Emrah SALMAN, Sibel GÖKAY
Turkish Journal of Immunology - 2026;14(2):99-109
Objective: The presence of antimitochondrial antibodies (AMAs) is strongly associated with primary biliary cholangitis (PBC), but serological reactivity alone may not consistently characterize a distinct clinical presentation. We aimed to determine whether a combination of mitochondrial-specific autoimmunity (M2 seropositivity) and cholestatic burden, quantified by alkaline phosphatase (ALP), is associated with a physiologically coherent pure PBC phenotype within an AMA-positive cohort. Materials and Methods: This retrospective cross-sectional study included 300 AMA-positive adult patients assessed at a tertiary referral institution. Clinical phenotypes were categorized as pure PBC, PBC-autoimmune hepatitis (AIH) overlap, or non-PBC based on accepted diagnostic criteria. Results: The study included 300 AMA-positive individuals, of which 80 were diagnosed with pure PBC, 37 with PBC-AIH overlap, and 183 were categorized as non-PBC. Seropositivity for M2 and ALP levels were independently associated with the pure PBC phenotype. M2 positivity was strongly associated with pure PBC (adjusted odds ratio [aOR] 14.60, 95% confidence interval [CI] 1.56-136.37, p=0.019), whereas each 10 U/L increment in ALP was associated with 18% higher odds of pure PBC (aOR 1.18, 95% CI 1.05-1.32, p=0.005). The multivariable model showed good internal discrimination (area under the receiver operating characteristic curve [AUC] 0.86, 95% CI 0.76-0.93), achieving 69.0% sensitivity and 89.2% specificity at the optimal probability threshold. In sensitivity analyses involving overlap syndromes, ALP remained independently correlated with disease phenotype, whereas the influence of M2 seropositivity diminished. Conclusion: Antimitochondrial antibody positivity alone does not define a consistent clinical phenotype. The integration of M2 seropositivity with ALP levels may provide a more informative immune-biochemical framework for phenotypic stratification among AMA-positive individuals.
