ArticleFrontiers in immunology2026
Cytokine and genetic crosstalk in patients with coexistent familial Mediterranean fever and celiac disease: a cross-sectional study from Türkiye.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Familial Mediterranean Fever (FMF) and Celiac Disease (CD) are two distinct inflammatory disorders that arise through different immunological pathways, yet they show a notable tendency to coexist, particularly in Mediterranean populations. The immunological consequences of this coexistence have not been adequately characterized. Objective: We set out to compare serum cytokine profiles and explore potential genetic interactions in patients with both FMF and CD versus those with FMF alone or CD alone. One hundred adult patients were enrolled and divided into three groups: 40 with coexistent FMF and CD, 30 with FMF only, and 30 with CD only. Serum concentrations of IL-1β, IL-6, TNF-α, and IL-10 were quantified by ELISA; CRP and SAA were measured using routine laboratory methods. MEFV mutations and HLA-DQ2/DQ8 genotypes were determined by PCR. Statistical evaluations included one-way ANOVA with Bonferroni correction, multivariable linear regression incorporating a formal interaction term, and principal component analysis to visualize cytokine clustering patterns. Results: Patients with both diseases exhibited significantly higher serum levels of IL-1β, IL-6, TNF-α, and CRP than those in either single-disease group (all p < 0.001), while IL-10 levels were notably lower (p = 0.02). Serum amyloid A levels were also significantly elevated in the coexistence group compared with both single-disease groups (p < 0.001) and correlated strongly with CRP (r = 0.69, p < 0.001). IL-6 emerged as the strongest independent predictor of CRP elevation (adjusted β = 0.47, 95% CI 0.31-0.63, p < 0.001). Principal component analysis identified a distinct pro-inflammatory cytokine cluster unique to the coexistence group. The simultaneous presence of HLA-DQ2 and the MEFV M694V variant was associated with a significant rise in IL-6 production (p < 0.001). Conclusion: When FMF and CD coexist, the resulting inflammatory state is substantially amplified and dysregulated, characterized by markedly elevated IL-6 and associated with a possible interaction between MEFV and HLA loci that requires confirmation in larger, independently sampled cohorts. These observations emphasize the importance of recognizing this overlap syndrome in clinical practice.
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