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Journal of Autoimmunity 99 (2019) 52–72

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Journal of Autoimmunity 99 (2019) 52–72 Journal of Autoimmunity 99 (2019) 52–72 Contents lists available at ScienceDirect Journal of Autoimmunity journal homepage: www.elsevier.com/locate/jautimm Primary immunodeficiency and autoimmunity: A comprehensive review T Laura Amaya-Uribea, Manuel Rojasa,b, Gholamreza Azizic, Juan-Manuel Anayaa, ∗ M. Eric Gershwind, a Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia b Doctoral Program in Biomedical Sciences, Universidad Del Rosario, Bogota, Colombia c Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran d Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, School of Medicine, Davis, CA, USA ARTICLE INFO ABSTRACT Keywords: The primary immunodeficiency diseases (PIDs) include many genetic disorders that affect different components Autoimmune diseases of the innate and adaptive responses. The number of distinct genetic PIDs has increased exponentially with Autoimmunity improved methods of detection and advanced laboratory methodology. Patients with PIDs have an increased Immunologic deficiency syndromes susceptibility to infectious diseases and non-infectious complications including allergies, malignancies and au- Immunodeficiencies toimmune diseases (ADs), the latter being the first manifestation of PIDs in several cases. There are two typesof Primary immunodeficiency PIDS. Monogenic immunodeficiencies due to mutations in genes involved in immunological tolerance thatin- crease the predisposition to develop autoimmunity including polyautoimmunity, and polygenic im- munodeficiencies characterized by a heterogeneous clinical presentation that can be explained by acomplex pathophysiology and which may have a multifactorial etiology. The high prevalence of ADs in PIDs demonstrates the intricate relationships between the mechanisms of these two conditions. Defects in central and peripheral tolerance, including mutations in AIRE and T regulatory cells respectively, are thought to be crucial in the development of ADs in these patients. In fact, pathology that leads to PID often also impacts the Treg/Th17 balance that may ease the appearance of a proinflammatory environment, increasing the odds for the devel- opment of autoimmunity. Furthermore, the influence of chronic and recurrent infections through molecular mimicry, bystander activation and super antigens activation are supposed to be pivotal for the development of autoimmunity. These multiple mechanisms are associated with diverse clinical subphenotypes that hinders an accurate diagnosis in clinical settings, and in some cases, may delay the selection of suitable pharmacological therapies. Herein, a comprehensively appraisal of the common mechanisms among these conditions, together with clinical pearls for treatment and diagnosis is presented. 1. Introduction mutation in the Bruton tyrosine kinase gene (BTK) characterized by the presence of recurrent infections in respiratory and gastrointestinal The primary immunodeficiency diseases (PIDs) include several ge- tracts. Since then, more than 350 unique immunodeficiency diseases netic anomalies that affect different components of the innate and have been identified [2]. Of these, selective immunoglobulin IgA defi- adaptive responses [1]. ADs include a heterogeneous group of disorders ciency (SIgAD) is the most frequent in children and adults, and the one of the immune system secondary to a loss of tolerance to self-antigens which is more frequently associated with ADs [3]. that may be organ specific or systemic [1]. Initially, PIDs and ADs were Although PIDs can affect both adults and children, they are more considered independent, or even polar opposites. However, due to ge- common during childhood. The distribution and prevalence of PIDs netic advances and a greater understanding of the pathophysiological varies between populations. Countries such as Iran, Australia, France, processes involving T-cell development, immune tolerance, T-cell sig- United States, Europe, and 12 Latin American countries have created naling, complement pathway and inflammation, they are now accepted national registries in order to identify the epidemiological distribution as interconnected processes, sharing some common mechanisms [1]. of these diseases. The French national registry center (CEREDIH) re- The first description of PIDs appeared in 1952 when Ogden Bruton ported a prevalence of 4.4 patients per 100,000 inhabitants [4], and discovered an X-linked agammaglobulinemia (XLA). XLA is caused by a data from the United States estimated a prevalence of 1/1200 people, ∗ Corresponding author. E-mail address: [email protected] (M.E. Gershwin). https://doi.org/10.1016/j.jaut.2019.01.011 Received 18 December 2018; Received in revised form 24 January 2019; Accepted 28 January 2019 Available online 20 February 2019 0896-8411/ © 2019 Elsevier Ltd. All rights reserved. L. Amaya-Uribe, et al. Journal of Autoimmunity 99 (2019) 52–72 Abbreviations HLH Hemophagocytic lymphohistiocytosis HT Hashimoto's thyroiditis AAD Autoimmune Addison disease HSCT Hematopoietic stem cell transplantation ACPA Anti-citrullinated protein antibodies IAA Insulin autoantibodies ADs Autoimmune diseases IA2 Protein tyrosine phosphatase antibodies AE Autoimmune encephalitis IBD Inflammatory bowel disease AGA Anti-gliadin antibodies IFNωAbs Interferon-omega autoantibodies AHP Autoimmune hypoparathyroidism IPEX Immune dysregulation, polyendocrinopathy, enteropathy, AIE Autoimmune enteropathy X-linked AIH Autoimmune hepatitis IRT Immunoglobulin G replacement therapy AIHA Autoimmune hemolytic anemia ITP Immune thrombocytopenic purpura AIL: Autoimmune leukopenia IVIg Intravenous gamma globulin infusions AIP Autoimmune pancreatitis JDM Juvenile dermatomyositis AIRE Autoimmune regulator JIA Juvenile idiopathic arthritis AIE Autoimmune enteropathy JMF Jeffrey Modell Foundation AIT Autoimmune thrombocytopenia LRBA Lipopolysaccharide responsive beige-like anchor AITD Autoimmune thyroid disease LoS Localized scleroderma ALPS Autoimmune lymphoproliferative syndrome MG Myasthenia gravis ALT Alanine aminotransferase MHC Major histocompatibility complex APECED Autoimmune polyendocrinopathy, candidiasis ecto- MMF Mycophenolate mofetil dermal, dystrophy mTOR Mammalian target of rapamycin APGS Autoimmune polyglandular syndrome MTX Methotrexate APRIL: A proliferation inducing ligand NALP5Ab NACHT leucine-rich-repeat protein 5 autoantibodies APS Antiphospholipid syndrome NSAIDs Nonsteroidal anti-inflammatory drugs AS Ankylosing spondylitis NADPH Nicotinamide adenine dinucleotide phosphate AST Aspartate transaminase OS Omenn syndrome A-T: Ataxia telangiectasia PA Pernicious anemia ATM ATM serine/threonine kinase PBC Primary biliary cholangitis AZA Azathioprine PID Primary immunodeficiency BAFF B-cell activating factor PolyA polyautoimmunity BCR B-cell receptor PSO Psoriasis BTK Bruton tyrosine kinase RA Rheumatoid arthritis CASP Caspase RAG Recombination-activating gene CaSR Calcium-Sensing Receptor ROS Reactive oxygen species CD Celiac disease RP Raynaud's phenomenon CGD Chronic granulomatous disease STAT Signal transducers and activators of transcription CLT Chronic lymphocytic thyroiditis SIgAD Selective immunoglobulin IgA deficiency CMC Chronic mucocutaneous candidiasis SLE Systemic lupus erythematosus CTLA4 Cytotoxic T-lymphocyte associated protein 4 SS Sjögren's syndrome CVID Common Variable Immunodeficiency T1D Type 1 diabetes DGS DiGeorge syndrome TCR T-cell receptor DL: Discoid lupus TLR Toll-like receptor DMARDs Disease-modifying antirheumatic drugs tTG Tissue Transglutaminase antibody DOCK8 Dedicator of cytokinesis 8 TPO Anti-thyroperoxidase antibodies EBV Epstein-Barr virus TRAb Thyroid-stimulating hormone receptor EMA Endomysial antibody assay 21-OHAbs 21- hydroxylase autoantibodies ES Evan's syndrome U Uveitis ESR Erythrosedimentation rate UC Ulcerative colitis FASL: FAS ligand VATS Video-assisted thoracoscopic FOXP3 Forkhead box P3 Vcr Vincristine. GAD65 Glutamic acid decarboxylase antibodies Vbl Vinblastine. GD Graves' disease VIT Vitiligo GLILD Granulomatous-lymphocytic interstitial lung WAS Wiskott-Aldrich syndrome HAE hereditary angioedema WASp: Wiskott-Aldrich syndrome protein HIES Hyper-IgE syndrome XLA X-linked agammaglobulinemia HIGM Hyper- IgM syndrome XLP X-linked lymphoproliferative disease which represents the highest prevalence worldwide [5]. In Europe, the knowledge about these diseases, delayed diagnosis, and underreporting European Society for Immunodeficiencies (ESID) registry identified [8]. 28,000 patients from more than 125 medical centers. To date, it is Patients with PIDs have an increased susceptibility to infectious considered the largest database of patients suffering from PIDs [6]. The diseases caused by either intracellular or encapsulated agents [2]. Latin American Group for Primary Immunodeficiency Diseases (LAGID) These patients may also be more susceptible to ADs, allergic diseases reports that out of 3321 patients, 53.2% have antibody deficiencies [7]. and malignancies [9]. Immunodeficiencies can be classified into two In underdeveloped countries, information is scarce due to lack of groups: 1) monogenic immunodeficiencies due to mutations in genes 53 L. Amaya-Uribe, et al. Journal of Autoimmunity 99 (2019) 52–72 that may also be involved in immunological tolerance [10], or 2) ectodermal dystrophy [14], ATM (ATM serine/threonine kinase) in ataxia- polygenic immunodeficiencies characterized
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