The role of granulocyte‐macrophage colony‐stimulating factor in the pathogenesis of neuromyelitis optica: A white or black knight?

Abstract

Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) not only induces the differentiation of hematopoietic cells into granulocytes and macrophages but also exerts immunomodulatory functions. GM‐CSF promotes experimental autoimmune encephalomyelitis, multiple sclerosis, and rheumatoid arthritis. Conversely, GM‐CSF ameliorates some type 2 helper T cell‐dominant diseases, including experimental autoimmune myasthenia gravis, experimental autoimmune thyroiditis, Crohn's disease, type 1 diabetes mellitus, autoimmune neutropenia, and juvenile systemic lupus erythematosus. However, the contribution of GM‐CSF to the pathogenesis of neuromyelitis optica (NMO) has not been studied. In this article, we review GM‐CSF roles in the central nervous system and report evidence that GM‐CSF may positively affect the pathogenesis of NMO. We have previously reported (i) that patients with NMO expressing antinuclear antibodies (ANA‐positive) have less severe disease activity and a better prognosis than ANA‐negative patients and (ii) an analysis of the cytokine/chemokine profiles of 24 patients with NMO. We investigated associations between cytokine expression, ANA‐positivity, and disease severity. Among the 24 patients, the six who were ANA positive had significantly elevated serum GM‐CSF concentrations than the ANA‐negative patients (medians: 7.0 vs 0.27 pg/mL, respectively; P = 0.001) and higher cerebrospinal fluid GM‐CSF concentrations (medians: 53.7 vs 47.0 pg/mL, respectively; P = 0.068). Although no other cytokine/chemokine profiles were different based on ANA status, cerebrospinal fluid GM‐CSF concentrations at relapse were negatively correlated with Kurtzke Expanded Disability Status Scale scores (R2 = 0.26, P = 0.009). Therefore, GM‐CSF may play a protective role in the pathogenesis of NMO.