Are individuals with an autoimmune disease at higher risk of a second autoimmune disorder?

Limited evidence suggests that autoimmune diseases tend to co-occur, although data are needed to determine whether individuals with an existing autoimmune disorder are at increased risk of a second disorder. The authors conducted a series of population-based cohort studies, utilizing the United Kingdom General Practice Research Database, to assess intraindividual risks of coexistence of rheumatoid arthritis (RA), autoimmune thyroiditis (AIT), multiple sclerosis (MS), and insulin-dependent diabetes mellitus (IDDM) during 1990-1999. Sex-specific age- and calendar-period standardized incidence ratios (SIRs) were calculated for development of a second autoimmune disease among index populations including 22,888 RA, 26,198 AIT, 4,332 MS, and 6,170 IDDM patients compared with the general population. Among those with IDDM, adjusted AIT rates were higher than expected for both males (SIR = 646.0, 95% confidence interval (CI): 466, 873) and females (SIR = 409.6, 95% CI: 343, 485), as were RA rates for females (SIR = 181.6, 95% CI: 136, 238). Coexistence of AIT and RA was also shown for either disease sequence (sex-specific SIRs = 130.4-162.0). However, point estimates suggested an inverse relation between RA and MS, irrespective of diagnostic sequence. This study demonstrates coexistence of RA, AIT, and IDDM at higher than expected rates but reduced comorbidity between RA and MS.

[1]  A. Ghezzi,et al.  Thyroid function and autoimmunity during interferon β-1b treatment : A multicenter prospective study , 2001 .

[2]  References , 1971 .

[3]  D. Alarcón-Segovia,et al.  Shared autoimmunity: The time has come , 2004, Current rheumatology reports.

[4]  D. Isenberg,et al.  The mosaic of autoimmunity. , 1989, Immunology today.

[5]  A. Silman,et al.  Anti-tumour necrosis factor α therapy in rheumatoid arthritis: an update on safety , 2004 .

[6]  N. Rose Autoimmune diseases. , 1981, Scientific American.

[7]  L. Calzà,et al.  Thyroid hormone and remyelination in adult central nervous system: a lesson from an inflammatory-demyelinating disease , 2005, Brain Research Reviews.

[8]  Simon C. Potter,et al.  Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls , 2007, Nature.

[9]  S. Walsh,et al.  Autoimmune diseases: a leading cause of death among young and middle-aged women in the United States. , 2000, American journal of public health.

[10]  A. Ghezzi,et al.  Thyroid function and autoimmunity during interferon beta-1b treatment: a multicenter prospective study. , 2001, The Journal of clinical endocrinology and metabolism.

[11]  A. Oliviero,et al.  Occurrence of thyroid autoimmunity and dysfunction throughout a nine-month follow-up in patients undergoing interferon-β therapy for multiple sclerosis , 1998 .

[12]  P. Box Interferon beta-1b treatment does not induce autoantibodies , 2005 .

[13]  E L Korn,et al.  Time-to-event analysis of longitudinal follow-up of a survey: choice of the time-scale. , 1997, American journal of epidemiology.

[14]  C. Pozzilli,et al.  Interferon beta-1b treatment does not induce autoantibodies , 2005, Neurology.

[15]  L. Smeeth,et al.  Incidence of systemic lupus erythematosus in the United Kingdom, 1990-1999. , 2007, Arthritis and rheumatism.

[16]  T. Evans,et al.  Thyroid disease. , 2003, Primary care.

[17]  R. Jonsson,et al.  Characterization of T cell receptor repertoire and anti-Ro/SSA autoantibodies in relation to sialadenitis of NOD mice. , 1995, Autoimmunity.

[18]  A. Muñoz,et al.  Left-truncated data with age as time scale: an alternative for survival analysis in the elderly population. , 1998, The journals of gerontology. Series A, Biological sciences and medical sciences.

[19]  J. Hollowell,et al.  The General Practice Research Database: quality of morbidity data. , 1997, Population trends.

[20]  P. Royston,et al.  Regression using fractional polynomials of continuous covariates: parsimonious parametric modelling. , 1994 .

[21]  Y. Shoenfeld,et al.  The kaleidoscope of autoimmunity: multiple autoimmune syndromes and familial autoimmunity , 2007, Expert review of clinical immunology.

[22]  A. Silman,et al.  Anti-tumour necrosis factor alpha therapy in rheumatoid arthritis: an update on safety. , 2004, Annals of the rheumatic diseases.

[23]  N. Sicotte,et al.  Onset of multiple sclerosis associated with anti-TNF therapy , 2001, Neurology.

[24]  W. Bilker,et al.  The relationship between time since registration and measured incidence rates in the General Practice Research Database , 2005, Pharmacoepidemiology and drug safety.

[25]  L. Smeeth,et al.  Autoimmune Diseases Co-occurring Within Individuals and Within Families: A Systematic Review , 2006, Epidemiology.

[26]  W. Robinson,et al.  Demyelination and inhibition of tumor necrosis factor (TNF). , 2004, Clinical and experimental rheumatology.

[27]  L. Murri,et al.  Discordant effect of IFN-beta1a therapy on anti-IFN antibodies and thyroid disease development in patients with multiple sclerosis. , 2002, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[28]  Norman E. Breslow,et al.  Multiplicative Models and Cohort Analysis , 1983 .

[29]  S J Gange,et al.  Epidemiology and estimated population burden of selected autoimmune diseases in the United States. , 1997, Clinical immunology and immunopathology.

[30]  Y. Shoenfeld The kaleidoscope of autoimmunity. , 1993, Autoimmunity.

[31]  A. Ghezzi,et al.  Autoantibodies in multiple sclerosis patients before and during IFN-beta 1b treatment: are they correlated with the occurrence of autoimmune diseases? , 2002, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[32]  G. Cooper,et al.  The epidemiology of autoimmune diseases. , 2003, Autoimmunity reviews.

[33]  K. Mossman The Wellcome Trust Case Control Consortium, U.K. , 2008 .

[34]  L. Calzà,et al.  Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[35]  D. Fox,et al.  Th17 cells in human disease , 2008, Immunological reviews.

[36]  T. Walley,et al.  The UK General Practice Research Database , 1997, The Lancet.

[37]  A. Verier,et al.  Multiple sclerosis, interferon beta and clinical thyroid dysfunction , 2003, Acta neurologica Scandinavica.

[38]  J. Anaya,et al.  The Nature and Nurture of Common Autoimmunity , 2007, Annals of the New York Academy of Sciences.