Background Several small clinical studies have reported that anti-centromere antibody (ACA)-positive Sjögren's syndrome (SS) differs from anti-SSA antibody (SSA)-positive SS in some clinical points [1,2]). However, the clinical role of ACA in SS is still unclear. To study the clinical features of ACA-positive SS, 3 groups should be compared; ACA-positive and SSA-positive SS (ACA+SSA+ group), ACA-negative and SSA-positive SS (ACA-SSA+ group), and ACA-positive and SSA-negative SS (ACA+SSA- group). However no reports have ever been designed to compare these 3 groups. There are no reports about ACA+SSA+ SS either.
Objectives We aimed to examine the clinical role of ACA in SS by clarifying the clinicopathological features of ACA- and/or SSA-positive SS.
Methods We evaluated 15 patients with ACA+SSA+ SS, 67 patients with ACA-SSA+ SS, and 24 patients with ACA+SSA- SS. All patients met the Japanese Ministry of Health revised criteria (1999) and/or the American College of Rheumatology classification criteria (2012). Patients who had collagen diseases other than systemic sclerosis and had a low titer of SSA were excluded. We performed minor labial salivary gland biopsy in all patients, evaluated focus scores, and compared the clinicopathological data of these 3 groups. Serum levels of many cytokines were also estimated using multiplex assays. In the assays, patients who were being treated with corticosteroid were excluded.
Results In the 2 ACA-positive groups, age at onset of SS and positive rate for Raynaud's phenomenon were higher than those of ACA-SSA+ SS. Sclerodactyly was observed in 13.3% of the ACA+SSA+ group, 37.5% of the ACA+SSA- group, and none of the ACA-SSA+ group. No patient developed new skin sclerosis during the follow-up period of mean 40 months. Follow-up period did not significantly differ among the 3 groups. Saxon's test in the ACA+SSA+ group was lower than that in the ACA-SSA+ group (0.43±0.35 vs 1.39±1.55 g, p=0.009). The 2 SSA-positive groups had lymphocytopenia and high serum IgG levels. The focus scores and fibrosis of the biopsy specimens did not differ significantly. Two ACA+SSA+ patients had pulmonary arterial hypertension. Other extraglandular involvement including malignant lymphoma showed no significant differences in the 3 groups. Serum IL-12 was high in the ACA+SSA+ group, while IFN-γ was high in the 2 SSA-positive groups.
Conclusions Clinicopathological data and serum cytokine profile in the 3 groups differed. Although the 2 ACA-positive groups had some features of systemic sclerosis such as Raynaud's phenomenon, not many patients showed sclerodactyly at diagnosis and no patient developed new skin sclerosis during the follow-up. The ACA+SSA+ group may be more likely to have features of SS than those of systemic sclerosis because they showed a lower salivary flow rate in Saxon's test than that in the ACA-SSA+ SS which was typical SS. Serum IL-12 was high in the ACA+SSA+ group, and there are reports that IL-12 transgenic mice mimic human Sjögren's syndrome . Thus, measuring ACA is an important component in the management of SS.
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Acknowledgements We thank John Gelblum for his critical reading of the manuscript.
Disclosure of Interest None declared