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What

Immunoglobulins (Ig) are antibodies (molecules that help the body identify and defend itself from foreign substances). There are five kinds of antibodies: IgG, IgM, IgA, IgD, and IgE. IgG is the most abundant of the different types of immunoglobulins. IgG is the antibody responsible for responding to viruses, bacteria, and antitoxins. IgG Subclass Deficiencies are categorized as immunodeficiency disorders and occur when one of the four IgG subclasses are not made. These subclasses are numbered in order of their relative amount in serum (the liquid part of blood); IgG1 is found in greatest amounts and IgG4 the least. If a child lacks a member of the IgG antibody family, his or her immune response is compromised. IgG subclass deficiencies often cause a child to become exceedingly prone to bacterial infections. These children are susceptible to repetitive infections because IgG molecules are important for a normal secondary immune response – recognition of a previously encountered antigen (foreign substance) and an appropriate accelerated defense.

Who

Both males and females are affected by this deficiency.

Signs and Symptoms

IgG1 Subclass Deficiency Recurrent respiratory tract infections, such as sinus infections, ear infections or pneumonia. Persistently low IgG1 level Normal total IgG, IgG2, IgG3 and IgG4 levels IgG2 Subclass Deficiency Recurrent sinopulmonary (sinus and respiratory tract) infections, such as sinusitis, pneumonia or bronchitis, otitis media (ear infection), and disseminated pneumococcal disease (a widespread infection with a specific type of bacteria called Streptococcus pneumoniae). Most common symptomatic IgG subclass deficiency in children One of the most commonly identified abnormalities in those with recurrent infections Varying degrees of severity and perseverance, from persistent, undetectable decreases to moderate, transient decreases in IgG2 concentrations. May occur as an isolated abnormality or in combination with IgG4 or IgA deficiency Most children with absent or very low concentrations of IgG2 also have an IgA deficiency. Some children with IgG2 deficiency develop other immunodeficiencies (such as CVID). Some scientists think that IgG2 subclass deficiency may indicate a more broad-spectrum immune dysfunction. IgG3 Subclass Deficiency Found in patients with recurrent sinopulmonary infections Many IgG3 deficiencies are moderate, with some IgG3 present in circulation. These abnormalities tend to be transient. More commonly detected in adults. IgG4 Subclass Deficiency Many healthy infants and children have low or absent concentrations of IgG4, so this deficiency cannot be reliably diagnosed in children. Undetectable amounts of IgG4 have been reported in up to 10% of healthy adults and 15% of healthy children.

Possible Causes

It is thought that the poor antibody production, and not the IgG subclass deficiency itself, is the reason for recurrent infections. The cause of IgG subclass deficiency, however, is not known.

Diagnosis

IgG subclass deficiency may be suspected in children and adults who have a history of recurrent infections of the sinuses, ears, bronchi and/or lungs. People without any symptoms, however, have been diagnosed with IgG subclass deficiencies. Commercial laboratory measurement of IgG subclasses is problematic because results are not always reliable. Interpretations of lab values may also vary greatly do to the wide range of normal age-related values. A diagnosis of an IgG subclass deficiency should be confirmed by another test at least 1 month later. It is also important to measure IgG subclasses every 3- to 6-months because levels may fluctuate.

Treatment

Replacement therapy is generally not given to patients with IgG subclass deficiency unless they have been shown to have a deficiency of antibody production and have failed antibiotic prophylaxis (taking antibiotics to prevent infection). In this case, replacement therapy with human immunoglobulin is the preferred therapeutic choice for antibody-deficient patients who have recurrent infections and who are deficient in IgG. One must keep in mind that infusions of immunoglobulin may cause some side effects. There are always risks associated with transfusions of blood products, such as this one. So far, no one has reported receiving HIV, yet hepatitis C virus infections have been transmitted this way. New safety measures are used for current commercial preparations. Some antibody-deficient patients develop symptoms of diaphoresis (sweating), tachycardia (fast heartbeat), flank pain (pain in their sides or back), and hypotension (low blood pressure) during immunoglobulin infusion. Most of these types of reactions can be controlled by altering the way the infusion happens. More serious anaphylactic (allergic) reactions may occur when the patient recognizes the donor’s immunoglobulins as “foreign material” and tries to get rid of them. Because of the chance for these side effects, it is important to take the first immunoglobulin infusion while under a doctor’s care at a hospital or clinic. If the first infusion goes well, home infusion therapy is now widely available. Additionally, a subcutaneous (a shot) infusion of immunoglobulins is a welcome alternative to intravenous (IV) infusions, with a low chance of the aforementioned side effects.

Prognosis

Most children with subclass deficiencies do very well, with few problems. For the children who have recurrent infections, their prognosis depends on the severity and frequency of their infections. In some children, the IgG subclass deficiency disappears spontaneously in later childhood. A few children may go on to develop other immunodeficiencies, such as common variable immunodeficiency, which will change their overall prognosis.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

The Immune Deficiency Foundation
Site provides links to well-written chapters on immunologic deficiencies. It also provides links to support groups. Parents can access this information by searching the site (upper left corner) for IgG subclass deficiencies and click on IDF - Patient and Family Handbook For The Primary Immune Deficiency Diseases, Third Edition and select Chapter X. The second way to access this chapter is to click on the direct link below: http://www.primaryimmune.org/pubs/book_pats/e_ch10.pdf

Primary immunodeficiency Association
A great website with information about these disorders as well as links to support networks.

Google Search for IgG Subclass Deficiencies

References and Sources

Cooper, M.D., Schroeder, H.W.: Primary Immune Deficiency Diseases, Chapter 308, Part 12: Disorders of the immune system, Connective Tissue, and Joints; Immunoglobulin Deficiency Syndromes Hoffman: Hematology: Basic Principles and Practice, 3rd ed., Copyright © 2000 Churchill Livingstone, Inc Sorensen, R.U., Moore, C.: Primary Immune Deficiencies: Presentation, Diagnosis, and Management antibody deficiency syndromes, Pediatric Clinics of North America, 47 (6), December 2000