HDAC7 and Systemic Lupus Erythematosus

In a study of early‑onset systemic lupus erythematosus (PMID:30008451), whole exome sequencing of seven unrelated probands revealed candidate variants in several genes known to affect complement function. Notably, a strong candidate variant in HDAC7 was identified in one patient, supporting a potential monogenic contribution in a subset of familial cases. The affected families exhibited an autosomal recessive inheritance pattern, yet for HDAC7 there is no available segregation data from additional affected relatives. Consequently, the genetic evidence specifically linking HDAC7 to SLE is limited by the single observation and the absence of detailed variant characterization using complete coding HGVS nomenclature.

Supportive functional studies, although evaluated in contexts beyond SLE, highlight HDAC7's central role in T‑cell regulation and chromatin remodeling. Experimental work, including in vitro assays and animal model investigations (PMID:36516268), has demonstrated that alterations in HDAC7 can modulate immune cell function, thereby providing a biologically plausible mechanism for its involvement in autoimmunity. These investigations underscore HDAC7’s impact on regulatory T‑cell gene expression and nuclear export mechanisms. Despite the limited direct genetic evidence in SLE, the convergence of functional data in immune regulation supports further evaluation of HDAC7 as a potential diagnostic marker in early‑onset SLE. Key take‑home message: While the genetic association is currently limited, the functional role of HDAC7 in immune modulation justifies continued research into its clinical utility in systemic lupus erythematosus.

References

• The Journal of rheumatology • 2018 • Whole Exome Sequencing in Early‑onset Systemic Lupus Erythematosus PMID:30008451
• Science translational medicine • 2022 • A multiple sclerosis‑protective coding variant reveals an essential role for HDAC7 in regulatory T cells PMID:36516268

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