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Multiple Sclerosis


Autoimmune Comorbid Conditions in Multiple Sclerosis Regina Berkovich, MD, PhD,1


Dawood Subhani, MBBS2


and Lawrence Steinman, MD3


1. Assistant Professor of Clinical Neurology, Keck School of Medicine University of Southern California; 2. Clinical Research Assistant, University of Southern California MS Comprehensive Care Center; 3. Professor of Neurology and Neurological Sciences, Stanford School of Medicine


Abstract


Autoimmune comorbidities occur frequently in multiple sclerosis (MS). They may arise as a consequence of a genetic susceptibility to autoimmunity. Certain pathological mechanisms are common to several autoimmune conditions. In the presence of comorbid autoimmune conditions, certain MS therapeutics may be preferable to others. Autoimmune comorbidity associated with MS could be a factor in predicting response to specific MS therapeutics. Treatment with interferon beta has been reported to precipitate immune-mediated abnormalities or to exacerbate existing autoimmune diseases. In comparison, there are fewer reported cases of treatment-associated comorbidities linked with autoimmune disease in patients taking glatiramer acetate. Knowledge of the factors influencing autoimmune comorbidities may provide insights into the complex pathogenesis of MS and help inform treatment choices.


Keywords Autoimmune, comorbidity, glatiramer acetate, interferon, multiple sclerosis


Disclosure: Regina Berkovich, MD, PhD, has served as a consultant on advisory boards for Acorda, Bayer, Biogen Idec, Questcor, and Teva, and has received research support from Biogen Idec, Questcor, Teva, and the National Multiple Sclerosis Society. Dawood Subhani, MBBS, and Lawrence Steinman, MD, have no conflicts of interest to declare. Acknowledgments: Editorial assistance was provided by Touch Briefings. Received: Febuary 6, 2012 Accepted: February 13, 2012 Citation: US Neurology, 2011;7(2):132–8 Correspondence: Regina Berkovich, MD, PhD, University of Southern California MS Comprehensive Care Center and Research Group, Healthcare Consultation Center II, 1520 San Pablo St., Suite 3000, Los Angeles, CA 90033. E: rberkovi@usc.edu


Support: The publication of this article was funded by Teva Neuroscience. The views and opinions expressed are those of the authors and not necessarily those of Teva Neuroscience.


Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS). Although it is generally considered to be an autoimmune disease, MS may be a heterogeneous condition incorporating different pathologies. The incidence of autoimmune comorbidities in MS patients may help us elucidate the autoimmune aspects of the disease. Furthermore, the presence of autoimmune comorbidities may help us discover new biomarkers with potential predictive value regarding response to treatment, and understand common factors in pathogenesis. This article aims to review autoimmune comorbidities in MS, their incidence and burden in the MS population, and their possible association with MS treatments. We will address potential measures that might reduce the impact of treatment in triggering comorbidities.


Multiple Sclerosis as an Autoimmune Disease The most widely accepted hypothesis for the pathogenesis of MS is that it is a primary autoimmune disease. This idea was reinforced following observations on experimental autoimmune encephalomyelitis (EAE) in the late 1960s and early 1970s.1–4


It has been repeatedly demonstrated


that EAE is an autoimmune disorder caused by T-cell sensitization to various myelin proteins capable of triggering encephalomyelitis. The hypothesis is further supported by considerable evidence, such as


132


the presence of elevated lymphocytes, macrophages, and microglia in MS lesions; strong genetic associations with genes in the major histocompatibility complex (MHC) region of chromosome 6; and the efficacy of new treatments that target the immune response. However, there are some aspects of the autoimmune pathogenesis hypothesis of MS that require further clarification. Much of this hypothesis is based on animal models of EAE; however, many agents that can successfully treat EAE have failed to show any clinical benefit in MS. This suggests that EAE is not an accurate model of MS and that the two conditions have some different pathophysiological characteristics.5


In order to yield


clues to the pathogenesis of MS, EAE experimental models should be critically coupled with actual findings in MS.6


The most compelling evidence that there is an immune pathogenesis in MS comes from the striking benefit seen when lymphocyte migration to the CNS is blocked with natalizumab, or when lymphocytes are trapped in regional lymph nodes with fingolimod.7,8


It is difficult to discount the


fact that, when monocytes are barred entry to the CNS, the rate of relapse and pace of progression of disability in MS are attenuated.


A further challenge to the autoimmune pathogenesis hypothesis of MS has arisen following findings that some of the antibodies identified in the


© TOUCH BRIEFINGS 2011


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