LAUSR

Sjögren’s syndrome (SS) is characterized by B cell hyperactivity reflected by hypergammaglobulinemia as well as a plethora of autoantibodies including antinuclear antibodies (ANA), anti-Ro/SSA, anti-La/SSB and rheumatoid factors (RF). Previous studies have focused on the phenotype of single positive (ANA or anti-Ro/SSA or anti-La/SSB) or double positive (anti-Ro/SSA and anti-La/SSB positive) SS patients, showing differences regarding the age of diagnosis, sicca manifestations and specific extraglandular manifestations. To our knowledge, no study has ever explored the clinical spectrum of triple seronegative (anti-Ro/SSA + anti-La/SSB + RF negative) and quadruple seronegative (ANA +anti-Ro/SSA + anti-La/SSB + RF negative) SS patients.To study the differences in the clinical phenotype of triple and quadruple seronegative (SS) patients in a large cohort of well characterized patients, after comparison with anti-Ro/SSA positive patients.From a total cohort of 1723 consecutive SS patients who fulfill the 2016 EULAR/ACR criteria and are followed up in 4 clinical centers ([Universities of Pisa and Athens, Harokopio and Ioannina, (PAHI)], those who have been found triple or quadruple seronegative were identified and compared with matched anti-Ro/SSA positive SS patients according to age of SS onset, disease duration and gender, in 1:1 and 1:2 ratio respectively. Glandular (dry mouth, dry eyes, parotid gland enlargement) and extra-glandular manifestations (Raynaud’s phenomenon, chronic fatigue arthralgias/myalgias, arthritis, palpable purpura, liver involvement, kidney involvement, lung involvement, neurologic involvement, long standing lymphadenopathy and lymphoma) were compared between the 2 seronegative groups and the anti-Ro/SSA positive control group. Statistical analysis for categorical variables was performed by Fisher exact or chi-square tests and for continuous variables with t test or Mann-Whitney accordingly.Two hundred and four SS patients (11,8%) were identified as triple negatives and 53 (3,0%) as quadruple, with a median disease duration of 6 years (range: 0-41) and 5 years (range: 0-32) respectively. The matched anti-Ro/SSA controls were 204 for the triple and 103 for the quadruple negatives. Triple negatives had lower frequency of monoclonal gammopathy (5,5% vs 12,1% p=0,04), low C4 serum levels (23% vs 36%, p=0,009) and lymphoma (3,4% vs 9,8%, OR= 3,06, 95% CI =1,27-7,85) while quadruple negatives exhibited higher prevalence of dry eyes (100% vs 90%) and lower prevalence of long standing lymphadenopathy (2,7% vs 19,5%, p=0,001) and lymphoma (0% vs 15%, p=0,001) compared to anti-Ro/SSA matched controls.Combined seronegativity account for more than 10% of SS population and is associated with lower prevalence of lymphoma compared to anti-Ro/SSA positive patients.Loukas Chatzis: None declared, Vasileios Pezoulas: None declared, Francesco Ferro: None declared, Valentina Donati: None declared, Aliki Venetsanopoulou: None declared, Evangelia Zampeli: None declared, Maria Mavromati: None declared, Paraskevi Voulgari: None declared, Clio Mavragani: None declared, Dimitris Fotiadis: None declared, Fotini Skopouli: None declared, Salvatore De Vita Consultant of: Roche, Human Genome Science, Glaxo Smith Kline and Novartis, Chiara Baldini: None declared, Haralampos M. Moutsopoulos: None declared, Athanasios Tzioufas: None declared, Andreas Goules: None declared