HLA-B27 and Ankylosing Spondylitis geographic distribution as the result of a genetic selection induced by malaria endemic? A review supporting the hypothesis
Section snippets
Worldwide distribution of HLA-B27
The observation of a non-homogeneous geographic distribution of HLA-B27 has been reviewed by Khan [5]. In fact, there is evidence for a latitude-dependence of the HLA-B27 frequency among world populations, with the lowest value (0%) in the equatorial area and the highest (40%) in the Arctic and farthest North lands [6], [7]. Accordingly, Ankylosing Spondylitis (AS) and other HLA-B27-associated diseases, show a similar distribution. This is compatible with the hypothesis that environmental
The spreading of HLA-B27 subtypes on the light of the proposed hypothesis
Disappearance of the selective pressure exerted by malaria in some geographic areas has left behind a number of gene variants which may eventually contribute to the spreading of new infectious diseases or to susceptibility to common complex diseases [23]. An example may be the resistance to malaria conferred by HLA-B53, and the susceptibility to AIDS associated with HLA-B35. In this context, it seems particularly informative the fact that B35PY subset, which differs only at position 116 from
Other genes within the HLA region may have contributed to the fixing of HLA-B27 variants
B⁎2709 and B⁎2705 in Sardinia are harboured by different extended HLA haplotypes which include also cytokine genes [31]. The association between severe cerebral malaria and TNFα (-308T and -857T) promoter polymorphisms has been reported in Africa and in East Asia, respectively [32], [33], [34], [35]. Noteworthy, in Sardinia -857T is in linkage disequilibrium with HLA-B⁎2705 whereas allele C co-occurs more frequently (95%) with the HLA-B⁎2709 [36]. It is possible that TNFα promoter polymorphisms
Concluding remarks
Genetic studies on HLA-B27 haplotypes carrying common B27 subtypes with a special attention to the TNFα promoter should shed some light on this hypothesis. Moreover, studies have shown that some malaria vaccines on trial are partially protective [38]. HLA typing of the non-responders may reveal a significant increase in some haplotypes, disclosing a more general issue that should be considered when vaccines are designed.
In conclusion, HLA genes for their function in antigen presentation are the
Take-home messages
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We hypothesize that the non-homogeneous distribution of HLA-B27 in the world populations, which is inverse to that of malaria endemic, is the result of a negative selective pressure exerted by P. falciparum.
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As a consequence of this selective pressure, a number of HLA-B27 variants have been fixed in areas where malaria was endemic.
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These HLA-B27 variants may have been selected because able to present relevant antigenic peptides from P. falciparum and/or because part of haplotypes carrying better
References (40)
- et al.
The HLA-A,B gene frequencies in the world: migration or selection?
Hum Immunol
(1980) - et al.
The epidemiology of malaria in Papua New Guinea
Trends Parasitol
(2003) - et al.
Genetic variability, molecular evolution, and geographic diversity of HLA-B27
Hum Immunol
(2001) - et al.
Allele-dependent similarity between viral and self-peptide presentation by HLA-B27 subtypes
J Biol Chem
(2005) - et al.
Multiple sclerosis and anti-Plasmodium falciparum innate immune response
J Neuroimmunol
(2007) - et al.
Malaria
Lancet
(2005) - et al.
The evolution of gene frequencies
- et al.
Heterozygote advantage for HLA class-II type in hepatitis B virus infection
Nat Genet
(1997) - et al.
Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA
Nature
(2004) - et al.
Genetics of susceptibility to human infectious disease
Nat Rev Genet
(2001)
HLA-B27 and its subtypes in world populations
Curr Opin Rheumatol
Spondyloarthropathies
Curr Opin Rheumatol
HLA-B27 polymorphism and worldwide susceptibility to ankylosing spondylitis
Tissue Antigens
Ankylosing spondylitis: prevalence and demography. Chapt.15: Spondyloarthropathies
HLA-B27 and ankylosing spondylitis geographic distribution versus malaria endemic: casual or causal liaison?
Ann Rheum Dis
Antigen and haplotype frequencies at three human leukocyte antigen loci (HLA-A, -B, -C) in the Pawaia region of Papua New Guinea
Am J Phys Anthropol
Swelling, spondylitis and spears
Ann Rheum Dis
HLA-B27, arthritis, spondylitis is an isolated community in Papua, New Guinea
Br J Rheumatol
Health impact assessments of malaria and Ross River virus infection in the Southern Highlands Province of Papua New Guinea
P N G Med J
HLA-B35 frequency variations correlate with malaria infection in Sardinia
Tissue Antigens
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2015, Seminars in Arthritis and RheumatismCitation Excerpt :Approximately one-third of patients will progress to severe disability [2]. The prevalence of AS, which ranges from less than 0.01% in Japan to 1.8% in Norwegian Samis (Lapps), tends to correlate with the prevalence of the HLA-B27 tissue type [3–5], but it varies substantially in epidemiologic reports from around the world [6]. The goal of AS treatment is to control symptoms and inflammation in order to prevent deformity and disability caused by new bone formation, and to halt or slow the decline in function and social participation, thus preserving patient quality of life (QoL) [7].