Elsevier

Clinical Immunology

Volume 217, August 2020, 108514
Clinical Immunology

Circulating anti-C3b IgG in lupus nephritis: A large cohort study

https://doi.org/10.1016/j.clim.2020.108514Get rights and content

Highlights

  • Patients with positive anti-C3b IgG had significantly higher SLEDAI, lower circulating C3 and C4 levels.

  • Anti-C3b IgG levels were positively correlated with C3 or C1q deposition in kidneys and active pathological lesions.

  • Anti-C3b IgG could be an independent risk factor in the proliferative lupus nephritis patients.

  • The purified IgG fractions from anti-C3b IgG positive patients interfered factor H and CR1 binding to C3b.

Abstract

The current study aimed to analyze the clinical significance and bio-functional properties of anti-C3b IgG based on a lupus nephritis cohort. We found that the prevalence of anti-C3b IgG in our cohort was 47.8%. Patients with positive anti-C3b IgG had significantly higher SLEDAI, lower circulating C3 and C4 levels. Anti-C3b IgG levels were positively correlated with C3 or C1q deposition in kidneys and several active pathological lesions. The positivity of anti-C3b IgG was an independent risk factor for the composite endpoints in the subgroup of proliferative lupus nephritis patients. In vitro, the purified IgG fractions from positive patients resulted in increased C3a generation through the alternative pathway, and interfered factor H and CR1 binding to C3b. Our findings indicated that anti-C3b IgG associated with local renal injury and long-term outcomes in lupus nephritis patients, possibly through leading to the complement alternative pathway over-activation.

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs and tissues, of which the development of kidney disease is the key predictor of morbidity and mortality for the disease. The pathogenesis of lupus nephritis has not been fully understood and the presence of autoantibodies that recognize various self-molecules [[1], [2], [3], [4], [5], [6]] and complement over-activation have been demonstrated to be involved in lupus progression. Autoreactivity to complement components may have considerable pathological consequences, for example, anti-C1q antibodies [1,5,6], anti-Factor H (FH) antibodies [2], C3 nephritic factor [3], and anti-C3b IgG [7,8], etc.

C3b was the convergent point of the three complement pathways of the cascade [[9], [10], [11]] and cleaved by Factor I (FI) to generate C3c, C3d, C3f and C3g. Autoantibodies against C3b were detected in SLE [[12], [13], [14], [15]] and other immune mediated diseases [[16], [17], [18], [19], [20], [21], [22]]. Limited functional studies showed that they could interfere the regulation of alternative pathway and might have pathological consequences in lupus nephritis [7], although the precision correlation between anti-C3b IgG and the local renal injury remained to be elucidated. More well-defined cohort studies with a long follow-up period to evaluate the clinical significance of the anti-C3b IgG in lupus nephritis are required.

Herein, we investigated the frequency of anti-C3b IgG based on a large Chinese lupus nephritis cohort. Their clinical features, immunological characteristics and bio-functions were also explored.

Section snippets

Patients

134 lupus nephritis patients who were diagnosed between January 2008 and December 2015 at Peking University First Hospital were enrolled, which was referred to the discovery cohort. (The study flow chart was shown in the Supplementary Fig. 1). Forty-two lupus nephritis patients from 4 other centers from North China were termed as the validation cohort. All the patients fulfilled the 1997 American College of Rheumatology revised criteria for SLE [23].

Plasma samples from the patients were

The immunologic features of anti-C3b IgG in lupus nephritis

The clinicopathologic characteristics of 134 lupus nephritis patients in the discovery cohort were shown in the Supplementary Table 1. The anti-C3b IgG was detected in 64/134 (47.8%) patients in the discovery cohort, and not detected in healthy subjects. No significant difference was found between the discovery and validation group (47.8% (64/134) vs. 42.9% (18/42), P = .174), which were significantly higher than that in healthy subjects (P < .001). Furthermore, the binding of anti-C3b IgG to

Discussion

The prevalence of anti-C3b IgG was nearly 30% in lupus nephritis cases and their pathogenic role in the disease has been suggested [7,8] which remained to be further elucidated. Herein, we explored its clinicopathological significances, immunological characteristics and some bio-functional effects based on a Chinese lupus nephritis cohort.

This study demonstrated that circulating anti-C3b IgG was present in almost 50% of our patients, which was higher than those in previous reports [7,8].

Financial supports

This work was supported by National Natural Science Foundation of China (No. 81670639, No. 81670640, No 81700610, and No. 81870479).

Disclosure

The authors declare that they have no competing financial interests.

Acknowledgements

We are very grateful to Qian Wang and Jing Wang from the State Key Laboratory of Natural and Biomimetic Drugs, Peking University, for technical assistance on the surface plasmon resonance analysis.

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