No significant antibody response to rTNC5 was recognized (p=0.527) (table 1, see online supplementary number S1). not all people who show early synovitis develop RA; for example, in some, synovial swelling resolves spontaneously.1 The factors that travel RA development remain unclear and clinical tools to predict RA development are imperfect. Tenascin-C is definitely a proinflammatory matrix molecule that is absent from healthy joints but highly indicated in the bones of individuals with RA.2 3 We identified an immunodominant peptide in citrullinated tenascin-C, cTNC5, antibodies against which are detected in around half of the individuals with RA, and may be found years before disease onset in some individuals.4 MT-DADMe-ImmA Here, we sought to determine if anti-cTNC5 antibodies can discriminate among people with early synovial swelling those who develop RA and those with other outcomes. Sera from 263 individuals in the Birmingham early arthritis cohort were analysed. Patients were disease-modifying antirheumatic drug (DMARD) na?ve with clinically apparent synovitis of 1 MT-DADMe-ImmA 1 joint and with inflammatory joint symptoms of 3?weeks duration. Patients were adopted for MT-DADMe-ImmA 18?weeks to ensure development of full disease phenotype and to allow any resolving arthritis time to resolve. At 18?weeks, individuals were assigned to the following outcome groups: persistent RA according to the American College of Rheumatology (ACR) 2010 criteria5 (RA, n=101), persistent non-RA arthritis (PNRA, n=66) and resolving arthritis (no clinically apparent joint swelling, no DMARD/steroid use in the previous 3?weeks, n=96). Demographic and medical guidelines were recorded, and individuals with RA divided into anti-cyclic citrullinated peptide (anti-CCP) antibody positive and negative subsets.6 7 Antibodies recognising cTNC5 or the non-citrullinated control peptide (rTNC5) were analysed by ELISA as described.4 Anti-cTNC5 antibodies were found in 40.6% of people with early synovitis who went on to develop RA, but were recognized in a low proportion of people who developed PNRA (6.1%), or whose disease resolved (3.1%). No significant antibody response to rTNC5 was recognized (p=0.527) (table 1, see online supplementary number S1). Anti-cTNC5 antibodies were significantly more common in anti-CCP antibody positive compared with anti-CCP antibody bad individuals with RA (81.3% vs 3.8%, p 0.0001) (table 1). Anti-cTNC5 antibody levels were higher in individuals with anti-CCP antibody-positive RA (193.1449.8 arbitrary units (AU)) compared with patients with anti-CCP antibody-negative RA (3.563.30?AU), PNRA (19.42122.7?AU) and resolving arthritis (6.6028.02?AU) (ANOVA p 0.0001). While anti-cTNC5 was not better at predicting the development of RA than anti-CCP antibody (specificity; level of sensitivity: 40.6%; 95.7% (cTNC5), 47.5%; 98.8% (CCP)), anti-cTNC5 did detect a subset of people who developed RA who were not anti-CCP antibody positive (3.8%). Individuals with anti-cTNC5 antibody-positive RA were more frequently anti-CCP antibody and rheumatoid element (RF) positive than anti-cTNC5 antibody-negative individuals (table 2). Table?1 Demographic, clinical and laboratory characteristics of individuals in each outcome group thead valign=”bottom” th rowspan=”1″ colspan=”1″ /th th align=”remaining” rowspan=”1″ colspan=”1″ Anti-CCP bad RA (n=53) /th th align=”remaining” rowspan=”1″ colspan=”1″ Anti-CCP positive RA (n=48) /th th align=”remaining” rowspan=”1″ colspan=”1″ Persistent non-RA (n=66) /th th align=”remaining” rowspan=”1″ colspan=”1″ Resolving arthritis (n=96) /th th align=”remaining” rowspan=”1″ colspan=”1″ p Value /th /thead Woman, n (%)27 (50.9)31 (64.6)37 (56.1)46 (47.9)0.274Age (years)55.615.755.514.452.118.945.916.8 0.0001Symptom duration (days)52.421.455.321.756.421.545.320.80.005CRP (mg/dL)10 (0C39)17.5 (6C43.8)20.5 (7.5C35.3)7 (0C17) 0.0001ESR (mm/hour)18 (11.5C44.5)27.5 (18.3C51.3)21.5 (7.8C45.8)12.5 (5C27) 0.0001DAS28 (CRP)4.41.44.41.43.61.22.81.3 0.0001DAS28 (ESR)4.61.54.71.63.61.82.91.5 0.001Smoking, n (%)0.07Ever smoker28/49 (57.1)27/47 (57.4)26/64 (40.6)35/89 (39.3)Never-smoker21/49 (42.9)20/47 (42.6)38/64 (59.4)54/89 (60.7)Anti-CCP positive, n (%)0 (0)48 (100)1 (1.5)1 (1.0) 0.0001RF IgG positive, n (%)9 (17)44 (91.7)5 (7.6)10 (10.4) 0.0001RF IgA positive, n (%)7 (13.2)26 (54.2)5 (7.6)10 (10.4) 0.0001Anti-cTNC5 positive, n (%)2 (3.8)39 (81.3)4 (6.1)3 (3.1) 0.0001Anti-rTNC5 positive, n (%)1 (1.9)1 (2.1)3 (4.5)1 (1.0)0.527 Open in a separate windows Data are shown as quantity (percentage), meanSD, or median (IQR) as appropriate. Comparisons have been performed with 2, analysis of variance (ANOVA) and Kruskal-Wallis checks for categorical, parametric continuous and non-parametric continuous data, respectively. CCP, cyclic citrullinated peptide; CRP, C reactive protein; cTNC, citrullinated tenascin-C; DAS, disease activity score; ESR, erythrocyte sedimentation rate; RA, rheumatoid arthritis; RF, rheumatoid element. Table?2 Characteristics of individuals with RA with and without anti-cTNC5 antibodies thead valign=”bottom” th rowspan=”1″ colspan=”1″ /th th align=”remaining” rowspan=”1″ colspan=”1″ Anti-cTNC5 bad br / RA (n=60) /th th align=”remaining” rowspan=”1″ colspan=”1″ Anti-cTNC5 positive br / LERK1 RA (n=41) /th th align=”remaining” rowspan=”1″ colspan=”1″ p Value /th /thead Woman, n (%)33 (55)25 (60.1)0.682Age (years)55.216.156.113.30.785Symptom duration (days)52.321.55621.50.400CRP (mg/dL)10.5 (0C43)18 (6C39)0.062ESR (mm/hour)18 (11C45)25 (19C46)0.372DAS28 (CRP)4.261.44.551.40.320DAS28 (ESR)4.511.54.821.60.32028 TJC7.226.59.110.40.26728 SJC7.67.26.95.50.595Smoking, n (%)?Ever smoker34/56 (60.7)21/40 (52.5)0.682?Never-smoker22/56 (39.3)19/40 (47.5)0.374Anti-CCP positive, n (%)9 (15)39 (95.1) 0.0001RF IgG positive, n (%)16 (26.7)37 (90.2) 0.0001RF IgA positive, n (%)10 (16.6)23 (56.1) 0.0001 Open in a separate window Data are shown as number (percentage), meanSD, or median (IQR) as appropriate. Comparisons have been performed with 2, Student’s t-test.