Igome Graphs Suggest the Changes in the IgM and IgG Repertoires in Antiphospholipid Syndrome Are in Part Idiotypically Defined
DOI:
https://doi.org/10.7546/CRABS.2024.11.05Keywords:
antiphospholipid syndrome, antibody repertoires, IgM, idiotypyAbstract
Antiphospholipid Syndrome (APS) is characterized by the persistence of high-affinity antiphospholipid antibodies, manifesting clinically as pregnancy complications, thrombosis, or neurological symptoms. This study explores the changes in the IgM and IgG antibody repertoires in APS patients using igome graphs, which represent antibody repertoires through peptide libraries selected from phage display on the complete immunoglobulin fraction of the serum. Serum samples from healthy women and APS patients were processed to isolate IgM and IgG fractions, which were then used for phage selection and next-generation sequencing. Peptide sequences were analyzed using graph representation, clustering, and spectral embedding to identify significant differences between the repertoires. The study revealed that while IgM repertoires in APS patients exhibit a loss of public reactivities, the IgG repertoires do not follow this trend. Three orthogonal sequence motifs were identified in the IgM and IgG repertoires, suggesting potential idiotypic interactions. These findings highlight the intricate mechanisms of antibody selection and cross-reactivity in APS, offering insights into potential therapeutic approaches. The study underscores the importance of system-level analysis in understanding immune mechanisms and suggests that idiotypic interactions, though complex, could play a crucial role in APS pathogenesis.
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