Are you the only member of your family that lives with an autoimmune disease? Do you have more than one autoimmune disease, a condition known as polyautoimmunity? We have talked about comorbidities, such as my dual diagnoses of MS and RA, but we haven’t talked much about autoimmune diseases which tend to cluster (aggregate) in our families.
Several studies have focused on an isolated autoimmune disease, often with complex genetic components, which might run in families (known as familial aggregation). When the same autoimmune disease affects members of a family, it is referred to as familial autoimmune disease. An example of this would be two sisters who both have lupus, or perhaps a mother and daughter who both have RA.
In my own family’s case, several female members have different autoimmune diseases, including RA, MS, lupus, scleroderma, and diabetes. The aggregation of diverse autoimmune diseases that occur in a family (known as familial autoimmunity) has not been studied as extensively as familial aggregation. Recently, researchers in Bogota, Colombia, conducted a systematic review and meta-analysis on the subject of familial autoimmunity, published in BMC Medicine (2013).
Familial autoimmunity was investigated in five major autoimmune diseases:
rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid disease, multiple sclerosis, and type 1 diabetes mellitus. Articles were searched in Pubmed and Embase databases and out of 61 articles discussing familial autoimmunity, 44 met criteria to be chosen for final analysis.
Familial autoimmunity was found in all the autoimmune diseases investigated. Autoimmune thyroid disease, followed by systemic lupus erythematosus and rheumatoid arthritis, were the most frequent autoimmune diseases encountered.
Autoimmune thyroid disease, including Hashimoto’s thyroiditis and Graves’ disease, was significantly associated with the presence of type 1 diabetes mellitus, rheumatoid arthritis, pernicious anemia, systemic lupus erythematosus, celiac disease, vitiligo, and multiple sclerosis. Compared with the general population, familial autoimmunity in Graves’ disease revealed that first degree family members were 14.1 and 13.5 times more likely to have pernicious anemia or RA, respectively.
Familial autoimmunity in rheumatoid arthritis was discussed in five articles, all of which linked autoimmune thyroid disease or type 1 diabetes to RA. One study (Thomas, 1983) reported type 1 diabetes as the disease responsible for familial autoimmunity. Researchers in another study (Taneja, 1993) stated that lupus, type 1 diabetes, autoimmune thyroid disease, SjÃ¶gren’s syndrome, psoriasis, and systemic sclerosis were also found in families with RA.
In another research study (Hemminki, 2009), it was reported that when a parent had ankylosing spondylitis (an auto-inflammatory disease which tends to aggregate in families), the risk of several diseases in offspring was increased significantly. Researchers determined the standardized incidence ratio (SIR) for each disease. Values more than one indicate an increased frequency of what is expected, whereas a value below one indicates a decreased frequency.
In the Hemminki study, it was observed that the incidence of RA in offspring of a parent diagnosed with ankylosing spondylitis was 2.96 times higher than expected (SIR=2.96). The standardized incidence ratios (SIR) were 2.25 for SjÃ¶gren’s syndrome, 2.13 for lupus, 1.65 for systemic sclerosis, 1.54 for autoimmune thyroid disease, 1.53 for pernicious anemia, 1.36 for psoriasis, and 1.34 for Wegener’s granulomatosis. In the same study, when a singleton sibling had psoriasis, the standardized incidence ratio for RA in another sibling was 2.01 and 2.77 for lupus.
Very interesting. This was the first I had come across studies which documented increased risk of autoimmune disease in first-degree relatives. Researchers conducting the meta-analyses noted that some studies showed a significant relationship of familial autoimmunity with RA and MS, and type 1 diabetes and autoimmune thyroid disease. However, some studies found a lack of disease clustering or aggregation in the case of MS and RA.
Authors of the meta-analysis suggest that further studies of familial autoimmunity will help increase the knowledge about the common mechanisms of autoimmunity. Doctors should be aware of familial autoimmunity when they are attending patients, or their first-degree relatives, who are diagnosed with autoimmune disease. Exploring the presence of auto-antibodies and other risk factors is encouraged.
Do any of your family members have RA or other autoimmune disease? If so, who and what do they have? It would be interesting to see if our community reflects this meta-analysis. For more statistics on connections between other diseases, you can read the study which is freely available.
Cardenas-Roldan J, Rojas-Villarraga A, Anaya JM. How do autoimmune diseases cluster in families? A systematic review and meta-analysis. BMC Med 2013 Mar 18; 11(1):73. doi:10.1186/1741-7015-11-73. [Epub ahead of print]
Hemminki K, Li X, Sundquist J, Sundquist K. Familial associations of rheumatoid arthritis with autoimmune diseases and related conditions. Arthritis Rheum 2009; 60:661-668.
Taneja V, Singh RR, Malaviya AN, Anand C, Mehra NK. Occurrence of autoimmune diseases and relationship of autoantibody expression with HLA phenotypes in multicase rheumatoid arthritis families. Scand J Rheumatol 1993; 22:152-157.
Thomas DJ, Young A, Gorsuch AN, Bottazzo GF, Cudworth AG. Evidence for an
association between rheumatoid arthritis and autoimmune endocrine disease. Ann Rheum Dis 1983; 42:297-300.
Lisa Emrich is a patient advocate, accomplished speaker, author of the award-winning blog Brass and Ivory: Life with MS and RA, and founder of the Carnival of MS Bloggers. Lisa uses her experience to educate patients, raise disease awareness, encourage self-advocacy, and support patient-centered research. Lisa frequently works with non-profit organizations and has brought the patient voice to health care conferences and meetings worldwide. Follow Lisa on Facebook, Twitter, and Pinterest.