# C1q Is Recognized as a Soluble Autoantigen by Anti-C1q Antibodies of Patients with Systemic Lupus Erythematosus

## TL;DR

This study shows that C1q, a protein involved in the immune system, is recognized by autoantibodies in patients with lupus both when it is free in solution and when it is attached to a surface.

## Contribution

The study demonstrates that C1q autoantibodies can bind to soluble C1q and its fragments, revealing conformational differences in epitope exposure.

## Key findings

- Anti-C1q autoantibodies from SLE and LN patients bind to both immobilized and soluble C1q and its globular fragments.
- A negative correlation was found between autoantibody levels against immobilized and soluble C1q and its fragments.
- The gC1q region undergoes conformational changes depending on its immobilized or soluble state, exposing different epitopes.

## Abstract

Background and Aims: C1q is an autoantigen in different autoimmune disorders, Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN) among them. The two functional domains of C1q, the collagen-like region (CLR) and the globular head region (gC1q), are frequently recognized by autoantibodies in SLE and LN when C1q is immobilized. We studied whether autoantibodies to C1q in SLE and LN patients recognized C1q as a soluble autoantigen and whether the act of immobilization was a prerequisite for the recognition of C1q autoepitopes localized on gC1q domains. Methods: The interaction of soluble C1q and its globular fragments ghA, ghB, and ghC with immobilized IgG autoantibodies (and vice versa) from sera of 48 patients with SLE and LN was studied with ELISA. Data were compared using Spearman correlation coefficient. Fluorescence spectroscopy was used to study the interaction between C1q and LN IgG autoantibodies both presented in solution. Results: We found that anti-C1q autoantibodies from SLE and LN patients specifically bound C1q and gC1q fragments, ghA, ghB, and ghC, both as immobilized and soluble antigens. Correlation analysis indicated a negative correlation between the levels of autoantibodies against immobilized and soluble C1q and immobilized and soluble gC1q fragments which indicates different epitopes when these proteins were recognized as autoantigens in soluble and immobilized conformations. Conclusions: Serum C1q in patients with SLE is a target molecule for binding from anti-C1q autoantibodies. The gC1q region undergoes a conformational change in an immobilized and a soluble form, thus exposing different epitope-binding sites.