Defects of congenital immunity and complement system

Defects of the complement system are the rarest variety of primary immunodeficiency states (1-3%). Hereditary defects of almost all components of complement are described. All genes (except for the gene forperdin) are found on autosomal chromosomes. The most common deficiency is the C2 component. Defects of the complement system are different in their clinical manifestations.

In general, defects of early complement fractions (C1-C4) are accompanied by a high incidence of autoimmune diseases, including systemic lupus erythematosus, infectious manifestations in these patients are rare. It is believed that the association of defects of complement components with the development and severity of systemic lupus erythematosus depends on the position of the defective component in the activation cascade. Thus, the homozygous deficiency of Clq, Clr or Cls, and also C4 is associated with the risk of developing systemic lupus erythematosus in 93%, 57% (for Clr and Cls together), and 75%, respectively. The probability of developing systemic lupus erythematosus with a deficiency of the C2 component is, according to different data, from 10% to 50%. There is an association of hereditary angioedema and systemic lupus erythematosus: the excess proteolysis of C4 and C2 in the absence of the C1 inhibitor probably leads to the acquired deficiency of C4 and C2, which increases the risk of systemic lupus erythematosus in these patients.

Defects of terminal components (C5-C9) predispose to the development of severe infections caused by representatives of the genus Neisseria. This is due to the fact that Neisseria is able to survive intracellularly, so cell lysis with the help of membrane-attack complex is the main mechanism for the destruction of this microorganism. In some parts of the world, where the meningococcal infection is highly endemic, a high incidence of patients with a deficiency in the components of the membrane-attack complex is revealed.

Deficiency of the C3 component often resembles humoral primary immunodeficiency states and is accompanied by severe recurrent infections: pneumonia, meningitis, peritonitis. On the other hand, some patients with deficiency of C2, C4, C9 may not have any clinical manifestations.

Deficiency of the function of mannose-binding lectin (MBL) leads to increased sensitivity to infections caused by bacteria with the terminal mannose group. The low level of MBL in children with frequent infections suggests that the mannose-binding lectin activation pathway is important between the decrease in passive immunity acquired from the mother and the development of one's own acquired immunity. Interestingly, in some groups there is a high prevalence of dominant alleles of the MBL gene leading to a low level of protein expression. Perhaps these people, defects noted in early childhood, have advantages in the future. Thus, there is evidence that a low level of MBL protects against mycobacterial infection. In patients with leprosy, a high level of MBL was revealed in comparison with their healthy compatriots.

The deficiency of the C1-inhibitor of complement, whose clinical manifestation is hereditary angioedema, stands apart.

In most cases of complement defects, etiopathogenetic and substitution therapy is not possible, due to the symptomatic therapy of the corresponding manifestations of deficits.

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