Autoimmune diseases are chronic conditions that are caused by the loss of immunological tolerance to self-antigens. When we look at autoimmune diseases separately, most of them individually are rare. Thought collectively they are affecting many people and are a leading cause of death among young and middle-aged women. The group of autoimmune diseases is a heterogeneous group of disorders. Different changes in the immune system lead to a range of syndromes that either target a specific organ or affect the body systematically. However, the underlying immunogenetic mechanism by autoimmune diseases is similar. Most of the factors involved in autoimmunity can be categorized into four groups: genetic, immune, hormonal and environmental. Autoimmune diseases are sharing a common origin. There are three levels of evidence supporting the idea that autoimmune diseases are part of a group of pathologies sharing a common origin: the kaleidoscope of autoimmunity, shared pathophysiological mechanisms among them and the genetic evidence. The term ‘kaleidoscope of autoimmunity’ describes the possible shift of one disease to another or to the fact that more than one autoimmune disease may coexist in a single person or in the same family. The coexistence of autoimmune diseases in a family, is called familial aggregation which does not mean that a disease must have a genetic contribution. Non genetic factors play the same effect – besides sharing alleles, families share culture, behaviour, diet and environmental exposure.
About 25 % of patients with autoimmune diseases have a tendency to develop additional autoimmune diseases. Population-based database studies demonstrated that autoimmune thyroid disease is frequently associated with other autoimmune diseases.
Other study analyzing the presence of polyautoimmunity (when more than one autoimmune disease in a single patient is present) in 1083 patients in four cohorts of autoimmune diseases found that 34.4% had more than one autoimmune disease.
In the graph below you can see the autoimmune diseases clustered.
Each node represets a stage from the clustering process. There were four clusters. The most hierarchical was composed of four ADs. AITD: autoimmune thyroid disease (including thyroiditis, Hashimoto disease, Graves disease); SLE: systemic lupus erythematosus; SS: Sjögren’s syndrome; APS: antiphospholipid syndrome; T1D: type 1 diabetes mellitus; SSc: scleroderma (including localized, systemic, diffuse, limited); BID: billiary inflammatory disease (including primary biliary cirrhosis, primary sclerosing cholangitis); CD: celiac disease; VIT: vitiligo; AIH: autoimmune hepatitis; RA: rheumatoid arthritis; MG: myasthenia gravis; PMDM: polymyositis/dermatomyositis; PA: pernicious anemia; DAD: demyelinating autoimmune diseases (including multiple sclerosis, transverse myelitis, optic neuromyelitis); AAI: autoimmune adrenal insufficiency (Addison disease); HA: autoimmune anemia; ITP: idiopathic thrombocytopenic purpura; AG: autoimmune gastritis; VAS: vasculitis (including Churg-Strauss syndrome, giant cell arteritis, microscopic polyangiitis, cryoglobulinemia, polyarteritis nodosa, Wegener granulomatosis); PF: pemphigus (including vulgaris, bulloso, foliaceous); IBD: inflammatory bowel disease (including ulcerative colitis, Crohn’s disease); AA: alopecia areata; PsA: psoriasis (including psoriatic arthritis); SAR: sarcoidosis; JCA: juvenile chronic arthritis; AS: ankylosing spondylitis; RePo: relapsing polychondritis.
As you can see, autoimmune thyroid disease was the most frequent polyautoimmunity found in 1,083 patients. Autoimmune thyroid disease is described as the most prevalent autoimmune disease and being associated with other organ-specific and non-organ-specific autoimmune diseases.
Why is that?
This can be explained by:
1) antithyroid antibodies can modifies the immune response or the functioning of the immune system, thus they have immunomodulatory effects
2) a genetic link between antithyroid autoimmunity and the susceptibility to autoimmune disease
3) molecular mimicry between thyroid and disease-specific epitopes: in genetically predisposed persons and under particular conditions, molecular mimicry between microbial and human antigens can turn a defensive immune response into autoimmunity.
It is so important screening for other autoimmune diagnoses if a person with autoimmune thyroid disease presents new or nonspecific symptoms.
Autoimmune diseases do not begin at the time of clinical appearance but many years before that. The implication of this concept lies in the possibility of predicting autoimmunity.
References:
Anaya, J.-M., Corena, R., Castiblanco, J., Rojas-Villarraga, A., & Shoenfeld, Y. (2014). The kaleidoscope of autoimmunity: multiple autoimmune syndromes and familial autoimmunity. Expert Review of Clinical Immunology, 3(4), 623-635. doi:10.1586/1744666x.3.4.623
Kunzler, E., Hynan, L. S., & Chong, B. F. (2018). Autoimmune Diseases in Patients With Cutaneous Lupus Erythematosus. JAMA Dermatology. doi:10.1001/jamadermatol.2018.0616
Nagy, K. H., Lukacs, K., Sipos, P., Hermann, R., Madacsy, L., & Soltesz, G. (2010). Type 1 diabetes associated with Hashimoto’s thyroiditis and juvenile rheumatoid arthritis: a case report with clinical and genetic investigations. Pediatric Diabetes, 11(8), 579-582. doi:10.1111/j.1399-5448.2010.00676.x
Rojas-Villarraga, A., Amaya-Amaya, J., Rodriguez-Rodriguez, A., Mantilla, R. D., & Anaya, J.-M. (2012). Introducing Polyautoimmunity: Secondary Autoimmune Diseases No Longer Exist. Autoimmune Diseases, 2012. doi:10.1155/2012/254319
Ruggeri, R. M., Trimarchi, F., Giuffrida, G., Certo, R., Cama, E., Campennì, A., . . . Wasniewska, M. (2017). Autoimmune comorbidities in Hashimoto’s thyroiditis: different patterns of association in adulthood and childhood/adolescence. European Journal of Endocrinology, 176(2), 133-141. doi:10.1530/eje-16-0737
Somers, E. C., Thomas, S. L., Smeeth, L., & Hall, A. J. (2006). Autoimmune Diseases Co-occurring Within Individuals and Within Families: A Systematic Review. Epidemiology, 17(2), 202. doi:10.1097/01.ede.0000193605.93416.df
Stohl, H. E., Ouzounian, J., Rick, A.-M., Hueppchen, N. A., & Bienstock, J. L. (2013). Thyroid disease and gestational diabetes mellitus (GDM): is there a connection? The Journal of Maternal-Fetal & Neonatal Medicine, 26(11), 1139-1142. doi:10.3109/14767058.2013.773309
