Antisynthetase syndrome in Chile: Experience from a clinical cohort

Antisynthetase syndrome (ASS) is an autoimmune disease characterised by the presence of autoantibodies against aminoacyl-tRNA synthetases and a variable spectrum of clinical manifestations. Its clinical expression appears to depend on the predominant antibody subtype. In Latin America, and particularly in Chile, published data on this condition remain scarce. The aim of this study was to describe and compare the clinical, immunological, and therapeutic characteristics of patients with ASS according to antibody subtype in a Chilean cohort.

An analytical cross-sectional observational study was conducted, including patients with a clinical diagnosis of ASS and positivity for an antisynthetase antibody (Jo-1, PL-7, PL-12, EJ, or OJ) from Hospital del Salvador and Instituto Nacional del Tórax between June 2018 and June 2022. Clinical manifestations were compared between Jo-1 and non-Jo-1 groups. Fulfillment of classification criteria (Connors, Solomon, and CLASS), first-line treatment strategies, and fatal outcomes were also evaluated.

A total of 60 patients was analyzed: 36.7% were anti-Jo-1 positive and 63.3% had other antisynthetase antibodies. Interstitial lung disease (ILD) was the most frequent manifestation (73.3%), predominating in the Jo-1 group (95.5% vs. 60.5%, p = 0.003). Myopathy and arthritis were more common in Jo-1 than in non-Jo-1 patients (p = 0.017 and p = 0.048, respectively). Patterns of clinical involvement differed significantly, with triple involvement (ILD, arthritis, and myopathy) observed in 52.4% of Jo-1 patients and 18.8% of non-Jo-1 patients (p = 0.0001). Only 56.6% of the cohort fulfilled Solomon criteria, whereas 80% fulfilled CLASS criteria, with lower fulfilment rates in the non-Jo-1 group. Mycophenolate mofetil was the most frequently used immunosuppressive therapy, particularly in patients with ILD, and methylprednisolone pulse therapy was associated with pulmonary involvement and more extensive clinical phenotypes. Ro52 positivity was associated with ILD (p = 0.002) and NSIP/OP patterns.

Antisynthetase syndrome in Chile demonstrated a heterogeneous clinical spectrum according to antibody subtype. Only one-third of patients were anti-Jo-1 positive, showing a more classic clinical phenotype, whereas non-Jo-1 patients tended to present with a more oligosymptomatic disease pattern. The high frequency of ILD and its association with Ro52 positivity highlight their clinical relevance. Current classification criteria appear insufficient for non-Jo-1 patients, emphasizing the need for validation studies in our region.