Effect of MEFV mutations and HLA-B27 on clinical findings of familial Mediterranean fever and spondyloarthritis

This study investigated the coexistence of familial Mediterranean fever (FMF) and spondyloarthritis (SpA), aiming to provide a comprehensive understanding of their clinical, radiological, and genetic features. A total of 127 patients with both FMF and SpA were evaluated, with data collected on demographic, clinical, and laboratory characteristics, including human leukocyte antigen (HLA)-B27 status, Mediterranean fever (MEFV) gene variants, and acute phase reactants. Pelvic radiographs and sacroiliac joint magnetic resonance imaging scans were reviewed when available. The median age of the cohort was 39 years (interquartile range: 30-50), and 48% were female, showing an equal sex distribution. Ankylosing spondylitis was the most common SpA subtype (76.4%), followed by nonradiographic axial SpA (10.2%), peripheral SpA (5.5%), undifferentiated SpA (6.3%), and psoriatic arthritis (1.6%). Most patients exhibited intermittent (90.8%) and oligoarticular (76.7%) joint involvement, typically affecting large joints of the lower extremities, while 23.6% had chronic arthritis. Patients with grade 4 sacroiliitis, chronic arthritis, or hip arthroplasty had a longer disease duration (P < .05). HLA-B27 positivity was identified in 30.4% of patients and was strongly associated with AA amyloidosis (odds ratio = 13.3, 95% confidence interval: 4-43.9). The most frequent MEFV mutation was homozygous M694V (69.3%), followed by M694V/M680I (14.7%) and M680I/V726A (5.3%). MEFV mutations were present in 83.1% of HLA-B27-negative patients. Collectively, these findings indicate that FMF-SpA coexistence defines a distinct clinical and genetic entity characterized by balanced sex distribution, lower HLA-B27 frequency compared to classic SpA, and a strong link between HLA-B27 positivity and amyloidosis risk, underscoring a complex genetic interaction between MEFV variants and HLA-B27 in disease expression.