Elevated serum Interleukin-39 in Myasthenia gravis: a possible biomarker

Interleukin-39 (IL-39) is a cytokine implicated in immune regulation and autoimmune diseases, but its role in myasthenia gravis (MG) is unknown. This study aimed to investigate serum IL-39 levels in MG patients.

Serum IL-39 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 51 acetylcholine receptor (AChR) antibody-positive MG patients without thymoma and 43 healthy controls (HCs). A subset of 20 patients who achieved sustained clinical remission after heterogeneous immunotherapy provided paired samples for longitudinal analysis.

Serum IL-39 levels were significantly higher in active MG patients compared to HCs [median: 5.09 pg/mL (IQR: 4.12-6.23) vs 1.83 pg/mL (IQR: 0.99-2.76); p < 0.001]. In the paired analysis, IL-39 levels were significantly lower during the remission phase than at the active disease baseline [median: 1.66 pg/mL (IQR: 0.94 ~ 3.31) vs 4.28 pg/mL (IQR: 3.69 ~ 5.33); p < 0.001]. IL-39 demonstrated high discriminatory capacity between active patients and HCs (AUC = 0.922). No correlation was found between baseline IL-39 levels and clinical severity scores (MG-ADL).

Serum IL-39 levels are dynamically associated with disease activity states in AChR + MG, decreasing with clinical remission. Its lack of correlation with symptom severity and its likely non-specific nature suggest it may serve as a marker of general immune activation rather than a specific diagnostic or severity biomarker. Further studies are needed to validate its specificity and define its role in MG immunopathology.