IgA1 Glycosylation Is Heritable in Healthy Twins

Lomax-Browne, Hannah J.; Visconti, Alessia; Pusey, Charles D.; Cook, H. Terence; Spector, Tim D.; Pickering, Matthew C.; Falchi, Mario

doi:10.1681/asn.2016020184

Cited by 28 publications

(27 citation statements)

References 37 publications

(44 reference statements)

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“…In vitro evidence supports a role for these IgA-containing immune complexes in driving glomerular injury through mesangial cell proliferation and secretion of cytokines, chemokines, growth factors and extracellular matrix components promoting glomerular inflammation and glomerulosclerosis [20][21][22] . Consistent with previous data, we show that Gd-IgA1 level is a heritable trait [23][24][25][26] and use a genome-wide approach to identify the common genetic factor that influences Gd-IgA1 levels in Caucasian and East Asian populations.…”

Section: Introductionsupporting

confidence: 90%

Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1

Gale

Molyneux

Wimbury

et al. 2017

JASN

105

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IgA nephropathy (IgAN), an important cause of kidney failure, is characterized by glomerular IgA deposition and is associated with changes in O-glycosylation of the IgA1 molecule. Here, we sought to identify genetic factors contributing to levels of galactose-deficient IgA1 (Gd-IgA1) in Caucasian and Chinese populations.Gd-IgA1 levels were elevated in IgAN patients compared with ethnically matched healthy subjects and correlated with evidence of disease progression. Caucasian IgAN patients exhibited significantly higher Gd-IgA1 levels than Chinese patients. Among individuals without IgAN, Gd-IgA1 levels were not correlated with kidney function. Gd-IgA1 level heritability (h ). This association was replicated in GWAS of separate cohorts comprising: 308 UK patients with membranous glomerulonephritis (p<10

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Section: Introductionsupporting

confidence: 90%

Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1

Gale

Molyneux

Wimbury

et al. 2017

JASN

105

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“…The extent of Mesangial Gd-IgA1 deposition and its serum levels was associated with disease progression [14,15]. However, in a recent multicentric study; there was no favorable effect of rituximab on the level of Gd-IgA1 [16]. Moreover, a recent study questioned the role of autoimmunity in the development of aggressive disease in IgAN and indicated that a higher level of Gd-IgA1 is a hereditary predisposition [17].…”

Section: Discussionmentioning

confidence: 99%

The limited role and risky profile of Rituximab in nephritis associated with Henoch-Schönlein purpura

El-Reshaid

Al-Bader

2019

J. Drug Delivery Ther.

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Adult-onset IgA vasculitis or Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized by IgA1-dominant deposits. The symptoms include cutaneous purpura, ankle arthritis, enteritis and nephritis. HSP nephritis (HSPN) can be severe and refractory to corticosteroids with/without immunosuppressive agents. The concept of depletion of antibody producing B cell with Rituximab is appealing despite the uncertainity of HSP pathogenesis. In the present case report; we describe our experience with Rituximab treatment in a patient with this disease. Our patient had different triggering factors for her relapses and lately Rituximab itself. Review of the literature indicates that autoantibodies to Gd-IgA1 did not decrease with Rituximab therapy and others indicated an inherited predisposition for higher levels in patients with progressive disease. Our findings confirm the limited role and risky profile of Rituximab in treatment of HSP. Keywords: HSP, IgA, Rituximab, vasculitis.

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“…There is convincing evidence that genetic factors play a major role in influencing the composition of circulating IgA1 O ‐glycoforms in serum with heritability of serum IgA1 O‐galactosylation being reported as high as 80% …”

Section: Differences In Pathogenic Pathways In Igan In Different Ethnmentioning

confidence: 96%

“…There is convincing evidence that genetic factors play a major role in influencing the composition of circulating IgA1 O-glycoforms in serum with heritability of serum IgA1 O-galactosylation being reported as high as 80%. [97][98][99][100] Ogalactosylation of the IgA1 hinge region is mediated by a series of complex stepwise co-/post-translational modifications and one of the key enzymes involved is core 1 beta 1, 3-galactosyltransferase(C1GalT1), whose activity catalyses the addition of galactose to N-acetylgalactosamine. In a recent quantitative trait GWAS multiple single nucleotide polymorphisms (SNP) were identified in the non-coding region of the C1GALT1 gene to be associated with the extent of serum IgA1 O-galactosylation in IgAN, healthy subjects, membranous nephropathy in Caucasian and Chinese cohorts.…”

Section: Differences In Pathogenic Pathways In Igan In Different Ethnmentioning

confidence: 99%

Is immunoglobulin A nephropathy different in different ethnic populations?

2019

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Immunoglobulin A nephropathy (IgAN) is one of the commonest global patterns of primary glomerulonephritis and remains a leading cause of chronic kidney disease and end‐stage renal disease. The sole diagnostic criterion of IgAN remains the presence of dominant mesangial immunoglobulin A deposits on kidney biopsy. Beyond this defining feature, there is significant heterogeneity in the epidemiology, clinical presentation, renal progression and long‐term outcomes of IgAN in different ethnic populations. Mirroring this heterogeneity in clinical phenotypes, there is also marked ethnic variation in the extent of histopathological lesions observed on kidney biopsy, which may partly explain the well‐documented differences in response to immunomodulatory agents reported in different regions of the world. In parallel, disparities have been identified in genetic association studies and key pathogenic pathways in different ethnic populations. Understanding the basis for these differences in IgAN has important implications for both clinical care and future research. In this review, we will examine the impact of ethnicity on the epidemiology, clinical presentation and outcomes, pathogenesis and genetic associations in IgAN.

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IgA1 Glycosylation Is Heritable in Healthy Twins

Cited by 28 publications

References 37 publications

Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1

Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1

The limited role and risky profile of Rituximab in nephritis associated with Henoch-Schönlein purpura

Is immunoglobulin A nephropathy different in different ethnic populations?

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