Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to clarify intraglomerular cellular activation and cytokine involvement in IgA nephropathy, the glomerular expression of MHC class II antigens (HLA-DR and DQ) and cellular proliferative nuclear antigen (Ki-67), and serum gamma-interferon (gamma-IFN) levels were evaluated in 49 patients with IgA nephropathy. HLA-DR was detected in all but 4 patients in whom glomerular sclerosis was present. HLA-DQ and Ki-67 were observed in 51 and 38% of the patients, respectively. Proteinuria, recent macroscopic hematuria, mesangial proliferation, and extracapillary and endocapillary lesions were more frequent and more severe in HLA-DQ-positive than in HLA-DQ-negative patients. In 10 patients with acute exacerbation, endocapillary lesions and HLA-DQ and Ki-67 expression were present in 70, 80 and 88%, respectively. Serum gamma-IFN levels were high in the patients (2.0 +/- 0.3 U/ml, n = 40), especially during acute exacerbation (3.4 +/- 1.1 U/ml, n = 9). Glomerular HLA-DO and Ki-67 expression correlated with serum gamma-IFN levels (r = 0.73, p less than 0.01 for HLA-DQ; r = 0.75, p less than 0.01 for Ki-67). Renal biopsy specimens taken before and after prednisolone and/or urokinase therapy were available from 4 patients. There was strong reactivity to HLA-DQ in the glomerular tufts of all 4 pretreatment samples. However, HLA-DQ reactivity disappeared after treatment in 3 samples, concomitant with normalization of serum gamma-IFN levels. We conclude that serum gamma-IFN levels are related to glomerular HLA-DQ and Ki-67 expression and acute exacerbation in patients with IgA nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraglomerular expression of MHC class II and Ki-67 antigens and serum gamma-interferon levels in IgA nephropathy. 143 9

We have investigated associations between HLA-DQ beta and TCRC beta gene polymorphisms and IgA nephropathy in Japanese children. DNA from 33 cases of IgA nephropathy, 29 cases of nephrotic syndrome and 29 cases of healthy volunteers were analyzed by Southern blotting using HLA-DQ beta and TCRC beta probes. A 2 kb (Taq I) polymorphic band that hybridized to the DQ beta probe was predominant in patients of IgA nephropathy (p < 0.05) compared to the controls. The 10 kb (Bgl II) polymorphic band of TCRC beta was also predominantly present (but not significantly) in the DNA of these patients. Proteinuria in IgA nephropathy patients was found to be associated with this 10 kb TCR polymorphism. We conclude that the HLA-DQ beta and TCR genes make major contributions to the genetic pathogenesis of IgA nephropathy in Japanese children.
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PMID:[HLA-DQ region and TCR gene polymorphism associated with primary IgA nephropathy in Japanese children]. 939 41

Increasing evidence suggests a detrimental effect of donor-specific antibodies directed against the human leukocyte antigen (HLA)-A, -B, and -DR loci on renal allograft outcomes. Limited data exist on the impact of de novo HLA-DQ antibodies. Over a 3-year period, we prospectively monitored 347 renal transplant recipients without pre-transplant donor-specific antibodies for their development de novo. After 26 months of follow-up, 62 patients developed donor-specific antibodies, of which 48 had a HLA-DQ antibody either alone (33 patients) or in combination with an HLA-A, -B, or -DR antibody (15 patients). Only 14 patients developed a donor-specific HLA-A, -B, or -DR antibody without a HLA-DQ antibody present. Acute rejection occurred in 21% of the HLA-DQ-only patients, insignificant when compared with 11% of patients without donor-specific antibodies. At the last follow-up, the mean serum creatinine and the fraction of patients with proteinuria were significantly higher in those that developed only HLA-DQ than those without antibodies. The 3-year graft survival was significantly worse when HLA-DQ antibodies were combined with non-DQ antibodies (52%) compared with HLA-DQ alone, non-DQ antibodies alone, or no antibodies (92-94%). Thus, our prospective monitoring study found that donor-specific HLA-DQ antibodies were the most common type detected and these antibodies may contribute to inferior graft outcomes. Ongoing surveillance is necessary to determine the long-term outcome of patients developing HLA-DQ donor-specific antibodies.
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PMID:Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal transplantation. 2262 4

Membranous nephropathy is a noninflammatory autoimmune disease of the kidney glomerulus, characterized by the formation of immune deposits, complement-mediated proteinuria, and risk of renal failure. Considerable advances in understanding the molecular pathogenesis have occurred with the identification of several antigens [neutral endopeptidase, phospholipase A2 receptor (PLA2R), thrombospondin domain-containing 7A (THSD7A)] in cases arising from the neonatal period to adulthood and the characterization of antibody-binding domains (that is, epitopes). Immunization against PLA2R occurs in 70% to 80% of adult cases. The development of highly specific and sensitive assays of circulating antibodies has induced a paradigm shift in diagnosis and treatment monitoring. In addition, several interacting loci in HLA-DQ, HLA-DR, and PLA2R1, as well as classical human leukocyte antigen (HLA)-D alleles have been identified as being risk factors, depending on a patient's ethnicity. Additionally, mechanisms of antibody pathogenicity and pathways of complement activation are now better understood. Further research is mandatory for designing new therapeutic strategies, including the identifying triggering events, the molecular bases of remission and progression, and the T cell epitopes involved.
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PMID:Molecular Pathogenesis of Membranous Nephropathy. 3162 60