Editors' ChoiceMultiple Sclerosis

Antibodies on the Brain

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Science Translational Medicine  08 Feb 2012:
Vol. 4, Issue 120, pp. 120ec21
DOI: 10.1126/scitranslmed.3003793

Multiple sclerosis (MS) is a debilitating disease of the central nervous system (CNS) in which the body’s own immune system damages the ability of nerve cells to communicate with each other. Patients with MS experience a variety of neurological symptoms, including weakness, problems with coordination and balance, and a decrease in cognitive function. MS can either be progressive or episodic, known as relapsing-remitting MS (RRMS), and invariably leads to total functional dependence within 10 to 20 years. There is no cure, although high-dose immunosuppresants such as corticosteroids can be used to induce and maintain remission. Molecularly, it has been shown that abnormal B cells and subsequent antibody responses play a crucial role in the development of MS. In the CNS, however, it is not known whether the antibody production is an epiphenomenon of autoimmunity, or whether it contributes to CNS immunopathology. Now, Quintana et al. have identified a CNS antibody signature in patients with RRMS and examined changes in this signature in the context of immunosuppressive therapy.

Using highly sensitive antigen microarray technology, previous studies have identified several patterns of serum antibody reactivity associated with different stages and subtypes of MS. This study, however, is a major step forward in examining patterns of CNS autoantibody production and correlation with serum antibody reactivity. The authors identified different antibody signatures in matched CNS and serum samples. The CNS antibody response was heterogeneous and targeted to known myelin antigens and heat shock proteins, validating the role of these antibodies in the development of RRMS (average 26.4 antigens in untreated RRMS patients). The authors further showed that these antibodies were produced locally in the CNS, and most importantly, showed decreased activity in response to treatment with corticosteroids.

Although this study did not identify a specific pathogenic autoantigen in RRMS and the pattern of antibody response identified was rather heterogeneous, the antigenic microarray approach here has the potential to allow disease classification according to antibody response as well as to assess treatment response according to individual reactivity pattern. Current measures, such as patients’ history and magnetic resonance imaging, do not provide enough information about the nature of the immune response to allow targeting by a specific immunomodulatory drug. Therefore, previously unidentified biomarkers such as autoantibodies identified by means of antigen microarray, if validated, may help link individual patients with best-bet therapies and improve the standard of care for this intractable disease.

F. J. Quintana et al., Antigen microarrays identify CNS-produced autoantibodies in RRMS. Neurology 18 January 2012 (10.1212/WNL.0b013e318247f9f3). [PubMed]

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