Rheumatoid Arthritis :: essays research papers

Rheumatoid arthritis is an inflammatory disease, chiefly of the joints, with autoimmune features and a complex genetic component.INHERITANCE Occasional families interpret a considerable number of cases of this common disorder. A simple Mendelian mechanism could not be proved, however. Indeed, some (Burch et al., 1964) could not demonstrate of import familial aggregation.Lynn et al. (1995) conducted family studies and segregation analyses of RA based on consecutive patients with RA ascertained without regard to family history or known chance factors. include in the analyses were first-degree relatives from 135 simplex and 30 multiplex families. A exceedingly penetrate recessive major gene, with a mutant allele oftenness of 0.005, was identified as the near parsimonious genetic risk factor. hearty evidence for heterogeneity in risk for RA was observed for proband sexual urge but not for proband age at onset. Kaplan-Meier risk analysis demo significant evidence for difference s in the distribution of risk among first-degree relatives. Although both proband sex activity and age at onset were identified as important risk factors, proband gender appeared to be the more important determinant of risk, with relatives of male probands having the sterling(prenominal) cumulative risk for RA. For future genetic analyses, Lynn et al. (1995) suggested that families with an excess of affected males having a young age at onset might be most informative in identifying the putative recessive gene and its modifiers. Hasstedt et al. (1994) studied 28 funds ascertained through pairs of first-degree relatives with RA. RA was confirmed in 77 pedigree members, including probands the absence of disease was verified in an additional 261 pedigree members. Members of the pedigrees were typed serologically for HLA. Analyses back up the existence of an HLA-linked RA susceptibility locus, estimated the susceptibility allele frequency as 0.0216, and estimated the lifetime penetra nce as 41% in male homozygotes and 48% in female homozygotes. Inheritance was recessive in males and was nearly recessive in females. In addition, the analysis attributed 78% of the variants with HLA genotypes to genetic or environmental cause shared by sibs. The genetic model inferred in this analysis was considered legitimate with previous association, linkage, and familial aggregation studies of RA. The inferred HLA-linked RA susceptibility locus accounted for virtually one-half of familial RA, although it accounted for only approximately one-fifth of the RA in the population. PATHOGENESIS In a T-cell receptor transgenic mouse model, an inflammatory arthritis that resembles human RA is initiated by T cells but is sustained by antibodies to GPI (172400).