Selective immunoglobulin A deficiency

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Selective immunoglobulin A deficiency

Immune system

General infections

Sepsis

Neonatal sepsis

Abscesses

Hypersensitivity reactions

Type I hypersensitivity

Food allergy

Anaphylaxis

Asthma

Type II hypersensitivity

Immune thrombocytopenic purpura

Autoimmune hemolytic anemia

Hemolytic disease of the newborn

Goodpasture syndrome

Rheumatic heart disease

Myasthenia gravis

Graves disease

Pemphigus vulgaris

Type III hypersensitivity

Serum sickness

Systemic lupus erythematosus

Poststreptococcal glomerulonephritis

Type IV hypersensitivity

Graft-versus-host disease

Contact dermatitis

Transplants

Transplant rejection

Graft-versus-host disease

Cytomegalovirus infection after transplant (NORD)

Post-transplant lymphoproliferative disorders (NORD)

Immunodeficiences

X-linked agammaglobulinemia

Selective immunoglobulin A deficiency

Common variable immunodeficiency

IgG subclass deficiency

Hyperimmunoglobulin E syndrome

Isolated primary immunoglobulin M deficiency

Thymic aplasia

DiGeorge syndrome

Severe combined immunodeficiency

Adenosine deaminase deficiency

Ataxia-telangiectasia

Hyper IgM syndrome

Wiskott-Aldrich syndrome

Leukocyte adhesion deficiency

Chediak-Higashi syndrome

Chronic granulomatous disease

Complement deficiency

Hereditary angioedema

Asplenia

Immune system organ disorders

Thymoma

Ruptured spleen

Immune system pathology review

Blood transfusion reactions and transplant rejection: Pathology review

Immunodeficiencies: T-cell and B-cell disorders: Pathology review

Immunodeficiencies: Combined T-cell and B-cell disorders: Pathology review

Immunodeficiencies: Phagocyte and complement dysfunction: Pathology review

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Selective immunoglobulin A deficiency

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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.



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

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Content Reviewers

Rishi Desai, MD, MPH

Contributors

Antonia Syrnioti, MD

Will Wei

Kara Lukasiewicz, PhD, MScBMC

Tanner Marshall, MS

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.

Summary

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.

Sources

  1. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  2. "CURRENT Medical Diagnosis and Treatment 2020" McGraw Hill Professional (2019)
  3. "Yen & Jaffe's Reproductive Endocrinology" Saunders W.B. (2018)
  4. "Bates' Guide to Physical Examination and History Taking" LWW (2016)
  5. "Robbins Basic Pathology" Elsevier (2017)
  6. "Practice parameter for the diagnosis and management of primary immunodeficiency" Annals of Allergy, Asthma & Immunology (2005)
  7. "Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID)" Clinical and Experimental Immunology (2000)
  8. "Update on the use of immunoglobulin in human disease: A review of evidence" Journal of Allergy and Clinical Immunology (2017)
  9. "Hypersensitivity transfusion reactions due to IgA deficiency are rare according to French hemovigilance data" Journal of Allergy and Clinical Immunology (2017)
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