Relation of mesangial IgA glomerulonephritis to polymorphism of immunoglobulin heavy chain switch region.

Demaine, Andrew; Rambausek, M.; Knight, John; Williams, D G; Welsh, Kenneth I.; Ritz, E

doi:10.1172/jci113361

Cited by 47 publications

(14 citation statements)

References 15 publications

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“…In fact, it has been reported that a polymorphism in the I α1 promoter region, the regulatory region in class switch recombination, possibly causes enhanced IgA production in some, but not all, patients with IgAN (Yano et al 1998). In addition, many other genetic polymorphisms, for example, specific human leukocyte antigen (HLA) encoded by the major histocompatibility complex (MHC) locus, genes within the Ig heavy chain loci, and T-cell receptor constant α chain gene, have been reported to be associated with IgAN (Fennessy et al 1996;Demaine et al 1988;Deenitchina et al 1999).…”

Section: Resultsmentioning

confidence: 99%

Genetic polymorphisms in the promoter and 5′ UTR region of the Fc α receptor (CD89) are not associated with a risk of IgA nephropathy

et al. 2001

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The molecular mechanisms of immunoglobulin A glomerulonephritis (IgAN), the most prevalent form of primary glomerulonephritis, remain poorly understood. Recently, the essential role of soluble Fc α receptor (FcαR) in the formation of the pathogenic immune complex has been revealed. We screened genomic DNA samples from patients with IgAN and those with other glomerular diseases for polymorphisms in the promoter and the 5Ј-untranslated region region of the FcαR gene by direct nucleotide sequencing. We found three common polymorphisms in this region, T-114C, T-27C, and Tϩ56C from the putative transcription initiation site. Each genotype was determined in 151 patients with IgAN and 163 patients with other glomerular diseases shown to have no mesangial IgA deposition by renal biopsy. The haplotype analysis revealed tight linkage disequilibrium among them. An association study for the genotype, allele, and haplotype frequencies of the polymorphisms between the patients with histologically proven IgAN and those with other glomerular diseases showed no significant difference in the genotype, allele, and haplotype distributions between the two groups. The present study indicates that the analyzed polymorphisms of the FcαR gene do not appear to be primarily involved in the susceptibility to IgAN.

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Section: Resultsmentioning

confidence: 99%

Genetic polymorphisms in the promoter and 5′ UTR region of the Fc α receptor (CD89) are not associated with a risk of IgA nephropathy

et al. 2001

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“…With regard to their T cells, reports describe hyperactivity of helper T cells [13], depression of IgA-specific suppressor T cells [14], and an increase in Fca-positive T cells [15]. Abnormalities in immunoglobulins include elevated serum IgA concentra tion [16,17], high serum level of polymeric macromolecular IgA [18], appearance of autoantibodies [19,20], and unusual variations in the switch region of immunoglobulin heavy chain [21]. However, the exact immunoregulatory defects responsible for the pathogenesis of IgAN are still obscure.…”

Section: Introductionmentioning

confidence: 99%

Neonatal Thymectomy Diminishes Renal IgA Deposition in IgA Nephropathy-Prone ddY Mice

Nagasawa

Mitarai

Utsunomiya

et al. 1994

Nephron

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To understand the role of thymus-derived T cells in the development of IgA nephropathy (IgAN), we performed neonatal thymectomies on ddY mice, in which this disease occurs spontaneously. Although these thymectomized mice developed a renal lesion closely resembling that typical of IgAN, the extent of their mesangial IgA deposition was significantly milder than in control sham-operated mice. The immunological mechanisms responsible for curbing this mesangial deposition of IgA were then analyzed. The percentage of splenic T cells and the magnitude of mitogenic responses both decreased markedly in thymectomized compared with control mice. These results suggested the hypofunction of thymus-derived T cells. However, serum IgA levels were almost identical in both groups. Furthermore, sera from both groups contained similar amounts of macromolecular IgA, of the type formerly eluted from the affected glomeruli of patients with IgAN. These results strongly indicate that thymus-derived T cells or their products determine the amount of IgA deposited in the kidneys of ddY mice.

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“…Manyother gene polymorphisms have been reported to be associated with IgAN. For example, polymorphisms of specific HLAantigen encoded by the MHClocus, genes within the Ig heavy chain loci, and T-cell receptor constant alpha chain gene were reported to be associated with IgAN (21)(22)(23). Genetic factors, which determine the susceptibility to dysregulation of the IgA immunesystem and to the pathogenesis of IgAN are thought to be heterogeneous.…”

Section: Discussionmentioning

confidence: 99%

Association of Gene Polymorphism of Polymeric Immunoglobulin Receptor and IgA Nephropathy.

et al. 2001

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Objective In order to explore the possibility that genetic predisposition to dysfunction of mucosal immunity and the IgA processing pathway plays a role in the pathogenesis of mesangial IgAl deposition in IgAN, we examined the possible association of the gene polymorphismof plgR in the patients with and without IgAN. Subjects and Methods Genomic DNAof peripheral blood cells was isolated from 372 individuals including 172 histologically confirmed IgAN patients. Segments of the plgR gene were PCRamplified and restriction fragment length polymorphism was determined as Al and A2 with and without Pvu II site, respectively. Results The plgR genotype distribution was significantly different between the patients with IgAN and those without IgAN. Allele frequency ofA2 was higher in IgAN than in other renal diseases (Al and A2; 0.516 and 0.484 in IgAN, 0.641 and 0.359 in others, %2=9.84, P=0.0017, Odds ratio=1.71). Moreover, the subjects with A2A2genotype were associated with a relatively low level of serum IgA only in the patients with IgANbut not in other renal diseases. The difference of allele frequencies was moreremarkable in the patients with a serum IgA level of less than 300 mg/dl (Al and A2; 0.439 and 0.561 in IgAN, 0.702 and 0.298 in others, %2=12.44, P=0.0004, Odds ratio=3.01). Conclusion This is the first demonstration of the plgR gene polymorphisms in IgANwhich are associated with its clinical phenotype. Gene polymorphisms of plgR may be candidate genetic markers of susceptibility to IgAN. (Internal Medicine 40: 867-872, 2001)

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Relation of mesangial IgA glomerulonephritis to polymorphism of immunoglobulin heavy chain switch region.

Abstract: We have investigated the switch regions of Ig heavy chain genes of patients with IgA glomerulonephritis (IgA-GN) using restriction fragment length polymorphism (RFLP) analysis.

Cited by 47 publications

References 15 publications

Genetic polymorphisms in the promoter and 5′ UTR region of the Fc α receptor (CD89) are not associated with a risk of IgA nephropathy

Genetic polymorphisms in the promoter and 5′ UTR region of the Fc α receptor (CD89) are not associated with a risk of IgA nephropathy

Neonatal Thymectomy Diminishes Renal IgA Deposition in IgA Nephropathy-Prone ddY Mice

Association of Gene Polymorphism of Polymeric Immunoglobulin Receptor and IgA Nephropathy.

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