AN-NAJAH NATIONAL UNIVERSITY
IgA and IgG subclass deficiencies
Abbas W. Abbas
Discussion a case has immune disease was diagnosed; IgA and IgG subclasses deficiencies and provide
explanation about this disease
IgA and IgG subclasses deficiencies
Antibodies (Abs) are produced by B cells. Decrease production of Abs the most common type
of immune deficiency, this deficiency range from 0-100% and can affect any isotope.
I emphasize on Ig deficiencies, specially decrease production of IgA and various IgG subclasses,
and their effect on response to specific antigens such as polysaccharide.
When B lymphocyte fail to mature into IgA-secreting plasma cells, serum IgA levels are
reduced, and IgA deficiency result, otherwise IgA deficiency may result from reduced numbers
of IgA-secreting B cells in circulation. The most common cases of IgA deficiency have little
number of that B cells in gastrointestinal lamina propria.
B cell may fail to differentiate into proper secreting pattern due to; intrinsic defect in it, problems
associated with T cells that may be either T-helper cells or suppressor T-cell-IgA specific, the
first may be inadequate or defective whereas the last excessive, and this failure may be due to
passage of maternal anti-IgA antibodies to the fetus and suppress fetal IgA development.
Some selective IgA deficiency patients have mutation in TACI gene, which encode receptor for
the cytokines BAFF and APRIL this mutation also responsible for another disease called
common variable immune deficiency. This deficiency in same patient may be asymptomatic.
Other have occasional respiratory infection and diarrhea, and rarely patient with sever recurrent
infections lead to permanent intestinal and air way damage, with occasional autoimmune disease.
In intrinsic B cell defect, homozygous deletion of large portion of the Ig-heavy chain locus result
in individual with complete absence of 3 or more Ig classes ( IgG2, IgG4, IgA, occasionally
IgE) . Selective IgG subclass deficiencies are usually due to abnormal B cell differentiation and
rarely to homozygous deletion of (CƔ) gene. Deficiency of IgG3 is the most common in adult,
and IgG2 deficiency in children.
IgG2 work against pneumococcal polysaeaide antigen in contrast IgG1 and to lesser degree IgG3
antibodies against protein antigen.
Many patients have selective IgA or IgG subclass deficiency or both remain asymptomatic, and
the risk for autoimmune disease or atopic should be taken in mind of physician and the treatment
depend on symptoms and clinical features, although they are asymptomatic, there are increase
frequency of chronic sinopulmonary infection for example patient with IgG subclass deficiency
appear to has increased incidence of asthma or sinusitis.
Most of IgA-deficient patient asymptomatic, this can be explained by increase in IgM
production in mucosal lumen but this not sure, another explanation is normal level of secretary
IgA despite decreased serum IgA levels. As I said previously the patient may present with severe
symptoms, and the disease may contribute to other dangerous diseases such as gastric carcinoma,
the same thing due to IgG subclass deficiencies the lack of symptoms may due to crossover
among IgG isotopes.
A 48-year-old man was admitted for investigation of weight loss associated with intermittent
Diarrhea. On examination he was thin but had no signs of malignancy. He had no clubbing and
his chest was clear on auscultation. There was no lymphadenopathy and no hepatosplenomegaly.
He was not anemic, had a normal serum albumin and normal liver function tests. Immunological
tests are done; No infective cause of the intermittent diarrhea was found. Barium enema was
normal. Endoscopic examination of his maxillary sinuses showed Considerable inflammation
and hypertrophy of the mucosa.
The case diagnosed IgA and IgG subclass deficiencies according to many tests, and by excluding
other disorder. The patient had chronic sinusitis and history of pneumonia as a child and again as
young man. Barium enema tests exclude that the patient has problem in colon and intestine.
Stool culture was performed and no infective cause of diarrhea. Immunological test ( table c3.3)
done and show reduced level of IgA and IgG subclasses; the IgA level was < 0.1 and IgG3 was
0.1 and IgG1 was 2.7 all of them were out of normal range.
And there are great discussions about treatment. We should use aggressively antibiotic in certain
bacterial infection such as H.influenza. And usage of intravenous immunoglobulin is
controversial and has many side effects.
These patients have less than normal IgG subclasses and IgA. There many approach to treatment;
one is intravenous Immunoglobulin, another approach to supply them with antibiotics and
vaccines, may go to surgery in some cases if otitis media and chronic sinusitis.
This disease is inherited and affects 1 in 700 Caucasians. The patient has recurrent respiratory
infection, and has high incidence of allergic and autoimmune disorder. Antibiotics are used as
prophylactic and as medication. Initial treatment should be administered under the close
supervision of experienced personnel. The risk of adverse reactions in the initial treatments is
high, especially in patients with infections and in those who form immune complexes.
IgA and IgG Subclass Deficiencies Author: Terry W Chin, MD, PhD; Chief Editor: Harumi
Cellular and molecular immunology abbas 7th edition