ALDH4A1 and anti-ALDH4A1 emerge as a novel antigenic axis linked to atherosclerosis in rheumatoid arthritis
Authors' conclusion
The ALDH4A1/anti-ALDH4A1 axis emerges as a novel player bridging lipid disturbances and atherosclerosis along the whole RA continuum, hence highlighting the involvement of mitochondrial targets. These components hold promise as functional players, clinical tools and therapeutic targets.
Study context
- Population
- Early rheumatoid arthritis (RA), clinically suspect arthralgia, healthy controls, and a validation cohort of established RA; a prospective cohort under TNF blockadeearly RA 82 · clinically suspect arthralgia 14 · healthy controls 70 · prospective cohort (TNF blockade) 13
- Exposure
- EARLY RA vs CLINICALLY SUSPECT ARTHRALGIA vs HEALTHY CONTROLS vs VALIDATION COHORT OF ESTABLISHED RA
- EARLY RAn = 82
- CLINICALLY SUSPECT ARTHRALGIAn = 14
- HEALTHY CONTROLSn = 70
- Outcome
- ALDH4A1 serum levels and apoptotic-related proteomic pathways, cell-free DNA and lipidomic signatures in early RA
Methodological detailsvalidation cohort of established RA
- Validation cohort of established RA
Main finding
As reported in the abstract
- ALDH4A1 serum levels were associated with apoptotic-related proteomic pathways, cell-free DNA and lipidomic signatures in early RA
Observational data: associations, not effects.
Further findings
Anti-ALDH4A1 antibodies
- Reduced anti-ALDH4A1 antibodies were found, although divergent patters were noted across isotypes; confirmed in a validation cohort
IgG anti-ALDH4A1 and lipoprotein traits and cardiometabolic risk factors
- IgG (predominantly IgG3) anti-ALDH4A1 correlated with favourable lipoprotein traits and cardiometabolic risk factors
Atherosclerosis
- Increased ALDH4A1 and reduced IgM/IgG anti-ALDH4A1 antibodies independently predicted atherosclerosis and improved risk stratification beyond mSCORE, most notably for IgG
Changes under TNF blockade
- ALDH4A1 tracked with TNF dynamics under TNF blockade, whereas increases in IgG antibodies occurred in responders and paralleled changes in lipoprotein features
Original publication
ALDH4A1 and anti-ALDH4A1 emerge as a novel antigenic axis linked to atherosclerosis in rheumatoid arthritis. Rheumatology (Oxford). Published 3 November 2026. doi:10.
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