Review and Theme Article
Mechanism-Based Strategies for the Management of Autoimmunity and Immune Dysregulation in Primary Immunodeficiencies

https://doi.org/10.1016/j.jaip.2016.08.004Get rights and content
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A broad spectrum of autoimmunity is now well described in patients with primary immunodeficiencies (PIDs). Management of autoimmune disease in the background of PID is particularly challenging given the seemingly discordant goals of immune support and immune suppression. Our growing ability to define the molecular underpinnings of immune dysregulation has facilitated novel targeted therapeutics. This review focuses on mechanism-based treatment strategies for the most common autoimmune and inflammatory complications of PID including autoimmune cytopenias, rheumatologic disease, and gastrointestinal disease. We aim to provide guidance regarding the rational use of these agents in the complex PID patient population.

Key words

Primary immunodeficiencies (PIDs)
Treatment
Autoimmunity
Cytopenias
Arthritis
Vasculitis
Lupus
Autoimmune enteropathy (AIE)
Inflammatory bowel disease (IBD)

Abbreviations used

AIE
Autoimmune enteropathy
AIHA
Autoimmune hemolytic anemia
ALPS
Autoimmune lymphoproliferative syndrome
BAFF
B-cell–activating factor
CGD
Chronic granulomatous disease
CID
Combined immunodeficiency
CTLA4
Cytotoxic T-lymphocyte antigen 4
CID
Combined immunodeficiency
CVID
Common variable immunodeficiency
GI
Gastrointestinal
GOF
Gain-of-function
HSCT
Hematopoietic stem cell transplantation
IBD
Inflammatory bowel disease
IPEX
Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome
ITP
Immune thrombocytopenic purpura
IVIG
Intravenous immunoglobulin
JIA
Juvenile idiopathic arthritis
LRBA
LPS-responsive vesicle trafficking, beach and anchor containing protein
PID
Primary immunodeficiency
RAG
Recombination activating gene
SCID
Severe combined immunodeficiency
SLE
Systemic lupus erythematosus
STAT
Signal transducer and activator of transcription
Treg
Regulatory T cell

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Conflicts of interest: J. E. Walter has been supported by grant number 5K08AI103035 and the Jeffrey Modell Foundation. J. R. Farmer is employed by Massachusetts General Hospital. T. R. Torgerson has consultancy arrangements with Baxalta Biosciences, CSL Behring, and ADMA Biologics; has received one or more grants from or has one or more grants pending with Baxalta Biosciences, CSL Behring, and the NIH; and has received one or more payments for the development of educational presentations for Baxalta Biosciences, CSL Behring, Questcor Pharmaceuticals, and Robert Wood Johnson Foundation. The rest of the authors declare that they have no relevant conflicts of interest.