Pulmonary and serum cytokine profiles of patients with anti-ARS and anti-MDA5 antibodies

Abstract

The present study aimed to determine the pulmonary cytokine profiles of patients with anti-RNA synthetase (ARS) and anti-melanoma differentiation-associated protein 5 (MDA5) antibodies. The study included patients with ARS and MDA5 whose serum or bronchoalveolar fluid (BALF) was available. Sandwich enzyme-linked immunoassay microarray multiplex assay was used to measure 18 cytokine levels in serum and BALF. The cytokine patterns were investigated using factor and cluster analyses. Pulmonary cytokine production was examined using the BALF/Seum cytokine ratio. Forty participants were enrolled in the study: 19 with ARS and 21 with MDA5. All patients had interstitial lung disease (ILD). BALF was collected from 10 patients with ARS and 6 with MDA5. Serum type 1 IFN, IP-10, MCP-1, and TNF-α were elevated in both ARS and MDA5. IL-6, IL-10, and IL-15 were elevated in MDA5. Serum cytokine patterns differed between ARS and MDA5. In BALF, IFN-α, IP-10, MCP-1, and ferritin were increased in both ARS and MDA5. Higher levels of IFN-α, IL-6, and ferritin were observed in MDA5. One patient with severe MDA5-ILD showed higher levels of multiple cytokines, including IL-6 and IFN-α. BALF cytokine patterns were similar in ARS and MDA5 cases except the one with severe MDA5-ILD. IL-6, IP-10, IL-15, MCP-1, and ferritin were produced in the lungs in ARS and MDA5 and IFN-α in MDA5. In conclusion, IFN-α and pulmonary macrophage activation play important roles in ILD development in both ARS and MDA5-ILD. MDA5-ILD could be characterized by higher production of multiple cytokines and macrophage activation, particularly in severe cases.