Tropomyosin autoantibodies associated with checkpoint inhibitor myositis

Abstract

This brief report details the measurement and identification of IgA antibodies to tropomyosin in a case of presumed ocular myositis with paraspinal myositis in a patient with metastatic uveal melanoma treated with checkpoint inhibitors. High-throughput functional protein microarray analysis and pathway analysis was conducted to identify IgG and IgA antibodies of interest. Antibody levels were compared to generic antibody screening results and levels of the antibodies in a cohort of melanoma patients without myositis (n = 100) at baseline prior to undergoing immunotherapy. The finding of specific muscle antibodies in this clinical case indicates the pathogenic potential of anti-tropomyosin IgA in the development of checkpoint inhibitor associated myositis and requires further investigation.

Keywords: Tropomyosin; autoantibody; immunotherapy; myositis; ocular melanoma.

Figure 1.

Comparison of IgA and IgG levels to tropomyosin isoforms 1, 2 and 3 in the reported clinical case study. IgA levels from the sera of a group of metastatic melanoma patients without myositis (n = 100) at baseline prior to undergoing immunotherapy are also illustrated. Levels are presented as Log2 fold changes (log2FC) and were calculated by dividing the case signal intensity for each antigen by the mean case signal intensity of all antigens or the median signal intensity of all antigens across the cohort of other metastatic melanoma samples. The horizontal line at log2FC = 3.47 represents the cutoff where the case Z score > 3, indicating a positive signal intensity.