Peripheral blood immunophenotypic diversity in patients with anti-MDA5+ dermatomyositis and its impact on prognosis

To explore the heterogeneity and the corresponding clinical significance of lymphocyte subsets in dermatomyositis patients with anti-melanoma differentiation-associated gene 5 positive autoantibody (anti-MDA5+ DM).

268 anti-MDA5+ DM patients and 536 gender-age matched healthy controls (HCs) were retrospectively enrolled. Patients' clinical data, serological parameters, peripheral blood lymphocyte subsets, imagological examinations, treatment regimens and follow-up were collected. Cluster analysis based on peripheral blood lymphocyte subsets was conducted in anti-MDA5+ DM patients.

The absolute number of CD3+ T lymphocytes, CD3+CD4+ T cells, CD3+CD8+ T cells, CD3-CD19+ B cells and CD16+CD56+ NK cells were significantly reduced in anti-MDA5+ DM patients compared with HCs. The absolute counts of the above cell subsets were remarkably reduced in non-survivors compared to the survivors of anti-MDA5+ DM. Cluster analysis based on lymphocyte subsets divided anti-MDA5+ DM patients into cluster 1(n=125) and cluster 2 (n=143). Patients in cluster 1 presented with lower counts of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, CD3-CD19+ B cells and NK cells compared with cluster 2. Notably, RP-ILD rate, three-month and six-month death rate in cluster 1 were dramatically higher than in cluster 2, p<0.001, respectively.

Lymphocytes and their subsets were significantly altered in anti-MDA5+ DM patients. There was remarkable heterogeneity of lymphocyte subsets in anti-MDA5+ DM patients between survivors and non-survivors. Anti-MDA5+ DM patients were divided into two groups with distinct symptoms and survival rate by cluster analysis based on lymphocyte subsets.