Role of the HLA System in the Pathogenesis of Dupuytren’s Disease

Dupuytren’s disease (DD) is a familial, fibroproliferative, irreversible, and progressive disease of the palmar fascia, yet with unknown etiology. However, there is compelling evidence which has consistently suggested a genetic ethiopathogenesis given the high occurrence among the Northern European extraction, familial nature, and demonstration of concordance in twins. DD is an incurable, recurrent, and potentially debilitating disease with limited and ineffective treatments. Although a number of possible candidate genes have been investigated including matrix metalloproteinases (MMPs) and transforming growth factor-beta (TGF-β) genes, as yet, no consistent genetic biomarker has been identified for DD. The highly polymorphic human leukocyte antigen (HLA) region is an ideal biomarker target. There have been some coherent data within the literature to suggest a genotype to phenotype association between certain HLA loci and a number of fibrotic disorders such as keloid and scleroderma, markedly with class II molecules and disease pervasiveness and clinical progression. The aim of this review, therefore, was to investigate the evidence indicative of both positive and negative associations between particular HLA alleles and DD. There is a clear association with specific HLA alleles and predilection or protection to DD, though there is a pressing need for further supportive data. The most promising of links to the HLA region in terms of a definitive genetic biomarker is with the class II HLA-DR loci. This paper presents a detailed account of the immunogenetic component of DD and explores the possible mechanisms of association between specific HLA molecules and susceptibility to DD

Biomarkers, genetic association, and genomic studies

Rheumatoid arthritis (RA) is a common autoimmune disorder which shows clinical heterogeneity. IT has multiple treatment options and there is individual variation in response to treatment. These features make RA an ideal condition to develop biomarkers for its pre-clinical detection, diagnosis, subtyping, prognostic stratification and selection of most optimal treatment. While a number of markers have been assessed for their biomarker quality, currently no marker has the statistical properties of a biomarker to be considered as a good classifier. In this chapter, a general review of biomarkers is followed by a detailed discussion of biomarker candidates for various aspects of RA. It is unlikely that a single marker will ever be sufficiently powerful as a biomarker, but combinations of clinical, biochemical, genetic, epigenetic, proteomic and metabolomic markers have the strongest potential to fulfill the requirements of biomarkers. Given the high heritability of RA and the progress in methodology of genome-wide association studies, genetic markers are the most promising group to be developed as biomarkers, in particular when epigenetic markers become more widely used. It is possible that in the near future, biomarkers with documented clinical utility will be available for use in clinical decision making and will most probably use multiple omics platforms