Serum levels of galactose-deficient immunoglobulin (Ig) A1 and related immune complex are associated with disease activity of IgA nephropathy

Abstract

BackgroundThe primary abnormal manifestation in immunoglobulin A nephropathy (IgAN) is recurring bouts of hematuria with or without proteinuria. Although immunohistochemical analysis of renal biopsy tissue remains the gold standard not only for diagnosis but also for evaluating the activity of IgAN, new sensitive and reasonably specific noninvasive tests are emerging to guide therapeutic strategy applicable to all stages of IgAN. The present study examined serum levels of galactose-deficient IgA1 (Gd-IgA1) and its immune complex (IgA/IgG-IC) as noninvasive markers for the disease activity.MethodsWe enrolled 50 IgAN patients (male 40 %, median age 37 years) showing complete or partial clinical remission after steroid pulse therapy with tonsillectomy (TSP) whose clinical data and serum could be followed up for 3–5 years.ResultsCross-sectional analysis revealed that the degree of hematuria and proteinuria were significantly associated with levels of Gd-IgA1 and levels of IgA/IgG-IC. Longitudinal analysis further showed that from the group of 44 patients with heavy hematuria before TSP, 31 patients showed complete disappearance of hematuria (group A), but the remaining patients did not (group B). Although the levels of Gd-IgA1 and IgA/IgG-IC in the two groups before TSP were similar, percentage decrease of Gd-IgA1 and IgA/IgG-IC levels in group A was significantly higher than in group B.ConclusionDisease activity of IgAN assessed by hematuria and proteinuria correlated with serum levels and changes of Gd-IgA1 and IgA/IgG-IC. These new noninvasive disease activity markers can be useful for future activity scoring system and guiding therapeutic approaches.

Biomarkers for IgA nephropathy on the basis of multi-hit pathogenesis

“…Cases with IgAN who showed significant decreases in serum Gd-IgA1 levels after tonsillectomy achieved significantly better improvement in hematuria [29]. Moreover, serum levels of Gd-IgA1 and IgA-IgG IC were examined before and after tonsillectomy with steroid pulse therapy [48]. Cross-sectional analysis revealed that the amounts of hematuria and proteinuria were significantly associated with serum levels of Gd-IgA1 and levels of IgA-IgG immune complexes [48].…”

Current Understanding of the Role of Complement in IgA Nephropathy

“…10 In IgAN, it is unclear whether IgA1-containing circulating immune complexes have complement elements. [77][78][79][80] Nevertheless, elevated serum concentrations of C3-derived products in patients with IgAN suggest a soluble-phase activation of the alternative pathway. 28 Proteomic analyses of patients' circulating immune complexes and complexes formed in vitro from Gd-IgA1 and antiglycan IgG revealed the presence of C3.…”

Decreased expression of follicular dendritic cell–secreted protein correlates with increased immunoglobulin A production in the tonsils of individuals with immunoglobulin A nephropathy

“…[15][16][17] IgAN usually has a poor prognosis, with about 50% of patients progressing to end-stage renal disease within 30 years despite treatment. 18 Mesangial deposition of IgA has been considered to be the initiating event in the pathogenesis of IgAN; however, the origin of the increased IgA remains unclear.…”