IgG4 antibody repertoire diversity is stable over several years in health and autoimmune disease

Recent research reveals that the diversity of IgG4 antibody repertoires remains stable over several years in both healthy individuals and those with autoimmune diseases. The study, which analyzed 218 samples from 69 donors using mass spectrometry-based antibody repertoire analysis, covered a period of up to eight years. Despite the seemingly minor differences in clonal diversity and abundances, researchers discovered a slightly higher number of IgG4 clones in patients with a disease called muscle-specific kinase myasthenia gravis (MuSK MG) compared to healthy donors.

However, this elevation in IgG4 clones did not correspond to significant changes in the overall antibody repertoire during treatment, indicating that most of the IgG4 repertoire remains unaffected by common MuSK MG treatment regimens.

Further analysis of all donors' IgG4 antibody repertoires showed an exceptional level of uniqueness for each individual. This finding is particularly intriguing when considering the expected constant adaptation of antibody repertoires. Surprisingly, a large portion of IgG4 clones remained stable without undergoing any additional maturation throughout the study period.

This observation held true even for patients receiving B cell depleting or IgG modulating treatments. The researchers propose that a dominant fraction of the IgG4 pool is produced by long-lived plasma cells, which are unaffected by disease or medical interventions. These findings suggest that the IgG4 antibody repertoire is remarkably resilient and stable, even in the face of autoimmune diseases and medical interventions targeting other aspects of the immune system.