TLR7 and IgM: Dangerous Partners in Autoimmunity.

Area of Science:

• Immunology
• Autoimmunity

Background:

• The B cell antigen receptor (BCR) repertoire can recognize numerous antigens, but random gene rearrangement inevitably produces autoreactive specificities.
• Failure of tolerance mechanisms can lead to the activation and differentiation of autoreactive B cells, resulting in harmful autoantibody production and autoimmune diseases.
• Both IgG and IgM autoantibodies are implicated in autoimmunity, with IgM potentially playing a crucial role at early stages of B cell activation.

Purpose of the Study:

• To summarize recent findings on the significance of autoreactive IgM in the pathogenesis of autoimmune diseases.
• To explore the potential role of IgM-BCR expressing B cells as an initial checkpoint in B cell-mediated autoimmunity.
• To discuss emerging evidence on the specific contributions of IgM autoantibodies in conditions like rheumatoid arthritis, AIHA, pemphigus, and autoimmune neuropathy.

Main Methods:

• Review of recent scientific literature and studies.
• Analysis of findings related to autoreactive IgM autoantibodies and their pathogenic functions.
• Comparison of IgM and IgG autoantibody recognition of autoantigens.

Main Results:

• Pentameric IgM autoantibodies are increasingly recognized for their substantial contribution to the pathogenesis of diverse autoimmune diseases.
• Recent studies indicate distinct autoantigen recognition patterns between IgG and IgM autoantibodies.
• Anti-ACE2-IgM autoantibodies are proposed to play a central role in severe COVID-19.

Conclusions:

• Autoreactive IgM antibodies are critical players in the establishment and progression of autoimmune diseases.
• Further research is needed to fully elucidate the precise mechanisms by which IgM autoantibodies contribute to autoimmunity.
• Understanding the role of IgM in autoimmunity may reveal novel therapeutic targets.