# Anti-C1q Autoantibody-Binding Engineered scFv C1q-Mimicking Fragment Enhances Disease Progression in Lupus-Prone MRL/lpr Mice

## TL;DR

This study shows that an engineered antibody fragment worsens lupus symptoms in mice by enhancing disease progression.

## Contribution

A novel scFv antibody was developed to bind anti-C1q autoantibodies and was shown to exacerbate lupus in a mouse model.

## Key findings

- scFv treatment altered immune cell populations in spleen and bone marrow.
- Increased levels of anti-C1q and anti-dsDNA antibodies were observed in treated mice.
- Treated mice showed severe lupus symptoms, including proteinuria and reduced survival.

## Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by tissue damage in multiple organs caused by autoantibodies and the resulting immune complexes. One possible way for complement system contribution to onset of autoimmune disorder could be realized by the impairment of C1q-mediated apoptotic clearance as part of human homeostasis. The capacity of C1q to bind early apoptotic cells could be decreased or even lost in the presence of anti-C1q antibodies. A monoclonal anti-idiotypic single-chain (scFv) antibody was selected from the phage library Griffin1” to recognize anti-C1q autoantibodies, purified from sera of lupus nephritis patients. Lupus-prone MRL/lpr mice were injected weekly with scFv A1 fragment-binding anti-C1q antibodies. The number of in vitro and ex vivo studies with collected cells, sera, and organs from the treated animals was performed. scFv treatment changed the percentage of different B-, T-, and NK-cell subpopulations as well as plasma cells and plasmablasts in the spleen and bone marrow. An increase in the levels of splenocyte proliferation, anti-C1q antibodies, and the number of plasma cells producing anti-dsDNA and anti-C1q antibodies were also observed in scFv-treated animals. High levels of proteinuria and hematuria combined with unstable levels of IL10 and IFNγ promote the development of severe lupus and shorten the survival of treated MRL/lpr mice. Therapy with the scFv A1 antibody resulted in BCR recognition on the surface of anti-C1q-specific B-cells and had a disease progression effect, enhancing lupus symptoms in the MRL/lpr mouse model of SLE.