Analysis of the 8.1 ancestral MHC haplotype in severe, pneumonia-related sepsis

Ancestral haplotype 8.1 and lung disease severity in European cystic fibrosis patients

“…The frequency of 8.1AH carriers did not change markedly with age (trend test, P =0.18). FEV 1 % predicted was smaller in 8.1AH carriers in each country and age class except in UK patients aged [26][27][28][29][30], with little heterogeneity among age classes and countries (Cochran's Q statistic for heterogeneity, P = 0.99).The random-effect pooled difference showed that 8.1AH carriers had significantly lower FEV 1 % predicted overall (P b 0.04, mean FEV 1 percent predicted difference, carriers vs. non carriers −6.4% CI95% [−12.4%, −0.5%], Fig. 1).…”

“…They concluded that the excessive inflammatory response associated with the 8.1AH may influence the defense system efficiency against some microorganisms. Another recent study also suggests a protective effect of 8.1AH carriage in a healthy population with severe pulmonary infection [30]. Several alterations of the immune response have also been shown to be correlated to AH 8.1, and even immunoglobulin (Ig) levels seem to be influenced by this haplotype [31,32].…”

Genomic evaluation of HLA‐DR3+ haplotypes associated with type 1 diabetes

“…Dominant selection of AH8.2 over AH8.1 in North Indians is analogous to the dominant selection of AH8.1 in Caucasians. In the latter, AH8.1 haplotype has recently been shown to confer protection against progression to bacterial infections as evidenced by the delayed bacterial colonization in cystic fibrosis . This could at least in part explain its high frequency in Caucasian populations.…”

“…In the latter, AH8.1 haplotype has recently been shown to confer protection against progression to bacterial infections as evidenced by the delayed bacterial colonization in cystic fibrosis. 29 This could at least in part explain its high frequency in Caucasian populations. It is conceivable that novel haplotypes generated through multiple recombination events and selection may eventually prove to be beneficial to the population against a recently introduced pathogen.…”

Inheritance of the 8.1 ancestral haplotype in recurrent pregnancy loss

“…The 8.1AH is remarkably long, spanning 2.9 MB and has >99.9% conservation [ 1 ]. It has been suggested that the high prevalence of the haplotype in Caucasian populations is due to increased resistance to infections, as the 8.1AH has been associated with a longer time to permanent infections with bacteria in the lungs of patients with mucoviscidosis (cystic fibrosis) [ 2 , 3 ] and a protective role against multi-organ failure (septic shock) in patients with blood infection (sepsis) due to bacterial lung infections (pneumonia) [ 4 ]. However, it also leads to an increased susceptibility to HIV and a higher frequency of progression to AIDS [ 5 ] and risk of field fever (leptospirosis) [ 6 ].…”