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IgG Subclass Deficiency in Children: Causes, Symptoms, Diagnosis, and Management

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IgG subclass deficiency may reflect slowed maturation of the immune system and is common in young children.

Medically reviewed by

Dr. Veerabhadrudu Kuncham

Published At October 13, 2023
Reviewed AtOctober 13, 2023

What Is IgG Subclass Deficiency?

Immunoglobulins are also called antibodies in the blood, which help the body fight against bacterial infections and prevent viral infections. Among all Immunoglobulins IgG (immunoglobulin G) is the primary immunoglobulin. IgG comprises four different types that are called IgG subclasses. These subclasses include IgG 1, IgG 2, IgG 3, and IgG 4. All these subclasses of IgG play different roles in the body to fight against infection. In case of lack of one or more of these subclasses may cause IgG subclass deficiency. IgG subclass deficiency is a group of conditions with one or more IgG subclasses having low levels in the blood. Still, measured levels of all other major immunoglobulins, including IgA, IgM, and the total IgG amount, are normal. Moreover, IgG subclass deficiency may also arise in concurrence with IgA deficiency. IgG subclass deficiencies fall under primary antibody immunodeficiencies in classification.

What Is the Cause of Igg Subclass Deficiency?

The definitive cause of IgG subclass deficiency is unknown, and no clear inheritance pattern is identified. However, many researchers believe that family history may play a part as in some families, there is more than one person impacted by IgG subclass deficiency or the presence of other family members affected by selective IgA deficiency. However, in a very small proportion of affected individuals, there is a complete absence of a particular IgG subclass with a deletion of a portion of the relevant gene complex on chromosome 14, which plays a role in the production of immunoglobulins. This rare condition is not necessarily associated with raised susceptibility to infection. It is more common to find lower levels of IgG than usual, signifying that the gene is present though it does not usually function.

What Are the Signs and Symptoms of IgG Subclass Deficiency?

The symptoms which may lead to the doctor for a diagnosis of IgG subclass deficiency are typically associated with recurrent respiratory infections. Especially infections affecting the upper airways that include infections of the following:

  • Sinuses, causing sinusitis.

  • Throat infections.

  • Ear infections.

However, in some cases, infections can also appear in the lower respiratory tract, including the lungs.

What Are the Common Causes of Infection in the Igg Subclass Deficiency?

The most common infections in IgG subclass deficiency include the followings:

  • Encapsulated bacteria, such as Haemophilus and Streptococcus pneumonia.

  • Viruses.

  • Influenza(in some cases causes severe lung infections).

In children with low IgG subclass levels, the symptoms are usually milder than those with other kinds of antibody deficiency, such as CVID (common variable immunodeficiency) or X-linked agammaglobulinemia (XLA).

How Is the Diagnosis of IgG Subclass Deficiency Done?

The doctor usually diagnoses using a sample of the affected person's blood. The diagnosis of IgH subclass deficiency involves blood tests for IgG, IgM, and IgA. Measurements of IgG subclass levels are only sometimes done as a part of the initial evaluation in individuals with recurrent infections. To diagnose IgG subclass deficiency, the immunologist will measure the total immunoglobulin levels, including IgG, IgA, and IgM. In case these immunoglobulin levels are all normal, despite there is still a problem with the frequency or severity of infections with no other explanation found, then the immunologist will measure the levels of IgG subclasses that are IgG1, IgG2, IgG3, and IgG4.

If IgG subclass levels are found to be low, the doctor may suggest this test be repeated at least once because the levels of IgG subclasses can change from time to time. In cases with IgA deficiency having more severe infections than anticipated, the doctor may measure IgG subclasses since there is a link between deficiencies of IgG2 and IgA.

If IgG subclass deficiency is suspected, then there is a requirement for further tests to help confirm a diagnosis of immunodeficiency. These evaluations include taking a careful and detailed history and additional laboratory investigations, including necessary tests to

Scan how the immune system responds and makes specific immunoglobulins in response to different sorts of vaccines. For that, the doctor will examine the affected individual's immune responses to proteins, for example, by vaccinating against tetanus.

The doctor will assess if there is the presence of antibodies in the blood against the protein. Most individuals with selective IgG subclass deficiency produce normal reactions to protein vaccines. The doctor may use a polysaccharide vaccine for older children and adults. Demonstration of poor antibody reactions to polysaccharide antigens in a person with an IgG subclass deficiency, especially IgG2 deficiency, along with or without IgA deficiency, may indicate a more substantial degree of immune deficiency and the probability of CVID development.

What Is the Treatment of IgG Subclass Deficiency?

The management of IgG subclass deficiency relies on the severity of the individual's symptoms. In many affected individuals, no regular treatment is needed. Suppose the severity and frequency of infections are low, and the quality of life of the affected individual is not significantly affected. In that case, the management can be limited to antibiotics whenever an infection occurs.

If the infections are more severe or are occurring oftentimes and hampering the work or schooling education, or if the growth and development of the child are being affected, then the doctor may suggest regular low doses of antibiotics as prophylactics to prevent the development of infections. In many affected individuals, this is very successful. In addition, the doctor will choose appropriate antibiotics according to the test of sensitivities of the organisms by isolation on culture. Moreover, the doctor may suggest additional immunization with the pneumococcal vaccine to enhance immunity.

However, a very small subgroup of individuals with IgG subclass deficiency with severe symptoms or serious infections may benefit from antibiotic prophylaxis. These cases may require immunoglobulin replacement therapy. These individuals usually have other associated abnormalities, including IgA deficiency or defective specific antibody production in response to vaccines. The decision for immunoglobulin replacement therapy involves careful consideration by immunologists. Indications for this therapy are:

  • Persistent low IgG subclass levels.

  • Poor antibody responses to vaccines.

  • Recorded evidence of failure to prevent infections using antibiotic prophylaxis.

Usually, the doctor will give therapeutic immunoglobulin as an initial preparation for an entire year to avoid seasonal variations of infections, along with strict monitoring to confirm its effectiveness.

However, children with low IgG subclasses levels are likely to improve with time, and many affected children will return to normal levels with time. Due to this reason, measuring the IgG subclasses in children is embarked only in exceptional circumstances.

In addition, most affected children require only intermittent or prophylactic antibiotics.

Can Immunization With Vaccines Be Done in Children With IgG Subclass Deficiency?

Most vaccines are safer to administer to children with low IgG subclass levels in cases where other immune function tests are regular. The doctor will follow the regular infant and childhood vaccination schedule. However, in children in whom immunoglobulin replacement therapy is started, the doctor will not give further routine infant or childhood immunizations while this treatment continues.

Conclusion:

IgG subclass deficiency is characterized by the lack of specific IgG subclasses, which can result in recurrent respiratory infections. The diagnosis of it involves blood tests for IgG, IgM, and IgA, while management varies based on symptom severity. However, many individuals with this deficiency may not require regular treatment.

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Dr. Veerabhadrudu Kuncham
Dr. Veerabhadrudu Kuncham

Pediatrics

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