[Pubmed] Muscle expression of PD1 and PD-L1 may predict the severity and outcomes of neuromuscular immune-related advers

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Clin Rheumatol. 2025 Dec 27. doi: 10.1007/s10067-025-07896-w. Online ahead of print.

ABSTRACT

OBJECTIVES: Immune-related adverse events (irAEs) affecting the nervous system, particularly neuromuscular disorders, are severe complications of immune checkpoint inhibitors. However, reports with neuromuscular pathology evidence remain scarce.

METHOD: We characterized the clinicopathologic features of a retrospective cohort of 42 patients with neuromuscular irAEs. Immunohistochemical analysis of CD3, CD4, CD8, CD20, CD68, programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) expression was performed on muscle and/or nerve biopsies from 25 patients. Additionally, immunotherapy responses and clinical outcomes were followed up for prognostic analysis.

RESULTS: The 42 patients had diagnoses including myositis (n = 21), peripheral neuropathy (n = 6), myasthenia gravis (n = 1), and overlapping syndromes (n = 14). The most prevalent clinical presentations were fatigue (54.8%), ptosis (52.4%), and proximal muscle weakness (52.4%). Muscle pathology exhibited a characteristic pattern of focal necrosis and inflammation with lymphocyte infiltration. PD-1 and PD-L1 were highly expressed on T lymphocytes and myofibers, and their expression was most frequently observed in the group with Common Terminology Criteria for Adverse Events grades 3-5. After follow-up for 3 to 26 months, during which immunotherapy was administered, 53.8% of patients achieved a good outcome (either complete recovery or a ≥ 2-point reduction in modified Rankin Scale score). PD-L1 (P = 0.046) and PD-L2 (P = 0.046) expression were more likely in patients with good outcomes.

CONCLUSIONS: The muscle pathology of neuromuscular irAEs featured focal necrosis and elevated PD-1 and PD-L1 expression on T lymphocytes and myofibers. PD-1, PD-L1, and PD-L2 expression may be associated with neuromuscular irAE severity and outcomes. Key Points • The muscle pathology of neuromuscular immune-related adverse events includes elevated PD-1 and PD-L1 expression on infiltrating T lymphocytes and muscle fibers. • PD-1, PD-L1, and PD-L2 expression are potential biomarkers for the severity and outcome of neuromuscular immune-related adverse events.

PMID:41454201 | DOI:10.1007/s10067-025-07896-w


Source: https://pubmed.ncbi.nlm.nih.gov/4145420 ... 22+67771e2