Atypical Autoantibodies in Patients with Primary Sjögren Syndrome: Clinical Characteristics and Follow-Up of 82 Cases

To analyze the clinical characteristics, follow-up, and fulfillment of classification criteria for other systemic autoimmune diseases (SAD) in patients with primary Sjögren syndrome (SS) and atypical autoantibodies. We studied 402 patients diagnosed with primary SS seen consecutively in our Department since 1994. We considered anti-DNA, anti-Sm, anti-RNP, antitopoisomerase1/Scl70, anticentromere (ACA), anti-Jo1, anti-neutrophil cytoplasmic antibodies (ANCA), anticardiolipin antibodies (aPL), and lupus anticoagulant as atypical autoantibodies. The patients were prospectively followed after inclusion into the protocol, focusing on the development of features that might lead to the fulfillment of classification criteria for additional SAD. As a control group, we selected an age–sex-matched subset of patients with primary SS without atypical autoantibodies. Eighty-two (20%) patients showed atypical autoantibodies (36 had aPL, 21 anti-DNA, 13 ANCA, 10 anti-RNP, 8 ACA, 6 anti-Sm, 2 anti-Scl70, and 1 anti-Jo-1 antibodies). There were 77 (94%) women and 5 (6%) men, with a mean age of 57 years. Patients with atypical autoantibodies had no statistical differences in the prevalence of the main sicca features, extraglandular manifestations (except for a higher prevalence of Raynaud’s phenomenon, 28% versus 7%, P = 0.001), immunological markers, and in the fulfillment of the 2002 classification criteria, compared with the control group. After a follow-up of 534 patient-years, 13 (16%) of the 82 patients with atypical autoantibodies developed an additional SAD (systemic lupus erythematosus in 5 cases, antiphospholipid syndrome in 4, limited scleroderma in 3, and microscopic polyangiitis in 1) compared with none in the control group ( P < 0.001). This study shows an immunological overlap (defined by the presence of autoantibodies considered typical of other SAD) in 20% of our patients with primary SS. However, the clinical significance of these atypical autoantibodies varies widely depending on the autoantibodies detected, with a broad spectrum of prevalence and clinical patterns of disease expression, and a specific predilection for association with some SAD in preference to others.