IL21 deficiency causes early-onset inflammatory bowel disease and primary immunodeficiency

Published Online: April 21, 2014

The immune system must maintain a tightly regulated balance of pro- and anti-inflammatory responses. Small alterations—such as the presence or absence of one factor—can tip the scale towards immunodeficiency and/or autoimmunity.

In a study recently published in The Journal of Allergy and Clinical Immunology (JACI), Salzer and colleagues investigated a patient with early-onset inflammatory bowel disease (IBD), who later also showed other symptoms of immunodeficiency, such as respiratory tract infections. During this investigation, the authors of this study identified a new disorder caused by a homozygous mutation in the IL21 gene. This mutation caused loss of function of the corresponding gene product and an aberrant B-cell phenotype, including decreased memory B-cells.

Thus, IL21 deficiency is a novel cause of early-onset IBD together with a common variable immunodeficiency-like primary immunodeficiency. In principle, the disease may be amenable to allogeneic hematopoietic stem cell transplantation. However, treatment with recombinant IL21 may represent an interesting alternative. Over the past years, IL21 has emerged as a critical cytokine regulating multiple arms of the immune system, and recently, interfering with IL21 signaling has been proposed as a treatment option for various autoimmune diseases. However, the observation that lack of IL21 is associated with autoimmunity raises a concern for therapeutic strategies interfering with IL21 in immune-mediated diseases.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

inflammatory bowel disease
Figure 1B: Histology consistent with Crohn’s disease

inflammatory bowel disease

Figure 1F: Structure simulation of mutant IL-21Leu49Pro overlapped with wildtype IL-21


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