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IgG subclass deficiency: causes, symptoms, diagnosis, treatment
Last reviewed: 07.07.2025

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A condition in which a deficiency of one of the IgG subclasses is determined with a normal or reduced level of total immunoglobulin G is called selective IgG subclass deficiency. A combination of deficiencies of several subclasses is often encountered.
Pathogenesis
The molecular mechanism of the subclass defects is unknown, but defects in transcription factors, translation factors, and abnormalities in post-transcriptional modifications are possible. Deletions of the gamma1-gamma4 and alpha 1 heavy chain genes have been described in several patients.
The nature of clinical manifestations of IgG subclass defects largely depends on their functional characteristics. For example, in the primary immune response, after the synthesis of IgM, IgGl and IgG3 are synthesized, and IgG2 and IgG4 are synthesized in the secondary immune response. IgG2 is mainly synthesized in response to polysaccharide antigens, antitetanus antibodies belong mainly to the IgGl subclass, and specific antibodies in patients with filariasis and schistosomiasis belong to IgG4.
Symptoms of IgG deficiency
Isolated or combined deficiencies of IgG1, IgG2 or IgG3 subclasses are associated with an increased risk of various respiratory tract infections (sinusitis, otitis, rhinitis). Mostly, these patients do not have life-threatening infections. Low IgG4 values are quite common in children, but in most cases do not manifest themselves in recurrent infections. However, a combination of IgG2 and IgG4 subclass deficiencies leads to frequent infectious diseases.
Considering the fact that selective deficiency of other subclasses (in particular IgG2) also often does not cause clinical manifestations, there is an opinion that the combination of subclass deficiency and impaired formation of specific antibodies is clinically significant.
Although the clinical data associated with IgG subclass deficiencies are heterogeneous, there are some symptoms that are specific to a decrease in a particular subclass.
IgG1 deficiency
IgGl deficiency is often associated with deficiencies in other subclasses and is usually accompanied by a decrease in total IgG. Often, IgG1 deficiency is classified as Common Variable Immunodeficiency, especially when associated with a decrease in other subclasses. Often, such patients have a long history of various bacterial infections, persistent or progressive lung disease.
IgG2 deficiency
Often, but not always, IgG2 deficiency is combined with a decrease in the IgG4 subclass and IgA deficiency. In children with frequent respiratory infections and IgG2 deficiency, a decrease in the synthesis of antibodies to polysaccharide antigens is almost always detected. In addition to respiratory tract infections, such children have recurrent meningitis caused by Neisseria meningitidis or infections caused by pneumococcus. At the same time, many patients have no deviations from the norm in their immunological status, and total IgG does not decrease.
LgG3 deficiency
Antibodies synthesized to protein antigens (including viral proteins) belong to the IgG1 and IgG3 subclasses. IgG3 antibodies are the most effective in antiviral protection. Deficiency of this subclass is associated with recurrent infections, often leading to chronic lung diseases. According to a study conducted in Sweden, deficiency of the IgG3 subclass is the most common among patients with recurrent infections. Thus, among 6,580 patients examined, 313 patients with subclass deficiency were identified. Of these, 186 had IgG3 deficiency, 113 had IgG1 deficiency, 14 had IgG2 deficiency, and 11 had a decrease in IgG3 and IgG4.
LgG4 deficiency
The diagnosis of IgG4 deficiency is quite difficult to establish, since the level of this subclass in children is normally quite low and is not determined by standard methods. IgG4 deficiency is said to occur when the subclass level is below 0.05 mg/ml. At the same time, children with such a defect often suffer from severe respiratory tract infections. There are reports of the development of bronchiectasis in such patients.
Almost all patients with IgG4 deficiency have normal levels of total IgG, other subclasses, IgA, IgM, and IgE. Only in some cases is IgG4 deficiency combined with IgG2 and IgA deficiencies.
Diagnosis of IgG deficiency
In many cases, making such a diagnosis is problematic, since, for example, the IgG4 level may be below the resolution of the method used to determine it, and IgGl deficiency is often identified as hypogammaglobulinemia G. Therefore, this diagnosis is made when there is a decrease (below 2 standard deviations from the mean age value) in one or more IgG subclasses, including patients with reduced total IgG with normal IgM and IgA values and children with impaired antibody formation.
Treatment of IgG deficiency
In most children with IgG subclass deficiencies, the number of respiratory infections decreases with age. Such children do not require additional therapy. If frequent and severe infections persist, especially in children with an associated defect in specific antibody formation, therapy with intravenous immunoglobulin may be possible. However, as a rule, these patients do not require lifelong replacement therapy.
Forecast
In most people with persistent laboratory defects, the number of infectious manifestations decreases significantly with age. However, some patients with a deficiency of IgG subclasses develop CVID, which is why children with this pathology require follow-up observation.
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