What Is Complement Deficiency?

Almost every component of the complement system can be genetically defective. Most of the complement genetic defects are autosomal recessive, a few are autosomal dominant, and the properdin deficiency is X-linked recessive. Complement deficiency is often accompanied by immune disease and repeated bacterial infections. In general, the first front-end response components of the complement system, such as C1, C4, and C2 defects, are often accompanied by immune complex diseases, especially systemic lupus erythematosus (SLE); C3, H, and factor I deficiency increases Patients are susceptible to purulent bacterial infections, while patients with deficiencies in properdin, C5, C6, C7, and C8 are susceptible to severe naphtha infections.

Basic Information

Visiting department: Division of Rheumatology
Common causes: Autosomal recessive

Common symptoms: Repeated bacterial infections
Contagious: no

Epidemiology of hereditary complement deficiency

The incidence of complement defects is similar in men and women, but C2 defects are more common in women, and properdin defects are only found in men. The incidence of hereditary complement defects is 1 in 10,000 in the entire population. C2 genetic defects are the most common complement defects, and the incidence of C2 heterozygous genetic defects can be as high as 1%.

Causes of hereditary complement deficiency

Most of the complement genetic defects are autosomal recessive, a few are autosomal dominant, and the properdin deficiency is X-linked recessive.

According to genetic characteristics, genetic defects of complement can be divided into 4 categories: homozygous genetic defects, heterozygous genetic defects, complement protein dysfunction and complement defects caused by allotypes. The complement component is completely absent in patients with homozygous genetic defects, often showing serum-free total complement activity (CH50 activity), while other complement levels are normal; patients with heterozygous defects have a complement level that is half the normal level, and CH50 is also Half of the normal level, and other complement components are normal; complement protein dysfunction, the patient's blood complement level is within the normal range, and sometimes even higher than the normal level, but complement protein function is very low; allogeneic defects of complement are usually It is an autosomal codominant inheritance. In addition, complement defects can be divided into complete defects and partial defects. This is because of the regulatory characteristics of complement and the correlation between its structures.

In the clinic, although in most cases the level of complement components that are defective is significantly reduced or undetectable, while other complement levels are normal, there are some exceptions. For example, when homozygous C1r defects, the concentration of C1s is also reduced. Some patients with C2 deficiency are associated with reduced factor B levels, which is due to the high degree of structural homology between the complement protein of the primary defect and the complement protein of the secondary defect. In addition, the genes of the factor B and C2 are on chromosome 6 The upper positions are very similar, so it is also related to their similar regulatory mechanisms. In hereditary angioedema (HAE), the levels of C4 and C2 decrease, and the decrease of B factor and C3 levels when factor I and factor H are defective are Due to the excessive activation of classical and alternative pathways, the lack of complement components impairs the function of classical and / or alternative activation systems and the lack of antibody responses to T-cell-dependent antigens, resulting in prolonged viral infection or immune complexation in patients The presence of substances in the circulation is prolonged.

Clinical manifestations of hereditary complement deficiency

The possibility of complement defects should be considered when patients have recurrent bacterial infections, especially suppurative bacterial infections or Naderella infections. Complement hemolysis test CH50 and CH100 can determine whether there are functional defects of C1, C2, C3, C4, C5, C16, C7 and C8. In the absence of any of the above components, CH50 will decrease. CH50 is caused by hemolysis of sheep erythrocytes sensitized by antibodies in the presence of complement, so it is determined by the classical pathway component. Hemolytic tests using the hypoxia-containing rabbit red blood cells, the complement bypass pathway hemolytic activity (APH50) assay, can detect component defects in the bypass pathway. APH50 normally indicates the presence of factor B, factor D, properdin, C3 and C5-8. If the results of the above screening test show that the activity of CH50 is very low, the detection of each complement component is required. If a patient has a severe infection but no antibody deficiency or abnormal phagocytic cells, a CH50 test should be performed; if the CH50 test result is normal, an APH50 test should be performed; if the APH50 is very low or its activity cannot be measured, a factor B measurement should be performed. When factor H or factor I is lacking, there will be excessive consumption of factor B, and the primary defect of factor B has not been found so far. If a family history suggests an X-linked inheritance, it may be a defect in properdin, but the final diagnosis still requires a quantitative analysis of each complement component.

Hereditary complement deficiency

Complement hemolysis test CH50 and CH100 can determine whether there are functional defects of C1, C2, C3, C4, C5, C16, C7 and C8. In the absence of any of the above components, CH50 will decrease. CH50 is caused by hemolysis of sheep erythrocytes sensitized by antibodies in the presence of complement, so it is determined by classical pathway components. Defects in the alternative pathway components can be detected by a hemolytic test using rabbit erythrocytes with low sialic acid, or APH50. APH50 normally indicates the presence of factor B, factor D, properdin, C3 and C5-8. If the results of the above screening test show that the activity of CH50 is very low, the detection of each complement component is required. If a patient has a severe infection but no antibody deficiency or abnormal phagocytic cells, a CH50 test should be performed; if the CH50 test result is normal, an APH50 test should be performed; if the APH50 is very low or its activity cannot be measured, a factor B measurement should be performed. Because in the absence of factor H or factor I, there will be excessive consumption of factor B, and the primary defect of factor B has not been found so far.

Diagnosis of hereditary complement deficiency

Diagnosis can be based on medical history, clinical symptoms, and laboratory tests.

Treatment of hereditary complement deficiency

In general, the response to antibiotic treatment is good when complement defects are complicated by infection, but the fundamental treatment should be to correct complement defects. Some scholars use alternative treatments, that is, the purification of defective components is introduced into patients to correct defects. Substitute therapies can supplement the levels of defective complement components to normal levels and improve clinical symptoms. Some scholars use the method of inputting fresh plasma to treat complement defects, but theoretically, multiple infusions can cause patients to have an immune response as a potential danger.

There are more researches on the treatment of HAE. There are 3 measures to treat HAE: Promote the expression of human complement C1 inhibitor (C1INH) on normal chromosomes. The synthetic androgen danazol and Stanozolol can stimulate the synthesis of more normal chromosomes (C1INH). To return the C1INH level to normal. This treatment is very effective and can effectively control the outbreak. Reduce the consumption of C1INH by inhibiting the enzymes that interact with it. Tranexamic acid, a derivative of 6-aminocaproic acid, can inhibit the formation of plasmin by plasminogen, and can also activate C1 to some extent through its own decomposition pathway. Tranexamic acid is very effective in controlling the onset of HAE. Both of the above treatments are preventive treatments. The optimal treatment is to restore C1INH to normal levels by intravenous infusion. Purified C1INH is better than plasma.