MICA protein as a plasma biomarker for dermatomyositis with malignancy: a proteome-wide Mendelian randomization and ELISA study.

INTRODUCTION

Dermatomyositis (DM) is an autoimmune disease marked by distinctive cutaneous manifestations and systemic involvement, including an increased risk of malignancy. Proteome-wide Mendelian randomization (MR) revealed plasma major histocompatibility complex class I-related chain A (MICA) as a potential malignancy biomarker in DM, followed by validation with the enzyme-linked immunosorbent assay (ELISA) method.

METHODS

We performed a proteome-wide MR analysis using protein quantitative trait loci data from the deCODE-2021 database and genome-wide association study data of DM from the Finnish Finngen R11 cohort. The causal relationship between plasma protein levels and DM was evaluated by a variety of MR techniques, such as weighted median, Wald ratio, MR-Egger, and inverse-variance weighted (IVW). Colocalization analysis was conducted to determine whether MICA shares genetic susceptibility loci with DM. To validate our findings, serum MICA levels were measured using ELISA in 47 patients with DM/CADM (clinically amyopathic dermatomyositis), eight cancer patients without DM/CADM, and 14 healthy controls.

RESULTS

MR analysis revealed that elevated plasma MICA levels are significantly associated with an increased risk of DM (OR = 1.56, 95% CI = 1.33-1.82, P = 4.90e-08). Colocalization analysis indicated that the genetic variant rs2853986 on chromosome 6 is shared between MICA and DM. ELISA validation confirmed significantly higher serum MICA levels in DM/CADM patients than in healthy controls (P = 0.001), with further elevation in DM/CADM patients with malignancy compared with those without malignancy (P = 0.004) and patients with malignancy alone (P = 0.033).

CONCLUSION

These results highlight MICA as a novel biomarker for malignancy risk in DM, providing potential clinical utility for identifying patients at high risk. Key Points • This study demonstrates a significant causal association between elevated plasma MICA protein levels and an increased risk of developing dermatomyositis using proteome-wide Mendelian randomization. • ELISA-based validation in a clinical cohort confirms that serum MICA levels were significantly elevated in patients with DM/CADM, especially those with malignancy, supporting its role as a malignancy biomarker.