Cellular and molecular mechanisms of immune dysregulation and autoimmunity.
Primary immunodeficiencies (PIDs) constitute a large group of rare disorders that affect the function of the immune system. A specific group of PIDs entitled "diseases of immune dysregulation" are developed due to mutation in the genes which have critical roles in the regulation of immune responses and immunological tolerance. This group of PID patients develop autoimmune and inflammatory disorders as a result of their impaired immunity, therefore they could be considered as a model for analyzing the link between immune dysregulation and autoimmunity. In this article, our aim is to describe the function of the mutated gene, the molecular and cellular mechanisms underlying the immune dysregulation and review the literature in regard with the reported autoimmune disorders in the main types of immunodysregulatory diseases including genetic defects of regulatory T cells, familial hemophagocytic lymphohistiocytosis syndromes, autoimmunity without lymphoproliferation, autoimmune lymphoproliferative syndrome, immune dysregulation with colitis, and type 1 interferonopathies.
Department of Laboratory Medicine, Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences, Karaj, Iran; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Gholamreza
G
Azizi
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Mohsen Rastegar
MR
Pouyani
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at the Karolinska University Hospital Huddinge, Stockholm, Sweden.
Hassan
H
Abolhassani
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Laleh
L
Sharifi
School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Majid Zaki
MZ
Dizaji
Department of Biomedical Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Javad
J
Mohammadi
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: mirshafiey@tums.ac.ir.
Abbas
A
Mirshafiey
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: aghamohamadi@sina.tums.ac.ir.
Asghar
A
Aghamohammadi
D000818:Animals; D015551:Autoimmunity; D006801:Humans; D007108:Immune Tolerance; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D009154:Mutation / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
Autoimmunity; Immune dysregulation; Primary immunodeficiency