RESUMO
Autoinflammatory bone disorders are characterized by chronic non-infectious osteomyelitis and inflammation-induced bone resorption and result from aberrant activation of the innate immune system. Sporadic chronic non-bacterial osteomyelitis (CNO) is the most common disease subtype. The clinical picture is highly variable and the exact underlying pathophysiology remains to be determined. Recently, novel insights in the pathophysiology of sterile bone inflammation have been gathered by analyzing patients with rare, monogenic inflammatory diseases. In this overview CNO and Majeed syndrome, cherubism, hypophosphatasia and primary hypertrophic osteoarthropathy will be discussed. For the latter four disorders, a genetic cause affecting bone metabolism and leading to chronic bone inflammation has been described. The exact pathophysiology of CNO remains to be determined. Insights from monogenic autoinflammatory bone diseases and the identification of distinct inflammatory pathways may help to understand the pathogenesis of bone inflammation and inflammation-induced bone resorption in more common diseases.
Assuntos
Doenças Ósseas/genética , Doenças Ósseas/imunologia , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/imunologia , Anemia Diseritropoética Congênita/genética , Anemia Diseritropoética Congênita/imunologia , Animais , Reabsorção Óssea/genética , Reabsorção Óssea/imunologia , Querubismo/genética , Querubismo/imunologia , Doença Crônica , Predisposição Genética para Doença , Humanos , Hipofosfatasia/genética , Hipofosfatasia/imunologia , Síndromes de Imunodeficiência , Inflamação/genética , Inflamação/imunologia , Camundongos , Osteoartropatia Hipertrófica Primária/genética , Osteoartropatia Hipertrófica Primária/imunologia , Osteomielite/genética , Osteomielite/imunologia , Doenças Raras/genéticaAssuntos
Genes MHC da Classe II/genética , Genes MHC Classe I/genética , Osteoartropatia Hipertrófica Primária/genética , Adolescente , Adulto , Frequência do Gene , Haplótipos , Humanos , Imunofenotipagem , Teste de Cultura Mista de Linfócitos , Masculino , México , Osteoartropatia Hipertrófica Primária/imunologiaRESUMO
Fourteen patients with cystic fibrosis arthritis and eight patients with cystic fibrosis and hypertrophic osteoarthropathy were typed for HLA-A, B, C, DR, and DQ antigens and were compared with age and sex matched controls with cystic fibrosis. The diagnosis of cystic fibrosis arthritis and hypertrophic osteoarthropathy was confirmed by radiography and bone scanning. The prevalence of HLA-A, B, C, D, antigens in the cystic fibrosis group (44 patients) did not differ from that in the control group. A comparison between patients with cystic fibrosis arthritis or hypertrophic osteoarthropathy and their respective controls did not show any significant differences in HLA prevalence. It is concluded that HLA antigens may not be a factor in the susceptibility of patients with cystic fibrosis to cystic fibrosis arthritis or hypertrophic osteoarthropathy.
Assuntos
Artrite/imunologia , Fibrose Cística/imunologia , Antígenos HLA/análise , Osteoartropatia Hipertrófica Primária/imunologia , Adulto , Fibrose Cística/complicações , Feminino , Humanos , Masculino , Osteoartropatia Hipertrófica Primária/complicaçõesRESUMO
Recent evidence suggests that a key feature in the pathogenesis of hypertrophic osteoarthropathy (HOA) is an enhanced local platelet vessel wall interaction in the affected extremities. In our investigation we measured plasma levels of von Willebrand Factor Antigen (vWF:Ag; ELISA assay), a marker of platelet and/or endothelial activation, in 5 patients with the primary form of HOA and in 6 patients with the secondary form (due to cyanotic heart disease). Seven subjects matched for sex and age were used as controls. Patients showed statistically significantly higher levels of vWF:Ag in the primary (163.8 +/- 13.9%) and secondary form (152.6 +/- 9.6%, p less than 0.001 for both) when compared to controls (100.4 +/- 6.3%). Our results support the notion that platelet endothelial cell interaction may play a key role in the development of HOA.
Assuntos
Antígenos/análise , Osteoartropatia Hipertrófica Primária/imunologia , Adolescente , Adulto , Criança , Endotélio Vascular/patologia , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino , Osteoartropatia Hipertrófica Primária/sangue , Osteoartropatia Hipertrófica Primária/etiologia , Estatística como Assunto , Fator de von Willebrand/imunologiaRESUMO
Few syndromic associations with Crohn's disease are described. The aim of this study was to characterize a new syndrome of Crohn's disease associated with pachydermoperiostosis in 3 brothers. Three probands, 6 siblings, both parents, 20 of 21 third-generation relatives, and 9 spousal controls were evaluated. Serological evaluation for antineutrophil cytoplasmic antibodies and human leukocyte antigens as well as genetic testing for tumor necrosis factor microsatellites, intercellular adhesion molecule 1 polymorphisms, the interleukin 1 receptor antagonist gene, and the interleukin 1 beta gene were performed. Only the 3 probands were affected and developed pachydermoperiostosis between ages 14 and 17 years. Pachydermoperiostosis preceded Crohn's ileocolitis by 6 and 20 years in two probands, excluding secondary hypertrophic osteoarthropathy. Two probands were antineutrophil cytoplasmic antibody positive vs. 1 of 27 unaffected relatives (P < 0.001, chi 2). Haplotypes for human leukocyte antigen and tumor necrosis factor microsatellites were discordant. The probands' generation was homozygous for the common allele 1 of the interleukin 1 receptor antagonist and interleukin 1 beta genes. Two probands carried a rare polymorphism of the intercellular adhesion molecule 1 gene. A new syndrome of Crohn's disease and pachydermoperiostosis associated with antineutrophil cytoplasmic antibodies is described. Inheritance is most likely autosomal recessive by pedigree. No clear association was found between this syndrome and the gene regions evaluated.