Immunodeficiencies due to insufficiency and weakening of the function of proteins of the complement system.

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Insufficiency of complement is no more than 2% of all primary immunodeficiencies. Most primary defects of one or more components of the complement system are inherited by an autosomal recessive trait and are manifested by a violation of opsonization, phagocytosis, and destruction of microorganisms.

It is accompanied by severe infections, up to sepsis. Insufficiency of complement is often observed in autoimmune diseases, for example, SLE (systemic lupus erythematosus).

Individuals with a C2 defect component are susceptible to diseases caused by encapsulated bacteria (eg S. pneumoniae).

Persons with a defect in the C3 component are predisposed to infections caused by pyogenic bacteria that activate the complement system through a lectin-mediated and alternative pathway (encapsulated bacteria, S. aureus, etc.), and also due to the opsonization of the phagocytosis object.

Persons with deficiency of the final components of complement activation (C5-C9) and also components of the alternative pathway - factor D and properdin are susceptible to infections caused by two species of Neisseria - N. gonorrhoeae and N. meningitidis. Persons with this pathology are very susceptible to inflammation of the meningitis caused by N. meningitidis. This also indicates that the presence of a membrane-attack complex is extremely important for protection against bacteria that are outside the target cells. This is confirmed by the fact of a 10 000-fold increase in the incidence of meningitis in persons who have genetic defects in the membrane-attack complex.

Since the early components of the complement system (C1q, C1r and C1s, C4 or C2) normally participate in the elimination of immune complexes and cells undergoing apoptotic death, their defect may lead to the development of autoimmune diseases, manifested, for example, in lupus-like syndrome.

The most severe clinical manifestations have a violation of complement functions associated with a deficiency of C1 inhibitor, which leads to hereditary angioedema. The disease is transmitted as an autosomal dominant trait. The inhibitor C1 blocks not only the classical pathway of complement activation, but also inhibits the activity of the elements of the kinin and plasmin system associated with it, as well as the blood coagulation system. The development of angioedema is caused by the accumulation of peptides C5a and C3a, which have a strong vasotropic effect and contribute to an increase in the permeability of capillaries. Accumulation of large fragments participating in the cascade of complement reactions is neutralized due to the active work of the complement control system.

It should be noted that the defect of a number of complement components does not lead to clinical manifestations, as it is overlapped by other components of this system. For example, the defect of components C1 and C4 does not lead to an increase in susceptibility to bacterial infections, since the complement system can also be activated by alternative and lectin-mediated pathways.

Thus, defects in the components of the complement system are accompanied by a decrease in resistance to certain infections (in particular, neisserial) and immunocomplex pathology with lupus syndrome. There is a certain selectivity in the relationship between the breakdown of genes of specific groups of factors and types of disturbances. For example:

1) a decrease in resistance to infection by Neisseria is characteristic for defects in the factors of the alternative complement pathway, as well as late components;

2) immunocomplex lesion is inherent in defects of early factors of the classical pathway;

3) in case of NW deficit all characteristic types of lesions are combined, which reflects the key position of this factor in the complement system.

Attention is drawn to the insignificance of the consequences of the disturbance of the lytic phase of complement activation (resistance only to Neisserias decreases, and genetic defects of factor C9 do not appear clinically at all), which obviously reflects the "modest" significance of the corresponding mechanism in immune defense.