Background Since 2002, the European American Consensus Group criteria required the presence of 4 criteria among whom the presence either anti-SSA/anti-SSB antibodies or a focus score upper or equal to 1 at the labial salivary gland biopsy for the diagnosis of pSS. The direct consequence of such classification criteria is the constitution of two different immunological patterns in pSS: one with positive anti-SSA or anti-SSB antibodies, representing 60 to 70% of patients (called seropositive pSS) and the second with negative anti-SSA and anti-SSB antibodies (seronegative pSS).
Objectives To analyze the clinical and biological differences between anti-SSA seropositive patients and seronegative patients from a cohort of 176 pSS patients.
Methods We included 176 patients fulfilling 2002-AECG criteria for pSS and retrospectively analyzed their clinical and biological features according to the presence or absence of anti-SSA antibodies.
Results The median age at pSS diagnosis was 54 years; 79% were female; 68% Caucasian and 13% Black. The median follow-up time was 41 months.
pSS criteria included xerostomia for 89% of patients, xerophtalmia 96%; a positive minor salivary glands biopsy 83% of 151 patients and anti-SSA antibodies 62% (109 patients) and anti-SSB antibodies 32%. Cumulative extraglandular manifestations included arthralgia in 66%, purpura 13%, lung involvement 10%, peripheral neuropathy 36%, central nervous system involvement 6% and B-NHL 6%. Peripheral neuropathy was small fiber neuropathy (24%), large fiber sensory neuropathy (6%) and sensorimotor neuropathy (4.5%).
Seropositive patients (109 patients, 62%), when compared to seronegative patients (67 patients, 38%), were younger at pSS diagnosis (49 vs 58 years; P=0.00015), more frequently Black (18% vs 4.5%; P=0.010) and had less frequently xerostomia (84% vs 97%; P=0.006), peripheral neuropathy (28% vs 51%; P=0.002), mainly small fiber neuropathy (16% vs 39%; P=0.001) but more often purpura (20% vs 3%; P=0.01). There was no significant difference regarding, articular or lung involvement or B-NHL. Biologically, they were hallmarked by a higher prevalence of 1) B-cell chronic activation markers which included hypergammaglobulinemia (61% vs 25%; P<10–5), rheumatoid factor (65% vs 32%; P<10–5), and abnormal FLC ratio (31% vs 0%; P<10–5), 2) peripheral cytopenia including anemia (27% vs 8%; P=0.003), leucopenia (17% vs 5%; P=0.03) and lymphopenia (50% vs 29%; P=0.01). There was no difference regarding mixed cryoglobulin (11% vs 6%) and monoclonal gammopathy (16%vs 16%).
Conclusions Our results showed that the presence or the absence of anti-SSA antibodies are associated with two distinct clinical and biological faces of the “same disease”. Anti-SSA positive patients are younger at diagnosis with a higher prevalence of purpura and B cell activation markers and cytopenia; inversely, anti-SSA negative patients are older at diagnosis with a lower prevalence of B cell activation and are more prompt to develop sensory neuropathies mainly small fiber neuropathies. These findings question the pSS clinical and biological homogeneity and the selection of patients for B cell targeting therapies.
Disclosure of Interest None declared