Studies of pathophysiological mechanisms and oral cavity manifestations in chronic inflammatory diseases

Sammanfattning: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with a 9:1 female predominance where many genetic and clinical characteristics overlap with other inflammatory conditions such as rheumatoid arthritis (RA). Closely monitoring and treating active disease leads to better prognosis and quality of life for these patients since a cure is to date not available. In this thesis, we explored the oral cavity and its potential to offer markers of systemic inflammation as well as its possible role in explaining pathophysiological mechanisms behind autoimmunity. In study I, we demonstrated that Sjögrens syndrome (SS) affects 1/4 of SLE patients, a higher prevalence than earlier reported (6-14%), which strengthens the importance of the oral cavity and the salivary glands in SLE. The SLE subsets with vs. without SS were compared clinically and immunologically, and we identified that potential markers of systemic inflammation were higher in the SLE with secondary SS group. In study II, we compared potential biomarkers for disease activity (DA) in parallel samples of serum, saliva, and urine from SLE patients. Colony-stimulating factor -1, tumor necrosis factor-α, interferon- γ-induced protein -10, and monocyte chemoattractant protein -1 as well as calprotectin in saliva, discriminated SLE patients from controls and were associated with higher DA. Our findings demonstrate the potential of saliva as an alternative provider of biomarkers often with similar results as serum and urine. In study III, we investigated the association of autoantibodies and antibodies towards Pg virulence factor arginine gingipain (Rgp) IgG with the occurrence and severity of periodontitis (PD) in three wellcharacterized study populations of SLE and PD patients. Anticitrullinated protein antibodies (ACPA) associated with the occurrence of PD, and ACPA and dsDNA antibodies associated with arginine gingipain (Rgp) IgG antibodies, which also associated with PD severity. The association of these autoantibodies with PD supports the rationale for further studies of oral pathways to autoimmunity. In study IV, we investigated Immunoglobulin and autoantibody levels in saliva. This is a pilot study and this far, the antibody measurements in saliva reflect the serum profiles in SLE with and without SS. Our long-term goal is to evaluate if salivary autoantibodies can be used to diagnose, monitor or predict SS or other autoimmune features in SLE. Overall, the studies in this thesis demonstrate that the oral cavity provides us with alternatives to explore biomarkers. These insights may help to identify novel pathways to autoimmunity. Our novel observations may also contribute to simplified testing and monitoring of DA, and possibly to earlier detection and treatment, to prevent organ damage in SLE and other autoimmune conditions.