IgA nephropathy (IgAN) is the most common form of primary GN and an important cause of kidney failure. Characteristically, patients with IgAN have increased serum levels of undergalactosylated IgA1 (gd-IgA1). To assess the degree to which serum gd-IgA1 levels are genetically determined in healthy individuals, we determined serum IgA and gd-IgA1 levels by ELISA in a sample of 148 healthy female twins, including 27 monozygotic and 47 dizygotic pairs. Using the classic twin model, we found the heritability of serum gd-IgA1 and IgA levels to be 80% (95% confidence interval, 66% to 89%) and 46% (95% confidence interval, 15% to 69%), respectively. These data indicate that serum gd-IgA1 levels are highly heritable. Elucidating the genetic basis of this heritability will be important in understanding the pathogenesis of IgAN.
Mucosal Immunity
34.5K views |
+31 today
 Your new post is loading...
Your new post is loading...
Scoop.it!
The TNF family member a proliferation-inducing ligand (APRIL; also known as TNFSF13), produced by myeloid cells, participates in the generation and survival of antibody–producing plasma cells. We studied the potential role of APRIL in the pathogenesis of IgA nephropathy (IgAN). We found that a significant proportion of germinal centers (GCs) in tonsils of patients with IgAN contained cells aberrantly producing APRIL, contributing to an overall upregulation of tonsillar APRIL expression compared with that in tonsils of control patients with tonsillitis. In IgAN GC, antigen–experienced IgD–CD38+/–CD19+ B cells expressing a switched IgG/IgA B cell receptor produced APRIL. Notably, these GC B cells expressed mRNA encoding the common cleavable APRIL-α but also, the less frequent APRIL-/ mRNA, which encodes a protein that lacks a furin cleavage site and is, thus, the uncleavable membrane-bound form. Significant correlation between TLR9 and APRIL expression levels existed in tonsils from patients with IgAN. In vitro, repeated TLR9 stimulation induced APRIL expression in tonsillar B cells from control patients with tonsillitis. Clinically, aberrant APRIL expression in tonsillar GC correlated with greater proteinuria, and patients with IgAN and aberrant APRIL overexpression in tonsillar GC responded well to tonsillectomy, with parallel decreases in serum levels of galactose-deficient IgA1. Taken together, our data indicate that antibody disorders in IgAN associate with TLR9–induced aberrant expression of APRIL in tonsillar GC B cells.
Scoop.it!
#AIBD2016 P-098 Epidemiology and Risk Factors of IgA Nephropathy in Patients with IBD https://t.co/9kyLJvIne3
Scoop.it!
Transplantation. 2016 Sep;100(9):1955-62. doi: 10.1097/TP.0000000000000962.
Gilbert C FAURE's insight:
IgA nephropathy
Scoop.it!
Tohoku J Exp Med. 2016;240(3):199-208.
Scoop.it!
There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease.
Scoop.it!
IgA nephropathy (IgAN) is well identified by dominant IgA glomerular deposits; however, this immunohistologic entity can be an asymptomatic chance finding or present with an extremely variable course.
Scoop.it!
Copy number variations play an important role in human disease development. In a new study, Ai et al. have investigated copy number variations of the α-defensin gene in Chinese patients with IgA nephropathy (IgAN) and healthy controls.
Scoop.it!
Although IgA nephropathy is a common primary glomerulonephritis, its exact pathogenesis is not well defined.
Scoop.it!
Video Journal Club describing the Review article in Nature Review
Scoop.it!
A recent genome–wide association study of IgA nephropathy (IgAN) identified 1q32, which contains multiple complement regulatory genes, including the complement factor H (CFH) gene and the complement factor H–related (CFHRs) genes, as an...
Scoop.it!
Original Article from The New England Journal of Medicine — Intensive Supportive Care plus Immunosuppression in IgA Nephropathy
Scoop.it!
Stem cell Therapy treatment for IgA nephropathy
|
Scoop.it!
Lower proteinuria in blisibimod versus placebo treated patients
Changes in circulating B-cells and serum immunoglobulins consistent with BAFF inhibition HAYWARD, Calif., Dec. 06, 2016 (GLOBE NEWSWIRE) -- Anthera Pharmaceuticals, Inc. (Nasdaq:ANTH) today announced positive trends from the Week 48 analysis of the Phase 2 BRIGHT-SC proof-of-concept study in 57 patients with IgA nephropathy. The effects of blisibimod versus placebo were assessed through at least the 48 week time point in all
Scoop.it!
J Am Soc Nephrol. 2016 Nov 7. pii: ASN.2016060640. [Epub ahead of print]
Gilbert C FAURE's insight:
doesn'twork?
Scoop.it!
What is IgA nephropathy? IgA nephropathy, sometimes called Berger disease, is a type of nephritic syndrome where abnormal IgA antibody is formed, whic
Scoop.it!
Nephrol Dial Transplant. 2016 Sep 28. pii: gfw343. [Epub ahead of print]
Scoop.it!
Exp Cell Res. 2016 Aug 16. pii: S0014-4827(16)30241-5. doi: 10.1016/j.yexcr.2016.08.011. [Epub ahead of print]
Scoop.it!
Clin Immunol. 2016 Jul 18. pii: S1521-6616(16)30180-2. doi: 10.1016/j.clim.2016.07.011. [Epub ahead of print]
Gilbert C FAURE's insight:
Abstract IgA nephropathy (IgAN) is the leading cause of primary glomerulonephritis in the world. The disease is characterized by the presence of immune complexes in the circulation and in mesangial deposits with ensuing glomerular injury. Although in humans there are two IgA subclasses, only IgA1 molecules are involved. The exclusivity of participation of IgA1 in IgAN prompted extensive structural and immunological studies of the unique hinge region (HR) of IgA1, which is absent in otherwise highly homologous IgA2. HR of IgA1 with altered O-glycans serves as an antigen recognized by autoantibodies specific for aberrant HR glycans leading to the generation of nephritogenic immune complexes. However, there are several unresolved questions concerning the phylogenetic origin of human IgA1 HR, the structural basis of its antigenicity, the origin of antibodies specific for HR with altered glycan moieties, the regulatory defects in IgA1 glycosylation pathways, and the potential approaches applicable to the disease-specific interventions in the formation of nephritogenic immune complexes. This review focuses on the gaps in our knowledge of molecular and cellular events that are involved in the immunopathogenesis of IgAN.
Scoop.it!
RT @Ped_Neph: NEW Review: Biomarkers and targeted new therapies for IgA nephropathy https://t.co/ezCa9KWjWU #springerlink
Scoop.it!
TNF superfamily member 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved.
Scoop.it!
An intronic variant at the complement factor H (CFH) gene on chromosome 1q32 (rs6677604) associates with risk of IgA nephropathy (IgAN), but the association signal has not been uniformly replicated in Han Chinese populations.
Scoop.it!
In progressive immunoglobulin (Ig)A nephropathy (IgAN), cyclophosphamide pulse therapy (CyP), high-dose intravenous immunoglobulins (IVIg) and mycophenolic acid (MPA) have been used to stop progressive loss of renal function, but disease...
Scoop.it!
Stem Cell Therapy for IgA Nephropathy
Gilbert C FAURE's insight:
??
|
