Ab0829 Autoimmune Thyroid Disease: Prevalence and Associations in a Sicca Cohort

Background: Sicca complaints are a frequent reason for rheumatology consultation in an outpatient setting. Though Sjögren's disease (SjD) and to a lesser extent systemic sclerosis (SSc) are the main systemic autoimmune disorders accounting for oral and ocular dryness, autoimmune thyroid disease (ATD) has been also previously associated with sicca features¹ and the presence of perivascular infiltrates in minor salivary gland (MSG) biopsies². However, data regarding the prevalence of ATD in an unselected sicca cohort is scarce. Objectives: To uncover the frequency and clinical associations of ATD in a well-investigated cohort of patients presenting with sicca complaints in an outpatient rheumatology setting. Methods: Demographic, clinical, laboratory, and histopathological data were thoroughly collected from 92 consecutive patients investigated for sicca complaints. Immune profile testing included rheumatoid factor, ANA titer/pattern, antibodies to nuclear extractable (Ro/SSA, La/SSB, U1RNP/Sm complex), and thyroid antigens [thyroglobulin, thyroid peroxidase (TPO)] as well as SSc-specific autoantibodies using a commercially available immunoblot kit [EuroLine Systemic Sclerosis Profile (IgG)]. Testing for chronic viral infections (HIV, HCV), chest X-ray (to exclude sarcoidosis) and MSG biopsy were also performed on all study participants. Additionally, available MSG biopsies from a subgroup of patients were subjected to real-time PCR for interferon (IFN) inducible genes (IFIGs), preferentially those induced by type I IFN. Statistical analysis was performed by GraphPad Prism 10.0 and SPSS 26.0. Results: Fifty-two out of 92 patients (56.5%) in the cohort fulfilled the classification criteria for SS, while 34 out of 92 (37%) for ATD, respectively. While the prevalence of ATD among patients with SS was 34.6% (18/52), in those not fulfilling SS criteria the corresponding value was 40% (16 out of 40). No association between ATD and anti-Ro/SSA status was observed. Interestingly, ATD displayed the highest frequency (52%) in the subgroup of patients not fulfilling SS criteria and lacking serum SSc-autoantibodies. The presence of ATD in the context of SS was associated with lower rates of salivary gland enlargement and anti-La/SSB positivity, while Schirmer's test was more often abnormal. Moreover, these patients exhibited lower urine PH, as well as lower neutrophil blood count compared to their SS counterparts without evidence of ATD. Of interest, overexpression of IFI44 (p=0.007) and its ligand IFI44L (p=0.003) transcripts was observed in MSG biopsies of sicca patients with TPO serum reactivity, as shown in Figure 1. Conclusion: ATD is frequently detected in sicca patients and is often the sole immunological abnormality in those lacking autoantibodies for SS and SSc. Furthermore, an increased IFN I signature -namely for IFI44 and IFI44L- in MSG tissue derived from anti-TPO+ sicca patients provides a possible immunopathological explanation for ATD sicca symptomatology. Testing for ATD should therefore be included in the diagnostic workup for SS. REFERENCES: [1] Mavragani CP, Niewold TB, Chatzigeorgiou A, Danielides S, Thomas D, Kirou KA, Kamper E, Kaltsas G, and Crow MK (2013): Increased serum type I interferon activity in organ-specific autoimmune disorders: clinical, imaging, and serological associations. Front.Immunol. 4:238. doi: 10.3389/fimmu.2013.00238 [2] Marketos N, Koulouri V, Piperi EP, Georgaki ME, Nikitakis NG, Mavragani CP. Scleroderma-specific autoantibodies: Should they be included in the diagnostic workup for Sjögren's syndrome? Semin Arthritis Rheum. 2022;55(May):152026. doi:10.1016/j.semarthrit.2022.152026 Acknowledgements: NIL. Disclosure of Interests: None declared.