CGRP levels in autoimmune diseases: a systematic review and meta-analysis of its potential role as a biomarker

AIM: This systematic review and meta-analysis aimed to quantitatively evaluate calcitonin gene-related peptide (CGRP) concentrations across autoimmune diseases (psoriasis, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis) and assess its clinical utility as a neuro-immune biofluid biomarker. MATERIALS AND METHODS: PRISMA-compliant meta-analyses using random-effects models calculated standardized mean differences (SMDs, Hedges' g) from major databases, evaluating circulating biofluids (serum/plasma; 10 studies, 16 cohorts) both overall across all selected autoimmune diseases and stratified by individual disease entities, separately from localized compartments. Subgroup analyses confirmed elevated circulating CGRP in rheumatoid arthritis (SMD = 0.72), psoriasis (SMD = 0.73), and IBD (SMD = 0.57). Multiple sclerosis showed elevated serum CGRP during progressive phases (SMD = 1.06) versus unchanged CSF levels (SMD = 0.04). Trim-and-fill analysis confirmed estimate stability (adjusted SMD = 0.58). CONCLUSION: Circulating CGRP is elevated across specific autoimmune pathologies, functioning as a dynamic indicator of active neuro-immune inflammation rather than a static universal marker. Clinical implementation requires prospective, longitudinal studies and standardized, isoform-specific quantification assays. PROSPERO REGISTRATION NUMBER: CRD420261458044.