrome (MFS), containing GM1-, GQ1b-, or GD1b-specific IgG or IgA, were tested for leukocyte activating capacity.

  8. Raised serum IgA to common cell envelope antigens supports enterobacterial inductive contribution to pathogenesis of secondary ankylosing spondylitis.

    Science.gov (United States)

    van Bohemen, C G; Weterings, E; Nabbe, A J; Mulder, C J; Goei The, H S; Zanen, H C

    1987-04-01

    Ankylosing spondylitis (AS) is closely associated with the histocompatibility antigen HLA-B27. Pathogenesis of AS is thought to involve interactions between B27 and certain enterobacterial antigens. However, enterobacterial involvement is uncertain and contested by some. The present paper demonstrates raised serum IgA to a common enterobacterial heat modifiable major outer membrane protein (h-momp; Mr 35,000) in active AS (N = 25; IgA = 1485 +/- 20) compared with controls, who were hospital patients without known arthropathies or gastro-intestinal disease (N = 12; IgA = 548 +/- 59). Serum IgG and IgM did not differ statistically. Raised serum IgA to h-momp might indicate enterobacterial antigenic stimulation from the gastro-intestinal tract and thus support an inductive contribution of enterobacterial antigens to the pathogenesis of secondary AS. It does not necessarily imply direct involvement in the pathogenesis of primary AS. H-momp appears to be a convenient tool for serological studies of AS and at present is likely to be more suitable than other bacterial antigens.

  9. Increased proportions of bacteria capable of cleaving IgA1 in the pharynx of infants with atopic disease

    DEFF Research Database (Denmark)

    Kilian, M; Husby, S; Høst, A

    1995-01-01

    , and Neisseria meningitidis, of which the first mentioned species was mainly responsible for the difference observed at the 18-mo examination. Percentage proportions of IgA1 protease-producing bacteria were significantly related to passive smoking which may stimulate the premature and more pronounced pharyngeal...

  10. Vitamin B12 deficiency

    DEFF Research Database (Denmark)

    Green, Ralph; Allen, Lindsay H; Bjørke-Monsen, Anne-Lise

    2017-01-01

    , subclinical deficiency affects between 2.5% and 26% of the general population depending on the definition used, although the clinical relevance is unclear. B12 deficiency can affect individuals at all ages, but most particularly elderly individuals. Infants, children, adolescents and women of reproductive age...... remain debated. Management depends on B12 supplementation, either via high-dose oral routes or via parenteral administration. This Primer describes the current knowledge surrounding B12 deficiency, and highlights improvements in diagnostic methods as well as shifting concepts about the prevalence, causes...

  11. Insulin-like growth factor binding protein-1 levels are increased in patients with IgA nephropathy

    International Nuclear Information System (INIS)

    Tokunaga, Koki; Uto, Hirofumi; Takami, Yoichiro; Mera, Kumiko; Nishida, Chika; Yoshimine, Yozo; Fukumoto, Mayumi; Oku, Manei; Sogabe, Atsushi; Nosaki, Tsuyoshi; Moriuchi, Akihiro; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito

    2010-01-01

    Research highlights: → IGFBP-1 mRNA over express in kidneys obtained from mice model of IgA nephropathy. → Serum IGFBP-1 levels are high in patients with IgA nephropathy. → Serum IGFBP-1 levels correlate with renal function and the severity of renal injury. -- Abstract: The mechanisms underlying the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN) are not well understood. In this study, we examined gene expression profiles in kidneys obtained from mice with high serum IgA levels (HIGA mice), which exhibit features of human IgAN. Female inbred HIGA, established from the ddY line, were used in these experiments. Serum IgA levels, renal IgA deposition, mesangial proliferation, and glomerulosclerosis were increased in 32-week-old HIGA mice in comparison to ddY animals. By microarray analysis, five genes were observed to be increased by more than 2.5-fold in 32-week-old HIGA in comparison to 16-week-old HIGA; these same five genes were decreased more than 2.5-fold in 32-week-old ddY in comparison to 16-week-old ddY mice. Of these five genes, insulin-like growth factor (IGF) binding protein (IGFBP)-1 exhibited differential expression between these mouse lines, as confirmed by quantitative RT-PCR. In addition, serum IGFBP-1 levels were significantly higher in patients with IgAN than in healthy controls. In patients with IgAN, these levels correlated with measures of renal function, such as estimated glomerular filtration rate (eGFR), but not with sex, age, serum IgA, C3 levels, or IGF-1 levels. Pathologically, serum IGFBP-1 levels were significantly associated with the severity of renal injury, as assessed by mesangial cell proliferation and interstitial fibrosis. These results suggest that increased IGFBP-1 levels are associated with the severity of renal pathology in patients with IgAN.

  12. Insulin-like growth factor binding protein-1 levels are increased in patients with IgA nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Tokunaga, Koki [Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan); Uto, Hirofumi, E-mail: hirouto@m2.kufm.kagoshima-u.ac.jp [Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan); Takami, Yoichiro; Mera, Kumiko; Nishida, Chika; Yoshimine, Yozo; Fukumoto, Mayumi; Oku, Manei; Sogabe, Atsushi; Nosaki, Tsuyoshi; Moriuchi, Akihiro; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito [Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan)

    2010-08-20

    Research highlights: {yields} IGFBP-1 mRNA over express in kidneys obtained from mice model of IgA nephropathy. {yields} Serum IGFBP-1 levels are high in patients with IgA nephropathy. {yields} Serum IGFBP-1 levels correlate with renal function and the severity of renal injury. -- Abstract: The mechanisms underlying the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN) are not well understood. In this study, we examined gene expression profiles in kidneys obtained from mice with high serum IgA levels (HIGA mice), which exhibit features of human IgAN. Female inbred HIGA, established from the ddY line, were used in these experiments. Serum IgA levels, renal IgA deposition, mesangial proliferation, and glomerulosclerosis were increased in 32-week-old HIGA mice in comparison to ddY animals. By microarray analysis, five genes were observed to be increased by more than 2.5-fold in 32-week-old HIGA in comparison to 16-week-old HIGA; these same five genes were decreased more than 2.5-fold in 32-week-old ddY in comparison to 16-week-old ddY mice. Of these five genes, insulin-like growth factor (IGF) binding protein (IGFBP)-1 exhibited differential expression between these mouse lines, as confirmed by quantitative RT-PCR. In addition, serum IGFBP-1 levels were significantly higher in patients with IgAN than in healthy controls. In patients with IgAN, these levels correlated with measures of renal function, such as estimated glomerular filtration rate (eGFR), but not with sex, age, serum IgA, C3 levels, or IGF-1 levels. Pathologically, serum IGFBP-1 levels were significantly associated with the severity of renal injury, as assessed by mesangial cell proliferation and interstitial fibrosis. These results suggest that increased IGFBP-1 levels are associated with the severity of renal pathology in patients with IgAN.

  13. Acquired cutis laxa following urticarial vasculitis associated with IgA myeloma.

    Science.gov (United States)

    Turner, Ryan B; Haynes, Harley A; Granter, Scott R; Miller, Danielle M

    2009-06-01

    Cutis laxa (CL) is an inherited or acquired connective tissue disorder characterized clinically by loosely hanging skin folds. There is often preceding cutaneous inflammatory eruption (ie, urticaria, eczema, erythema multiforme), and there is frequently internal organ involvement of the gastrointestinal, urogenital, pulmonary, and cardiovascular systems. Histologically, there are degenerative changes in the dermal elastic fibers. Of the few reports on this rare disorder, authors have speculated about an immune-mediated destruction of elastic fibers, and monoclonal gammopathies, such as multiple myeloma or heavy chain deposition disease, have a recognized association with CL. We report an unusual case of rapidly progressing acquired CL associated with leukocytoclastic vasculitis, IgA myeloma, and an immune complex-mediated glomerulonephritis. Light microscopy of the lax skin revealed complete absence of elastic fibers in areas of vasculitis.

  14. IgA vasculitis as a presentation of human immunodeficiency virus infection.

    Science.gov (United States)

    Brandy-García, Anahy M; Santos-Juanes, Jorge; Suarez, Silvia; Caminal-Montero, Luis

    2018-05-15

    IgA vasculitis is a small-vessel vasculitis mediated by immune complexes. In clinical terms, it is characterized by palpable purpura in the lower limbs, joint involvement in the form of arthralgia or arthritis, and gastrointestinal and renal involvement (this will mark a poorer prognosis in adults). Infectious processes, mainly in the upper respiratory tract, are frequently found to be triggers. On the other hand, human immunodeficiency virus (HIV) causes immune dysfunction, which triggers hypergammaglobulinemia and can trigger autoimmune disorders. At times, this can affect the vascular endothelium, giving rise to vasculitic manifestations, although there are few reports in the literature of its role in the presentation of HIV. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Diagnostic accuracy of serum iga anti-tissue transglutaminase antibody in the diagnosis of celiac disease

    International Nuclear Information System (INIS)

    Lodhi, M. A.; Ayub, A.; Saleem, M. Z.; Munir, T.

    2017-01-01

    Objective: To determine the diagnostic accuracy of serum IgA anti-tissue transglutaminase antibody in the diagnosis of celiac disease taking histopathology as gold standard. Study Design: Cross-sectional survey. Place and Duration of Study: This study was conducted at the department of Pediatrics, Military Hospital Rawalpindi from April 2015 to July 2016. Patients and Methods: Ninety-five consecutive children presenting with suspicion of celiac disease were included in this study after taking written informed consent. A predesigned proforma was used to record patient’s demographic details. Anti-tTG level of >=25 U/ml was taken as diagnostic of celiac disease while results of histopathology on endoscopic biopsy were taken as gold standard. Results: The mean age of the patients was 6.48 ± 3.20 years and majority (n=53, 55.8 percent) of the children were aged between 5 to 10 years. The serum anti-tTG level ranged from 8.0 U/ml to 759.0 U/ml with a mean of 298.75 ± 225.51 U/ml. Taking a cut-off value of >=25 U/ml for anti-tTG, 81 (85.3 percent) children were suspected of celiac disease. Histopathology of endoscopic biopsy confirmed celiac disease in 68 (71.6 percent) children with 62 true positive, 19 false positive, 6 false negative and 8 true negative cases. It yielded 91.18 percent sensitivity, 29.63 percent specificity and 73.68 percent accuracy for anti-tTG (>=25 U/ml) in the diagnosis of celiac disease with positive and negative predictive values of 76.54 percent and 57.14 percent respectively. Conclusion: IgA anti-tissue transglutaminase antibody (>=25 U/ml) was found to be highly sensitive test for the detection of celiac disease in children. (author)

  16. Intermittent fasting modulates IgA levels in the small intestine under intense stress: a mouse model.

    Science.gov (United States)

    Lara-Padilla, Eleazar; Godínez-Victoria, Marycarmen; Drago-Serrano, Maria Elisa; Reyna-Garfias, Humberto; Arciniega-Martínez, Ivonne Maciel; Abarca-Rojano, Edgar; Cruz-Hernández, Teresita Rocío; Campos-Rodríguez, Rafael

    2015-08-15

    Intermittent fasting prolongs the lifespan and unlike intense stress provides health benefits. Given the role of the immunoglobulin A (IgA) in the intestinal homeostasis, the aim of this study was to assess the impact of intermittent fasting plus intense stress on secretory IgA (SIgA) production and other mucosal parameters in the duodenum and ileum. Two groups of six mice, with intermittent fasting or fed ad libitum for 12weeks, were submitted to a session of intense stress by a bout of forced swimming. Unstressed ad libitum fed or intermittently fasted groups were included as controls. After sacrifice, we evaluated intestinal SIgA and plasma adrenal hormones, lamina propria IgA+ plasma-cells, mRNA expression of polymeric immunoglobulin receptor, α- and J-chains in the liver and intestinal mucosa, as well as pro- (tumor necrosis factor-α, interleukin-6 and Interferon-γ) and anti- (interleukin-2, -4, -10 and transforming growth factor-β) inflammatory cytokines in mucosal samples. Under intense stress, intermittent fasting down- or up-modulated the levels of most parameters in the duodenum and ileum, respectively while up-regulated corticosterone levels without affecting epinephrine. Our data suggest intermittent fasting plus intense stress elicited neuroendocrine pathways that differentially controlled IgA and pIgR expression in duodenum and ileum. These findings provide experimental foundations for a presumable impact of intermittent fasting under intense stress on the intestinal homeostasis or inflammation by triggering or reducing the IgA production in ileum or duodenum respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Clinical efficacy of anti-glycopeptidolipid-core IgA test for diagnosing Mycobacterium avium complex infection in lung.

    Science.gov (United States)

    Numata, Takanori; Araya, Jun; Yoshii, Yutaka; Shimizu, Kenichiro; Hara, Hiromichi; Nakayama, Katsutoshi; Kuwano, Kazuyoshi

    2015-11-01

    It is difficult to verify the bacteriological diagnosis of Mycobacterium avium complex (MAC) infection. The anti-glycopeptidolipid (GPL)-core IgA antibody test was recently developed as a diagnostic method for MAC pulmonary disease. Only a few studies evaluate its clinical efficacy. We conducted retrospective evaluations of clinical characteristics of patients suspected of MAC infection to explore the usefulness of the anti-GPL-core IgA antibody test. We retrospectively evaluated 296 patients who were suspected to have MAC infection and underwent anti-GPL-core IgA antibody test between March 2013 and July 2014 in Jikei University hospital. A total of 29 patients were diagnosed with 'definite MAC' based on the American Thoracic Society (ATS) criteria with multiple identifications of MAC. On the other hand, 106 patients were diagnosed with other pulmonary diseases than MAC. The sensitivity and specificity of anti-GPL-core IgA antibody test for MAC diagnosis were 58.6% and 98.1%, respectively. The definite MAC group showed no significant differences in strains, treatment history or number of segments involved. The duration of MAC disease in the positive-antibody group was significantly longer than in the negative-antibody group (P = 0.046). A significant increase in the false-negative rate was observed in patients with malignant disease (P = 0.029). The anti-GPL-core IgA antibody test demonstrated high sensitivity and specificity for the diagnosis of MAC infection especially in patients without malignant diseases. © 2015 Asian Pacific Society of Respirology.

  18. Corticotherapy response in primary IgA nephropathy Resposta à corticoterapia na nefropatia da IgA primária

    Directory of Open Access Journals (Sweden)

    Natália Novaretti

    2013-03-01

    Full Text Available INTRODUCTION: Some beneficial effects from long-term use of corticosteroids have been reported in patients with IgA nephropathy. OBJECTIVE: This retrospective study aimed to evaluate the outcome of proteinuria and renal function according to a protocol based on a 6-month course of steroid treatment. METHOD: Twelve patients were treated with 1 g/day intravenous methylprednisolone for 3 consecutive days at the beginning of months 1, 3, and 5 plus 0.5 mg/kg oral prednisone on alternate days for 6 months (treated group. The control group included 9 untreated patients. RESULTS: Proteinuria (median and 25th and 75th percentiles at baseline in the treated group was 1861 mg/24h (1518; 2417 mg/24h and was 703 mg/24h (245; 983 and 684 mg/24h (266; 1023 at the 6th (p INTRODUÇÃO: Tem sido sugerido que tratamento mais prolongado com corticosteroides pode ser benéfico em pacientes com nefropatia da IgA primária. OBJETIVO: Neste estudo retrospectivo avaliamos os efeitos na proteinúria e na função renal após 12 meses do protocolo baseado no uso por 6 meses de corticosteroides. MÉTODO: Doze pacientes receberam pulsos de 1 g/dia de metilprednisolona intravenosa por 3 dias consecutivos no início dos meses 1, 3 e 5, seguidos por prednisona (0,5 mg/kg por via oral em dias alternados após cada pulso durante 6 meses (grupo tratado. O grupo controle foi composto por nove pacientes não tratados. RESULTADOS: A proteinúria (mg/24h; mediana; 25º; 75º percentis no período basal no grupo tratado foi de 1861 (1518; 2417 e de 703 (245; 983 e de 684 (266; 1023 nos 6º (p < 0,05 vs. basal e 12º (p < 0,05 vs. basal meses, respectivamente. No grupo controle, a proteinúria foi de 1900 (1620; 3197 no período basal e de 2290 (1500; 2975 e de 1600 (1180; 2395 nos 6º e 12º meses, respectivamente (não significantes vs. basal. Comparado com o grupo controle, o grupo tratado teve menor proteinúria (p < 0,05 e número maior de pacientes em remissão (p < 0,05 nos 6º

  19. Iron-Deficiency Anemia

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  20. Iron-Deficiency Anemia

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  1. Iron-Deficiency Anemia

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  4. Vitamin D Deficiency

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    ... to other diseases. In children, it can cause rickets. Rickets is a rare disease that causes the bones ... and children are at higher risk of getting rickets. In adults, severe vitamin D deficiency leads to ...

  5. Iron-Deficiency Anemia

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  7. Iron-Deficiency Anemia

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  9. Iron-Deficiency Anemia

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  12. Iron-Deficiency Anemia

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  14. Iron-Deficiency Anemia

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  16. Iron-Deficiency Anemia

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    Full Text Available ... diagnoses you with iron-deficiency anemia, your treatment will depend on the cause and severity of the ... of iron. The recommended daily amounts of iron will depend on your age, sex, and whether you ...

  17. Iron-Deficiency Anemia

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  18. Iron-Deficiency Anemia

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  19. Iron-Deficiency Anemia

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  20. Iron-Deficiency Anemia

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    Full Text Available ... absorb iron and lead to iron-deficiency anemia. These conditions include: Intestinal and digestive conditions, such as ... tract. Inflammation from congestive heart failure or obesity . These chronic conditions can lead to inflammation that may ...

  1. Iron-Deficiency Anemia

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    Full Text Available ... Blood Disorders and Blood Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine ... prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the current ...

  2. Iron-Deficiency Anemia

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  3. Factor V deficiency

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    ... this page: //medlineplus.gov/ency/article/000550.htm Factor V deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  4. Factor II deficiency

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    ... this page: //medlineplus.gov/ency/article/000549.htm Factor II deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  5. Factor X deficiency

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    ... this page: //medlineplus.gov/ency/article/000553.htm Factor X deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... is caused by strong muscle contractions and the impact of feet repeatedly striking the ground, such as ... funding on iron-deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision Medicine (TOPMed) ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... may be diagnosed with iron-deficiency anemia if you have low iron or ferritin levels in your blood. More testing may be needed to rule out other types of anemia. Tests for gastrointestinal ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... for your body to absorb iron from the gastrointestinal tract (GI tract). Blood loss When you lose blood, ... iron deficiency. Endurance athletes lose iron through their gastrointestinal tracts. They also lose iron through the breakdown of ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... vegetables. Foods rich in vitamin C, such as oranges, strawberries, and tomatoes, may help increase your absorption ... deficiency anemia, your doctor may recommend erythropoiesis stimulating agents (esa) . These medicines stimulate the bone marrow to ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... were born prematurely may be at an even higher risk, as most of a newborn’s iron stores ... men of the same age. Women are at higher risk for iron-deficiency anemia under some circumstances, ...

  11. Iron-Deficiency Anemia

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  12. Iron-Deficiency Anemia

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    Full Text Available ... may recommend erythropoiesis stimulating agents (esa) . These medicines stimulate the bone marrow to make more red blood ... NHLBI is funding on iron-deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... tests, especially in infants and small children Heavy menstrual periods Injury or surgery Urinary tract bleeding Consuming ... iron-deficiency anemia from trauma, surgery, or heavy menstrual periods. Individuals with a gene for hemophilia, including ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... and naproxen Certain rare genetic conditions such as hereditary hemorrhagic telangiectasia, which causes bleeding in the bowels ... iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... lead in their blood from their environment or water. Lead interferes with the body’s ability to make ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... also often take other medicines—such as proton pump inhibitors, anticoagulants, or blood thinners—that may cause iron-deficiency anemia. Proton pump inhibitors interfere with iron absorption, and blood thinners ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in a clinical trial . View all trials from ClinicalTrials.gov . Visit Children and Clinical Studies to hear experts, parents, and ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... Look for Treatment will discuss medicines and eating pattern changes that your doctors may recommend if you ... iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... girls. From birth to 6 months, babies need 0.27 mg of iron. This number goes up ... screen blood donors for low iron stores. Reliable point-of-care testing may help identify iron deficiency ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... striking the ground, such as with marathon runners. Sex Girls and women between the ages of 14 ... developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, ...

  1. Iron-Deficiency Anemia

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    Full Text Available ... increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron- ... factors , such as if you are following a vegetarian eating pattern, your doctor may recommend changes to ...

  2. Iron-Deficiency Anemia

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    Full Text Available ... deficiency anemia. Proton pump inhibitors interfere with iron absorption, and blood thinners increase the likelihood of bleeding ... oranges, strawberries, and tomatoes, may help increase your absorption of iron. If you are pregnant, talk to ...

  3. Iron-Deficiency Anemia

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    Full Text Available ... screen for iron-deficiency anemia, your doctor may order a blood test called a complete blood count ( ... your risk factors , do a physical exam, or order blood tests or other diagnostic tests. Physical exam ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... duodenum, the first part of the small intestine just beyond the stomach. Even if you have enough ... clamping of your newborn’s umbilical cord at the time of delivery. This may help prevent iron-deficiency ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... less than 12 g/dl for women is diagnostic of anemia. In iron-deficiency anemia, red blood ... both full-term and preterm infants. Look for Diagnosis will explain tests and procedures that your doctor ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... less than 12 g/dl for women is diagnostic of anemia. In iron-deficiency anemia, red blood ... physical exam, or order blood tests or other diagnostic tests. Physical exam Your doctor may ask about ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, ... iron-fortified foods that have iron added. Vegetarian diets can provide enough iron if you choose nonmeat ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... bleeding. If undiagnosed or untreated, iron-deficiency anemia can cause serious complications, including heart failure and development ... iron is too low. Low intake of iron can happen because of blood loss, consuming less than ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... improved health for people with iron-deficiency anemia. Recipient Epidemiology Donor Studies program findings help to protect blood donors . NHLBI’s Recipient Epidemiology Donor Studies (REDS) program , which began in ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... a frequent blood donor living in New York City? This study is looking at how iron-deficiency ... frequently. This study is located in New York City, and is recruiting by invitation only. View more ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... to 11 mg for children ages 7 to 12 months, and down to 7 mg for children ... deficiency at certain ages: Infants between 6 and 12 months, especially if they are fed only breast ...

  12. Iron-Deficiency Anemia

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  13. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough ... prevent complications such as abnormal heart rhythms and depression. Learn the warning signs of serious complications and ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... prevent complications such as abnormal heart rhythms and depression. Learn the warning signs of serious complications and ... donors for low iron stores. Reliable point-of-care testing may help identify iron deficiency before potentially ...

  15. Iron-Deficiency Anemia

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  16. Iron-Deficiency Anemia

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  17. Iron-Deficiency Anemia

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    Full Text Available ... starch. Restless legs syndrome Shortness of breath Weakness Complications Undiagnosed or untreated iron-deficiency anemia may cause ... as complete blood count and iron studies. Prevent complications over your lifetime To prevent complications from iron- ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... you do not have enough iron in your body. People with mild or moderate iron-deficiency anemia ... and where to find more information. Causes Your body needs iron to make healthy red blood cells. ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia. Learn about the current and future NHLBI efforts to improve health through research and ... blood donors. Cardiovascular Health Study identifies predictors of future health problems in older adults. The NHLBI-sponsored ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... as most of a newborn’s iron stores are developed during the third trimester of pregnancy. Children between ... This makes it harder to stop bleeding and can increase the risk of iron-deficiency anemia from ...

  1. Iron-Deficiency Anemia

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    Full Text Available ... an MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such ... explain our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and ...

  2. Iron-Deficiency Anemia

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    Full Text Available ... Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, ... iron-deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this ...

  3. Iron-Deficiency Anemia

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    Full Text Available ... symptoms. More severe iron-deficiency anemia may cause fatigue or tiredness, shortness of breath, or chest pain. ... in the hands and feet Difficulty concentrating Dizziness Fatigue, or feeling tired, is the most common symptom. ...

  4. Manganese deficiency in plants

    DEFF Research Database (Denmark)

    Schmidt, Sidsel Birkelund; Jensen, Poul Erik; Husted, Søren

    2016-01-01

    Manganese (Mn) is an essential plant micronutrient with an indispensable function as a catalyst in the oxygen-evolving complex (OEC) of photosystem II (PSII). Even so, Mn deficiency frequently occurs without visual leaf symptoms, thereby masking the distribution and dimension of the problem...... restricting crop productivity in many places of the world. Hence, timely alleviation of latent Mn deficiency is a challenge in promoting plant growth and quality. We describe here the key mechanisms of Mn deficiency in plants by focusing on the impact of Mn on PSII stability and functionality. We also address...... the mechanisms underlying the differential tolerance towards Mn deficiency observed among plant genotypes, which enable Mn-efficient plants to grow on marginal land with poor Mn availability....

  5. Iron-Deficiency Anemia

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    Full Text Available ... to learn more about iron-deficiency anemia, our role in research and clinical trials to improve health, ... of Blood Diseases and Resources (DBDR) is a leader in research on the causes, prevention, and treatment ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... Treatment will explain treatment-related complications or side effects. Diagnosis Iron-deficiency anemia may be detected during ... to your doctor if you are experiencing side effects such as a bad metallic taste, vomiting, diarrhea, ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... an increased risk for iron-deficiency anemia because of your age, unhealthy environments, family ... 12 months, especially if they are fed only breast milk or are fed formula that is not fortified ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... blood tests, especially in infants and small children Heavy menstrual periods Injury or surgery Urinary tract bleeding ... of iron-deficiency anemia from trauma, surgery, or heavy menstrual periods. Individuals with a gene for hemophilia, ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, ... is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and iron- ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... Individuals with a gene for hemophilia, including symptomatic female carriers who have heavy menstrual periods, may be ... anemia. Endurance activities and athletes. Athletes, especially young females, are at risk for iron deficiency. Endurance athletes ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... and Strategic Vision Leadership Scientific Divisions Operations and Administration Advisory Committees Budget and Legislative Information Jobs and ... blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron is too ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such as ... our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and Complications ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ... heavy menstrual bleeding, your doctor will want to control these other conditions to prevent you from developing ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... lead to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. People who have chronic kidney disease also often take other medicines—such as ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... may be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk ... upper endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily recommended ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily recommended iron ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... Chest pain Coldness in the hands and feet Difficulty concentrating Dizziness Fatigue, or feeling tired, is the ... Our support of SBIR/STTR programs is helping advance research in iron-deficiency anemia, in part by ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... infancy has lasting effects. We are interested in learning how having iron-deficiency anemia early in life ... Customer Service/Center for Health Information Email Alerts Jobs and Careers Site Index About NHLBI National Institute ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... family history and genetics , lifestyle habits, or sex. Age You may be at increased risk for iron ... Signs, Symptoms, and Complications Iron-deficiency anemia can range from mild to severe. People with mild or ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... iron to prepare for blood loss during delivery. Screening and Prevention Your doctor may screen you for ... and symptoms of iron-deficiency anemia. Return to Screening and Prevention to review tests to screen for ...

  1. Lactobacillus reuteri supplements do not affect salivary IgA or cytokine levels in healthy subjects: A randomized, double-blind, placebo-controlled cross-over trial

    DEFF Research Database (Denmark)

    Jørgensen, Mette Rose; Keller, Mette Kirstine; Kragelund, Camilla

    2016-01-01

    Objectives: To evaluate the effect of daily ingestion of probiotic lactobacilli on the levels of secretory IgA (sIgA) and selected cytokines in whole saliva of healthy young adults. Materials and methods: The study group consisted of 47 healthy adults (18–32 years) who volunteered for a randomize....... reuteri do not seem to modulate the salivary oral immune response in healthy young subjects (ClinicalTrials.gov NCT02017886).......Objectives: To evaluate the effect of daily ingestion of probiotic lactobacilli on the levels of secretory IgA (sIgA) and selected cytokines in whole saliva of healthy young adults. Materials and methods: The study group consisted of 47 healthy adults (18–32 years) who volunteered for a randomized...... and 3 weeks post-intervention levels. No side- or adverse effects were reported. Conclusions: Supplementation with two strains of the probiotic L. reuteri did not affect sIgA or cytokine levels in whole saliva in healthy young adults. The results thereby indicate that daily oral supplementation with L...

  2. [Iron deficiency and pica].

    Science.gov (United States)

    Muñoz, J A; Marcos, J; Risueño, C E; de Cos, C; López, R; Capote, F J; Martín, M V; Gil, J L

    1998-02-01

    To study the relationship between pica and iron-lack anaemia in a series of iron-deficiency patients in order to establish the pathogenesis of such relationship. Four-hundred and thirty-three patients were analysed. Pica was studied by introducing certain diet queries into the clinical history. All patients received oral iron and were periodically controlled with the usual clinico-haematological procedures. Pica was present in 23 patients (5.3%). Eight nourishing (namely, coffee grains, almonds, chocolate, ice, lettuce, carrots, sunflower seeds and bread) and 2 non-nourishing (clay and paper) substances were involved. A second episode of pica appeared in 9 cases upon relapsing of iron deficiency. Both anaemia and pica were cured by etiologic and substitutive therapy in all instances. No clear correlation was found with either socio-economic status or pathogenetic causes of iron deficiency and pica, and no haematological differences were seen between patients with pica and those without this alteration. (1) The pathogenesis of pica is unclear, although it appears unrelated to the degree of iron deficiency. (2) According to the findings in this series, pica seems a consequence of iron deficiency rather than its cause. (3) Adequate therapy can cure both conditions, although pica may reappear upon relapse of iron deficiency.

  3. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Man [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Li, Fu-gang [Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China); Xie, Xi-sheng [Department of Nephrology, Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital), Nanchong City 637400 (China); Wang, Shao-qing [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Fan, Jun-ming, E-mail: junmingfan@163.com [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China)

    2014-02-07

    Highlights: • CagA stimulated cell proliferation and the production of IgA1 in DAKIKI cells. • CagA promoted the underglycosylation of IgA1 in DAKIKI cells. • CagA decreased the expression of C1GALT1 and its chaperone Cosmc in DAKIKI cells. • Helicobacter pylori infection may participate in the pathogenesis of IgAN via CagA. - Abstract: While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells.

  4. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells

    International Nuclear Information System (INIS)

    Yang, Man; Li, Fu-gang; Xie, Xi-sheng; Wang, Shao-qing; Fan, Jun-ming

    2014-01-01

    Highlights: • CagA stimulated cell proliferation and the production of IgA1 in DAKIKI cells. • CagA promoted the underglycosylation of IgA1 in DAKIKI cells. • CagA decreased the expression of C1GALT1 and its chaperone Cosmc in DAKIKI cells. • Helicobacter pylori infection may participate in the pathogenesis of IgAN via CagA. - Abstract: While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells

  5. The role of interleukin-5 (IL-5 in vivo: studies with IL-5 deficient mice

    Directory of Open Access Journals (Sweden)

    Klaus I Matthaei

    1997-12-01

    Full Text Available Eosinophil recruitment is a characteristic feature of a number of pathological conditions and was the topic of the recent International Symposium on allergic inflammation, asthma, parasitic and infectious diseases (Rio de Janeiro, June 3-5, 1996. Since interleukin5 (IL5 is believed to regulate the growth, differentiation and activation of eosinophils (Coffman et al. 1989, Sanderson 1992, the role of eosinophils and IL5 are closely linked. Although IL5 specifically regulates eosinophilia in vivo and this is its most well established activity, it is becoming clear that IL5 also has other biological effects. The recent derivation of an IL5 deficient mouse (Kopf et al. 1996, provides a model for exploring not only the role of IL5 and eosinophils but also other novel activities of IL5. Of note is that although the IL5 deficient mice cannot elicit a pronounced eosinophilia in response to inflammatory stimulation following aeroallergen challenge or parasite infection they still produce basal levels of eosinophils that appear to be morphologically and functionally normal. However, the basal levels of eosinophils appear insufficient for normal host defence as IL5 deficiency has now been shown to compromise defence against several helminth infections. In addition, IL5 deficient mice appear to have functional deficiencies in B-1 B lymphocytes and in IgA production.

  6. IgA anti-Streptococcus mutans em crianças com e sem cárie dentária Anti-Streptococcus mutans IgA in children with and without dental caries

    Directory of Open Access Journals (Sweden)

    Suzete Cristina YAZAKI

    1999-07-01

    Full Text Available A cárie dentária é uma doença infecciosa crônica que necessita pelo menos quatro componentes para desenvolver-se: hospedeiro suscetível, microbiota patogênica, dieta rica em sacarose e tempo. Este trabalho estuda as correlações existentes entre estreptococos salivares do grupo mutans, placa bacteriana e anticorpos IgA anti-Streptococcus mutans em crianças com e sem experiência de cárie. Para tanto, utilizou-se o meio Mitis Salivarius (DIFCO para determinar o número de Unidades Formadoras de Colônias (UFC/ml, o Índice de Higiene Oral Simplificado (IHOS para mensurar a quantidade de placa bacteriana e a técnica ELISA para detectar anticorpos anti-S. mutans. Os resultados obtidos mostraram que não existe uma correlação entre os níveis salivares de estreptococos (UFC/ml e IgA anti-S. mutans na população estudada. No grupo com cárie, uma correlação positiva, estatisticamente significante, foi observada entre o Índice de placa e IgA específica.Dental caries is a chronic infectious disease that needs at least four components to develop. As a susceptible host, a pathogenic microbiota, a high-sucrose diet and time. This work assess the relationships between Streptococcus mutans and dental plaque; Streptococcus mutans and IgA antibodies in children with and without caries experience. In order to achieve this goal we have used Mitis Salivarius bacitracin agar (DIFCO to determine the colony forming units (CFU/mL, the simplified oral hygiene index (SOHI for measuring bacterial plaque and ELISA for antibody detection. The results obtained have not shown any correlations between colony forming units of S. mutans and IgA antibodies. A significant correlation was found between bacterial plaque index and specific IgA in children with carious lesions.

  7. CD4+ T follicular helper and IgA+ B cell numbers in gut biopsies from HIV-infected subjects on antiretroviral therapy are comparable to HIV-uninfected individuals

    Directory of Open Access Journals (Sweden)

    John Zaunders

    2016-10-01

    Full Text Available Background: Disruption of gastrointestinal tract epithelial and immune barriers contribute to microbial translocation, systemic inflammation and progression of HIV-1 infection. Antiretroviral therapy (ART may lead to reconstitution of CD4+ T cells in gastrointestinal-associated lymphoid tissue (GALT, but its impact on humoral immunity within GALT is unclear. Therefore we studied CD4+ subsets, including T follicular helper cells (Tfh, as well as resident B cells that have switched to IgA production, in gut biopsies, from HIV+ subjects on suppressive ART, compared to HIV-negative controls.Methods: 23 HIV+ subjects on ART and 22 HIV-negative controls (HNC undergoing colonoscopy were recruited to the study. Single cell suspensions were prepared from biopsies from left colon (LC, right colon (RC and terminal ileum (TI. T and B lymphocyte subsets, as well as EpCAM+ epithelial cells, were accurately enumerated by flow cytometry, using counting beads. Results: No significant differences in the number of recovered epithelial cells were observed between the two subject groups. However, the median TI CD4+ T cell count/106 epithelial cells was 2.4-fold lower in HIV+ subjects versus HNC (19,679 vs 47,504 cells; p=0.02. Similarly, median LC CD4+ T cell counts were reduced in HIV+ subjects (8,358 vs 18,577; p=0.03, but were not reduced in RC. Importantly, we found no significant differences in Tfh or IgA+ B cell counts at either site between HIV+ subjects and HNC. Further analysis showed no difference in CD4+, Tfh or IgA+ B cell counts between subjects who commenced ART in primary compared to chronic HIV-1 infection. Despite the decrease in total CD4 T cells, we could not identify a selective decrease of other key subsets of CD4+ T cells, including: CCR5+ cells; CD127+ long-term memory cells; CD103+ tissue resident cells; or CD161+ cells (surrogate marker for Th17, but there was a slight increase in the proportion of T regulatory cells. Conclusion: While there

  8. IgA and neutralizing antibodies to influenza a virus in human milk: a randomized trial of antenatal influenza immunization.

    Science.gov (United States)

    Schlaudecker, Elizabeth P; Steinhoff, Mark C; Omer, Saad B; McNeal, Monica M; Roy, Eliza; Arifeen, Shams E; Dodd, Caitlin N; Raqib, Rubhana; Breiman, Robert F; Zaman, K

    2013-01-01

    Antenatal immunization of mothers with influenza vaccine increases serum antibodies and reduces the rates of influenza illness in mothers and their infants. We report the effect of antenatal immunization on the levels of specific anti-influenza IgA levels in human breast milk. (ClinicalTrials.gov identifier NCT00142389; http://clinicaltrials.gov/ct2/show/NCT00142389). The Mother's Gift study was a prospective, blinded, randomized controlled trial that assigned 340 pregnant Bangladeshi mothers to receive either trivalent inactivated influenza vaccine, or 23-valent pneumococcal polysaccharide vaccine during the third trimester. We evaluated breast milk at birth, 6 weeks, 6 months, and 12 months, and serum at 10 weeks and 12 months. Milk and serum specimens from 57 subjects were assayed for specific IgA antibody to influenza A/New Caledonia (H1N1) using an enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay, and for total IgA using ELISA. Influenza-specific IgA levels in breast milk were significantly higher in influenza vaccinees than in pneumococcal controls for at least 6 months postpartum (p = 0.04). Geometric mean concentrations ranged from 8.0 to 91.1 ELISA units/ml in vaccinees, versus 2.3 to 13.7 ELISA units/mL in controls. Virus neutralization titers in milk were 1.2 to 3 fold greater in vaccinees, and correlated with influenza-specific IgA levels (r = 0.86). Greater exclusivity of breastfeeding in the first 6 months of life significantly decreased the expected number of respiratory illness with fever episodes in infants of influenza-vaccinated mothers (p = 0.0042) but not in infants of pneumococcal-vaccinated mothers (p = 0.4154). The sustained high levels of actively produced anti-influenza IgA in breast milk and the decreased infant episodes of respiratory illness with fever suggest that breastfeeding may provide local mucosal protection for the infant for at least 6 months. Studies are needed to determine the

  9. Compressed Sensing with Rank Deficient Dictionaries

    DEFF Research Database (Denmark)

    Hansen, Thomas Lundgaard; Johansen, Daniel Højrup; Jørgensen, Peter Bjørn

    2012-01-01

    In compressed sensing it is generally assumed that the dictionary matrix constitutes a (possibly overcomplete) basis of the signal space. In this paper we consider dictionaries that do not span the signal space, i.e. rank deficient dictionaries. We show that in this case the signal-to-noise ratio...... (SNR) in the compressed samples can be increased by selecting the rows of the measurement matrix from the column space of the dictionary. As an example application of compressed sensing with a rank deficient dictionary, we present a case study of compressed sensing applied to the Coarse Acquisition (C...

  10. Antepartum Ornithine Transcarbamylase Deficiency

    Directory of Open Access Journals (Sweden)

    Hitoshi Nakajima

    2014-11-01

    Full Text Available Ornithine transcarbamylase deficiency (OTCD is the most common type urea cycle enzyme deficiencies. This syndrome results from a deficiency of the mitochondrial enzyme ornithine transcarbamylase, which catalyzes the conversion of ornithine and carbamoyl phosphate to citrullin. Our case was a 28-year-old female diagnosed with OTCD following neurocognitive deficit during her first pregnancy. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. Plasma amino acid and urine organic acid analysis revealed OTCD. After combined modality treatment with arginine, sodium benzoate and hemodialysis, the patient's plasma ammonia level stabilized and her mental status returned to normal. At last she recovered without any damage left.

  11. The IgA nephropathy Biobank. An important starting point for the genetic dissection of a complex trait

    Directory of Open Access Journals (Sweden)

    Alexopoulos Efstathios

    2005-12-01

    Full Text Available Abstract Background IgA nephropathy (IgAN or Berger's disease, is the most common glomerulonephritis in the world diagnosed in renal biopsied patients. The involvement of genetic factors in the pathogenesis of the IgAN is evidenced by ethnic and geographic variations in prevalence, familial clustering in isolated populations, familial aggregation and by the identification of a genetic linkage to locus IGAN1 mapped on 6q22–23. This study seems to imply a single major locus, but the hypothesis of multiple interacting loci or genetic heterogeneity cannot be ruled out. The organization of a multi-centre Biobank for the collection of biological samples and clinical data from IgAN patients and relatives is an important starting point for the identification of the disease susceptibility genes. Description The IgAN Consortium organized a Biobank, recruiting IgAN patients and relatives following a common protocol. A website was constructed to allow scientific information to be shared between partners and to divulge obtained data (URL: http://www.igan.net. The electronic database, the core of the website includes data concerning the subjects enrolled. A search page gives open access to the database and allows groups of patients to be selected according to their clinical characteristics. DNA samples of IgAN patients and relatives belonging to 72 multiplex extended pedigrees were collected. Moreover, 159 trios (sons/daughters affected and healthy parents, 1068 patients with biopsy-proven IgAN and 1040 healthy subjects were included in the IgAN Consortium Biobank. Some valuable and statistically productive genetic studies have been launched within the 5th Framework Programme 1998–2002 of the European project No. QLG1-2000-00464 and preliminary data have been published in "Technology Marketplace" website: http://www.cordis.lu/marketplace. Conclusion The first world IgAN Biobank with a readily accessible database has been constituted. The knowledge gained

  12. Presença de Candida nas mucosas vaginal e bucal e sua relação com IgA salivar Relationship between Candida in vaginal and oral mucosae and salivary IgA

    Directory of Open Access Journals (Sweden)

    Célia Regina Gonçalves e Silva

    2008-06-01

    Full Text Available OBJETIVO: correlacionar a presença de leveduras do gênero Candida na cavidade bucal e vaginal de mulheres com e sem candidíase vulvovaginal (CVV com os níveis de IgA secretora (IgAs presentes na saliva. MÉTODOS: cinqüenta e uma mulheres foram incluídas; 13 apresentaram CVV e 38 formaram o Grupo Controle. De cada paciente, foram coletados 2,0 mL de saliva sem estimulação e secreção vaginal com o auxílio de swab, que foi imerso a seguir em 2,0 mL de solução fisiológica. As amostras foram semeadas em ágar Sabouraud dextrose com cloranfenicol para isolamento e contagem de colônias, e os isolados foram identificadas fenotipicamente. Na saliva de ambos os grupos foi quantificada IgA pela técnica ELISA. RESULTADOS: nas 13 pacientes com diagnóstico clínico e micológico de CVV, a média de unidades formadoras de colônias de Candida por mililitro de secreção vaginal (ufc/mL foi de 52.723 e 23,8% dos pacientes apresentaram colonização na mucosa bucal com menor quantidade de ufc/mL (6.030. Os níveis de IgAs na saliva foram mais baixos no grupo com CVV (média de densidade: 0,3 quando comparados aos níveis de IgA do Grupo Controle (média de DO: 0,6. Onze pacientes (37% do Grupo Controle apresentaram colonização por Candida na cavidade bucal, com média de ufc/mL mais baixa quando comparada ao grupo com CVV. O Grupo Controle também apresentou menor quantidade de ufc/mL (1.973 na cavidade vaginal quando comparado com o Grupo CVV (52.942. CONCLUSÕES: os resultados demonstraram que os pacientes com diagnóstico clínico de candidíase vulvovaginal apresentaram maior quantidade de Candida, tanto na cavidade vaginal quanto na bucal, e apresentaram menores níveis de IgA anti-Candida na saliva.PURPOSE: to correlate the presence of yeast from the Candida genus in the oral and vaginal cavity of women with and without vulvovaginal candidiasis (VVC, with secretor IgA levels (IgAs present in the saliva. METHODS: among the 51 women

  13. Vitamin Excess and Deficiency.

    Science.gov (United States)

    Diab, Liliane; Krebs, Nancy F

    2018-04-01

    The published literature supports the high prevalence of supplement use in children and adolescents in the United States. Pediatricians today are faced with questions from parents and patients about the benefits, safety, efficacy, and correct dose of vitamins and minerals. In this article, we review 7 vitamins with the most clinical relevance as judged by abundance in food, risks and symptoms of deficiency, and potential for toxicity. Specifically, we focus on possible clinical scenarios that can be indicative of nutritional deficiency. We synthesize and summarize guidelines from nutrition experts, various medical societies, the World Health Organization, and the American Academy of Pediatrics. © American Academy of Pediatrics, 2018. All rights reserved.

  14. Effect of salivary secretory IgA on the adhesion of Candida albicans to polystyrene.

    Science.gov (United States)

    San Millán, R; Elguezabal, N; Regúlez, P; Moragues, M D; Quindós, G; Pontón, J

    2000-09-01

    Attachment of Candida albicans to plastic materials of dental prostheses or to salivary macromolecules adsorbed on their surface is believed to be a critical event in the development of denture stomatitis. In an earlier study, it was shown that adhesion of C. albicans to polystyrene, a model system to study the adhesion of C. albicans to plastic materials, can be partially inhibited with an mAb directed against cell wall polysaccharides of C. albicans. In the present study, the role of whole saliva in the adhesion of C. albicans to polystyrene has been investigated, and three mAbs directed against epitopes of cell wall mannoproteins have been used to mimic the inhibitory effect observed with salivary secretory IgA (sIgA) on the adhesion of C. albicans to polystyrene. In the absence of whole saliva, adherence of C. albicans 3153 increased with germination. However, the presence of whole saliva enhanced the adhesion to polystyrene of C. albicans 3153 yeast cells but decreased the adhesion of germinated cells. The enhancement of adhesion of yeast cells to polystyrene mediated by saliva was confirmed with an agerminative mutant of C. albicans 3153. The inhibition of the adhesion of C. albicans 3153 germ tubes to polystyrene was due to the salivary sIgA since sIgA-depleted saliva enhanced the adhesion of C. albicans 3153 to polystyrene. The inhibitory effect mediated by sIgA was not related to the inhibition of germination but to the blockage of adhesins expressed on the cell wall surface of the germ tubes. The three mAbs studied reduced the adhesion of C. albicans 3153 to polystyrene at levels equivalent to those for purified sIgA. The highest reduction in the adhesion was obtained with the IgA mAb N3B. The best results were obtained when the three mAbs were combined. The results suggest that whole saliva plays a different role in the adhesion of C. albicans to polystyrene depending on the morphological phase of C. albicans. These results may give new insights into the

  15. Serum IgG and IgA levels in polio and non-polio acute flaccid paralysis cases in western Uttar Pradesh, India.

    Science.gov (United States)

    Mohanty, Madhu C; Nalavade, Uma P; Deshpande, Jagadish M

    2015-03-08

    IgG and IgA immunocompetence of children with wild poliovirus poliomyelitis and non-polio acute flaccid paralysis. 932 cases of acute flaccid paralysis, reported in 2008-2009, were tested for presence of polio and non-polio enteroviruses according to the WHO standards. Serum IgA and IgG levels were determined by sandwich ELISA. Mean (SD) IgA levels [0.87 (0.62)g/L; n=28] of virologically confirmed poliomyelitis cases were lower than those of virus negative [1.21 (0.83)g/L; n=612] and non-polio Enterovirus positive [1.22 (0.79)g/L; n=240] cases of acute flaccid paralysis. No significant difference was observed in the concentration of IgG among these groups. IgA plays an important role in protection against poliomyelitis.

  16. Clinical significance of determination of changes of serum IL-6, hs-CRP and saliva secretory IgA levels after treatment in patients with periodontitis

    International Nuclear Information System (INIS)

    Wang Tongwu

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IL-6, hs-CRP and saliva secretory IgA levels after treatment in patients with periodontitis. Methods: Serum IL-6, saliva secretory IgA (with RIA) and serum hs-CRP (with immuno-tarbility method) levels were measured in 42 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment serum IL-6, hs-CRP and saliva secretory IgA levels in the patients wree significantly higher than those in controls (P 0.05). However, the saliva secreatory IgA levels were still significantly higher than those in controls (P<0.05). Conclusion: There was disturbance of immunomodulation in patients with periodontitis as expressed by the changes of cytokines levels in the course of the diseases. (authors)

  17. IgA against gut-derived endotoxins: does it contribute to suppression of hepatic inflammation in alcohol-induced liver disease?

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schäfer, C.; Bode, C.

    2002-01-01

    Endotoxins of intestinal origin are supposed to play an important role in the development of alcoholic hepatitis in man. To estimate the role of immunoglobulin response to gut-derived endotoxin in the development of alcohol-induced liver disease, serum levels of IgA and IgG against fecal endotoxin......, endotoxin, and acute-phase proteins were measured in patients with different stages of alcoholic liver disease and in healthy controls. Antibodies of type IgA, but not IgG, against fecal endotoxins were significantly increased in patients with alcohol-induced liver disease. IgA antibodies against fecal...... endotoxin were found to be closely correlated with the plasma concentrations of alanine aminotransferase, gamma-glutamyl transferase, and C-reactive protein in patients with alcoholic liver disease. In conclusion, as IgA located in body tissue was shown to suppress the inflammatory process, enhanced...

  18. Allergen-specific IgG and IgA in serum and bronchoalveolar lavage fluid in a model of experimental feline asthma.

    Science.gov (United States)

    Norris, C R; Byerly, J R; Decile, K C; Berghaus, R D; Walby, W F; Schelegle, E S; Hyde, D M; Gershwin, L J

    2003-12-15

    Allergic asthma, a Th2 cell driven response to inhaled allergens, has classically been thought of as predominantly mediated by IgE antibodies. To investigate the role of other immunoglobulin classes (e.g., IgG and IgA) in the immunopathogenesis of allergic asthma, levels of these allergen-specific immunoglobulins were measured in serum and mucosal fluids. Bermuda grass allergen (BGA)-specific IgG and IgA ELISAs in serum and bronchoalveolar lavage fluid (BALF) were developed and optimized in an experimental model of BGA-induced feline asthma. Levels of BGA-specific IgG and IgA significantly increased over time in serum and BALF after allergen sensitization. Additionally, these elevated levels of BGA-specific IgG and IgA were seen in conjunction with the development of an asthmatic phenotype indicated by positive intradermal skin tests, enhanced airways hyperreactivity, and increased eosinophil percentages in the BALF.

  19. Large Scale Generation and Characterization of Anti-Human IgA Monoclonal Antibody in Ascitic Fluid of Balb/c Mice

    OpenAIRE

    Fatemeh Ezzatifar; Jafar Majidi; Behzad Baradaran; Leili Aghebati Maleki; Jalal Abdolalizadeh; Mehdi Yousefi

    2015-01-01

    Purpose: Monoclonal antibodies are potentially powerful tools used in biomedical research, diagnosis, and treatment of infectious diseases and cancers. The monoclonal antibody against Human IgA can be used as a diagnostic application to detect infectious diseases. The aim of this study was to improve an appropriate protocol for large-scale production of mAbs against IgA. Methods: For large-scale production of the monoclonal antibody, hybridoma cells that produce monoclonal antibodies again...

  20. What Is Combined Deficiency of Vitamin K-Dependent Clotting Factors?

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  1. Erkko Autio : igaühest ei saa hiilgavat ettevõtjat / Erkko Autio ; interv. Toivo Tänavsuu

    Index Scriptorium Estoniae

    Autio, Erkko

    2007-01-01

    Londoni Imperial Kolledzhi professor Erkko Autio kommenteerib oma ettekannet Tallinnas toimunud gasellikonverentsil ning usub, et gasell ei ole sektoripõhine fenomen, vaid võimalik peaaegu igas majandusvaldkonnas kui riik loob soodsa ettevõtluskeskkonna. Vt. samas: iPoint haaras härjal sarvist; MySQL - lihtsalt geniaalne!; Värvikas gaselliguru Erkko Autio; Pille-Liis Kello. Kuidas Eestis toetatakse gaselle?

  2. The gut-kidney axis in IgA nephropathy: role of microbiota and diet on genetic predisposition.

    Science.gov (United States)

    Coppo, Rosanna

    2018-01-01

    Recent data suggest that gut-associated lymphoid tissue (GALT) plays a major role in the development of immunoglobulin A (IgA) nephropathy (IgAN). A genome-wide association study showed that most loci associated with the risk of IgAN are also associated with immune-mediated inflammatory bowel diseases, maintenance of the intestinal barrier and regulation of response to gut pathogens. Studies involving experimental models have demonstrated a pivotal role of intestinal microbiota in the development of IgAN in mice producing high levels of IgA and in transgenic mice overexpressing BAFF, a B-cell factor crucial for IgA synthesis, indicating the role of genetic background, B-cell activity, GALT intestinal immunity and diet. The effect of diet was suggested by pilot studies carried out 30 years ago which showed that a gluten-rich diet induced IgAN in mice and that some patients benefited from a gluten-free diet. A recent experimental model in mice expressing human IgA1 and Fc alpha receptor CD89 reported clinical and histological improvement after a gluten-free diet. Clinical observations have elicited new interest in GALT hyper-reactivity in IgAN patients. In a pilot study, a reduction in proteinuria was attained using an enteric controlled-release formulation of the corticosteroid budesonide targeted to the Peyer's patches at the ileocecal junction. This formulation was tested in the placebo-controlled NEFIGAN phase 2b trial, with a reduction in proteinuria after 9 months of treatment together with stabilization of renal function in patients with persistent proteinuria. In conclusion, the gut-kidney axis modulated by microbiota and diet is a promising target for focused treatment of IgAN in genetically predisposed patients at risk of progression.

  3. Idiopathic linear IgA bullous dermatosis: prognostic factors based on a case series of 72 adults.

    Science.gov (United States)

    Gottlieb, J; Ingen-Housz-Oro, S; Alexandre, M; Grootenboer-Mignot, S; Aucouturier, F; Sbidian, E; Tancrede, E; Schneider, P; Regnier, E; Picard-Dahan, C; Begon, E; Pauwels, C; Cury, K; Hüe, S; Bernardeschi, C; Ortonne, N; Caux, F; Wolkenstein, P; Chosidow, O; Prost-Squarcioni, C

    2017-07-01

    Linear IgA bullous dermatosis (LABD) is a clinically and immunologically heterogeneous, subepidermal, autoimmune bullous disease (AIBD), for which the long-term evolution is poorly described. To investigate the clinical and immunological characteristics, follow-up and prognostic factors of adult idiopathic LABD. This retrospective study, conducted in our AIBD referral centre, included adults, diagnosed between 1995 and 2012, with idiopathic LABD, defined as pure or predominant IgA deposits by direct immunofluorescence. Clinical, histological and immunological findings were collected from charts. Standard histology was systematically reviewed, and indirect immunofluorescence (IIF) on salt-split skin (SSS) and immunoblots (IBs) on amniotic membrane extracts using anti-IgA secondary antibodies were performed, when biopsies and sera obtained at diagnosis were available. Prognostic factors for complete remission (CR) were identified using univariate and multivariate analyses. Of the 72 patients included (median age 54 years), 60% had mucous membrane (MM) involvement. IgA IIF on SSS was positive for 21 of 35 patients tested; 15 had epidermal and dermal labellings. Immunoelectron microscopy performed on the biopsies of 31 patients labelled lamina lucida (LL) (26%), lamina densa (23%), anchoring-fibril zone (AFz) (19%) and LL+AFz (23%). Of the 34 IgA IBs, 22 were positive, mostly for LAD-1/LABD97 (44%) and full-length BP180 (33%). The median follow-up was 39 months. Overall, 24 patients (36%) achieved sustained CR, 19 (29%) relapsed and 35% had chronic disease. CR was significantly associated with age > 70 years or no MM involvement. No prognostic immunological factor was identified. Patients with LABD who are < 70 years old and have MM involvement are at risk for chronic evolution. © 2017 British Association of Dermatologists.

  4. IgA antibodies against β2 glycoprotein I in hemodialysis patients are an independent risk factor for mortality.

    Science.gov (United States)

    Serrano, Antonio; García, Florencio; Serrano, Manuel; Ramírez, Elisa; Alfaro, F Javier; Lora, David; de la Cámara, Agustín Gómez; Paz-Artal, Estela; Praga, Manuel; Morales, Jose M

    2012-06-01

    Cardiovascular complications are the most important cause of death in patients on dialysis with end-stage renal disease. Antibodies reacting with β-glycoprotein I seem to play a pathogenic role in antiphospholipid syndrome and stroke and are involved in the origin of atherosclerosis. Here we evaluated the presence of anticardiolipin and anti-β-glycoprotein I antibodies together with other vascular risk factors and their relationship with mortality and cardiovascular morbidity in a cohort of 124 hemodialysis patients prospectively followed for 2 years. Of these, 41 patients were significantly positive for IgA anti-β-glycoprotein I, and the remaining had normal values. At 24 months, overall and cardiovascular mortality and thrombotic events were all significantly higher in patients with high anti-β-glycoprotein I antibodies. Multivariate analysis using Cox regression modeling found that age, hypoalbuminemia, use of dialysis catheters, and IgA β-glycoprotein I antibodies were independent risk factors for death. Thus, IgA antibodies to β-glycoprotein I are detrimental to the clinical outcome of hemodialysis patients.

  5. Human milk containing specific secretory IgA inhibits binding of Giardia lamblia to nylon and glass surfaces.

    Science.gov (United States)

    Samra, H K; Ganguly, N K; Mahajan, R C

    1991-06-01

    The effects of human milk, containing specific secretory IgA, on the adherence of Giardia lamblia trophozoites in the presence and in the absence of intestinal mucus in vitro were studied. It was found that the trophozoites treated with breast milk, containing specific secretory IgA to G. lamblia, showed a significant decrease (p less than 0.01) in adherence to nylon fibre columns and glass surfaces than did trophozoites treated with milk containing no SIgA antibodies. The adherence to glass surfaces was significantly more (p less than 0.01) in the presence of intestinal mucus than when the mucus was absent. Milk that did not contain specific secretory SIgA to G. lamblia did not decrease the adherence to glass surfaces either in the presence or in the absence of mucus. The fluorescence study revealed the binding of specific secretory IgA on the trophozoite surface. The results suggest that binding of SIgA antibodies in milk to G. lamblia trophozoites inhibits parasite adherence, thus protecting against this infection in breast-fed babies.

  6. Oral immunization with rotavirus VP7 expressed in transgenic potatoes induced high titers of mucosal neutralizing IgA

    International Nuclear Information System (INIS)

    Wu Yuzhang; Li Jintao; Mou Zhirong; Fei Lei; Ni Bing; Geng Miao; Jia Zhengcai; Zhou Wei; Zou Liyun; Tang Yan

    2003-01-01

    Rotaviruses (RV) are a common cause of severe diarrhea in young children, resulting in nearly one million deaths worldwide annually. Rotavirus VP7 was the rotavirus neutralizing protein. Previous study reported that VP7 DNA vaccine can induce high levels of IgG in mice but cannot protect mice against challenge (Choi, A.H., Basu, M., Rae, M.N., McNeal, M.M., Ward, R.L., 1998. Virology 250, 230-240). We found that rotavirus VP7 could maintain its neutralizing immunity when it was transformed into the potato genome. Mice immunized with the transformed tubers successfully elicited serum IgG and mucosal IgA specific for VP7. The mucosal IgA titer was as high as 1000, while serum IgG titer was only 600. Neutralizing assays indicated that IgA could neutralize rotavirus. These results indicate the potential usefulness of plants for production and delivery of edible rotavirus vaccines

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... grams per deciliter (g/dl) for men and less than 12 g/dl for women is diagnostic of anemia. In iron-deficiency anemia, ... blood levels of iron will be low, or less than 10 micromoles per liter (mmol/L) for both men and women. Normal levels are 10 to 30 mmol/L. ...

  8. Alpha1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Stolk, Jan; Seersholm, Niels; Kalsheker, Noor

    2006-01-01

    The Alpha One International Registry (AIR), a multinational research program focused on alpha1-antitrypsin (AAT) deficiency, was formed in response to a World Health Organization recommendation. Each of the nearly 20 participating countries maintains a national registry of patients with AAT defic...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... is blood loss during dialysis. People who have chronic kidney disease also often take other medicines—such as proton ... reduces iron absorption. Other treatments If you have chronic kidney disease and iron-deficiency anemia, your doctor may recommend ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) ... We are interested in learning how having iron-deficiency anemia early in life ...

  11. Arginase-1 deficiency.

    Science.gov (United States)

    Sin, Yuan Yan; Baron, Garrett; Schulze, Andreas; Funk, Colin D

    2015-12-01

    Arginase-1 (ARG1) deficiency is a rare autosomal recessive disorder that affects the liver-based urea cycle, leading to impaired ureagenesis. This genetic disorder is caused by 40+ mutations found fairly uniformly spread throughout the ARG1 gene, resulting in partial or complete loss of enzyme function, which catalyzes the hydrolysis of arginine to ornithine and urea. ARG1-deficient patients exhibit hyperargininemia with spastic paraparesis, progressive neurological and intellectual impairment, persistent growth retardation, and infrequent episodes of hyperammonemia, a clinical pattern that differs strikingly from other urea cycle disorders. This review briefly highlights the current understanding of the etiology and pathophysiology of ARG1 deficiency derived from clinical case reports and therapeutic strategies stretching over several decades and reports on several exciting new developments regarding the pathophysiology of the disorder using ARG1 global and inducible knockout mouse models. Gene transfer studies in these mice are revealing potential therapeutic options that can be exploited in the future. However, caution is advised in extrapolating results since the lethal disease phenotype in mice is much more severe than in humans indicating that the mouse models may not precisely recapitulate human disease etiology. Finally, some of the functions and implications of ARG1 in non-urea cycle activities are considered. Lingering questions and future areas to be addressed relating to the clinical manifestations of ARG1 deficiency in liver and brain are also presented. Hopefully, this review will spark invigorated research efforts that lead to treatments with better clinical outcomes.

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Science Science Home Blood Disorders and Blood Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision ... prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... infection. A history of gastrointestinal surgery, such as weight-loss surgery—especially gastric bypass—or gastrectomy. Certain rare ... prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the ...

  14. Vitamin B12 deficiency

    Science.gov (United States)

    Vitamin B12 (B12; also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. Clinical B12 deficiency with classic haematological and neurological manifestations is relatively uncommon. However, sub...

  15. Leukocyte adhesion deficiencies

    NARCIS (Netherlands)

    van de Vijver, Edith; van den Berg, Timo K.; Kuijpers, Taco W.

    2013-01-01

    During inflammation, leukocytes play a key role in maintaining tissue homeostasis through elimination of pathogens and removal of damaged tissue. Leukocytes migrate to the site of inflammation by crawling over and through the blood vessel wall, into the tissue. Leukocyte adhesion deficiencies (ie,

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron supplements work best to treat iron-deficiency anemia in children who do not consume the daily recommended amount ... and Clinical Studies to hear experts, parents, and children talk about their experiences with clinical ... Anemia Arrhythmia Blood Donation Blood Tests Blood ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Working at the NHLBI Contact and FAQs Accessible Search Form Search the NHLBI, use the drop down list to ... treatment of blood diseases, including iron-deficiency anemia. Search the NIH Research Portfolio Online Reporting Tools (RePORT) ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or even heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, ... Upper endoscopy to look for bleeding in the esophagus, stomach, and the first part of the ... blood, and sleep disorders, including iron-deficiency anemia. Learn about the current ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... how having iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature or very small newborns . In collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how ...

  20. Iron deficiency in children

    African Journals Online (AJOL)

    cell and excess iron is stored as ferritin to protect the cell from oxidative ... iron deficiency has negative effects during pregnancy and in the postpartum period, which affects maternal health ... use of undiluted cow's milk and a predominant cow's milk intake in .... on bone marrow smear or biopsy for the definitive diagnosis of.

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Certain conditions or medicines can decrease your body’s ability to absorb iron and lead to iron-deficiency ... environment or water. Lead interferes with the body’s ability to make hemoglobin. Family history and genetics Von ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... supplements. Iron supplements can change how certain medicines work. Your doctor may suggest check-ups to make sure your ... To prevent complications from iron-deficiency anemia, your doctor may ... during certain stages of life when more iron is needed, such as childhood ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... an MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such as if you are following a ... unhealthy environments, or other factors that increase your risk of developing iron-deficiency ... to Screening and Prevention to review tests to screen for and strategies ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Services’ National Institutes of Health (NIH)—the Nation’s biomedical research agency that makes important scientific discoveries to improve ... efforts for iron-deficiency anemia. Learn about exciting research areas that ... This could help develop new therapies for conditions that affect the balance of iron ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Complications Undiagnosed or untreated iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough hemoglobin-carrying red blood cells, your heart has to work harder to move oxygen-rich blood through your ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how best to treat premature newborns with low hemoglobin levels. We also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children ...

  7. MCAD deficiency in Denmark

    DEFF Research Database (Denmark)

    Andresen, Brage Storstein; Lund, Allan Meldgaard; Hougaard, David Michael

    2012-01-01

    Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common defect of fatty acid oxidation. Many countries have introduced newborn screening for MCADD, because characteristic acylcarnitines can easily be identified in filter paper blood spot samples by tandem mass spectrometry (MS/M...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... NHLBI News NHLBI in the Press Research Features All Events Past Events Upcoming Events About NHLBI About NHLBI Home Mission and Strategic Vision ... deficient Donors: Recovery and Storage Quality. Learn more about ... trial . View all trials from ClinicalTrials.gov . Visit Children and Clinical ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our ... more information about Donor Iron Deficiency Study - Red Blood Cells ...

  10. Isolated sulfite oxidase deficiency.

    Science.gov (United States)

    Rupar, C A; Gillett, J; Gordon, B A; Ramsay, D A; Johnson, J L; Garrett, R M; Rajagopalan, K V; Jung, J H; Bacheyie, G S; Sellers, A R

    1996-12-01

    Isolated sulfite oxidase (SO) deficiency is an autosomal recessively inherited inborn error of sulfur metabolism. In this report of a ninth patient the clinical history, laboratory results, neuropathological findings and a mutation in the sulfite oxidase gene are described. The data from this patient and previously published patients with isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are summarized to characterize this rare disorder. The patient presented neonatally with intractable seizures and did not progress developmentally beyond the neonatal stage. Dislocated lenses were apparent at 2 months. There was increased urine excretion of sulfite and S-sulfocysteine and a decreased concentration of plasma cystine. A lactic acidemia was present for 6 months. Liver sulfite oxidase activity was not detectable but xanthine dehydrogenase activity was normal. The boy died of respiratory failure at 32 months. Neuropathological findings of cortical necrosis and extensive cavitating leukoencephalopathy were reminiscent of those seen in severe perinatal asphyxia suggesting an etiology of energy deficiency. A point mutation that resulted in a truncated protein missing the molybdenum-binding site has been identified.

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... do not have enough iron in your body. People with mild or moderate iron-deficiency anemia may ... as a TMRPSS6 gene mutation that causes a person’s body to make too much of a hormone ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in ... deficiency anemia, your doctor may recommend heart-healthy eating and choosing iron-rich foods, especially during certain stages of life when more ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature or very small newborns . In collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how best to treat ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in you getting less than the recommended daily amount of iron. Frequent blood donation. Individuals who donate blood often may be ...

  15. Familial lipoprotein lipase deficiency

    Science.gov (United States)

    ... lack an enzyme called lipoprotein lipase. Without this enzyme, the body cannot break down fat from digested food. Fat particles called chylomicrons build up in the blood. Risk factors include a family history of lipoprotein lipase deficiency. The condition is usually ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies Women’s Health All Science A-Z Grants ... health for people with iron-deficiency anemia. Recipient Epidemiology Donor Studies program findings help to protect blood ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and save lives. We are committed to advancing science and translating discoveries into clinical practice to promote the prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the current and future NHLBI efforts to improve health through ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature or very small newborns . In collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how best to treat premature newborns with low hemoglobin levels. We also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... of the body. When your heart has to work harder, this can lead to several conditions: irregular heartbeats called arrhythmias , a heart murmur , an ... chronic conditions, iron-deficiency anemia can make their condition worse or result in treatments not working as well. Look for Diagnosis will discuss any ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... normally stores but has used up. Increase your intake of vitamin C to help your body absorb iron. Avoid drinking black tea, which reduces iron absorption. Other treatments If you have chronic kidney disease and iron-deficiency anemia, your doctor may recommend ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision Medicine (TOPMed) Program now includes ... Studies (REDS) program Blood Disorders and Blood Safety Trans-Omics for Precision Medicine (TOPMed) Program Non-NHLBI ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Medicine (TOPMed) Program Non-NHLBI resources Anemia (National Library of Medicine, MedlinePlus) Anemia in Chronic Kidney Disease ( ... Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library of Medicine, MedlinePlus) Building 31 31 Center Drive ...

  4. Iodine-deficiency disorders

    NARCIS (Netherlands)

    Zimmermann, M.B.; Jooste, P.L.; Pandav, C.S.

    2008-01-01

    billion individuals worldwide have insufficient iodine intake, with those in south Asia and sub-Saharan Africa particularly affected. Iodine deficiency has many adverse effects on growth and development. These effects are due to inadequate production of thyroid hormone and are termed

  5. Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut.

    Science.gov (United States)

    Mantis, N J; Rol, N; Corthésy, B

    2011-11-01

    Secretory IgA (SIgA) serves as the first line of defense in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms. Through a process known as immune exclusion, SIgA promotes the clearance of antigens and pathogenic microorganisms from the intestinal lumen by blocking their access to epithelial receptors, entrapping them in mucus, and facilitating their removal by peristaltic and mucociliary activities. In addition, SIgA functions in mucosal immunity and intestinal homeostasis through mechanisms that have only recently been revealed. In just the past several years, SIgA has been identified as having the capacity to directly quench bacterial virulence factors, influence composition of the intestinal microbiota by Fab-dependent and Fab-independent mechanisms, promote retro-transport of antigens across the intestinal epithelium to dendritic cell subsets in gut-associated lymphoid tissue, and, finally, to downregulate proinflammatory responses normally associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. This review summarizes the intrinsic biological activities now associated with SIgA and their relationships with immunity and intestinal homeostasis.

  6. Status of IGA in Japanese plants and results of S/G pulled tube examinations

    International Nuclear Information System (INIS)

    Takamatsu, H.

    1986-01-01

    Currently there are 14 operating PWRs in Japan. Five of the plants have been affected by the intergranular stress corrosion cracking (IGSCC). The experience of the 14 plants with regard to tube plugging is summarized. The five affected plants are: Mihama 2, Takahama 1, Takahama 2, Ohi 1 and Genkai 1. The first two plants experienced IGSCC in the tube sheet crevice region (55 and 124 tubes plugged) and a slight problem with IGSCC in tube support plate crevices (13 and 8 tubes plugged). The other three plants have experienced extensive IGSCC in their tube support plate crevices (1330, 773 and 667 tubes plugged, respectively). The Japanese consider that their IGSCC (IGA) problem is caused by a combination material and environmental factors. All three factors must be present for attack to take place. If the two environmental factors can be controlled, then the attack will stop. The preventive measures being employed by the Japanese are given. These include: prevention of free caustic (i.e., sludge lancing, crevice cleaning, boron injection and improvement in water treatment) and maintenance of deoxidation environment (i.e., hydrazine soaking before operation and enriching the concentration of hydrazine in the secondary water)

  7. Prevalence of serological markers for celiac disease (IgA and IgG class antigliadin antibodies and IgA class antiendomysium antibodies in patients with autoimmune rheumatologic diseases in Belo Horizonte, MG, Brazil Pesquisa de anticorpos antigliadina (classes IgA e IgG e anticorpos antiendomísio classe IgA, em pacientes com doenças reumatológicas autoimunes em Belo Horizonte, Brasil

    Directory of Open Access Journals (Sweden)

    Victor de Barros Koehne

    2010-09-01

    Full Text Available CONTEXT: Patients with autoimmune rheumatologic conditions and celiac disease tend to have a variety of autoantibodies, many of which have no clear pathogenic role. The literature contains frequent reports of celiac disease being more prevalent in patients with rheumatologic diseases, although this remains controversial. OBJECTIVES: To investigate the prevalence of positive serum tests for celiac disease, particularly IgA and IgG antigliadin (AGA antibodies and IgA antiendomysium antibodies (EmA in patients with autoimmune rheumatologic diseases. A second aim was to correlate positive serum tests with prednisone and immunosuppressant medication. METHODS: A total of 190 adults and pediatric patients with a variety of autoimmune rheumatologic diseases (systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis and spondyloarthrophathies were evaluated and tested for IgA and IgG antigliadin-antibodies and IgA antiendomysium antibodies. Patients with positive serum tests underwent endoscopic duodenal biopsies for pathology studies. RESULTS: There were four positive sera (2.1% for AGA IgA, all of which tested negative for AGA IgG and EmA. Three sera (1.6% tested positive for AGA IgG; all were negative for AGA IgA and EmA. The EmA test at a 1:2.5 serum dilution tested positive in 94 patients (49.5%; at a 1:5 serum dilution it was positive in 41 patients (21.6%. Eleven subjects tested positive for EmA at 1:40 dilution; and all of these tested negative for IgA tissue antitransglutaminase (tTG antibodies. Nine of the 11 EmA-positive patients and all 7 patients with positive antigliadin antibodies tests underwent duodenal endoscopic biopsies, and no significant changes were demonstrated in their duodenal mucosa. A positive EmA was associated with elevated optical density AGA IgA readings; however, there was no relationship between positive EmA and AGA IgG optical density readings. Prednisone and immunosuppressant use were unrelated

  8. IgA, IgE e subclasses de IgG anti-Candida albicans no soro e lavado vaginal de pacientes com candidíase vulvovaginal IgA, IgE and IgG subclasses to Candida albicans in serum and vaginal fluid from patients with vulvovaginal candidiasis

    Directory of Open Access Journals (Sweden)

    Ricardo José Victal de Carvalho

    2003-01-01

    with clinical symptoms of vulvovaginal candidiasis (15 positive vaginal culture to C. albicans, 11 negative culture and 4 positive culture to non-C. albicans and 12 asymptomatic control women were selected. Serum and vaginal wash samples were obtained for the detection of anti-C. albicans antibodies by ELISA. RESULTS: Symptomatic patients with positive culture showed significantly higher levels of specific IgA in vaginal washes and lower in serum than those with negative culture. Specific serum IgE levels were very low compared to vaginal IgE. High levels of total specific IgG were found in serum and vaginal washes in both groups, regardless the fungal presence or absence. Specific IgG1 e IgG4 levels were significantly higher only in vaginal washes from symptomatic patients with positive culture, with a slightly higher IgG1/IgG4 ratio, indicating that the IgG1 antibody response may be predominantly involved in the fungal clearance. CONCLUSION: Our results indicate a pronounced antibody response of IgA, IgG1 and IgG4 to C. albicans in vaginal washes in symptomatic patients with positive culture, suggesting a important role of these antibodies in the local immune response triggered by the presence of the fungus.

  9. Inmunodeficiencias humorales: Un estudio en tres Centros de Inmunología Clínica de adultos en la Ciudad de Buenos Aires Antibody deficiencies: A survey from three Clinical Immunology Centers for adults in Buenos Aires City

    Directory of Open Access Journals (Sweden)

    Diego S. Fernández Romero

    2011-08-01

    infections of the respiratory tract. The aim of our study was to describe the clinical characteristics of 128 patients with suspected or confirmed AD who were referred to 3 immunodeficiency centers for adults, from June 2004 to December 2009. Three of these patients (2.3% consulted for recurrent infections only once, without sufficient data for a proper classification, and were excluded. Of the remaining 125 patients, in 21 (16.8% AD was excluded, 8 cases (6.4% were diagnosed with sec ondary antibody immunodeficiency (SAD and 96 (76.8% with primary antibody immunodeficiency (PAD. SAD causes were: one renal failure, one phenytoin use, two monoclonal gammopathy and four B cell lymphoma. The causes of these 96 PAD were: 57 common variable immunodeficiency, 12 X-linked agammaglobulinaemia, 10 selective IgA deficiency, seven IgG1 deficiency, three hyper- IgM syndrome, three IgM deficiency, two X-linked proliferative syndrome, one Good syndrome and one antibody functional deficiency. Sixty-seven patients were in follow up at the time of completion of the study, 25 of them were on follow up at the beginning of the study. Among the 58 patients with indication of gamma globulin replacement therapy, 54 were in treatment at the end of the study. In four patients the initial diagnosis of PAD was not confirmed.

  10. Ocular toxoplasmosis: evaluation of lacrimal - specific secretory IgA levels in both patients with active and inactive phases of the disease

    Directory of Open Access Journals (Sweden)

    Luiz Felipe Lynch

    2011-08-01

    Full Text Available Ocular toxoplasmosis can result in recurrent uveitis. Studies have shown that a correlation between active ocular toxoplasmosis and the presence of anti-Toxoplasma gondii secretory IgA (SIgA in tears. This study compares anti-T. gondii SIgA levels in patients' tears during the acute and inactive phases of toxoplasmic uveitis. Twenty-nine positive tear specific SIgA for T. gondii patients with acute toxoplasmic uveitis were selected and were followed-up for at least two years, when the anti-T. gondii SIgA tears levels were determined. Specific SIgA for T. gondii was negative in 22 patients (75.86% and positive in seven patients (24.13% of whom six (85.7% were followed over three years. Average SIgA levels during the acute phase are 1.54 and decrease significantly to 0.72 (p = 0.0001 during the inactive phase of disease. Because anti-T. gondii SIgA in the tear is negative in 75.86% of patients after the acute phase of infection, T. gondii SIgA levels may be used as a complementary diagnostic marker for active ocular toxoplasmosis.

  11. Iron deficiency and cognitive functions

    Directory of Open Access Journals (Sweden)

    Jáuregui-Lobera I

    2014-11-01

    Full Text Available Ignacio Jáuregui-Lobera Department of Nutrition and Bromatology, Pablo de Olavide University, Seville, Spain Abstract: Micronutrient deficiencies, especially those related to iodine and iron, are linked to different cognitive impairments, as well as to potential long-term behavioral changes. Among the cognitive impairments caused by iron deficiency, those referring to attention span, intelligence, and sensory perception functions are mainly cited, as well as those associated with emotions and behavior, often directly related to the presence of iron deficiency anemia. In addition, iron deficiency without anemia may cause cognitive disturbances. At present, the prevalence of iron deficiency and iron deficiency anemia is 2%–6% among European children. Given the importance of iron deficiency relative to proper cognitive development and the alterations that can persist through adulthood as a result of this deficiency, the objective of this study was to review the current state of knowledge about this health problem. The relevance of iron deficiency and iron deficiency anemia, the distinction between the cognitive consequences of iron deficiency and those affecting specifically cognitive development, and the debate about the utility of iron supplements are the most relevant and controversial topics. Despite there being methodological differences among studies, there is some evidence that iron supplementation improves cognitive functions. Nevertheless, this must be confirmed by means of adequate follow-up studies among different groups. Keywords: iron deficiency, anemia, cognitive functions, supplementation

  12. Adult growth hormone deficiency

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Adult growth hormone deficiency (AGHD is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1 (insulin like growth factor-1. It is generally well tolerated at the low-doses used in adults. Pegylated human growth hormone therapy is on the horizon, with a convenient once a week dosing.

  13. Biotin and biotinidase deficiency

    OpenAIRE

    Zempleni, Janos; Hassan, Yousef I; Wijeratne, Subhashinee SK

    2008-01-01

    Biotin is a water-soluble vitamin that serves as an essential coenzyme for five carboxylases in mammals. Biotin-dependent carboxylases catalyze the fixation of bicarbonate in organic acids and play crucial roles in the metabolism of fatty acids, amino acids and glucose. Carboxylase activities decrease substantially in response to biotin deficiency. Biotin is also covalently attached to histones; biotinylated histones are enriched in repeat regions in the human genome and appear to play a role...

  14. Vitamin D Deficiency in Patients with Tuberculosis

    International Nuclear Information System (INIS)

    Iftikhar, R.; Kamran, S. M.; Haider, E.; Qadir, A.; Usman, H. B.

    2013-01-01

    Objective: To determine the frequency and association of Vitamin D deficiency in patients with tuberculosis. Study Design: Case control study. Place and Duration of Study: Medical Department, Combined Military Hospital, Kharian, from July 2010 to June 2012. Methodology: One hundred and five outdoor patients of tuberculosis were selected with 255 gender matched controls. Tuberculosis was diagnosed by presence of acid fast bacilli in sputum smears, positive culture for Mycobacterium tuberculosis or demonstration of chronic caseating granulomatous inflammation in tissue specimens. Controls were drawn randomly from general population. Serum 25 hydroxyvitamin D [25 (OH) D3] levels < 25 ng/ml was considered Vitamin D deficiency. The results were analyzed on SPSS version 17. Results: Mean Vitamin D levels were 23.23 A+- 6.81 ng/ml in cases, 29.27 A+- 8.89 ng/ml in controls (p < 0.0001). Vitamin D deficiency was found in 57% of cases and 33% controls (p < 0.0001). Mean Vitamin D levels were significantly lower in females with tuberculosis (20.84 ng/ml) as compared to males (25.03 ng/ml, p = 0.002). Mean BMI in patients of tuberculosis with Vitamin D deficiency were 19.51 A+- 1.77 kg/m2 and in patients with normal Vitamin D were 21.65 A+- 1.79 kg/m2 (p < 0.0001). Mean Vitamin D levels in patients with multi-drug resistant tuberculosis was lower to a mean of 15.41 A+- 4.67 ng/ml (p < 0.0001). Conclusion: There is significant deficiency of Vitamin D in patients with tuberculosis as compared to controls. This deficiency is more pronounced in females, individuals with low BMI, extra pulmonary and MDR tuberculosis. (author)

  15. Profiling and initial validation of urinary microRNAs as biomarkers in IgA nephropathy

    Directory of Open Access Journals (Sweden)

    Nannan Wang

    2015-06-01

    Full Text Available Background. MicroRNAs (miRNAs have been found in virtually all body fluids and used successfully as biomarkers for various diseases. Evidence indicates that miRNAs have important roles in IgA nephropathy (IgAN, a major cause of renal failure. In this study, we looked for differentially expressed miRNAs in IgAN and further evaluated the correlations between candidate miRNAs and the severity of IgAN.Methods. Microarray and RT-qRCR (real-time quantitative polymerase chain reaction were sequentially used to screen and further verify miRNA expression profiles in urinary sediments of IgAN patients in two independent cohorts. The screening cohort consisted of 32 urine samples from 18 patients with IgAN, 4 patients with MN (membranous nephropathy, 4 patients with MCD (minimal changes disease and 6 healthy subjects; the validation cohort consisted of 102 IgAN patients, 41 MN patients, 27 MCD patients and 34 healthy subjects. The renal pathological lesions of patients with IgAN were evaluated according to Lee’s grading system and Oxford classification.Results. At the screening phase, significance analysis of microarrays analysis showed that no miRNA was differentially expressed in the IgAN group compared to all control groups. But IgAN grade I–II and III subgroups (according to Lee’s grading system shared dysregulation of two miRNAs (miR-3613-3p and miR-4668-5p. At the validation phase, RT-qPCR results showed that urinary level of miR-3613-3p was significantly lower in IgAN than that in MN, MCD and healthy controls (0.47, 0.44 and 0.24 folds, respectively, all P < 0.01 by Mann–Whitney U test; urinary level of miR-4668-5p was also significantly lower in IgAN than that in healthy controls (0.49 fold, P < 0.01. Significant correlations were found between urinary levels of miR-3613-3p with 24-hour urinary protein excretion (Spearman r = 0.50, P = 0.034, eGFR (estimated glomerular filtration rate (r = − 0.48, P = 0.043 and Lee’s grades (r = 0.57, P

  16. Patients with IgA nephropathy exhibit high systemic PDGF-DD levels.

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    Boor, Peter; Eitner, Frank; Cohen, Clemens D; Lindenmeyer, Maja T; Mertens, Peter R; Ostendorf, Tammo; Floege, Jürgen

    2009-09-01

    Platelet-derived growth factor (PDGF) is a central mediator of mesangioproliferative glomerulonephritis (GN). In experimental mesangioproliferative GN, PDGF-DD serum levels, unlike PDGF-BB, increased up to 1000-fold. We assessed disease activity in 72 patients with GN, established a novel PDGF-D ELISA and then determined their PDGF-DD levels. In parallel, we studied renal PDGF-DD mRNA expression by RT-PCR. PDGF-DD serum levels in patients with IgA nephropathy (IgAN) were significantly higher (1.67 +/- 0.45 ng/ml) and in patients with lupus nephritis significantly lower (0.66 +/- 0.86 ng/ml) compared to healthy controls (1.17 +/- 0.46 ng/ml), while patients with focal segmental glomerulosclerosis, membranous GN and ANCA-positive vasculitis did not differ from controls. The subgroup of IgAN patients with elevated PDGF-DD levels (27% of samples) did not differ in their clinical features from those with normal PDGF-DD levels. In IgAN patients with repetitive PDGF-DD determinations, most exhibited only minor fluctuations of serum levels over time. Intrarenal PDGF-DD mRNA expression did not differ between controls and patients, suggesting an extrarenal source of the elevated PDGF-DD in IgAN. Serum PDGF-DD levels were specifically elevated in patients with IgAN, in particular in those with early disease, i.e. preserved renal function. Our data support the rationale for anti-PDGF-DD therapy in mesangioproliferative GN.

  17. Ambulatory blood pressure and tubulointerstitial injury in patients with IgA nephropathy.

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    Haruhara, Kotaro; Tsuboi, Nobuo; Koike, Kentaro; Kanzaki, Go; Okabayashi, Yusuke; Miyazaki, Yoichi; Kawamura, Tetsuya; Ogura, Makoto; Yokoo, Takashi

    2015-12-01

    Few studies have been conducted to assess the ambulatory blood pressure (ABP) in IgA nephropathy (IgAN) patients. This study aimed to determine the relationships between ABP and renal histopathological findings assessed using the Oxford classification (OC) and the Japanese classification (JC), which have recently established histopathological criteria for IgAN. This cross-sectional study included biopsy-diagnosed IgAN patients, in whom both a renal biopsy and ABP measurement were performed. The histopathological findings were assessed using the OC and the JC and were analyzed in relation to the ABP. A total of 111 IgAN patients were included. The score of interstitial fibrosis and tubular atrophy (T score) using the OC was a significantly associated factor with both the daytime and nighttime ABP values. In contrast, the other histopathological scores, including mesangial hypercellularity, endocapillary hypercellularity and segmental glomerulosclerosis, did not show significant associations with the ABP. The histological grade (H-grade) using the JC, which was based on the sum of injured glomeruli, was associated with the daytime ABP, but not with the nighttime ABP. The associations between the T score using the OC (%) and the daytime and nighttime ABP values were independent of age, gender, renal function, proteinuria and the use of antihypertensive medications, whereas the H-grade using the JC (%) did not show significant associations after adjusting for these clinical parameters. These results suggest that the T score using the OC is the most relevant renal histopathological parameter associated with abnormalities of circadian blood pressure in IgAN patients.

  18. Predicting Post-Transplant Recurrence of IgA Nephropathy: The Importance of Crescents.

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    Avasare, Rupali S; Rosenstiel, Paul E; Zaky, Ziad S; Tsapepas, Demetra S; Appel, Gerald B; Markowitz, Glen S; Bomback, Andrew S; Canetta, Pietro A

    2017-01-01

    Most studies that have assessed the predictors of recurrent IgA nephropathy (IgAN) in the renal allograft have focused on post-transplant features. Identifying high-risk pre-transplant features of IgAN is useful for counseling patients and may help in tailoring post-transplant immunosuppression. We investigated the pre-transplant clinical and biopsy features of 62 patients with IgAN who received transplants at Columbia University Medical Center from 2001 to 2012 and compared the characteristics and outcomes of patients with IgAN recurrence to those without recurrence. The primary outcome was time to recurrent IgAN. Secondary outcomes were a composite of doubling of creatinine or allograft failure, and recurrent IgAN as a cause of allograft dysfunction. Of the 62 patients, 14 had recurrent IgAN in the allograft. Mean time to recurrence was 2.75 years. Those with recurrent disease were younger at the time of native kidney biopsy (29 vs. 41 years, p < 0.0009). Black race and Hispanic ethnicity composed a higher proportion of the recurrent disease group. On multivariable analysis, significant predictors of recurrent IgAN included age at diagnosis (hazards ratio (HR) 0.911, 95% CI 0.85-0.98), burden of crescents on native biopsy (HR 1.21 per 10% increase in crescents, 95% CI 1.00-1.47) and allograft rejection (HR 3.59, 95% CI 1.10-11.7). Features of native IgAN can help predict the risk of recurrent disease in the renal allograft. In particular, immunologically active disease represented by earlier age of onset and greater burden of crescents on native biopsy is more likely to recur after transplant. © 2017 S. Karger AG, Basel.

  19. Association between polymorphisms in Interleukin-17 receptor A gene and childhood IgA nephropathy

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    Seung-Ah Baek

    2010-02-01

    Full Text Available Purpose : Interleukin-17 (IL-17 is produced by activated CD4+T cells and exhibits pleiotropic biological activity on various cell types. IL-17 was reported to be involved in the immunoregulatory response in IgA nephropathy (IgAN. Our aim was to investigate the association between single-nucleotide polymorphisms (SNPs in IL-17 receptor A (IL-17RA gene and childhood IgAN. Methods : We analyzed the SNPs in the IL-17RA in 156 children with biopsy-proven IgAN and 245 healthy controls. We divided the IgAN patients into 2 groups and compared them with respect to proteinuria (?#180; and &gt;4 mg/m2/h, ?#180;0 and &gt;40 mg/m2/h, respectively and the presence of pathological levels of biomarkers of diseases such as interstitial fibrosis, tubular atrophy, or global sclerosis. Results : No difference was observed between the SNP genotypes rs2895332, rs1468488, and rs4819553 between IgAN patients and control subjects. In addition, no significant difference was observed between allele frequency of SNPs rs2895 332, rs1468488, and rs4819553 between patients in the early and advanced stage of the disease. However, significant difference was observed between the genotype of SNP rs2895332 between patients with proteinuria (&gt;4 mg/m2/h and those without proteinuria (codominant model OR 0.36, 95% CI 0.19&#8211;0.66, P&lt;0.001; dominant model OR 0.35, 95% CI 0.17&#8211;0.69 P=0.002; recessive model OR 0.12, 95% CI 0.01&#8211;1.06 P=0.025. Conclusion : Our results indicate that the SNP in IL-17RA (rs2895332 may be related to the development of proteinuria in IgAN patients.

  20. The importance of sensitive screening for abnormal glucose metabolism in patients with IgA nephropathy.

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    Jia, Xiaoyuan; Pan, Xiaoxia; Xie, Jingyuan; Shen, Pingyan; Wang, Zhaohui; Li, Ya; Wang, Weiming; Chen, Nan

    2016-01-01

    To investigate the prevalence of abnormal glucose metabolism, insulin resistance (IR) and the related risk factors in IgA nephropathy (IgAN) patients. We analyzed oral glucose tolerance test (OGTT) and clinical data of 107 IgAN patients and 106 healthy controls. Glucose metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) and the insulin sensitivity index (ISI) of both groups were evaluated. The prevalence of abnormal glucose metabolism was significantly higher in the IgAN group than in the control group (41.12% vs. 9.43%, p glucose, fasting insulin, OGTT 2-hour blood glucose, OGTT 2-hour insulin, HOMA-IR, and lower ISI than healthy controls. Triglyceride (OR = 2.55), 24-hour urine protein excretion (OR = 1.39), and age (OR = 1.06) were independent risk factors for abnormal glucose metabolism in IgAN patients. BMI, eGFR, 24-hour urine protein excretion, triglyceride, fasting blood glucose, fasting insulin, OGTT 2-hour blood glucose, and OGTT 2-hour insulin were significantly higher in IgAN patients with IR than in IgAN patients without IR, while HDL and ISI were significantly lower. BMI, serum albumin, and 24-hour urine protein excretion were correlated factors of IR in IgAN patients. Our study highlighted that abnormal glucose metabolism was common in IgAN patients. Triglyceride and 24-hour urine protein excretion were significant risk factors for abnormal glucose metabolism. Therefore, sensitive screening for glucose metabolism status and timely intervention should be carried out in clinical work.