Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis

a descriptive study

Lisa F. Barcellos, Brinda B. Kamdar, Patricia P. Ramsay, Cari DeLoa, Robin R. Lincoln, Stacy Caillier, Silke Schmidt, Jonathan L. Haines, Margaret A Pericak-Vance, Jorge R. Oksenberg, Stephen L. Hauser

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Background: Autoimmune mechanisms are thought to have a major role in the pathogenesis of multiple sclerosis. We aimed to identify coexisting autoimmune phenotypes in patients with multiple sclerosis from families with several members with the disease and in their first-degree relatives. Methods: A total of 176 families (386 individuals and 1107 first-degree relatives) were characterised for a history of other autoimmune disorders. Family-based or case-control analyses were done to assess the association of cytotoxic T-lymphocyte-antigen 4 (CTLA4) and protein tyrosine phosphatase (PTPN22) variants with susceptibility to multiple sclerosis. Findings: 46 (26%) index cases reported at least one coexisting autoimmune disorder. The most common were Hashimoto thyroiditis (10%), psoriasis (6%), inflammatory bowel disease (3%), and rheumatoid arthritis (2%). 112 (64%) families with a history of multiple sclerosis reported autoimmune disorders (excluding multiple sclerosis) in one or more first-degree relatives, whereas 64 (36%) families reported no history of autoimmunity. Similar to index cases, Hashimoto thyroiditis, psoriasis, and inflammatory bowel disease were also the most common disorders occurring in family members. A common variant within CTLA4 was strongly associated with multiple sclerosis in families who had other autoimmune diseases (p=0·009) but not in families without a history of other autoimmune disorders (p=0·90). Interpretation: The presence of various immune disorders in families with several members with multiple sclerosis suggests that the disease might arise on a background of a generalised susceptibility to autoimmunity. This distinct multiple-sclerosis phenotype, defined by its association with other autoimmune diseases, segregates with specific genotypes that could underlie the common susceptibility.

Original languageEnglish
Pages (from-to)924-931
Number of pages8
JournalLancet Neurology
Volume5
Issue number11
DOIs
StatePublished - Nov 1 2006
Externally publishedYes

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Autoimmune Diseases
Multiple Sclerosis
Cluster Analysis
CTLA-4 Antigen
Hashimoto Disease
Autoimmunity
Psoriasis
Phenotype
Protein Tyrosine Phosphatases
Immune System Diseases
Inflammatory Bowel Diseases
Rheumatoid Arthritis
Genotype

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Barcellos, L. F., Kamdar, B. B., Ramsay, P. P., DeLoa, C., Lincoln, R. R., Caillier, S., ... Hauser, S. L. (2006). Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis: a descriptive study. Lancet Neurology, 5(11), 924-931. https://doi.org/10.1016/S1474-4422(06)70552-X

Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis : a descriptive study. / Barcellos, Lisa F.; Kamdar, Brinda B.; Ramsay, Patricia P.; DeLoa, Cari; Lincoln, Robin R.; Caillier, Stacy; Schmidt, Silke; Haines, Jonathan L.; Pericak-Vance, Margaret A; Oksenberg, Jorge R.; Hauser, Stephen L.

In: Lancet Neurology, Vol. 5, No. 11, 01.11.2006, p. 924-931.

Research output: Contribution to journalArticle

Barcellos, LF, Kamdar, BB, Ramsay, PP, DeLoa, C, Lincoln, RR, Caillier, S, Schmidt, S, Haines, JL, Pericak-Vance, MA, Oksenberg, JR & Hauser, SL 2006, 'Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis: a descriptive study', Lancet Neurology, vol. 5, no. 11, pp. 924-931. https://doi.org/10.1016/S1474-4422(06)70552-X
Barcellos, Lisa F. ; Kamdar, Brinda B. ; Ramsay, Patricia P. ; DeLoa, Cari ; Lincoln, Robin R. ; Caillier, Stacy ; Schmidt, Silke ; Haines, Jonathan L. ; Pericak-Vance, Margaret A ; Oksenberg, Jorge R. ; Hauser, Stephen L. / Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis : a descriptive study. In: Lancet Neurology. 2006 ; Vol. 5, No. 11. pp. 924-931.
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AU - DeLoa, Cari

AU - Lincoln, Robin R.

AU - Caillier, Stacy

AU - Schmidt, Silke

AU - Haines, Jonathan L.

AU - Pericak-Vance, Margaret A

AU - Oksenberg, Jorge R.

AU - Hauser, Stephen L.

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