VWA8 – Rheumatoid Arthritis

In a recent study of familial autoimmunity, VWA8 (HGNC:29071) was identified as a candidate gene associated with rheumatoid arthritis (MONDO_0008383) alongside other T cell receptor signaling genes. In this study, whole‐exome sequencing of 31 families with autoimmune disorders (including rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren's syndrome) revealed rare candidate variants in several immune‐related genes, with VWA8 recurring in up to 14 of these families (PMID:31848144). However, specific segregating VWA8 variants in rheumatoid arthritis cases were not reported, and the observed association is based on its inclusion within a broader gene set implicated in T cell–driven autoimmunity. This has resulted in an initial yet limited gene–disease association that warrants further targeted investigation.

The genetic evidence for VWA8 in rheumatoid arthritis remains limited because only candidate gene screening data are available, and no unique RA‐specific variants have been conclusively demonstrated. Moreover, functional studies of VWA8 have been performed in the context of retinitis pigmentosa (PMID:37012052), and these do not directly support its pathogenicity in rheumatoid arthritis. Key take‑home: while VWA8 is a promising candidate for contributing to the genetic architecture of familial rheumatoid arthritis, further replication and functional analyses in the RA context are essential for confirming its clinical utility in diagnostic decision‑making.

References

• Annals of the rheumatic diseases • 2020 • Germline genetic patterns underlying familial rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren's syndrome highlight T cell‑initiated autoimmunity PMID:31848144
• Journal of medical genetics • 2023 • Mutations in VWA8 cause autosomal‑dominant retinitis pigmentosa via aberrant mitophagy activation PMID:37012052

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