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Mannose-binding lectin and meningococcal disease

1999; Elsevier BV; Volume: 354; Issue: 9175 Linguagem: Inglês

10.1016/s0140-6736(05)75241-7

1474-547X

Peter Garred, Hans O. Madsen, Arne Svejgaard, Terje E. Michaelsen,

Cystic Fibrosis Research Advances

Martin Hibberd and colleagues1Hibberd ML Sumiya M Summerfield JA Booy R Levin M the Meningococcal Research GroupAssociation of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease.Lancet. 1999; 353: 1049-1053Summary Full Text Full Text PDF PubMed Scopus (345) Google Scholar report an increased frequency of MBL variant alleles causing dominant decrease in the MBL serum concentration in English patients with meningococcal disease. In 1993, we reported a lack of association with low serum concentrations of MBL and tendency to meningococcal serogroup B (n=74) or serogroup C (n=25) disease in Norwegian patients (52 females) aged 12–21 years compared with controls.2Garred P Michealsen TE Bjunc G Thiel S Svejgaard A A low serum concentration of mannan-binding protein is not associated with serogroup B or C meningococcal disease.Scan J Immunol. 1993; 37: 468-470Crossref PubMed Scopus (34) Google Scholar These patients also took part in a national, randomised trial of vaccine efficacy against serogroup B meningococcal disease, which comprised 171800 students in Norwegian secondary school3Bjune G Høiby EA Grønneby JK et al.Effect of outer membrane vescicle vaccine against group B meningococcal disease in Norway.Lancet. 1991; 2: 1093-1096Summary Scopus (571) Google Scholar and 54000 military recruits. 119 individuals of the study population developed meningococcal disease during the 3-year observation period. Serum samples from 13 fatal cases were not available for the investigation. Among the 106 survivors, serum samples were taken from the 99 included patients, which were collected at least 6 months after the onset of disease. Because of the complexity of the MBL polymorphisms,4Garred P Madsen HO Svejgaard A Genetics of human mannan-binding protein.in: Ezekowitz RAB Sastry K Reid KBM Collectins and innate immunity. G Landes Company, Austin, TX1996: 139-164Google Scholar our serum measurement may not adequately reflect the MBL polymorphisms in the patients, which could explain the discrepancy between our results and those of Hibberd and colleagues. Therefore, our patients were asked to donate an additional blood sample for DNA analysis; 75 of the previously included patients agreed to take part in the genetic study. The overall frequency of MBL variant alleles in the patients with meningococcal disease was almost identical to that found in Norwegian controls (0·19 and 0·21, respectively, *Full data available from authors, on request *Full data available from authors, on request which lends support to the conclusion in our earlier study.2Garred P Michealsen TE Bjunc G Thiel S Svejgaard A A low serum concentration of mannan-binding protein is not associated with serogroup B or C meningococcal disease.Scan J Immunol. 1993; 37: 468-470Crossref PubMed Scopus (34) Google Scholar There were an excess of MBL-variantalleles homozygotes, in the English patients, but no excess in the Norwegian patients (1·3% vs 3% in the controls). In addition, no association was found with an MBL promoter allele in position -221 (X/Y), which is also associated with low MBL serum concentrations. Stratification in receipt of active vaccine versus placebo did not change the overall conclusion. The discrepancies between the English and the Norwegian studies are not clear. It may be argued that we studied only survivors and, thus, missed fatal cases who might have been deficient in MBL. However, in the English study, the patients homozygous for MBL variant alleles had a lower mortality rate and less use of intensive care than their MBL competent counterparts, which argues against such a bias in our patients. The English study comprised one hospital-based study (n=194, mean age 3·5 years) and one community-based study (n=72, mean age 15 years). In the Norwegian study the median age was 16 years. However, with stratification according to genotype, carriers of MBL variant alleles tended to be younger when they contracted meningococcal disease than those homozygous for the normal allele (median age 15 years and 17 years, respectively; Mann-Whitney, p=0·05). The MBL variant allele frequency in those below 16 years was 0·25, compared with 0·15 in those 16 years or older (Fisher's p=0·06). This result indicates that MBL may have an immune protective role against meningococcal disease in young patients, whereas it is less important in the older patients. This could partly explain the differences between the English and Norwegian findings. Thus, the MBL variant alleles did not contribute to the overall protection against meningococcal disease in Norwegian patients, but an age-dependent effect seems possible and needs to be further investigated, for example, in the community-based part of the study by Hibberd and colleagues. Mannose-binding lectin and meningococcal diseaseAuthors' reply Full-Text PDF