Supplement Article |
OP3. IMMUNOGENETICS OF GCA AND PMR
Centre for Integrated Genomic Medical Research, The University of Manchester, UK
Giant cell (temporal) arteritis (GCA and polymyalgia rheumatica (PMR) are different but overlapping diseases. GCA is a common vasculitic syndrome in Western countries that involves the large and middle sized blood vessels with predisposition to the cranial arteries in the elderly. PMR is also a common condition of the elderly with symptoms of pain and morning stiffness involving the neck, shoulder and hip girdle, which are generally associated with a raised ESR. PMR is observed in up to 50% of patients with GCA.
The aetiology of these conditions remain unknown but are likely to represent dysregulation of an ageing immune system in genetically susceptible individuals. Both conditions represent complex clinical phenotypes and are likely to be due to the interactions of multiple genetic factors and environmental triggers.
Both GCA and PMR have been associated with HLA and other immunoregulatory candidate genes largely using case-control association studies. These have indicated that some genetic associations are restricted to GCA and others to just PMR. In contrast, some associations appear to be common to both. These may explain the overlap of phenotype in some patients.
To date, the selection of which candidate genes to test has come from what is known about the regulation of immune response and macrophage activation (cytokines, adhesion molecules, inflammatory molecules) and what has been identified from immunohistology (cytokines, metalloproteinases and gene expression profiling).
Other routes for genetic analysis such as performing linkage-based approaches are not possible in these conditions due to late age at disease onset and lack of suitable pedigrees. New whole genome based screening for disease genes by association using high density single nucleotide polymorphism arrays are now available. These approaches will be discussed.