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Autoimmune disease in people with multiple sclerosis and their relatives: a systematic review and meta-analysis

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Abstract

Additional autoimmune diseases in people with multiple sclerosis (MS) and their relatives have been studied many times. Studies have employed different designs, and yielded conflicting results. We performed a systematic review, and calculated overall risk of additional autoimmune diseases in people with MS and their first-degree relatives. PubMed and Web of Science were searched. Thyroid disease, diabetes, inflammatory bowel disease, psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were studied. A generic inverse variance model was used, and subgroup analysis was used to explore heterogeneity. The OR of thyroid disease was increased in both people with MS (OR 1.66; p < 0.00001) and their relatives (OR 2.38; p < 0.00001). A similar association was seen between MS and inflammatory bowel disease (OR 1.56; p < 0.0001) and psoriasis (OR 1.31; p < 0.0001), although not in relatives. There was no increase in the rate of either SLE or RA. Studies examining diabetes showed significant heterogeneity and evidence of publication bias. There is an increase in the rate of certain autoimmune diseases in people with MS and their first-degree relatives. However, this does not extend to all conditions studied. Given the nonspecific clinical presentation of thyroid disease, it should be considered in all people with MS presenting with nonspecific symptoms.

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Acknowledgments

The authors would like to thank Dr. Sreeram Ramagopalan for invaluable assistance with locating archived manuscripts, and comments on the final text. R.D. is funded by an Association of British Neurologists/MS Society of Great Britain Clinical Research Fellowship. G.G. receives grant support from the Medical Research Council, National MS Society, MS Society of Great Britain and Northern Ireland, AIMS2CURE and the Roan Charitable Trust.

Conflicts of interest

R.D. has no conflicts of interest to declare. G.G. has received research grant support from Bayer-Schering Healthcare, Biogen-Idec, GW Pharma, Merck Serono, Merz, Novartis, Teva and Sanofi-Aventis. G.G. has received personal compensation for participating on advisory boards in relation to clinical trial design, trial steering committees and data and safety monitoring committees from: Bayer-Schering Healthcare, Biogen-Idec, Eisai, Elan, Fiveprime, Genzyme, Genentech, GSK, Ironwood, Merck-Serono, Novartis, Pfizer, Roche, Sanofi-Aventis, Synthon BV, Teva, UCB Pharma and Vertex Pharmaceuticals.

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  1. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK

    Ruth Dobson & Gavin Giovannoni

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  1. Ruth Dobson
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Correspondence to Ruth Dobson.

Electronic supplementary material

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415_2012_6790_MOESM1_ESM.jpg

Supplementary material 1 (a) Funnel plot demonstrating the lack of publication bias when examining the frequency of diabetes in people with MS. (b) Funnel plot demonstrating the lack of publication bias when examining the frequency of diabetes in relatives of people with MS (JPEG 20 kb)

Supplementary material 2 (JPEG 19 kb)

Supplementary material 3 (JPEG 17 kb)

Supplementary material 4 (JPEG 18 kb)

415_2012_6790_MOESM5_ESM.jpg

Supplementary material 5 (a) Funnel plot demonstrating the lack of publication bias when examining the frequency of inflammatory bowel disease in people with MS. (b) Funnel plot demonstrating the lack of publication bias when examining the frequency of inflammatory bowel disease in relatives of people with MS (JPEG 17 kb)

Supplementary material 6 (JPEG 18 kb)

415_2012_6790_MOESM7_ESM.jpg

Supplementary material 7 (a) Funnel plot demonstrating the lack of publication bias when examining the frequency of psoriasis in people with MS. (b) Funnel plot demonstrating the lack of publication bias when examining the frequency of psoriasis in relatives of people with MS (JPEG 18 kb)

Supplementary material 8 (JPEG 18 kb)

415_2012_6790_MOESM9_ESM.jpg

Supplementary material 9 (a) Funnel plot demonstrating the lack of publication bias when examining the frequency of RA in people with MS. (b) Funnel plot demonstrating the lack of publication bias when examining the frequency of RA in relatives of people with MS (JPEG 19 kb)

Supplementary material 10 (JPEG 18 kb)

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Dobson, R., Giovannoni, G. Autoimmune disease in people with multiple sclerosis and their relatives: a systematic review and meta-analysis. J Neurol 260, 1272–1285 (2013). https://doi.org/10.1007/s00415-012-6790-1

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