%0 Journal Article
%T Clinical features associated with the presence of anti-Ro52 and anti-Ro60 antibodies in Jo-1 antibody-positive anti-synthetase syndrome.
%A Yamaguchi K
%A Tang Q
%A Poland P
%A Reay DP
%A Gregory A
%A Aggarwal R
%A Oddis CV
%A Ascherman DP
%J Front Immunol
%V 15
%N 0
%D 2024
%M 38895121
%F 8.786
%R 10.3389/fimmu.2024.1399451
%X <B>UNASSIGNED: </B>Anti-SSA antibodies target two unrelated proteins, Ro52 (E3 ligase) and Ro60 (RNA binding protein). Previous studies indicate that anti-Ro52 antibodies are frequently associated with various myositis-specific autoantibodies (MSAs)-including anti-tRNA synthetase antibodies-and that the coexistence of MSAs and anti-Ro52 antibodies may portend worse clinical outcomes. Although not well-described in the setting of myositis, work from our animal model of HRS (histidyl-tRNA synthetase)-induced myositis suggests that anti-Ro60 antibodies may also be linked to specific MSAs such as anti-HRS/Jo-1. We therefore aimed to demonstrate the prevalence and clinical characteristics of Ro52 and Ro60 antibody positivity in patients possessing Jo-1 antibodies.<BR><B>UNASSIGNED: </B>To establish the immunological link between anti-synthetase, anti-Ro52, and anti-Ro60 antibodies, we evaluated the relative titers of these antibodies in blood and bronchoalveolar lavage fluid (BALF) of mice following immunization with HRS/Jo-1. In parallel, we used ELISA-based approaches to assess sera from 177 anti-Jo1 antibody-positive patients for the presence of anti-Ro52 and/or anti-Ro60 antibodies. We then determined statistical associations between co-existing anti-Jo-1, anti-Ro52, and/or anti-Ro60 antibodies and clinical manifestations associated with the anti-synthetase syndrome.<BR><B>UNASSIGNED: </B>Mice immunized with HRS had higher levels of anti-Ro52 and anti-Ro60 antibodies in serum and BALF than PBS-immunized mice. In 177 anti-Jo-1 antibody-positive patients, the prevalence of anti-Ro52 and anti-Ro60 antibodies was 36% and 15%, respectively. The frequency of dry eye/dry mouth, interstitial pneumonia, and pulmonary events over time differed between patients with various combinations of anti-Ro52 and anti-Ro60 antibodies. While anti-Ro52 antibodies generally correlated with statistically significant increases in each of these clinical manifestations, the presence of Ro60 antibodies alone was associated with decreased frequency of ILD.<BR><B>UNASSIGNED: </B>Anti-Ro52 and/or anti-Ro60 antibodies are often co-expressed with anti-Jo1 antibodies, defining clinical subsets with different disease course/outcomes.