Anti-Ro52 antibodies frequently co-occur with anti-Jo-1 antibodies in sera from patients with idiopathic inflammatory myopathy

Abstract

SUMMARYWe analysed 112 idiopathic inflammatory myopathy (IIM) sera for the presence of anti-Ro, anti-La and anti-histidyl-tRNA synthetase (Jo-1) autoantibodies, and subsequently mapped B cell epitopes on the Ro52 protein recognized by anti-Ro52 þ IIM sera. Sera were characterized by immunoblotting, ELISA and RNA precipitation. Both anti-Ro60 and anti-La activity was found in 4% of IIM sera. Anti-Ro52 antibodies were present in 20% of IIM sera. However, in anti-Jo-1 þ IIM sera (21%), the frequency of the anti-Ro52 antibodies was found to be much higher (58%). No cross-reactivity between anti-Ro52 and anti-Jo-1 antibodies could be detected in these sera. To learn more about the nature of anti-Ro52 antibodies occurring in IIM sera, we analysed the major epitopes of the Ro52 protein targeted by antiRo52 þ IIM sera by immunoprecipitation of in vitro translated Ro52 deletion mutants. The major epitope was mapped in the region bordered by amino acids 126 and 252. This part of the protein includes a long a-helical region which contains two potential coiled-coil domains as well as a leucine zipper motif. Although no difference in Ro52 epitope recognition between anti-Jo-1 þ and anti-Jo-1 ¹ IIM sera could be observed, our results suggest that the autoimmune response against Ro52 and Jo-1 in IIM patients is coupled.

A possible mechanism for endogenous activation of the type I interferon system in myositis patients with anti–Jo‐1 or anti–Ro 52/anti–Ro 60 autoantibodies

“…These immune complexes may act as endogenous IFN␣ inducers by activating BDCA-2-positive PDCs and perpetuating an immune response directed against a ubiquitous antigen. The same mechanism could also be of relevance for anti-Ro 52/anti-Ro 60 autoantibodies in myositis, and anti-Ro 52 antibodies frequently co-occur with anti-Jo-1 antibodies (29). We also found a correlation between the IFN␣-inducing capacity of sera and the presence of ILD, one of the major extramuscular features of anti-Jo-1 antibodypositive patients (3,30), suggesting that IFN␣ production could have a role in the development of ILD in these patients.…”

Histidyl-tRNA Synthetase

“…The missing region is predicted to have a coiled-coil structure that resembles the coiled-coil arm at the N-terminus of SerRS, which has not been found in HisRS from E. coli and yeast. Peptides consisting of amino acid residues 1 -60 and 1 -47 of human HisRS have a high helical content and compete with HisRS for the autoantibody sites; comparison with other antibodies has suggested that a long ␣-helical region which contains two potential coiled-coil domains and a leucine zipper motif may be the main epitope (Rutjes et al, 1997). In a more detailed study, amino acid residues 2 -44 and 286 -509 of the human HisRS were identified as epitopes (Martin et al, 1995).…”

“…Antibodies against an antigen called Jo-1 were found in 20 -30% of the sera of myositis patients (Mathews and Bernstein, 1983;Dang et al, 1985Targoff et al, 1988;Targoff and Arnett, 1990;Marguerie et al, 1990;Goldstein et al, 1990;Tsui and Siminovitch, 1991;Shi et al, 1991;Lopez et al, 1991;Targoff, 1991Targoff, , 1993Hirakata et al, 1992;Treher et al, 1993;Garlepp, 1993;O'Neill and Maddison, 1993;Mitra et al, 1994;O'Hanlon et al, 1994;Chmiel et al, 1995;Fischer et al, 1995;Gelpi et al, 1996;Vazquez-Abad and Rothfield, 1996a;Friedman et al, 1996;Rutjes et al, 1997;Kalenian and Zweiman, 1997;Miller et al, 1998). Immunoblot assays (Williams et al, 1986;Fonong et al, 1990) and ELISA tests were developed (Biswas et al, 1987b;Targoff and Reichlin, 1987) for detection of anti-Jo-1, which does not seem to correlate with cellular muscle damage (Suzuki et al, 1993).…”

Serological Aspects of Myositis

“…These observations underline previous conclusions (Peene et al, 2002) that anti-Ro52 is indeed an independent aab in myositis. Rutjes et al (Rutjes et al, 1997) found anti-Ro52 reactivity in 58 % of Jo-1 positive myositis sera, an observation confirmed in the subsequent years by Rozman et al (2000), Brouwer et al (2001) and Koenig et al (2007) (Rozman et al, 2000;Brouwer et al, 2001;Koenig et al, 2007). In contrast, Langguth et al (Langguth et al, 2007) indicated that isolated anti-Ro52 reactivity has limited clinical value in a non-obstetric population, a conclusion that could not be confirmed.…”