Heterogeneous nuclear ribonucleoproteins (hnRNPs) are potent autoantigenic targets in systemic autoimmune rheumatic diseases (SARD). Loss of tolerance to the RA33 complex consisting of hnRNP A2 and its alternatively spliced variants B1 and B2 has been the interest of rheumatologists. A novel ELISA for the detection of anti-hnRNP B1 autoantibodies has been developed to investigate the prevalence thereof in 397 patients with SARD, including patients with rheumatoid arthritis (RA), spondyloarthropathy (SPA), juvenile chronic arthritis, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren's syndrome (SS), in comparison to 174 controls. Anti-hnRNP B1 autoantibodies were significantly more prevalent in patients with SARD than controls (47/397, 11.8% versus 2/174, 1.1%; P < 0.001). In particular, anti-hnRNP B1 were found more frequently in the disease cohorts than in the controls and were present in 24/165 (14.5%) patients with RA, 6/58 (10.3%) SPA, 11/65 (16.9%) SSc, and 4/50 (8.0%) SLE. In RA patients, anti-hnRNP B1 autoantibodies correlated significantly with C-reactive protein levels and erythrocyte sedimentation rate, while in patients with SSc it was associated with features of arterial wall stiffness and presence of hypertension. Anti-hnRNP B1 autoantibodies occur in SARD and seem to be correlated with distinct clinical characteristics in patients with RA and SSc.

О р и г и н а л ь н ы е и с с л е д о в а н и я

Background Systemic sclerosis (SSc) is an autoimmune disease characterized by the occurrence of a wide range of autoantibodies (Aab) which can predict distinct clinical features of SSc. Aab to hnRNP A2 and its alternatively spliced variants B1 (anti-hnRNP B1) and B2 are generally referred to as anti-RA33 and have been extensively studied in rheumatoid arthritis (RA) [1]. However, the prevalence of anti-RA33 Aab in other autoimmune diseases, such as scleroderma, mixed connective tissue disease and systemic vasculitides, is far from determined [2–4]. Objectives To compare the frequency of anti-hnRNP B1 with other SSc-specific Aab and to determine an association thereof with the clinical phenotype in patients with SSc Methods We studied Aab prevalence in 64 patients with SSc, 29 with diffuse cutaneous SSc and 26 with limited cutaneous disease as well as 9 patients with overlap syndrome. Diagnosis of SSc in all patients was based on 1980 ACR (ARA) criteria and the disease phenotype was analyzed according to LeRoy's classification criteria [7]. Serum samples from clinically healthy blood donors (n=174) were used as a control group. Skin involvement and disease severity was measured with Rodnan's skin score and Valentini activity index. Vascular involvement was accessed by measurement of pulse wave velocity (PWV) and augmentation index (AI) with applanation tonometry (SphygmoCor system, AtCor Medical Pty Ltd., Sydney, Australia). Anti-hnRNP B1 IgG was assessed by an ELISA employing recombinant human hnRNP B1 expressed in E.coli (in.vent DIAGNOSTICA GmbH, Germany). SSc-specific Aab were measured with line immunoassay (Euroimmun AG, Germany) according to the manufacturer's instructions. Results Anti-hnRNP B1 were found in 18.5% (12/64) of SSc patients and in 1.1% (2/174) of controls (p<0.001). Median concentrations were also significantly higher in SSc patients (p<0.001). There were no significant associations of anti-hnRNP B1 level with any other particular SSc-specific Aab, clinical form of the SSc, degree of skin involvement, and clinical activity. We found that anti-hnRNP B1 antibodies directly correlated with the presence (r=0.33 p=0.009) of arterial hypertension and vessel-wall stiffness parameters like PWV (r=0.39, p=0.004) and AI (r=0.35, p<0.001). Conclusions Anti-hnRNP B1 (RA33) is an independent serological marker in SSc and is associated with vascular involvement. References Nell-Duxneuner Vet al. Ann Rheum Dis. 2010; 69(1):169-74. Tomoum HY et al. Pediatr Int. 2009;51(2):188-92. Siapka Set al. Autoimmunity. 2007;40(3):223-33. Cho SBetal.J Invest Dermatol. 2012;132:601-8. Hoffmann MH et al. J Immunol. 2007;179(11):7568-76. Steiner Get al. ClinExpRheumatol. 2002 Jul-Aug;20(4):517-24. LeRoy EC, et al. J Rheumatol 1988; 15:202-205. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2222

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