Objective: Recent studies reported contrasting results with respect to the presence of anti-myelin protein antibodies in Multiple Sclerosis (MS) and their relation with disease activity. This may be due to the heterogeneous specificity of autoantibodies in MS and the inability of most methods to detect pathogenically relevant antibodies. Here, myelin particles were used to detect anti-myelin antibodies in cerebrospinal fluid (CSF) of MS patients. Subsequently, their relation with MRI parameters was evaluated.
Methods: Anti-myelin IgG antibody reactivity was determined in CSF of MS patients (n=65) and clinically isolated syndrome (CIS) patients (n=37) using a novel flow cytometry-based assay. In addition, CSF of patients with other neurological diseases (OND, n=17), inflammatory neurological diseases (IND, n=33) and controls (HC, n=22) was tested.
Results: Compared to HC, increased anti-myelin IgG antibody reactivity was most frequently found in CSF of CIS patients (46%, p=0.002), relapsing-remitting (RR) MS patients (56%, p<0.001) and secondary progressive (SP) MS patients (55%, p<0.001), together constituting 85 % of all positive CSF samples. In contrast, elevated anti-myelin IgG antibody reactivity was present in a minority of the IND patients (21%), marginally present in controls (5%) and absent in OND patients (0%). Most strikingly, anti-myelin IgG antibody reactivity was related to the number of T2 lesions (r = 0.31, p = 0.041) and gadolinium-enhancing T1 lesions (r=0.37, p = 0.016) on brain MRI in CIS and relapse-onset MS patients.
Conclusion: CSF anti-myelin IgG antibodies are promising, specific biomarkers in CIS and relapse-onset MS and correlate to MR measures of disease activity.