Autoantibodies in juvenile-onset myositis: Their diagnostic value and associated clinical phenotype in a large UK cohort

Abstract

ObjectivesJuvenile myositis is a rare and heterogeneous disease. Diagnosis is often difficult but early treatment is important in reducing the risk of associated morbidity and poor outcomes. Myositis specific autoantibodies have been described in both juvenile and adult patients with myositis and can be helpful in dividing patients into clinically homogenous groups. We aimed to explore the utility of myositis specific autoantibodies as diagnostic and prognostic biomarkers in patients with juvenile-onset disease.MethodsUsing radio-labelled immunoprecipitation and previously validated ELISAs we examined the presence of myositis specific autoantibodies in 380 patients with juvenile-onset myositis in addition to, 318 patients with juvenile idiopathic arthritis, 21 patients with juvenile-onset SLE, 27 patients with muscular dystrophies, and 48 healthy children.ResultsAn autoantibody was identified in 60% of juvenile-onset myositis patients. Myositis specific autoantibodies (49% patients) were exclusively found in patients with myositis and with the exception of one case were mutually exclusive and not found in conjunction with another autoantibody. Autoantibody subtypes were associated with age at disease onset, key clinical disease features and treatment received.ConclusionsIn juvenile patients the identification of a myositis specific autoantibody is highly suggestive of myositis. Autoantibodies can be identified in the majority of affected children and provide useful prognostic information. There is evidence of a differential treatment approach and patients with anti-TIF1γ autoantibodies are significantly more likely to receive aggressive treatment with IV cyclophosphamide and/or biologic drugs, clear trends are also visible in other autoantibody subgroups.

Clinical significance of myositis-specific autoantibodies

“…The difference in the frequency of anti-SRP may be related to genetic or environmental factors, selection bias of patients, or different detection systems (immunoprecipitation, enzyme-linked immunosorbent assay or line immunoassay). In JIIM, anti-SRP was detected in 2-4% of cases, which is lower than that observed for adult patients [5,8]. According to a literature review [93], anti-SRP-positive JIIM patients were associated with severe proximal weakness in the absence of typical DM skin lesions.…”

“…Anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are associated with IMNM. MSAs are detected in 45-85% of adult IIM patients and in 50-70% of juvenile IIM (JIIM) patients [1][2][3][4][5][6][7][8]. In adult patients, anti-ARSs are most frequently detected (20-40% of IIM cases) followed by anti-MDA5 (8-20%), anti-SRP (3-10%), anti-TIF1-c (5-7%), anti-Mi-2 (3-8%) and anti-NXP2 (5-8%) [2,9].…”

“…Subsequently, the 155 kDa autoantigen was identified as transcription intermediary factor 1 (TIF1) c. Moreover, Fujimoto et al showed the 140 kDa antigen was TIF1a, and that anti-TIF1b (120 kDa protein) was present in some DM patients with or without anti-TIF1 a/c. Anti-TIF1 autoantibodies are specifically found in DM (15-20% of adult DM and 20% of JDM cases) [5,8,63,64]. Anti-TIF1c has a positive association with malignancy, especially when it appears with anti-TIF1a, and a negative association with ILD [64].…”

“…Anti-NXP2 was originally reported as anti-MJ, which targeted a 140 kDa protein in a US cohort of JDM patients [68]. Anti-NXP2 is also specific for DM (6-30% in adult DM and about 20% in JDM) [5,8,[68][69][70]. Espada et al [71] suggested an association between anti-NXP2 and a significant compromise of functional status characterized by muscle contractures and atrophy in an Argentine pediatric cohort.…”

Dermatomyositis antibodies continue to mys TIF y

“…Autoantibodies against the first three proteins have been described in DM . Antibodies against TIF‐1γ are most commonly (17–41%) found in DM, but they often co‐occur with anti‐TIF‐1α antibodies . TRIM 28 (TIF‐1β) is the least commonly targeted, found in 1·5–3% of patients with DM .…”