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Autoantibodies are key features of several immune-mediated inflammatory diseases and may serve as biomarkers for diagnosis, prognosis, and disease stratification. The overall aim of this thesis was to investigate the role of autoantibodies for diagnosis and prognosis of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), with emphasis on their associations with age, sex, disease phenotype, severity, and preclinical disease development.

In Study I, the occurrence of RA-associated autoantibodies was analysed in relation to age at diagnosis and sex. Anti-cyclic citrullinated peptide 2 (anti-CCP2) positivity was associated with younger age, whereas IgA rheumatoid factor (RF) was associated with higher age at diagnosis. These findings demonstrate that demographic factors influence serological phenotypes and should be considered in studies of RA.

In Study II, individual autoantibodies and their combinations were examined in relation to clinical features at RA diagnosis. Anti-citrullinated protein/peptide antibodies (ACPAs) were associated with lower swollen and tender joint counts, while RF was associated with elevated inflammatory markers in an ACPA-dependent manner. No significant associations were observed for the composite DAS28 score, indicating that individual DAS28 components should be analysed separately when evaluating serological phenotypes.

In Study III, the diagnostic and prognostic potential of IgG anti-integrin αvβ6 autoantibodies (anti-αvβ6) was investigated in newly diagnosed IBD. Anti-αvβ6 demonstrated high diagnostic accuracy for ulcerative colitis (UC) and was associated with greater disease extent and inflammatory activity. Although prognostic discrimination between indolent and aggressive UC was modest, persistent antibody levels were linked to a more severe disease course.

In Study IV, the predictive ability of anti-αvβ6 for future UC was evaluated in population-based cohorts. Anti-αvβ6 was detectable years before clinical diagnosis, with predictive performance increasing closer to disease onset. Elevated levels were also observed in early life, indicating loss of tolerance long before clinical manifestation.

Together, these findings demonstrate that autoantibody profiles reflect biologically meaningful heterogeneity in both RA and IBD, and support measurement of autoantibodies for risk stratification and biomarker-guided approaches in immune-mediated inflammatory diseases.