How do autoimmune diseases cluster in families? A systematic review and meta-analysis
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RESEARCH ARTICLE
Open Access
How do autoimmune diseases cluster in families? A systematic review and meta-analysis Jorge Cárdenas-Roldán, Adriana Rojas-Villarraga and Juan-Manuel Anaya*
Abstract Background: A primary characteristic of complex genetic diseases is that affected individuals tend to cluster in families (that is, familial aggregation). Aggregation of the same autoimmune condition, also referred to as familial autoimmune disease, has been extensively evaluated. However, aggregation of diverse autoimmune diseases, also known as familial autoimmunity, has been overlooked. Therefore, a systematic review and meta-analysis were performed aimed at gathering evidence about this topic. Methods: Familial autoimmunity was investigated in five major autoimmune diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid disease, multiple sclerosis and type 1 diabetes mellitus. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Articles were searched in Pubmed and Embase databases. Results: Out of a total of 61 articles, 44 were selected for final analysis. Familial autoimmunity was found in all the autoimmune diseases investigated. Aggregation of autoimmune thyroid disease, followed by systemic lupus erythematosus and rheumatoid arthritis, was the most encountered. Conclusions: Familial autoimmunity is a frequently seen condition. Further study of familial autoimmunity will help to decipher the common mechanisms of autoimmunity. Keywords: Autoimmune diseases, familial autoimmunity, aggregation, genetic epidemiology, autoimmune tautology
Background Autoimmune diseases (ADs) are chronic conditions initiated by the loss of immunological tolerance to selfantigens; they represent a heterogeneous group of disorders that afflict specific target organs or multiple organ systems [1]. The chronic nature of these diseases places a significant burden on the utilization of medical care, increases direct and indirect economic costs, and diminishes quality of life. The estimated incidence of ADs is approximately 80 per 100,000 person years and their prevalence could be well beyond 3% of the population [2]. Most of the ADs asymmetrically affect middle-aged women and are among the leading causes of death for this group of patients. Although the frequency of ADs varies
* Correspondence: [email protected] Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Carrera 24 #63-C-69, Bogota, Colombia
between countries [3], various studies have shown that, for some ADs, associations are found across populations [4]. ADs share several clinical signs and symptoms (that is, subphenotypes), physiopathological mechanisms, and genetic factors. These shared characteristics have been grouped under the term autoimmune tautology [5-10]. In clinical practice two conditions support this theory, namely, polyautoimmunity and familial autoimmunity, both of which are considered as being part of the ‘kaleido
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