Such an interaction could partly be the result of idiotype–anti-idiotype recognition, the presence of

IgA rheumatoid factor (an IgA autoantibody specific to the Fc region of IgG), or IgG–anti-IgA as well as IgA1 anti-glycan antibodies [24]. Indeed, idiotype-positive antibody levels correlated with the clinical status of IgAN patients, as defined by their urinary abnormalities [36]. Recently, it was suggested that IgAN is characterized by a circulating IC composed of Selleckchem WH-4-023 Gd-IgA1 and a glycan-specific IgG antibody. Suzuki et al. [18] reported that serum Autophagy Compound Library cost glycan-specific IgG antibody levels could differentiate between IgAN patients and healthy or diseased controls, with 88 % specificity and 95 % sensitivity. In addition, increased levels of this antibody in sera of IgAN patients correlated well with proteinuria. This study evaluated serum IgA/IgG-IC levels, and our findings

regarding proteinuria and IgA/IgG-IC levels are consistent with buy PCI-34051 previous studies [18, 35]. O-linked carbohydrates in the hinge region of IgA1 considerably affect IgA1 reactivity with such glycan-specific autoantibodies, and the subsequent IC formation may incite glomerular damage, leading to proteinuria and hematuria [18]. Gharavi et al. [29] reported that blood relatives of IgAN patients had increased serum Gd-IgA1 levels even in the absence of nephropathy, suggesting that additional events may be required for complete IgAN progression. Thus, IC formation with Gd-IgA1 and glycan-specific IgG antibody may be one of the second ‘hit’ events [18, 20]. It is generally known that higher molecular ICs have a higher phlogogenic capacity via the activation of Fc receptors [37]; hence, serum IgA/IgG-IC levels may correlate with severity of glomerular damage leading to proteinuria better than Gd-IgA1 alone. These facts are consistent with present findings in a cross-sectional analysis that serum levels of IgA/IgG-IC were more correlated with severity of urinary abnormalities than those of Gd-IgA1. In conclusion, we showed in this study that disease

activity assessment by hematuria and proteinuria correlated with changes in serum Gd-IgA1 and IgA/IgG-IC levels in most IgAN patients, providing novel value STK38 for these new noninvasive and real-time disease activity markers. Although further validation with a larger cohort will be required, clinical application, such as IgAN activity score or risk score, with these markers as principal components could be extremely useful for guiding the therapeutic approaches applicable in all stages of IgAN. Acknowledgments This study was supported in part by Grant-in-Aids for Progressive Renal Diseases Research, Research on Intractable Disease, from the Ministry of Health, Labour and Welfare of Japan and by a grant from Strategic Japanese (JST)-Swiss (ETHZ) Cooperative Scientific Program.