Selective immunoglobulin A deficiency

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.Since that’s a very hostile environment, a portion of this receptor, known as secretory component, wraps around IgA like a protective armor and keeps it from getting broken down by degradative enzymes.

This way it can stop toxins or pathogens from attaching to mucosal surfaces of the gut or airways and invading the body’s tissues.

Apart from secretory IgA, there’s also a small amount of IgA in the serum, called serum IgA, which exists as a monomer.In IgA deficiency, there are extremely low levels of both secretory and serum IgA, because B cells are unable to secrete IgA.

This is due to a defect in B cells, in T cells, or in cytokine signaling between the two. Regardless of the exact cause, the result is that B cells can’t class switch to produce IgA or they can’t differentiate into IgA-secreting plasma cells, so IgA remains bound to their surface, along with IgM and IgD.

In other cases, IgA- secreting plasma cells die prematurely. Finally, there are also cases when IgA is secreted normally, but can’t get across the mucosa, due to the absence of poly-Ig receptor.

In all of these situations, there are decreased IgA levels along mucosal surfaces and that makes it easier for pathogens to cause infections.Sometimes, these pathogens look a lot like self-antigens, and that can cause the immune system to start attacking our own cells, through a process called molecular mimicry.

Apart from infectious agents, there’s also no protection against ingested or inhaled carcinogens.Meanwhile, B cells sometimes try to compensate for the lack of IgA by increasing the production of IgE, which can lead to allergic reactions.

In the majority of cases, the underlying cause is not known, but sometimes there’s a genetic component, so multiple members of the same family are affected.Most individuals with selective IgA deficiency generally appear healthy, with no major symptoms.

Sometimes they may have more infections or more chronic infections. There’s also an increased frequency of atopy and asthma, as well as autoimmune diseases like rheumatoid arthritis.Selective IgA deficiency is associated with increased risk of some malignancies, like gastric and colon cancer.

Finally, some individuals develop severe reactions, when they’re transfused with blood containing IgA, because the IgA is treated like a foreign antigen.Diagnosis is based on decreased IgA levels in the blood, with normal levels of the other antibody classes, like IgM, IgD, and IgG, and slightly elevated levels of IgE.Unfortunately, there’s no effective treatment for selective IgA deficiency.

And if a blood transfusion is necessary, washed erythrocytes should be used, if possible.All right, as a quick recap… Selective IgA deficiency is a common cause of immunodeficiency caused by low amounts of IgA, resulting in low protection against infections of the mucous membranes lining the respiratory and gastrointestinal tracts.

There are normal levels of the IgM, IgD, and IgG, and slightly elevated levels of IgE. A because I G A is treated like a foreign antigen diagnosis is based on decreased IGA levels in the blood with normal levels of the other antibody classes like I G M I G D and I G and slightly elevated levels of I G E Unfortunately there's no effective treatment for selective iga deficiency And if a blood transfusion is necessary washed erythrocyte should be used if possible All right as a quick recap selective IGA deficiency is a common cause of immunodeficiency caused by low amount of I G A resulting in low protection against infection to the mucous membranes lining the respiratory and gastrointestinal tracts There are normal levels of I G M I G D and I G and slightly elevated levels of I G Thanks for watching If you're interested in a deeper dive on this topic take a look at osmosis dot org where we have flashcards questions and other awesome tools to help you learn medicine Otherwise you can always support us by donating on patry in subscribing to our