Intrathecal lipid-specific oligoclonal IgM synthesis associates with retinal axonal loss in multiple sclerosis

Objective: It has been suggested that autoantibodies may induce axonal damage in multiple sclerosis (MS). Optical coherence tomography (OCT) showed that thinning of peripapillary retinal nerve fiber layer (RNFL) and ganglion cell layer/inner plexiform (GCIPL) measurements reflect axonal loss in the disease. We investigated whether the intrathecal synthesis of lipid-specific oligoclonal IgM bands (LS-OCMB) associates with thinning of these structures in MS patients.

Methods: 58 consecutive MS patients and 70 age-matched healthy controls were assessed. LS-OCMB was studied in cerebrospinal fluid by isoelectric focusing and immunoblotting. RNFL and GCIPL imaging were quantified by spectral domain OCT.

Results: RNFL and GCIPL were significantly reduced in MS patients compared to controls (p<0.01). RNFL thickness was further reduced in LS-OCMB positive MS patients compared to LS-OCMB negative MS subjects mainly in papillomacular bundle (p<0.05), temporal and inferior quadrants (p<0.05) and inferotemporal sector (p=0.01).

Conclusions: The presence of LS-OCMB associates with increased retinal axonal loss in MS. This reinforces the relationship found between the intrathecal synthesis of IgM and the axonal damage observed in immunological and pathological studies even in normal-appearing white matter. OCT seems an optimal tool to monitor axonal damage in LS-OCMB positive patients, relevant for therapeutic decisions and quantification of the effects of new neuroprotective treatments.