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

Abstract

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.

Recent advances in the understanding of Dupuytren’s disease

“…It has been suggested that DD is a T cell–mediated autoimmune disorder, largely based on the discovery of dense T-cell infiltrates in DD nodules 24 . Other studies have confirmed the presence of different T-cell populations in nodules, including T helper cells 27 . A recent study showed the presence of an activated T-cell infiltrate adjacent to blood vessels within the nodules and these cells expressed a restricted T-cell receptor repertoire in vitro .…”

Pathogenetic and clinical significance of fungal infection of the palmar aponeurosis in Dupuytren's contracture

“…Группы сопоставимы по клинико-демографическим характеристикам, но достоверно отличаются по частоте ранних рецидивов контрактуры Дюпюитрена, что свидетельствует о патогенетически значимой роли грибковой инвазии как повреждающего фактора, инициирующего активность фасциального фиброматоза. Характерные для болезни Дюпюитрена иммуногенетические особенности [28] формируют общие (системные) факторы риска грибковой инвазии. Вовлечение в фиброматозный процесс кожи [29] нарушает её барьерные свойства и создаёт местные условия для внедрения возбудителей инфекции в глубже лежащие ткани.…”

Overview of the pathogenesis, diagnosis and treatment of Dupuytren's disease

“…A maternally transmitted inheritance pattern has been shown among Caucasian DD patients; 90% showed a mutation within the mitochondrial 16s rRNA gene [8]. Specific human leukocyte alleles, in particular the class II HLA-DR loci, are associated with a predilection for or protection against DD [9]. A study in 960 patients with Dupuytren's identified nine different loci involved in genetic susceptibility to the disease; six of these loci harbored genes encoding the Wnt signaling pathway [10], part of…”