RESUMEN
HLA-A,B,C,DR and DQ antigens were tested in 53 British Caucasian patients with polyarticular onset seronegative juvenile chronic arthritis (JCA); C4 allotypes were also tested in 46. A strong association with HLA-DRw8 was found (RR = 6.1, Fp = 7.6 x 10(-5)), with increased -B5(51) and C4A QO, and decreased -DR7 frequencies. DRw8 incidence correlated with an onset under 5 years, 9 of 12 DRw8+ cases being in this subgroup (Fp = less than 0.06), whereas B5 and C4A QO were prevalent in late onset (greater than or equal to 5 years). Erosions after 5 years associated with HLA-DRw6, and their absence with -Cw1 and -DR5. Genetic susceptibility factors and a further subdivision by onset age are thus demonstrated in this disease. Comparative data suggest that the genetic basis of susceptibility to early onset disease is similar to that of pauciarticular JCA.
Asunto(s)
Artritis Juvenil/inmunología , Complemento C4/análisis , Antígenos HLA-DR/análisis , Adolescente , Factores de Edad , Artritis Juvenil/genética , Artritis Juvenil/cirugía , Niño , Preescolar , Complemento C4a , Complemento C4b , Susceptibilidad a Enfermedades , Femenino , Estudios de Seguimiento , Tamización de Portadores Genéticos , Antígenos HLA/análisis , Subtipos Serológicos HLA-DR , Haplotipos , Prótesis de Cadera , Humanos , Lactante , Masculino , Factor Reumatoide/análisisRESUMEN
Amyloidosis is seen in a small number of patients with juvenile chronic arthritis (JCA). In order to determine whether particular HLA markers might predispose to the development of amyloid in JCA a group of 45 patients with amyloidosis confirmed by biopsy was typed for the HLA-A, B, C and DR loci. The results confirmed previous smaller studies that no HLA antigen detected by standard serological techniques was associated specifically with the development of amyloidosis. Those antigens which showed an altered frequency (ie. DR4 and DRw8) were known to be associated with the different types of JCA onset represented in this group.
Asunto(s)
Amiloidosis/complicaciones , Artritis Juvenil/complicaciones , Antígenos HLA , Amiloidosis/genética , Amiloidosis/inmunología , Artritis Juvenil/genética , Artritis Juvenil/inmunología , Frecuencia de los Genes , Antígenos HLA/genética , Humanos , InmunogenéticaRESUMEN
To investigate the genetics of susceptibility to early onset pauciarticular juvenile chronic arthritis (JCA), 158 unrelated ethnic British patients with a mean disease onset of 3.2 years, together with controls, were tested for HLA-A, B, C, and DR antigens. Additionally, 117 patients were also investigated for complement Bf and C4 markers. New observations included an increased frequency of the C4B 2 allotype (p corrected (pc) less than 0.02) and C4A 4,B 2 phenotype (p less than 0.0005). Findings suggested a unique increase of the haplotype HLA-DRw8, Bf*S, C4A*4, C4B*2, HLA-B39, possibly predisposing to more severe disease. Strong positive associations were confirmed with HLA antigens A2 (pc = 2.5 X 10(-8)), DRw8 (pc = 3.5 X 10(-14)), DR5 (pc less than 0.02), DRw52 (pc = 2.8 X 10(-6)) and DR5, w8 phenotype (pc = 3.9 X 10(-6)), and negative associations with DR7 (pc = 5.8 X 10(-7)), DR4 (pc less than 0.002), and DRw53 (pc = 0.004). Antinuclear antibody (ANA) seropositivity correlated with DR5 (p less than 0.02), and in children with chronic iridocyclitis (CIR) Bw62 incidence was raised (p less than 0.03) and B44 reduced (p less than 0.03). HLA-A2 was found in 88% of ANA+, CIR+ patients (p less than 0.01). A significant excess of DR5, w8 heterozygotes was present (relative risk = 41.1) and a lack of corresponding homozygotes. Results are inconsistent with a recessive, dominant, or intermediate mode of inheritance of susceptibility, and favour the existence of at least two DR linked 'disease' genes. Moreover, there may be an interaction in heterozygotes of combinatorial factors associated with DR5 and DRw8 in enhancing susceptibility. Possible immunogenetic mechanisms underlying the observed associations with three antigen classes are discussed. Evidence here suggests a role for the HLA-DQ locus in determining susceptibility to this disease.
Asunto(s)
Artritis Juvenil/genética , Complemento C4/genética , Factor B del Complemento/genética , Precursores Enzimáticos/genética , Antígenos HLA/genética , Factores de Edad , Anticuerpos Antinucleares/genética , Artritis Juvenil/complicaciones , Artritis Juvenil/inmunología , Niño , Preescolar , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lactante , Masculino , Fenotipo , Uveítis Anterior/etiologíaRESUMEN
This study of children with chronic arthritis confirms that patients at greatest risk for chronic iridocyclitis have a young age of onset and positive antinuclear antibodies (ANA). Children who are ANA negative have a low risk of iridocyclitis. When it occurs it is at a significantly older age. No child developing juvenile chronic arthritis over 9, even with positive ANA, had chronic iritis. There was remarkable variation in ANA titres; these correlated with erythrocyte sedimentation rate, active arthritis, and iridocyclitis. Maximum ANA titres were often seen very early in the disease but at this time were usually not associated with a poor prognosis. Histocompatibility antigens A2 and DRw8 were significantly increased, suggesting primary associations in pauciarticular arthritis with ANA. HLA-DR5 was associated with mild forms of arthritis and with absence of, or only mild, iritis. HLA-B15/w62 was associated with severe forms of eye involvement.