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
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.