Inherited complement deficiency states: implications for immunity and immunological disease

Abstract

The study of complement deficiency states and their influence on immune function has generated new insights and still provides a challenge to continued investigation. The association of classical pathway deficiencies (C1, C4, C2 or C3) with immunological diseases such as SLE and glomerulonephritis has contributed to current knowledge concerning complement‐dependent immune complex handling and elimination. Susceptibility to systemic infection with encapsulated bacteria is encountered in most forms of inherited complement deficiency. Recurrent neisserial infection is the only clinical manifestation clearly associated with defects of the mem‐branolytic sequence C5‐C9, while deficiency of properdin, a component of the alternative activation pathway, appears to predispose to nonrecurrent meningococcal disease. Inherited complement deficiency is rare, but the perspective is widened by the more common occurence of acquired defects in immunological diseases, and the apparent requirement for efficient complement recruitment in host defense. Another aspect is the possibility that complement deficiency might alleviate or prevent inflammatory symptoms. Notably, complement deficiency has not been reported in classical rheumatoid arthritis. Considerations of this kind would be refuted or modified by findings of complement deficiency in single patients.

Vaccination of patients deficient in a late complement component with tetravalent meningococcal capsular polysaccharide vaccine

“…Because the complement system interacts with the immune system [16][17][18] it is a priori possible that the immune response of LCCD patients to both capsuiar polysaccharide and other types of antigens would be impaired. Our data show that the median concentrations of antibodies to the four vaccine polysaccharides increased within the first week, reached their maximum in I month, and persisted elevated for at least 1 year after vaccination.…”

Low Concentrations of Immunoglobulin G Antibodies to Salmonella Serogroup C in C2 Deficiency: Suggestion of a Mannan‐Binding Lectin Pathway‐Dependent Mechanism

“…The question emerges if reduced immune responses, secondary to complement dysfunction, contributes to the decreased immunity encountered in conditions associated with impaired recruitment of C3 [10,11]. An important point is that immune responses to thymus-independent antigens mainly appears to require complement, when antigen is presented at low concentrations [1,12,32].…”

“…Deficiencies of the classical complement pathway (C1, C2, C4 and C3) are associated with infections caused by encapsulated bacteria [10,11]. The main reason for this is probably the reduced efficiency of opsonic and bactericidal defence mechanisms caused by complement dysfunction.…”

Molecular characterisation of 10 Dutch properdin type I deficient families: mutation analysis and X-inactivation studies

“…2 Properdin deficiency type I is characterised by complete absence of the properdin factor in the alternative pathway of the complement system. The two other types of properdin deficiency are characterised by serum properdin levels at less than 10% of normal values (type II) and normal concentrations of circulating dysfunctional properdin (type III).…”

“…10 It has been proposed that these extreme values are caused by uneven Lyonisation of normal and mutated X chromosomes. 2 In this study we have investigated the genetic defects leading to the type I properdin deficiency in 10 Dutch families. The inactivation status of the X chromosomes in carrier females was analysed in relation to the concentration of circulating properdin protein.…”