Genetics & Arthritis Research - Genetics and Arthritis

Genetics & Arthritis Research

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Group Leader
Jácome Armas

We have identified in Terceira Island, the Azores, twelve families that are multiple affected with musculoskeletal ectopic calcifications(EC) (Bruges Armas J, et al. 2006). The pattern of calcifications allowed the classification of these patients as DiffuseIdiopathic Skeletal Hyperostosis (DISH), Condrocalcinosis (CC) or both. EC wereidentified in axial and / or peripheralskeleton, and main symptoms were axial pain, elbow, knee and metacarpophalangeal joint pain, swelling, and / or deformity, and radiographic enthesopathic changes. The pattern of disease transmission was compatible with an autosomal-dominant monogenic disease. Some findings, mainly in the axial skeleton were quite similar toAnkylosing Spondylitis (AS), another inflammatory rheumatic disorder, characterised also by enthesopathic axial skeleton ectopic calcifications. The search that is going on through a genome-wide screening in these families may bring new light on the genes involved in the mechanisms of ectopic calcification in bothdiseases. Also, and in collaboration with an Oviedo group (Lopéz-Larrea C. et al. 2006), we have identified an association between the Killerimmunoglobulin-like receptor genes (KIR)and AS. Genome scans have identified regions in chromosomes 2q, 6p, 6q, 10q,11q, 17q, and 19q in AS. KIR genes encode a group of proteins that are expressed in natural-killer cells and in some T cells that act as receptors recognising major histocompatibility complex (MHC) class Imolecules and are directly involved in the activation and inhibition of NK and CD8+ Tcells. Comparing HLA B27 AS patients and controls in both populations (Spanish and Azorean) we found that the KIR3DL1 gene was found to be decreased in AS patients compared with B27-positive controls. On the HGGD Genetics & Arthritis Research Report 2006/2007100contrary the KIR3DS1 allele was over represented in the AS group compared withB27-positive controls. Further we classified the HLA-B alleles of the subjects studied according to the presence of the Bw4/Bw6epitopes. We found that the inhibitory3DL1/Bw4-I80 genotype was found to be increased in the control groups compared with patients in both populations. We also find that B alleles in trans position with aBw4 -I80 combined with 3DS1 (3DS1/B27genotypes with Bw4-I80 in trans) was increased in AS patients when compared with controls in both populations. Both KIR3DS1/3DL1 genes are polymorphic and it has been described that this polymorphism mayinfluence the expression or the inhibitory effect of the different alleles. These findings may be important for the understanding of the role of these genes in the susceptibility to AS.

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