Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Characterization of Anti Sjgren's Syndrome Nuclear Antigen-1 (SSNA-1) Novel Autoantibody in Patients with Primary Sjgren's Syndrome.
Hiruma1, Kaori, Nozawa1, Kazuhisa, Ikeda2, Keigo, Yamaguci1, Ayako, Sekigawa2, Iwao, Chan3, Edward K.L., Takasaki1, Yoshinari
Sjogren's syndrome nuclear antigen-1 (SSNA-1)/nuclear antigen of 14 kDa (NA14) is a novel autoantigen which were recently identified. SSNA-1 belongs to a coiled coil protein superfamily and the coiled coil proteins are known to often elicit autoimmune reaction in Sjogren's syndrome. Although we previously have reported that autoantibody against SSNA-1 was often produced in patients sera with primary Sjogren syndrome (pSS), the detailed autoantigen characteristics about the SSNA-1 remains poorly described. Therefore, we conducted the present study to clarify characteristics of SSNA1 regarding clinical association of pSS and mechanism of the autoantibody production.
Total 332 sera with various rheumatic diseases including pSS positive for standard autoantigens (SS-A/SS-B, centromere, U1-RNP, ds-DNA, Jo-1, and nucleolar related proteins) were obtained from serum bank of our university hospital approved by the local ethics committee. Reactivity for recombinant SSNA-1 protein in these autoimmune sera was measured by direct ELISA and immunoblotting. Statistical analysis was performed by c2test compared to those of normal control. SSNA-1, interferon g inducible protein of 10 kDa (IP-10) and B cell-activating factor belonging to the TNF family (BAFF) expression in human salivary cells line (HSG) was monitored by quantitative real-time PCR. Serum levels of IP-10 and BAFF were measured by sandwich ELISA. IIF analysis was performed to characterize staining pattern of anti-SSNA-1 antibody.
High frequency of positive sera against SSNA-1 was observed in anti- SS-A/SS-B, centromere, and U1-RNP positive autoimmune sera significantly compared to normal controls, and was not observed in anti-ds-DNA, Jo-1 and nucleolar related proteins positive autoimmune sera. Although the anti-SSNA-1 antibody was predominantly recognized in pSS among various systemic rheumatic diseases as we expected, patients with mix connective tissue disease (MCTD) showed high prevalence of anti-SSNA antibody as well as pSS. IIF analysis revealed that anti-SSNA-1 monoclonal antibody stained only G2-M phase mitotic cells and did not stain G1-S phase cells. IFNg treatment resulted in 10-fold increase of SSNA-1 mRNA expression on the HSG cells. Serum levels of IP-10 and BAFF, which were also positively regulated by IFNg in HSG cells, were statistically greater in anti-SSNA-1 positive sera with pSS compared to those in the anti-SSNA-1 negative sera.
In the present study, we clarified that anti-SSNA-1 antibody is frequently recognized in anti-SS-A/SS-B, centromere, and U1-RNP positive autoimmune sera. The production of anti-SSNA-1 antibody had unique disease specificity for pSS and MCTD. In addition, SSNA-1 appeared to be classified as novel mitotic apparatus autoantigen. Regarding to an important factors of the anti-SSNA-1 autoantibody production, IP-10 and BAFF played an important role for the autoantibody production. Overexpression of IP-10 and BAFF induced by abnormal IFNg regulation in pSS may possibly induce autoreactive T cells infiltration and abnormal B cells activation in salivary gland with pSS consequently resulting in anti-SSNA-1 autoantibody production.
To cite this abstract, please use the following information:
Hiruma, Kaori, Nozawa, Kazuhisa, Ikeda, Keigo, Yamaguci, Ayako, Sekigawa, Iwao, Chan, Edward K.L., et al; Characterization of Anti Sjgren's Syndrome Nuclear Antigen-1 (SSNA-1) Novel Autoantibody in Patients with Primary Sjgren's Syndrome. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :467