Glial fibrillary acidic protein in fibromyalgia: its serum levels and antibodies A proof-of-concept study

Background: Fibromyalgia is a stress-related disorder in which dorsal root ganglia (DRG) may play an important pathogenetic role. DRG exhibit unique stress-induced, pro-algesic physio-anatomy, where each pain-sensing nerve fiber soma is encased and interacts with immune-competent satellite glial cells (SGCs). Patients suffering from fibromyalgia harbor anti-SGCs antibodies; however,the specific SGCs antigen(s) remain unidentified. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein serving as early SGCs activation marker. Different environmental stressors induce GFAP upregulation and structural modifications, including citrullination, potentially rendering it immunogenic. GFAP antibodies are implicated in autoimmune encephalomyelitis. We determine whether the serum of patients with fibromyalgia, collected before the COVID-19 pandemic, overexpresses GFAP and/or harbors antibodies against GFAP. Methods: We studied 47 women with fibromyalgia and 31 healthy women. For GFAP antibody detection,a sensitive ELISA was developed using recombinant human GFAP. A commercial human GFAP ELISA Kit was used to measure GFAP serum levels. Results: Significantly higher serum GFAP antibody optical density (OD) was detected in patients with fibromyalgia (median 0.04, 0.02–0.10 vs. 0.02, 0.01–0.05; p = 0.025). When the control group 99th percentile value (0.127 OD) was used as positive threshold, 9/47 (19%) patients tested positive for anti-GFAP antibodies. Patients with fibromyalgia showed numerically higher GFAP serum levels: (244.0 pg/ml ± 82.5 SD versus 211.4 ± 65.2) with borderline statistical significance ( p = 0.057). Conclusion: In this proof-of-concept study, patients suffering from fibromyalgia exhibit higher serum anti-GFAP antibodies and numerically augmented circulating GFAP levels. GFAP may be involved in fibromyalgia pathogenesis.