Cerebrospinal fluid-specific immunoglobulins in people with multiple sclerosis are of diagnostic and prognostic value. Deposition of immunoglobulins in plaques is well described. Immunoglobulin may originate from local production within lesions or leakage through a disrupted blood brain barrier. Spinal cord disease is an important driver of disability, which led to the current study.

Controls were older than MS cases (mean age 77 vs 64 years). Mean disease duration was 30 years. Lesions were found in 38% of MS sections. In MS and controls, IgG and IgM were detected in a predominantly perivascular distribution throughout the cord. All cases exhibited immunoglobulin within astrocytes, especially within MS lesions. Outside lesions, more abundant astrocytic immunoglobulin was seen in MS compared to control (p=0.03 and 0.001 respectively). Non-lesional astrocytic IgG expression correlated with axonal loss (ρ -0.32, p=0.002) and PGM1 inflammation (ρ 0.321 p=0.002). Lesion presence was associated with increased IgG deposition in adjacent non-lesional areas. Occasional axonal staining for IgG was seen in a subset of cases with no differences between groups.

Our findings expand the relevance of immunoglobulins to MS progression by demonstrating a relationship with axonal loss in the MS spinal cord. The striking perivascular distribution of IgM in both lesional and non-lesional areas raises the possibility that vascular alterations contribute to irreversible disability accumulation in progressive MS.