Serological and genetic factors in early recurrence of IgA nephropathy after renal transplantation

Coppo, Rosanna; Amore, Alessandro; Chiesa, Monica; Lombardo, Federica; Cirina, Paola; Andrulli, Simeone; Passerini, Patrizia; Conti, Giovanni; Peruzzi, Licia; Giraudi, Roberta; Messina, Maria; Segoloni, Giuseppe; Ponticelli, Claudio

doi:10.1111/j.1399-0012.2007.00730.x

Cited by 31 publications

(22 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our study, IgA-sCD89 was detected on PEG-precipitated sera (which are enriched in large immune complexes), whereas Vuong's study was conducted on the whole sera. Moreover, Coppo et al 17 previously studied the predictive value of Gd-IgA1 for recurrence of the disease and showed a borderline association between increased Gd-IgA1 levels and recurrence. These authors used purified IgA using jacalin lectin and then tested the glycosylation, whereas in the present study we directly assessed the O-glycosylation of serum IgA without the purification step.…”

Section: Discussionmentioning

confidence: 96%

Recurrent IgA nephropathy is predicted by altered glycosylated IgA, autoantibodies and soluble CD89 complexes

Berthelot

Robert

Vuiblet

et al. 2015

Kidney International

103

View full text Add to dashboard Cite

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, frequently leads to end-stage renal disease and kidney transplantation. However, disease recurrence often occurs after transplantation. Here we evaluated the predictive value of three markers for IgAN recurrence: the presence of galactose-deficient IgA1, IgG anti-IgA autoantibodies, and IgA-soluble (s) CD89 complexes. This was analyzed in 38 kidney transplant recipients with IgAN recurrence and compared with 22 patients transplanted for IgAN but without recurrence and with 17 healthy controls. Pre-transplantation galactose-deficient IgA1 serum levels were significantly higher in the recurrence compared with the no recurrence or control groups. IgA-IgG complexes were significantly elevated in the recurrence group. Both the recurrence and no recurrence groups had increased values of IgA-sCD89 complexes compared with healthy controls, but values were significantly lower in patients with recurrence compared with no recurrence. Areas under the receiver operating curve of the markers in pre-transplantation sera were 0.86 for galactose-deficient-IgA, 0.82 for IgA-IgG, and 0.78 for sCD89-IgA; all significant. Disease recurrence was associated with decreased serum galactose-deficient IgA1 and appearance of mesangial-galactose-deficient IgA1 deposits, whereas increased serum IgA-sCD89 complexes were associated with mesangial sCD89 deposits. Thus, galactose-deficient-IgA1, IgG autoantibodies, and IgA-sCD89 complexes are valuable biomarkers to predict disease recurrence, highlighting major pathogenic mechanisms in IgAN.

show abstract

Section: Discussionmentioning

confidence: 96%

Recurrent IgA nephropathy is predicted by altered glycosylated IgA, autoantibodies and soluble CD89 complexes

Berthelot

Robert

Vuiblet

et al. 2015

Kidney International

103

View full text Add to dashboard Cite

show abstract

“…53 High levels of aberrantly glycosylated IgA 1 do not seem to predict recurrence. 54 Patients with certain polymorphisms of the genes for tumor necrosis factor and interleukin 10, which are downregulators of type 2 T-helper lymphocytes, have a reduced likelihood of experiencing recurrence. 54 Alport syndrome Alport syndrome exists in three genetic forms: X-chromosome-linked (85%), autosomal recessive (14%), and autosomal dominant (1%).…”

Section: Iga Nephropathymentioning

confidence: 99%

“…54 Patients with certain polymorphisms of the genes for tumor necrosis factor and interleukin 10, which are downregulators of type 2 T-helper lymphocytes, have a reduced likelihood of experiencing recurrence. 54 Alport syndrome Alport syndrome exists in three genetic forms: X-chromosome-linked (85%), autosomal recessive (14%), and autosomal dominant (1%). The X-linked variant arises from mutations in the COL4A5 gene, which encodes the type IV collagen α 5 chain.…”

Section: Iga Nephropathymentioning

confidence: 99%

A primer on recurrent and de novo glomerulonephritis in renal allografts

Iványi

2008

Nat Rev Nephrol

View full text Add to dashboard Cite

Accumulating evidence indicates that recurrent glomerulonephritis is the third most important cause of renal allograft loss at 10 years after transplantation. The proteinuria and elevated serum creatinine levels that result from recurrent glomerulonephritis are associated with cardiovascular morbidity and mortality. The exact prevalence of either recurrent or de novo post-transplantation glomerulonephritis is unknown because a considerable number of patients never undergo allograft biopsy, meaning that glomerulonephritis remains undiagnosed and a diagnosis of 'chronic rejection/chronic allograft nephropathy' is sometimes presumed. The lack of consensus regarding evaluation of kidney transplant recipients who exhibit slow deterioration of graft function is a major reason for underdiagnosis. All forms of glomerular disease can recur after transplantation, but the likelihood of recurrence differs according to type. Focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, IgA nephropathy and idiopathic diarrhea-negative hemolytic uremic syndrome often recur. Membranous nephropathy, focal segmental glomerulosclerosis, anti-glomerular basement membrane nephritis associated with Alport syndrome, and drug-induced thrombotic microangiopathy are the most common forms of de novo glomerulonephritis. This Review discusses the prevalence, risk factors, pathogenesis, clinicopathological features, and effects on graft outcome of recurrent and de novo glomerulonephritis in renal allografts. Treatment options are briefly outlined.

show abstract

“…Serum levels of Gd-IgA1 are increased in patients with severe IgAN who progressed to end-stage renal failure and renal transplantation. Nonetheless, because the levels overlap between patients grouped by recurrence of IgAN in the grafted kidney, altered IgA1 O-glycosylation alone is insufficient to trigger disease development and progression (14). Indeed, 4% to 16% of apparently healthy individuals in the general population have IgA deposits in their glomeruli (15,16), although it is unknown whether these deposits consist of Gd-IgA1.…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress and Galactose-Deficient IgA1 as Markers of Progression in IgA Nephropathy

Camilla

Suzuki

Daprà

et al. 2011

Clinical Journal of the American Society of Nephrology

Self Cite

107

View full text Add to dashboard Cite

Summary Background and objectives We assessed the activation of the oxidative stress pathway in patients with IgA nephropathy (IgAN), while evaluating the classic marker of the disease (galactose-deficient serum IgA1). Design, setting, participants, & measurements Sera from 292 patients and 69 healthy controls from Italy and the United States were assayed for advanced oxidation protein products (AOPPs), free sulfhydryl groups on albumin (SH-Alb), and IgA1 with galactose-deficient hinge-region O-glycans (Gd-IgA1). Gd-IgA1 was detected by binding to Helix aspersa agglutinin (HAA) and expressed as total Gd-IgA1 or as degree of galactose deficiency relative to a standard Gd-IgA1 myeloma protein (%HAA). Results Sera from IgAN patients showed higher levels of Gd-IgA1, %HAA, and AOPPs, but lower levels of SH-Alb in comparison to that from healthy controls. Serum levels of AOPPs significantly correlated with serum Gd-IgA1 and %HAA. The relationship between these biomarkers and clinical features at sampling and during follow-up was assessed in 62 patients with long-term follow-up. AOPPs and %HAA correlated with proteinuria at sampling and independently associated with subsequent proteinuria. Levels of AOPPs correlated with rate of decline in renal function after sampling. The combination of a high level of AOPPs and a high level of %HAA associated with decline in estimated GFR. Conclusions Serum levels of aberrantly glycosylated IgA1 are elevated and oxidative stress pathways are activated in patients with IgAN; the intensity of the stress correlated with expression and progression of the disease. We speculate that oxidative stress may modulate the nephrotoxicity of aberrantly glycosylated IgA1 in IgAN.

show abstract

Serological and genetic factors in early recurrence of IgA nephropathy after renal transplantation

Abstract: High levels of aberrantly glycosylated IgA1 do not appear to play a strong crucial role in recurrence of IgAN. Polymorphisms of TNFalpha and IL-10 known to condition Th1 prevalence were associated with protection from early recurrence of IgAN.

Cited by 31 publications

References 29 publications

Recurrent IgA nephropathy is predicted by altered glycosylated IgA, autoantibodies and soluble CD89 complexes

Recurrent IgA nephropathy is predicted by altered glycosylated IgA, autoantibodies and soluble CD89 complexes

A primer on recurrent and de novo glomerulonephritis in renal allografts

Oxidative Stress and Galactose-Deficient IgA1 as Markers of Progression in IgA Nephropathy

Contact Info

Product

Resources

About