Association of anti-glycolipid IgG with respiratory function decline in amyotrophic lateral sclerosis

OBJECTIVE: Effective treatments for amyotrophic lateral sclerosis (ALS) remain limited, underscoring the need to identify robust biomarkers associated with disease severity and prognosis. This study investigated whether immunoglobulin G (IgG) and immunoglobulin M (IgM) anti-glycolipid antibodies are associated with clinical manifestations of ALS, particularly decline in respiratory function. METHODS: This was a retrospective observational cohort study of the patients with ALS. Among patients with definite or probable limb-onset ALS, 11 patients in the glycolipid IgG-positive group were compared with 15 patients in the IgG-negative group, and 5 patients in the glycolipid IgM-positive group were compared with 9 patients in the IgM-negative group, with adjustment for age. Associations between anti-glycolipid antibody status and respiratory function were assessed using Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: The time to decline of percent forced vital capacity (%FVC) below 80% and 60% was significantly shorter in the IgG-positive group than in the IgG-negative group (p = 0.002 and p = 0.025, respectively). Cox proportional hazards analysis demonstrated that IgG antibody positivity was an independent risk factor for earlier decline in %FVC to 80%. INTERPRETATION: These findings suggest that anti-glycolipid IgG antibodies may be associated with respiratory function decline in ALS. Larger comprehensive studies will be required to validate these results and to elucidate the underlying pathophysiological mechanisms.