Serum Galactose-Deficient IgA1 Level Is Not Associated with Proteinuria in Children with IgA Nephropathy

Hastings, Margaret; Afshan, Sabahat; Sanders, John T.; Kane, Oulimata; Eison, T. Matthew; Lau, Keith K.; Moldoveanu, Zina; Julian, Bruce A.; Novák, Jan; Wyatt, Robert

doi:10.1155/2012/315467

Cited by 18 publications

(19 citation statements)

References 27 publications

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“…Serum Gd-IgA1 level did not associate with degree of proteinuria for adults [28,32] or children [48]. In a study that combined pediatric and adult patients, absolute serum Gd-IgA1 level did not correlate with decline in estimated GFR (eGFR) or degree of proteinuria at biopsy, but an elevated percent of Gd-IgA1/total IgA correlated with these clinical risk factors [32].…”

Section: Biomarkers Of Iga Nephropathymentioning

confidence: 99%

Biomarkers in IgA nephropathy: relationship to pathogenetic hits

Hastings

Moldoveanu

Suzuki

et al. 2013

Expert Opinion on Medical Diagnostics

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Introduction IgA nephropathy, the most prevalent glomerular disease in the world, requires a renal biopsy for diagnosis. Reliable biomarkers are needed for the non-invasive diagnosis of this disease and to more fully delineate its natural history and risk for progression. Areas covered In this review, the authors examine serum levels of galactose-deficient IgA1 (Gd-IgA1) and glycan-specific IgG and IgA autoantibodies that are integral to pathogenesis of IgA nephropathy. They also explore biomarkers related to alternative and lectin pathways of complement activation and serum and urinary peptide biomarkers detected by mass spectrometric methods. The literature search included review of all publications having IgA nephropathy in the title that were cited in PubMed and Scopus over the past 10 years and a non-systematic review of abstracts published for the annual meetings of the American Society of Nephrology and the International Symposia on IgA Nephropathy. Expert opinion Serum Gd-IgA1 level and glycan-specific autoantibody levels are prime candidates to become diagnostic biomarkers for IgA nephropathy because of their central role in the earliest stages of disease pathogenesis. Assays for serum levels of complement proteins C3 and factor H are readily available in clinical practice and deserve continued study, either alone or in tandem with total serum IgA or serum Gd-IgA1 levels, as prognostic biomarkers for patients with IgA nephropathy. Urinary peptidomic data are also reviewed because this approach can successfully differentiate patients with IgA nephropathy from healthy controls and from patients with other forms of renal disease.

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Section: Biomarkers Of Iga Nephropathymentioning

confidence: 99%

Biomarkers in IgA nephropathy: relationship to pathogenetic hits

Hastings

Moldoveanu

Suzuki

et al. 2013

Expert Opinion on Medical Diagnostics

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“…Some studies have suggested that variants of galactose-deficient IgA1(Gd-IgA1) are more common in the sera of IgAN patients compared with the sera of healthy individuals or with sera from patients with other types of renal disease[4,5]. Furthermore, some researchers have reported that the level of Gd-IgA1 in the sera of patients with IgAN is associated with disease progression[6], though others have found that serum Gd-IgA1 level is not associated with proteinuria in children with IgAN[7]. In the current study, a meta-analysis was done to determine differences in Gd-IgA1 serum levels between IgAN patients and healthy controls and to clarify whether serum assays for Gd-IgA1 are reliable and useful for predicting renal pathological progression of IgAN.…”

Section: Introductionmentioning

confidence: 99%

Aberrant IgA1 Glycosylation in IgA Nephropathy: A Systematic Review

Sun

Zhang

et al. 2016

PLoS ONE

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ObjectiveGalactose-deficient IgA1 was evaluated in patients with IgA nephropathy(IgAN) and controls in order to determine the predictive value of galactose-deficient IgA1 in cases of IgA nephropathy.MethodsPubMed, EMBASE, Cochrane central register of controlled trials, CNKI, CBM disc, and VIP database were searched to identify eligible studies that evaluated a difference in aberrant IgA1 glycosylation in IgAN patients compared with controls. A meta-analysis was conducted to evaluate the impact of galactose-deficient IgA1(Gd-IgA1) levels in different groups.ResultsA total of 22 studies (n = 1657) met inclusion criteria. The mean Newcastle-Ottawa Scale (NOS) score was 7.2 and ranged from 6 to 8. The standard mean difference(SMD) in the meta-analysis of 20 studies of the level of Gd-IgA1 in the serum and/or supernatant of cultured cells was higher in the IgAN group compared with healthy controls as well as in those with other renal diseases (SMD = 1.76, 95% CI = 1.18–2.34, P<0.00001; SMD = 1.05, 95% CI = 0.05–2.04, P = 0.04). The data synthesis suggested that IgAN patients had similar levels of serum Gd-IgA1, with no significant differences, compared with first-degree relatives and Henoch-Schonlein purpura nephritis (HSPN) patients (MD = 0.04, 95% CI = 0.00–0.08, P = 0.05; MD = -46.03, 95% CI = -217.70–125.64, P = 0.60). In addition, the combined MD of 5 studies indicated that there were no significant differences in Gd-IgA1 levels among patients with varying severities of IgAN (MD = 0.02, 95% CI = -0.02–0.05, P = 0.28).ConclusionsThe pooled evidence suggests that the level of Gd-IgA1 in the serum or supernatant of cultured cells from peripheral blood or tonsils may be a useful biomarker for predicting IgA nephropathy, though the level of Gd-IgA1 was not significantly associated with disease severity.

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“…The development of a monoclonal antibody specific to Gd-IgA1 could offer a new appropriate biomarker [18]; however, using this specific test, only one third of IgAN patients had values higher than those of other diseases. Levels of Gd-IgA1 in children were related neither to proteinuria [15] nor to treatment outcome in our IgACE trial [19]. Moreover, Gd-IgA1 are increased in patients, but also in healthy relatives [20].…”

Section: Biomarkers Specific To Iganmentioning

confidence: 64%

“…In patients with IgAN there is a high frequency of O-glycans consisting of GalNAc alone due to defective galactosylation (Gd-IgA1) [1,2]. Although Gd-IgA1 is a rather sensitive and specific marker for IgAN, as reported by most studies (with a sensitivity of 56-76 % and a specificity of 89-94 %) [14][15][16], discrepancies exist likely because of the technical pitfalls for detecting Gd-IgA1 based on lectin binding assays [17]. The development of a monoclonal antibody specific to Gd-IgA1 could offer a new appropriate biomarker [18]; however, using this specific test, only one third of IgAN patients had values higher than those of other diseases.…”

Section: Biomarkers Specific To Iganmentioning

confidence: 99%

“…Moreover, Gd-IgA1 are increased in patients, but also in healthy relatives [20]. In conclusion, high levels of Gd-IgA1 are necessary for the development of IgAN, but not sufficient for the full clinical expression of the renal damage, and in most reports this biomarker is not associated with signs of progressive disease with proteinuria and glomerular filtration rate (GFR) decline [10,11,15]. However, higher levels of Gd-IgA1 are present in a subset of IgAN with severe clinical and renal features and predict a poor prognosis, and in recurrent IgAN after transplantation [21].…”

Section: Biomarkers Specific To Iganmentioning

confidence: 99%

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Biomarkers and targeted new therapies for IgA nephropathy

Coppo

2016

Pediatr Nephrol

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IgA nephropathy (IgAN) has variable clinical presentation and outcome. There is a need to identify children who have the potential to progress to end stage renal disease (ESRD). Biomarkers related to the pathogenetic process of IgAN can detect risk factors and identify targets for new therapies. Galactose-deficient IgA1 (Gd-IgA1) is a specific biomarker of IgAN and could be the first treatment target. In experimental mice, reduction of IgA1 deposits and hematuria was observed after treatment with a bacterial protease that selectively cleaves human IgA1. Glycan-targeted drugs that may act to neutralize Gd-IgA1 inhibit abnormal enzymatic glycosylation of IgA1 or deplete cells producing Gd-IgA1. The autoimmune response to Gd-IgA1 produces autoantibodies that are sensitive and specific biomarkers of IgAN development and progression and suggests the possible benefits of anti-B cell therapies directed against CD20, B-cell activating factor (BAFF), or B cell receptor, and also proteasome inhibitors. The activation of complement in IgAN offers new biomarkers and the rationale for using complement inhibitors, including eculizumab. Renal pathological features represent sensitive biomarkers of added value over clinical data and may drive steroid therapy in selected cases. Finally, the hypothesis of the involvement of intestinal mucosal immunity in the pathogenesis of IgAN suggests the possibility of avoiding the systemic effect of steroid. Enteric budesonide targeting Peyer's patches at the ileocecal junction is an interesting option that has provided some preliminary favorable results in IgAN. In conclusion, the identification of new biomarkers is a promising area for therapies targeting IgAN in patients at risk of progression.

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Serum Galactose-Deficient IgA1 Level Is Not Associated with Proteinuria in Children with IgA Nephropathy

Cited by 18 publications

References 27 publications

Biomarkers in IgA nephropathy: relationship to pathogenetic hits

Biomarkers in IgA nephropathy: relationship to pathogenetic hits

Aberrant IgA1 Glycosylation in IgA Nephropathy: A Systematic Review

Biomarkers and targeted new therapies for IgA nephropathy

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