TESPA1 – Systemic Lupus Erythematosus

TESPA1 has emerged as a candidate gene in familial autoimmune conditions, with recent studies implicating rare variants in T cell receptor signalling pathway genes in systemic lupus erythematosus. Although TESPA1-specific variants have not been individually reported, its inclusion in gene sets identified by whole‑exome sequencing and heterozygous filtering across several families provides an important link to the disease process (PMID:31848144).

The inheritance pattern observed is consistent with autosomal dominant transmission, as heterozygous variants in immune‐related genes have been detected in affected individuals. TESPA1 was nominated from analyses that integrated variant filtering with cosegregation approaches in families exhibiting autoimmunity, thereby lending support to its involvement (PMID:31848144).

Segregation analyses across multiple families, including up to 14 families with systemic lupus erythematosus among other autoimmune phenotypes, have provided genetic evidence in support of the T cell receptor signalling complex. While the number of affected relatives with TESPA1 variants is not explicitly delineated, the repeated observation of variants in this pathway underscores its clinical relevance (PMID:31848144).

In the absence of a directly reported TESPA1 variant (e.g., a c. HGVS string) from the available mutation list, the genetic evidence is driven by pathway-level and segregation data. This cohesion of evidence from multi‑patient studies positions TESPA1 among the key genes contributing to familial systemic lupus erythematosus, even though a specific coding change has yet to be documented.

Functional evidence for TESPA1’s involvement remains limited. No targeted in vitro or in vivo functional assays have been detailed to validate its mechanistic role in SLE. However, the fact that TESPA1 is a component of the T cell receptor signalling complex and is enriched in pathway analyses suggests a possible role through haploinsufficiency or dominant‐negative effects, warranting further experimental investigation.

In summary, the integration of genetic data—derived from family‐based sequencing, heterozygous filtering, and segregation analyses—with supportive pathway enrichment findings provides a strong basis for the association of TESPA1 with systemic lupus erythematosus. This evidence is valuable for diagnostic decision‑making, guides commercial genetic testing strategies, and informs future research publications. Key take‑home: TESPA1 represents a compelling candidate gene in systemic lupus erythematosus, meriting further functional validation to elucidate its role in T cell‑mediated autoimmunity.

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

Evidence Based Scoring (AI generated)