Σάββατο, 25 Αυγούστου 2012

HLA B27,http://rheumatology.my/?p=1185

Less than 5% of individuals who are HLA B27 positive develop ankylosing spondylitis. However, in relatives of AS patients, who are HLA B27 positive, 20% of them will develop AS.

Although HLA B27 is the primary susceptibility gene in AS, it is not a pre-requisite for developing AS.  Homozygous HLA B27 tends to have a more severe disease as opposed to heterozygous HLA B27. The sensitivity of HLA B27 is also variable depending on the population in question. So local data may be important. Non-HLA genes may also have a role. There are other gene loci that may also be associated with AS, eg ERAP 1. Apart from ERAP1, IL23R polymorphisms or IL17 polymorphisms may have a role.

Here we are introduced to the existence of HLA B27 negative AS, where the diagnosis is delayed by 11.5 years as opposed to 8.5 years. In those who are HLA B27 negative, screening other HLA regions HLA B60 may yield positive results. There are 70 HLA B27 subtypes with HLA B2*705 being the most common. HLA B2*706 and HLA B2*709 is not associated with AS however.

HLA B27 misfolding has been implicated in disease pathogenesis.  HLA-B27 misfolding is associated with Endoplasmic Reticulum stress that results in activation of the Unfolded Protein Response(UPR).
Turner et al, HLA-B27 Misfolding in Transgenic Rats Is Associated with Activation of the Unfolded Protein Response, The Journal of ImmunologyAugust 15, 2005 vol. 175 no. 4 2438-2448

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