A high incidence of C9 deficiency among healthy blood donors in Osaka, Japan

Abstract

By the use of sucrose gelatin veronal buffer (SGVB), a simple screening test was developed by us to detect sera with low complement activity, including C9-deficient sera. Using this screening test, we were able to identify sera with low complement activity including C9-deficient sera among a large number of samples. Further examinations, estimation of the protein concentration of C9, C4, C3, etc., enabled classification of serum with low complement activity into C9-deficient serum, serum deficient in the other components, and serum with low complement activity caused by non-specific activation of complement through the classical pathway by low temperature in vitro. Among 145,640 sera from Osaka donors, 138 sera were found to be deficient in C9 by these methods. The whole complement activity (CH50) of the 138 sera was 13.1 +/- 3.0 U/ml. The C9 protein in these sera was undetectable, not only by the single radial immunodiffusion method, but also by the sensitive ELISA method. C9 activities in these sera were less than 0.1% of the level in pooled normal human serum. These findings and the family studies revealed that 138 blood donors unquestionably had a hereditary C9 deficiency. The incidence of C9 deficiency among Osaka donors was calculated to be 0.095%.

High prevalence of complement component C6 deficiency among African-Americans in the South-eastern USA

“…This is much higher than the 0´0025% prevalence of C6D calculated from our data for the white population of this region and the 0´0027% prevalence of C6D found previously for healthy Japanese blood donors [20]. Therefore, our estimated prevalence of C6D among African-Americans is similar to the most common complement component de®ciencies, C9D among Japanese and C2D among Europeans, which are estimated at 0´095% and 0´01%, respectively [24,25]. The epidemiological data on meningococcal meningitis in this County (Fig.…”

Molecular epidemiology of C9 deficiency heterozygotes with an Arg95Stop mutation of the C9 gene in Japan

“…The carrier frequency was calculated to be 6.7%. The estimated frequency of the C9 deficiency with the homozygous Arg95Stop mutation in our hospitalbased DNA study was 0.12%, which was similar to the frequencies of the C9 deficiency determined by serum studies, including both hospital-based (Hayama et al 1989) and blood donor-based (Fukumori et al 1989) studies. There were no significant differences in the incidence of C9 deficiency among the eight areas of the four main islands in Japan (Hayama et al 1989).…”

“…In Japan, it is one of the most frequent genetic disorders, with its incidence being approximately one in 1000 (Hayama et al 1989;Fukumori et al 1989), whereas only a few patients with C9 deficiency have been identified in European countries. Although most individuals with C9 deficiency appear to be healthy, our previous study ) demonstrated that the risk of development of meningococcal meningitis in C9-deficient individuals was much higher than that in normal individuals, based on the incidence of C9 deficiency among blood donors in Fukuoka and the number of C9-deficient individuals in that area who developed meningococcal meningitis.…”

Hepatitis C Virus Suppresses C9 Complement Synthesis and Impairs Membrane Attack Complex Function

“…Predisposition to meningococcal disease is strongly linked to the efficiency of complement-dependent bactericidal activity. An epidemiological study provided strong evidence for a relationship between C9 deficiency and meningococcal sepsis and meningitis (25). An Arg95 stop mutation of exon 4 in the complement C9 gene is common in individuals in Japan with C9 deficiency, and the lack of the membrane attack complex due to this mutation predisposed patients to pathognomonic glomerulonephritis (26).…”