Anti-DNA antibodies cross-react with C1q

Area of Science:

• Immunology
• Rheumatology
• Nephrology

Background:

• Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs.
• Anti-double-stranded DNA (anti-dsDNA) antibodies are key players in SLE pathogenesis, forming immune complexes and driving inflammation.
• Anti-C1q antibodies are implicated in lupus nephritis, and C1q deficiency is a major SLE risk factor.

Purpose of the Study:

• To investigate the interaction between a specific subset of anti-dsDNA antibodies and C1q.
• To determine the role of this antibody-C1q interaction in lupus nephritis and immune homeostasis.

Main Methods:

• Characterization of anti-dsDNA antibodies binding to the N-methyl-D-aspartate receptor.
• Assessment of binding of mouse and human anti-dsDNA antibodies to C1q.
• Evaluation of glomerular deposition of these antibodies in the presence and absence of C1q.

Main Results:

• A subset of anti-dsDNA antibodies, previously identified as binding the N-methyl-D-aspartate receptor, also binds C1q.
• These antibodies bind C1q within glomeruli.
• Glomerular deposition of these antibodies is reduced in the absence of C1q.

Conclusions:

• This subset of anti-dsDNA antibodies targets C1q in the glomeruli, contributing to lupus nephritis.
• These antibodies may exacerbate SLE by removing soluble C1q, thereby impairing immune homeostasis.