Hereditary deficiency of the seventh component of complement and recurrent meningococcal infection: investigations of an Irish family using a novel haemolytic screening assay for complement activity and C7 M/N allotyping

Abstract

Terminal complement component deficiency predisposes to meningococcal infection and is inherited in an autosomal co-dominant manner. An Irish family is described, in which 2 of 3 brothers had recurrent meningococcal infection. A novel screening assay was used to investigate for terminal complement deficiency and the 2 affected brothers were found to be completely deficient in the seventh component of complement (C7). Enzyme-linked immunosorbent assay for C7 revealed lower than normal levels in the remaining brother and parents. C7 M/N protein polymorphism allotyping, used to investigate the segregation of the C7 deficiency genes, showed that the apparently complement sufficient brother was heterozygous C7 deficient and a carrier of one of the deficiency genes. Complement screening should be carried out in any individual suffering recurrent meningococcal infection or infection with an uncommon meningococcal serogroup. Identification of complement deficient patients allows the implementation of strategies to prevent recurrent infection.

C7 deficiency in an Irish family: a deletion defect which is predominant in the Irish

“…In family A, subjects II.1 and II.4, both C7 deficient, have not to date developed meningococcal infection, highlighting that deficiency is not incompatible with apparently normal health [5]. Diagnosis of underlying deficiency in patients presenting with meningococcal infections does allow appropriate precautions to be taken to minimize the risk of further infections [25]. DNA polymorphisms can be detected irrespective of whether the sequence change affects the phenotype, and prior knowledge of the molecular defect responsible for the deficiency is not required.…”

“…Total functional complement activity and C7 functional activity in the serum of members of family A were tested by haemolytic assays and double diffusion haemolytic assays in 1% agarose gels [6,25].…”

C7 complement deficiency in an Israeli Arab village

“…Deficiencies of terminal complement components (TCC), particularly of C5, C6, C7, and C8, are often detected because of increased susceptibility to Neisserial infections [Ross and Densen, 1984]. Much of the literature is comprised of surveys in various communities of patients with meningococcal infections who were subsequently tested for terminal component deficiencies [Eng, 1980; Ellison et al, 1983; Merino et al, 1983; Beatty et al, 1986; Leggiadro and Winklestein, 1987; Orren et al, 1987; Rasmussen et al, 1987, 1988; Zimran et al, 1987; Brai et al, 1989; Rogde et al, 1990; Schlesinger et al, 1990; Platonov et al, 1993; Egan et al, 1994]. Of interest is the nonuniform association between any specific geographic/ethnic group and meningococcal diseases.…”

Expression Profiling of the Cellular Processes in Uterine Leiomyomas: Omic Approaches and IGF-2 Association with Leiomyosarcomas

“…C7 is a component of the complement system. People with down-regulated C7 are prone to recurrent bacterial infections (22). As with other chemokines, the protein encoded by CCL21 inhibits hemopoiesis, and stimulates chemotaxis.…”