Early-Onset Pauciarticular Juvenile Rheumatoid Arthritis Associated with Human Leukocyte Antigen-DRw5, Iritis, and Antinuclear Antibody

The HLA-D region antigens DR5 (wll,w12), DRw6 (w13,w14), DRw8, DRw52, and DQwl have previously been shown to be increased in frequency in subsets of patients with juvenile arthritis. Since the HLA-D region is complex (composed of at least 3 subregions encoding multiple molecules, each in turn presenting multiple alloantigenic epitopes), we sought to clarify whether one strongly associated factor might explain the previous findings. To search for the pertinent HLA-D region stimulatory epitopes, alloreactive T cells were primed against DR5 and DRw6 haplotypes and cloned by limiting dilution. Three T cell clones and I alloantiserum met the criteria for significant association with juvenile arthritis on patient testing, including DR5, DRw6, and DRw8 haplotypes. Monoclonal antibody blocking revealed that all 4 recognized epitopes on DR subregion products. For 2 of the clones, the relative risks for JA (10.5 and 9.4) were higher than the risks with any other previously described typing reagents.

Section: Discussionmentioning

confidence: 79%

HLA–D region epitopes associated with juvenile arthritis. recognition by alloreactive t cell clones and alloantisera

Myers

Ball

Núñez

et al. 1987

“…They may serve, therefore, not only as genetic markers for the disease but also as important prognostic indicators in early disease, knowledge of which may eventually alter our therapeutic approach to this condition. The high frequency of HLA-DRS in those patients with severe anterior uveitis and the MS phenotype may be important in view of the recently reported increased incidence of this antigen in those patients with the chronic anterior uveitis of juvenile chronic arthritis (3). Such a small sample may be unrepresentative, however, and needs confirmation.…”

Section: Discussionmentioning

confidence: 96%

Immunogenetic factors in inflammatory eye disease. influence of hla–b27 and alpha₁‐antitrypsin phenotypes on disease expression

Wakefield

Breit

Clark

et al. 1982

The relationship between the nature and severity of inflammatory eye disease was analyzed with respect to HLA antigens and alphal-antitrypsin phenotypes. Using standard ophthalmologic criteria, we divided patients with anterior uveitis into acute, chronic (>3-month duration), bilateral, or recurrent disease. There was a significantly increased incidence of alphal-antitrypsinaeficient phenotypes in anterior uveitis, especially in those patients with severe (chronic, bilateral, or recurrent) disease. HLA-B27 acts as an independent predisposing factor: it was present in 22% of patients with their first attack of acute uveitis compared with 51% of patients with recurrent disease. Together, these genetic factors are present in 63% of patients with severe anterior uveitis and represent the most significant predisposing and prognostic factors so far detected.Despite extensive investigations, the pathogenesis of uveitis remains largely unknown. There is

“…It might also be relevant that an HLA gene associated with early onset pauciarticular J R A , HLABw35 (2,20) has been shown t o be increased in frequency in couples with infertility (21). In addition, when couples share HLA antigens, more commonly than expected there is an increased risk for recurrent fetal loss (22,23), although in an inbred human population the sharing of HLA antigens was associated with increased fertility (24).…”

Section: Discussionmentioning

confidence: 99%

Sex ratio and sibship size in juvenile rheumatoid arthritis kindreds

Aaron¹,

Fraser²,

Jackson³

et al. 1985

In a study of sibship size and sex ratio in juvenile rheumatoid arthritis, the anticipated sex ratios, including a marked female predominance in early onset pauciarticular disease and in polyarticular disease, were found. The size of the sibship showed a progressive excess of females prompted an examination of the sex ratio of JRA patients as a whole, and the sex ratio of their siblings. PATIENTS AND METHODSincrease with increasing age of the proband at onset of disease. In addition, the sex ratios of the sibs deviated from expected, among families where the proband's disease was characterized as either early onset pauciarticular or polyarticular in its presentation.Young children with juvenile rheumatoid arthritis (JIRA) presenting with a limited form of arthritis (pauciarticular) and with antinuclear antibody in their serum are predominantly female (1). In a recently reported series (2), 35 of 38 children selected for the preseince of iridocyclitis in addition to JRA were girls and in the majority, the arthritis started before 5 years of age. The female preponderance in these probands and the identification of several sibships with a marked The pedigrees of 327 white patients with JRA were examined. The probands met the American Rheumatism Association's criteria for diagnosis of JRA (3) and were classified into I of its 3 major clinical groups: pauciarticular, polyarticular, or systemic onset. The 327 patients were selected on the basis of their availability and willingness to participate, from approximately 500 patients of the Robert B. Brigham (now Brigham and Women's) Hospital in whom the diagnosis of JRA had been made. Twelve patients who did not want to be involved and approximately 160 not currently attending the JRA clinic and who could not be contacted were excluded from the study. The mean duration of followup was 12.2 years with a range of 3-55 years. Many patients participated in earlier clinical studies (4). Data on sex, age, and type of onset were obtained for each proband, and sex and age data were obtained for each member of the sibship. All sibs surviving the perinatal period were counted except half sibs, who were excluded. The early clinical evaluations were made by Drs. JS Stillman and PE Barry (4), and the more recent evaluations were made by 2 of the authors (JMJ and PAF). Data were gathered by retrospective chart analysis and by telephone inquiry. One member of the JRA clinic staff made the initial inquiry and another staff member made a confirmatory call 3 years later.For each JRA type (pauciarticular, polyarticular, systemic), the probands were tabulated by sex and age at disease onset (0-3,4-7,8-11, 12-16 years). Comparisons by sex were made of the age distribution of probands. If the age distribution differed between males and females, secondary analyses were conducted by regrouping age categories: early onset (0-7 years) versus late onset (8-16 years); within early onset (0-3 versus 4-7 years); and within late onset (8-11 versus 12-16 years).Next we counted siblings for each category...