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MTHFR risk alleles associate with Th17 immunity and spinal damage in axial spondyloarthritis
Ting Sun1, Yuxian Wu2, Jingtong Wang3
1School of Medicine, Shanghai University, Shanghai, China; Department of Biological Therapy, The Third Affiliated Hospital of Naval Medical University, Shanghai, China; Department of Intensive Care Medicine, Chinese People's Liberation Army Naval Medical Center, Naval Medical University of PLA, Shanghai, China.
Background:
MTHFR polymorphisms regulate homocysteine metabolism, yet their role in clinical heterogeneity, immune dysregulation, and treatment outcomes in axial spondyloarthritis (axSpA) remains undefined.
Methods:
This cross-sectional study included 180 axSpA patients and a retrospective TNF inhibitor (TNFi) cohort (n = 50). CD4+ T-cell subsets were profiled by flow cytometry. Patients were stratified by cumulative MTHFR risk allele load into MTHFRR0, MTHFRR1, and MTHFRR2 groups.
Results:
Cumulative MTHFR risk allele load showed graded associations with GGT, ALP, mSASSS (p = 0.008, 0.037, 0.038) and Th17/Treg ratio (p = 0.036), all BH-adjusted. In TNFi treatment cohort, the proportion of patients achieving clinically important improvement did not differ significantly across genotype groups.
Conclusion:
In axSpA, cumulative MTHFR risk allele load associated with metabolic disturbances, Th17 polarization, and spinal damage. Treatment response analyses detected no significant TNFi genotype-response link. These findings support a gene-metabolism-immunity axis requiring prospective validation.
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