Deficiency of IgG subclasses: causes, symptoms, diagnosis, treatment

A condition in which the deficit of one of the IgG subclasses is determined at a normal or reduced level of total immunoglobulin G is called a selective deficiency of the IgG subclass. Often there is a combination of deficits in several subclasses.

Pathogenesis

The molecular mechanism of defects of subclasses is not known, however, defects of transcription factors, translation, and anomalies of post-transcriptional modifications are possible. Several patients described deletions of the genes of the heavy chain gamma1-gamma4 and alpha 1.

The nature of clinical manifestations of defects in subclasses of IgG largely depends on their functional characteristics. For example, with the primary immune response after synthesis of IgM, IgGl and IgG3 are synthesized, and IgG2 and IgG4 are synthesized with a secondary immune response. IgG2 is predominantly synthesized in response to polysaccharide antigens, tetanus antibodies refer primarily to the IgGl subclass, and specific antibodies in patients with filariasis and schisto-oomatosis belong to IgG4.

Symptoms of IgG deficiency

Isolated or combined deficiencies of IgG1, IgG2 or IgG3 subclasses are associated with an increased risk of infection with various respiratory tract infections (sinusitis, otitis, rhinitis). Basically, these patients do not have life-threatening infections. Low values of IgG4 are quite common in children, but in most cases it does not manifest themselves as relapsing infections. However, the combination of deficiency of IgG2 and IgG4 subclasses leads to frequent infectious diseases.

Given the fact that other subclasses (in particular, IgG2) also lack clinical manifestations, there is an opinion that the combination of subclass deficiency and the formation of specific antibodies is clinically significant.

And, although the clinical data associated with deficiency of IgG subclasses are heterogeneous, there are some symptoms inherent in the decline of a certain subclass.

IgG1 deficiency

IgG1 deficiency is often associated with insufficiency of other subclasses and, as a rule, is accompanied by a decrease in total IgG. Often, the IgG1 deficiency is classified as General Variable Immune Deficiency, especially in combination with a decrease in other subclasses. Often such patients have a long history of the disease with various bacterial infections, persistent or progressive lung disease.

IgG2 deficiency

Often, but not always, IgG2 deficiency is combined with a decrease in IgG4 subclass and IgA deficiency. In children with frequent respiratory infections and IgG2 deficiency, the synthesis of antibodies to polysaccharide antigens is almost always reduced. In addition to infections of the respiratory tract, these children have recurrent meningitis caused by Neisseria meningitidis or pneumococcal infections. At the same time, many patients in immunological status do not have any abnormalities, the total IgG does not decrease.

LgG3 deficiency

Antibodies synthesized to protein antigens {including virus proteins) belong to IgG1 and IgG3 subclasses. IgG3 antibodies are the most effective in antiviral protection. Deficiency of this subclass is associated with relapsing infections, often leading to chronic lung diseases. According to a study in Sweden, IgG3 subclass deficiency is the most common among patients with recurrent infections. Thus, among the 6580 patients examined, 313 patients with subclass deficiency were identified. Of these, 186 had a deficiency of IgG3,113 - deficiency of IgG1, 14 - deficiency of IgG2, and 11 - a decrease of IgG3 and IgG4.

LgG4 deficiency

The diagnosis of IgG4 deficiency is 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 when the subclass level is below 0.05 mg / ml, while children with such a defect often suffer from severe respiratory tract infections. There are reports of the development of bronchoectaemia in such patients.

Virtually all patients with IgG4 deficiency have normal values of total IgG, other subclasses, IgA, IgM and IgE. Only in some cases, the deficit of IgG4 is combined with IgG2 and IgA deficiencies.

Diagnosis of IgG deficiency

In many cases, the diagnosis is problematic, because, for example, the IgG4 level may be below the resolving power of the method used to determine it, and IgG1 deficiency is often identified as hypogammaglobulinemia G. Therefore, this diagnosis is made when there is a decrease (below 2 standard deviations from the median age) of one or more IgG subclasses, including patients with reduced total IgG at normal IgM and IgA values and children with impaired antibody formation.

Treatment of IgG deficiency

In most children with IgG subclass deficiency, the number of respiratory infections decreases with age. Such children do not need additional therapy. With the persistence of frequent and severe infections, especially in children with a concomitant defect of specific antibody formation, therapy with intravenous immunoglobulin is possible. However, as a rule, these patients do not need lifelong replacement therapy.

Forecast

In most people with persistent laboratory defects with age, the number of infectious manifestations is significantly reduced. However, in some patients with a deficiency of subclasses of IgG, the development of CVID is noted, and therefore children with this pathology require follow-up.