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

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. 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. Primary synthesis of circulating biofluids (533 cases, 363 controls) showed significant systemic CGRP elevation in autoimmune conditions (SMD = 0.63, 95% CI: 0.46–0.80, p < 0.0001; I2 = 14.4%). 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). 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. CRD420261458044.