Due to its strong association with
Ankylosing Spondylitis and the other
Spondyloarthropathies, the
HLA-B27 family of
alleles and, in particular, the ancestral HLA-B2705, has been the object of numerous studies. More recently, some novel interesting features have emerged such as the ability of
HLA-B27 to confer resistance to the progression of
HIV infection and to promote a spontaneous
CD8+ T
cell-mediated viral clearance of HCV. The co-occurrence of these protective and
pathogenic features suggests a common ground, i.e. to promote a more pronounced
immune/
inflammatory response leading to an effective clearance of some
pathogens on one side and to
autoimmunity on the other. This might be due to the
antigen presenting properties and/or to the co-inheritance of gene variants that contribute to an altered homeostasis in case of
microbial infections or tissue
injury. The existence of conserved HLA
haplotypes have since long been thought to result from a
selective pressure by some
pathogens that have edited the
immune response genes. The peculiar distribution of the ancestor HLA-B2705 along a latitude-dependent gradient and the opposite distribution of their variants have suggested a
correlation with endemic
malaria. In this respect, Sardinia, a small Mediterranean island plagued by
malaria, represents an interesting laboratory since its population is enriched in conserved HLA
haplotypes and several
genetic studies have disclosed their
correlation with infectious and
autoimmune diseases.
