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IgG4 anti-phospholipase A2 receptor might activate lectin and alternative complement pathway meanwhile in idiopathic membranous nephropathy: an inspiration from a cross-sectional study

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Abstract

The deposition of IgG4 of antibodies against phospholipase A2 receptor (anti-PLA2R) is predominating in the kidneys of patients with idiopathic membranous nephropathy, while its predictive value has not been determined. It was a retrospective study, and 438 patients were included. Serum samples of two time points [before intervention (baseline) and after 1.5-year treatment (endpoint)] were detected for total and IgG4 anti-PLA2R. IgG4 <0.26 RU/mL or total <20 RU/mL was considered as seronegativity. Bi-positivity/bi-negativity was defined when patients'antibodies were found positive or negative both at the baseline and endpoint. Completed remission (CR) was a major clinical outcome. A series of complement ingredients (MASP-1/2, MBL, C3a, C5a, Factor B, Ba, Bb and C5b-9) were measured in the patients of bi-positivity and bi-negativity: (1) meta-analysis based on six papers conducted seropositivity of anti-PLA2R was a useful predictor for achieving CR, but there was a high heterogeneity; (2) there was significant correlation between the baseline and decrease in IgG4 subclass and the achievement of CR; (3) bi-negativity of IgG4 has a high accuracy of predicting CR compared with total antibodies; (4) in patients of bi-positivity, those achieving CR showed lower MASP-1/2, MBL, C3a, C5a, FB, Ba and Bb than patients failing to achieve CR; (5) the titers of endpoint and decrease in Ba and Bb were associated with improvement of 24 h-UP in those of bi-positivity; and (6) the decrease in Ba was a significant factor for achieving CR in those of bi-positivity. Continuous IgG4 negativity was a useful tool to predict the achievement of CR; however, in patients of continuous IgG4 positivity, those with lower activation of lectin and alternative pathways would still more probably achieve CR.

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    Authors and Affiliations

    1. PLA Kidney Therapeutic Center Integrated Traditional and Western Medicine, Beidaihe Sanatorium of Beijing Military Region, West Beach Road, No. 4, Beidaihe District, Qinhuangdao, China

      Yang Yang, Chao Wang, Liping Jin, Fagui He, Changchun Li, Qingman Gao, Guanglei Chen, Zhijun He, Minghui Song, Zhuliang Zhou, Fujun Shan, Ka Qi & Lu Ma

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    1. Yang Yang
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    2. Chao Wang
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    Correspondence to Lu Ma.

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    Yang Yang and Chao Wang have contributed as much to the work as the first author.

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    Yang, Y., Wang, C., Jin, L. et al. IgG4 anti-phospholipase A2 receptor might activate lectin and alternative complement pathway meanwhile in idiopathic membranous nephropathy: an inspiration from a cross-sectional study. Immunol Res 64, 919–930 (2016). https://doi.org/10.1007/s12026-016-8790-1

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