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Selective immunoglobulin A deficiency



Immune system


General infections
Hypersensitivity reactions
Immune system organ disorders
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Selective immunoglobulin A deficiency


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High Yield Notes
10 pages

Selective immunoglobulin A deficiency

8 flashcards

USMLE® Step 1 style questions USMLE

1 questions

A 20-year-old man comes to his primary care physicians office for evaluation of chronic diarrhea and associated nausea and bloating. He visited a local health care clinic and was prescribed a course of antibiotics, without relief of symptoms. Past medical history is significant for asthma, eczema and an anaphylactic reaction to blood transfusion two years ago. Family history is noncontributory. He does not use tobacco, alcohol or illicit drugs. Temperature is 37.2 C (99.0 F), pulse is 90/min, respirations are 17/min and blood pressure is 100/60 mmHg. Microscopic examination of his stool for ova and parasites is shown.

Reproduced from Wikimedia Commons

Which of the following pathophysiologic findings is most strongly associated with this patient’s disease?


Content Reviewers:

Rishi Desai, MD, MPH

Selective immunoglobulin A deficiency is a condition where there’s a lack of immunoglobulin or antibody A, called IgA for short. It’s called “selective” because all the other antibody classes, IgM, IgG, IgE and IgD are produced normally. IgA is in charge of protecting the mucosal surfaces of the body against foreign invaders, so without it, there’s a higher risk of mucosal infections.

Now, B cells make antibodies, and normally, B cells are “born” in the bone marrow, which is the spongy tissue inside some bones of the body. This is where they develop their B cell receptors on their surface which eventually can get released - and when they’re freely floating in the blood they’re called antibodies.

Antibodies are Y- shaped protein molecules, formed by two heavy and two light chains, each of which has a variable region, at one end, and a constant region (C region) at the other end. Variable regions are unique to each B cell and they are designed to bind to a very specific antigen, whereas C regions determine the antibody class.

Initially all of the B cells have IgM and IgD class antibodies on their surface, with each B cell recognizing and binding to its own unique antigen. Mature B cells leave the bone marrow and migrate to peripheral lymphoid organs, like the spleen, lymph nodes or mucosa-associated lymphoid tissue, which is also called MALT.

MALT is composed of clusters of lymphoid tissue scattered under the mucous membranes lining the mouth, airways, and digestive tract. This is a really strategic position, because a variety of antigens are constantly being picked up and filtered from these body tissues. As a result, B cells are likely to encounter an antigen they recognize. A bit like spending time at a train station during rush hour to look for someone that catches your eye.

If two of a B cell’s receptors bind to the same antigen, they can cross-link - meaning that two adjacent receptors on the B cell surface can get pulled close together. When that happens the B cell will often take in the antigen, digest it, and present pieces of it on another cell surface protein called a major histocompatibility class II molecule, or MHC class II.

If a nearby T cell receptor recognizes this antigen bound to an MHC class II molecule, the T cell releases cytokines that make the B cell differentiate into a plasma cell, which is a cell that makes lots of antibodies.

The specific set of cytokines received by the B cell determine how it class-switches, meaning whether it switches from making IgM and IgD to making IgG, IgE or IgA. In class switching, what changes is only the constant region, and not the variable region of the antibody, meaning that the antigen specificity remains the same.

IgA is primarily produced when B cells are stimulated by interleukin- 5 (IL-5) or transforming growth factor- β or TGF- β. Class switching to IgA usually happens in mucosa-associated lymphoid tissue, or MALT, from where IgA is secreted into the saliva, sweat, or intestinal juices.

When IgA is secreted, it’s called secretory IgA, and it’s a dimer, meaning that two IgA molecules are joined together by a joining chain or J chain. This J chain is recognized by a poly-Ig receptor on the basolateral side of the mucous membrane, which helps it move across the epithelial cells and into the lumen.


Selective IgA deficiency is a common cause of immunodeficiency caused by low amounts of immunoglobulin A (IgA), resulting in low protection against infections of the mucous membranes lining the respiratory and gastrointestinal tracts. It is typically accompanied by normal levels of IgM, IgD, and IgG, and slightly elevated levels of IgE. Affected people are susceptible to infections of the mucous membranes lining the mouth, airways, and digestive tract.

Selective IgA deficiency often results from a failure of B cells to differentiate into IgA-secreting plasma cells, so IgA remains bound to their surface, along with IgM and IgD. Most people with selective IgA deficiency generally appear healthy, with no major symptoms. Sometimes, however, they may have more chronic infections, an increased frequency of atopy and asthma, as well as autoimmune diseases like rheumatoid arthritis. Selective IgA deficiency is associated with an increased risk of some malignancies, like gastric and colon cancer.

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