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Gastrointestinal manifestations in primary immunodeficiency

Asghar Aghamohammadi, MD, PhD
Atefeh Zeinoddini, MD
Payam Mohammadinejad, MD
Nima Rezaei, MD, PhD
Section Editor
Luigi D Notarangelo, MD
Deputy Editor
Anna M Feldweg, MD


Gastrointestinal (GI) manifestations are the second most common complications of primary immunodeficiency (PID) after pulmonary disease and have been reported in approximately 5 to 50 percent of patients with different types of PID [1,2]. PID may initially present with GI manifestations, such as intractable diarrhea, malabsorption, failure to thrive (FTT), or inflammatory bowel disease, which often do not respond as expected to conventional therapies [3].

This topic review will provide a brief overview of the GI immune system, review the most common GI complications of PID, and discuss specific GI disorders in some of the more common PIDs. Initial testing for immune problems, monitoring for GI complications among PID patients, and treatment considerations are also reviewed. More detailed approaches to patients with suspected PID and the medical management of immunodeficiency are discussed separately. (See "Approach to the child with recurrent infections" and "Approach to the adult with recurrent infections" and "Laboratory evaluation of the immune system" and "Primary immunodeficiency: Overview of management".)


The gastrointestinal (GI) tract is considered the largest organ in the immune system, with a vast surface area and the largest reservoir of lymphocytes in the human body [4]. The GI immune system consists of physical barriers, gut-associated lymphoid tissue (GALT), and other lymphoid organs. Components of the GI immune system are discussed in more detail separately. (See "Pathogenesis of food allergy", section on 'The gut immune system'.)

The GI immune system is constantly exposed to a variety of foreign antigens including those from bacteria, viruses, and parasites, as well as foreign dietary proteins [5]. A balance between immune responses to harmful micro-organisms and tolerance to nonpathogenic antigens is essential for immune homeostasis in the GI tract, a process that generally favors the development of tolerance. The GI immune system is mainly regulated by T lymphocytes, specifically regulatory T (Treg) cells, which are also responsible for cellular immunity and initiation of antigen-specific immune responses [6,7].

In addition, dimeric secretory immunoglobulin A (IgA), which is synthesized and secreted in the GI tract (and thus distinct from monomeric serum IgA), plays an active role in the regulation of the GI immune system by inducing tolerance to antigens with insignificant pathogenesis as well as providing protection against invasive micro-organisms. It is possible that dysregulation of IgA could result in inflammatory processes in the GI tract [8]. In addition, defects in either humoral or cellular immunity could result in uncontrolled inflammatory processes, damage to the mucosal surface of the GI tract, and increased risk of developing chronic inflammatory, autoimmune, and even malignant disorders.

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Literature review current through: Sep 2017. | This topic last updated: Jan 26, 2016.
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