Primary immunodeficiency and autoimmunity: A comprehensive review

Laura Amaya-Uribe; Manuel Rojas; Gholamreza Azizi; Juan-Manuel Anaya; M Eric Gershwin

doi:10.1016/j.jaut.2019.01.011

Primary immunodeficiency and autoimmunity: A comprehensive review

J Autoimmun. 2019 May:99:52-72. doi: 10.1016/j.jaut.2019.01.011. Epub 2019 Feb 20.

Authors

Laura Amaya-Uribe¹, Manuel Rojas², Gholamreza Azizi³, Juan-Manuel Anaya¹, M Eric Gershwin⁴

Affiliations

¹ Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia.
² Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia; Doctoral Program in Biomedical Sciences, Universidad Del Rosario, Bogota, Colombia.
³ Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.
⁴ Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, School of Medicine, Davis, CA, USA. Electronic address: megershwin@ucdavis.edu.

PMID: 30795880
DOI: 10.1016/j.jaut.2019.01.011

Abstract

The primary immunodeficiency diseases (PIDs) include many genetic disorders that affect different components of the innate and adaptive responses. The number of distinct genetic PIDs has increased exponentially with improved methods of detection and advanced laboratory methodology. Patients with PIDs have an increased susceptibility to infectious diseases and non-infectious complications including allergies, malignancies and autoimmune diseases (ADs), the latter being the first manifestation of PIDs in several cases. There are two types of PIDS. Monogenic immunodeficiencies due to mutations in genes involved in immunological tolerance that increase the predisposition to develop autoimmunity including polyautoimmunity, and polygenic immunodeficiencies characterized by a heterogeneous clinical presentation that can be explained by a complex 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 development 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.

Keywords: Autoimmune diseases; Autoimmunity; Immunodeficiencies; Immunologic deficiency syndromes; Primary immunodeficiency.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Autoimmune Diseases / diagnosis
Autoimmune Diseases / etiology
Autoimmune Diseases / metabolism
Autoimmune Diseases / therapy
Autoimmunity*
Disease Management
Disease Susceptibility / immunology
Epitopes / immunology
Humans
Immune Tolerance
Immunologic Deficiency Syndromes / diagnosis
Immunologic Deficiency Syndromes / etiology
Immunologic Deficiency Syndromes / metabolism
Infections / complications
Molecular Mimicry
Primary Immunodeficiency Diseases / diagnosis
Primary Immunodeficiency Diseases / etiology*
Primary Immunodeficiency Diseases / metabolism
Primary Immunodeficiency Diseases / therapy
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism

Substances

Epitopes