Early predictors of longterm outcome in patients with juvenile rheumatoid arthritis: subset-specific correlations

OBJECTIVE: To determine early predictors of longterm outcome in juvenile rheumatoid arthritis (JRA) in a multicenter cohort. METHODS: Patients were selected if they were > or = 8 years of age; the onset of arthritis occurred > or = 5 years before study; and a diagnosis of JRA was made at a participating center. Outcome variables were scores on self-administered Childhood Health Assessment Questionnaires (CHAQ) and active disease duration. Possible explanatory variables assessed included characteristics present at onset, HLA alleles, in particular the rheumatoid arthritis associated shared epitope (RASE), and radiographic indicators of joint damage within 2 years of onset. Data for 393 patients were available. Multivariate analyses were performed for the total group and for each onset subtype. RESULTS: Male sex correlated with worse disability in systemic onset JRA but less disability in RF negative, and a shorter active disease duration in RF positive polyarticular onset JRA. Positive antinuclear antibody correlated with a longer active disease duration in patients with pauciarticular onset JRA. Younger age at onset predicted longer active disease duration in pauciarticular and RF negative polyarticular, and a shorter active disease duration in systemic onset JRA. Residence on a reserve, rather than native North American race, correlated with worse disability. The RASE correlated with less disability in systemic JRA; but no correlation with outcome was evident for patients with rheumatoid factor positive polyarticular JRA. CONCLUSION: Variables predictive of longterm outcome in JRA are specific for each onset subtype. The most important early predictors were age at onset and sex of the patient. Place of residence may have a greater effect on disability than race. RASE may associate with a more favorable outcome in systemic onset disease.     

Prognostic factors in juvenile rheumatoid arthritis: a case-control study revealing early predictors and outcome after 14.9 years

OBJECTIVE: To describe the physical and psychosocial outcome in patients with juvenile rheumatoid arthritis (JRA), compared with subjects in the general population, and to determine patient characteristics, HLA alleles, and disease variables within the first 6 months of disease onset that predict persistent disease, joint erosions, and physical disability. METHODS: A cohort of 268 (85%) of 316 patients with JRA first admitted to the hospital between 1980 and 1985 were examined after a median of 14.9 years (range 11.7-25.1) of disease duration. Controls matched for age, sex, and geographic region were randomly selected from the general population. Patients' medical records were retrospectively reviewed. Clinical examinations and radiographs of the hips, ankles, and affected joints were obtained. HLA-DRB1 and DPB1 alleles were determined by genotyping and HLA-B27 by serologic testing. Physical and psychosocial health status was assessed using the Short-Form Health Survey (SF-36) and the Health Assessment Questionnaire (HAQ). RESULTS: At followup, 133 patients with JRA (50%) were in remission, 63 (24%) had developed joint erosions, and 93 (36%) had impaired physical functioning (HAQ > 0.0). Patients had greater disability, more bodily pain, and poorer general health than controls. Comparable levels of education, social function, and mental health were found, but the patients had higher rates of unemployment than controls (19% vs 7%; p < 0.001). Predictors of persistent disease and joint erosions were: young onset age and large numbers of affected joints, long duration of elevated erythrocyte sedimentation rate (ESR), and positive IgM rheumatoid factor (RF) within the first 6 months. Additionally, persistent disease was predicted by the presence of DRB1*08, and joint erosions were predicted by symmetric arthritis and DRB1*08 and HLA-B27 in combination. DRB1*01 was a predictor of joint erosions in the pauciarticular onset type (n = 163). Predictors of physical disability were: female sex, symmetric arthritis, hip joint involvement, long duration of elevated ESR and IgM RF. CONCLUSION: Compared with healthy controls, patients with JRA had impaired physical health and lower employment rates after more than 11 years of disease duration. Elevated ESR, extensive and symmetric arthritis, positive IgM RF, DRB1*08, DRB1*01, HLA-B27 and DRB1*08 in combination, early onset, and female sex were early risk factors for an unfavorable outcome.     

Growth patterns in juvenile rheumatoid arthritis

OBJECTIVE: To define patterns of growth in juvenile rheumatoid arthritis (JRA) and to evaluate possible associated clinical and laboratory correlates. METHODS: The study population comprised 67 children with JRA who had been followed for 5 years or longer and whose follow-up period did not extend beyond 18 years of age. Height and weight z scores were calculated with reference to age-related standards for each of the annual follow-up intervals and correlated with JRA subtype, the presence of rheumatoid factor (RF), the erythrocyte sedimentation rate (ESR), alkaline phosphatase level (ALP) and medication history. RESULTS: Initial height-for-age (HAZ) scores for pauciarticular, polyarticular and systemic JRA onset groups (PaJRA, PoJRA and SJRA respectively) were +0.27, -0.07 and +0.40 respectively. A significantly lower HAZ score in the SJRA population compared to the PaJIA population first became apparent at year 2 and the difference was maintained throughout the 9-year follow-up period. A significantly lower HAZ score in the SJRA population compared to the PoJRA population first became apparent at year 6 and the difference was maintained until the ninth year. During the 9-year follow-up period, RF-positive children tended to have negative HAZ scores whereas RF-negative children tended to have positive HAZ scores. The SJRA onset group displayed significantly lower HAZ scores, as compared to the HAZ score at onset, for 7 of the 9 subsequent follow-up intervals. Only 2 patients had heights < 2SD below the mean at final determination. Delay in generalized linear growth occurred predominantly in the SJRA population and to a lesser degree in those with PoJRA associated with RF positivity. CONCLUSIONS: Delay in linear growth occurs in some children with JRA. Patients with pauciarticular and RF-negative polyarticular disease can have growth patterns similar to normal children. Children with RF-positive polyarticular and systemic JRA have more significant growth retardation that occasionally can be sustained and extreme.     

Declines in the range of motion and malalignment in hands of patients with juvenile rheumatoid arthritis studied over 6 years

Quantitative total joint scores including range of motion, malalignment, opposition of the thumb to the digits and combined distal-proximal-metacarpophalangeal joint flexion were determined in the hands and wrists of 56 patients with juvenile rheumatoid arthritis over six years. Most of the patients with duration of disease less than 5 years showed relatively normal hand function, reflected by low total and subtotal scores. However, significant declines of the respective variables reflected by pathological total and subtotal scores were seen in patients with duration of disease longer than 5 years. Decrease of the range of motion, total joint scores and malalignment were significantly correlated with the duration of disease.     

Age-specific effects of juvenile rheumatoid arthritis-associated HLA alleles.

OBJECTIVE: To define the onset and duration of effect of the HLA alleles that are associated with disease susceptibility and protection in juvenile rheumatoid arthritis (JRA) and 2 of its subtypes. METHODS: We typed 680 patients with JRA and 254 ethnically matched unrelated controls for HLA class I and II genes. The frequency of each allele was calculated for each of the age-at-onset, onset type, and sex categories and plotted against the allele frequency in the control population. Survival analysis (with onset of disease as the terminating event) was used to calculate the age by which 50% (St0.5) and 80% (St0.2) of the children with particular alleles and combinations of alleles develop disease. This allele-specific survival analysis also allowed for the comparison of the overall survival functions for the various JRA subtype and sex categories. RESULTS: Certain alleles are strongly associated with early susceptibility to pauciarticular JRA, including HLA-A2, DR8, DR5, and DPB1*0201. Fifty percent of the children carrying at least 1 of these alleles had disease onset prior to their third birthday. Among children who carried HLA-A2 and any 2 HLA-DR alleles (DR3, DR5, DR6, or DR8), the median age at the onset of pauciarticular disease was 2.7 years. Combinations of A2 and DPB1*0201 and one DR allele narrowed the window further to a median age at onset of 2.4 years. B27 and DR4 were associated with protection early in life but with increased risk later in childhood, with St0.5 values of 7.3 and 6.6 years, respectively, for pauciarticular JRA and St0.5 values of 10.2 and 10.7 years, respectively, for polyarticular JRA. Sex strongly influenced the age at which many of the alleles have their effect. CONCLUSION: These data define at what age and for how long various HLA alleles influence susceptibility and protection (window-of-effect) in patients with JRA. In addition, these data establish more clearly the boundaries of ages-at-onset for 2 of the subtypes of the disease.     

Chlamydial associated syndrome of arthritis and eye involvement in young children.

The current classification of juvenile rheumatoid arthritis (JRA) consists of several distinct subsets. We describe 6 children (2 boys, 4 girls, mean age 3.7 years, range 2.0-4.9 years) with arthritis and eye involvement associated with infection with Chlamydia trachomatis. In some of the children, the clinical picture was similar to early onset pauciarticular JRA: onset within the first 4 years of life, predominance of girls, pauciarticular arthritis, subacute uveitis, and presence of antinuclear antibodies. Joint involvement was pauciarticular in 4 patients and polyarticular in 2. Two patients had clinical symptoms of Reiter's disease. Further investigations of this post chlamydial associated syndrome should be performed to establish appropriate diagnostic, therapeutic and prognostic measures.     

Circulating immune complexes and antinuclear antibodies in juvenile rheumatoid arthritis

Materials with the Clq binding properties of soluble immune complexes (IC) were found in sera from 11 of 51 consecutive (22%) children with juvenile rheumatoid arthritis (JRA) and in 17 of 20 adults with active sero-positive rheumatoid arthritis (RA). IC appeared more frequently in children with systemic onset disease whereas antinuclear antibody (ANA) was found more frequently in sera from those with pauciarticular disease. Only 3 JRA sera contained anti-immunoglobulin (rheumatoid factor); those 3 also had high Clq binding activities. Seven of 50 patients (14%) carried HLA-B27 but B27 was not associated with high Clq binding activity or presence of ANA. The presence of free ANA more frequently in children with mild disease and IC more frequently in children with relatively severe disease suggests that children with systemic JRA may have a relative defect in antibody-forming capacity or reticuloendothelial function which results in decreased clearance of circulating IC. Alternatively, systemic, polyarticular, and pauciarticular JRA may represent a spectrum of clinically similar diseases resulting from different etiologic agents.     

Radiologic outcome and its relationship to functional disability in juvenile rheumatoid arthritis

OBJECTIVE: To determine the radiologic outcome in juvenile rheumatoid arthritis (JRA) and the relationship of radiologically detected joint damage to functional disability using multivariate analyses. METHODS: Selection criteria included a diagnosis of JRA made by 1977 American College of Rheumatology criteria, onset of arthritis > or = 5 years prior to study, current age > or = 8 years, a minimum grade 3 reading ability, and the availability of radiographs. Disability was measured by the Childhood Health Assessment Questionnaire (CHAQ) and Steinbrocker classifications. Radiographs taken within 2 years after onset (early) and the most recent radiographs (late) were examined by a single pediatric radiologist blinded to patients' identities, diagnoses, and outcomes. Multiple regression analyses were performed. RESULTS: On late radiographs the frequencies of joint space narrowing were 38, 14, 43, and 79%, respectively, among patients with systemic, pauciarticular, rheumatoid factor (RF) negative polyarticular, and RF positive polyarticular onset; erosions occurred in 63, 25, 39, and 75%, respectively. Early erosions were most frequent in patients with RF+ polyarticular onset, while both joint space narrowing and erosions occurred early in systemic onset. Radiologic signs of joint damage were most frequent at hips and wrists, while knees and ankles were relatively spared. Based on patients who had radiographs performed within one year of clinical study, 17.7% of the variation in CHAQ score was explained by joint space narrowing, 32.4% by pain, and 5% by a severe rating on physician's global estimate of disease activity. The odds of a Steinbrocker class > I were increased by joint space narrowing, pain, systemic onset, and active joint count. CONCLUSION: Differences in the frequencies and patterns of joint damage occur both among JRA onset subtypes and among individual joints. Radiographic damage, especially joint space narrowing, correlates with functional disability. However, pain is the major contributor to variation in CHAQ scores.     

DNA analysis of HLA-DR, DQ, and DP alleles in children with polyarticular juvenile rheumatoid arthritis.

HLA-DR, DQ and DP alleles were determined by restriction fragment length polymorphism analysis and oligonucleotide probe hybridization of polymerase chain reaction amplified genomic DNA in 94 Caucasian children with polyarticular juvenile rheumatoid arthritis (JRA) [13 rheumatoid factor (RF)+ and 81 RF-] and 100 healthy controls. HLA-DRw8, DQw4, DQA1*0401, DQB1*0402 were increased in frequency in those patients with RF seronegative disease, with highest frequencies seen in patients with young age at onset (< 5 years of age). These findings were similar to what we observed in children with pauciarticular JRA, especially those with young age at onset. DPB1*0301 was also found in increased frequency in the RF- group, and in particular those seronegative for antinuclear antibody. In contrast to what is observed in patients with pauciarticular JRA, the frequency of DPB1*0201 was not increased in any polyarticular JRA patient group. These data suggest that polyarticular JRA shares many genetic features with pauciarticular JRA.     

Disease course and outcome of juvenile rheumatoid arthritis in a multicenter cohort

OBJECTIVE: To determine the disease course and outcome in a multicenter cohort of patients with juvenile rheumatoid arthritis (JRA). METHODS: All patients with JRA seen at 3 pediatric rheumatology centers were identified from databases and/or clinic records. Inclusion criteria were a diagnosis of JRA (1977 American College of Rheumatology criteria), a followup period of at least 5 years since onset, and a minimum age of 8 years. Patients were examined and completed a Childhood Health Assessment Questionnaire (CHAQ). Kaplan-Meier curves were constructed to estimate rates of remission, relapse, and arthroplasty. Remission was defined as absence of active arthritis while off treatment for at least 2 years. Outcome measures were active disease duration, CHAQ scores, pain determined by visual analog scales, physician's global assessments, and Steinbrocker functional classifications. Years of education and employment status were ascertained. RESULTS: We studied 392 patients of 652 (60%) who met the selection criteria. The probabilities of remission at 10 years after onset were 37, 47, 23, and 6% for patients with systemic, pauciarticular, RF- polyarticular, and RF+ polyarticular JRA, respectively. The probability of relapse varied from 30 to 100% at 15 years. The probability of arthroplasty varied from 13 to 57% after 15 years of active disease. We found 2.5% of patients assessed were in Steinbrocker Classes III or IV and 6% were in the highest CHAQ score (> 1.5) group. Compared with national statistics, fewer female patients received post-secondary education and unemployment rates for patients 20 to 24 years of age were higher. CONCLUSION: Our results indicate that JRA is a disease that often extends into adulthood. Compared to previous decades, functional outcome has improved; however, the estimated rate of arthroplasty remains very high. Patients with JRA may have difficulty entering the workforce.     

The early clinical recognition of juvenile-onset ankylosing spondylitis and its differentiation from juvenile rheumatoid arthritis

Objective. To determine which early clinical data differentiate juvenile-onset ankylosing spondylitis (AS) from juvenile rheumatoid arthritis (JRA). Methods. Medical records of 35 patients with juvenile-onset AS and 75 with JRA (excluding type II pauciarticular JRA), all of whom had disease onset at age ≤16 years, disease duration of ≤2½ years at the initial visit to the rheumatology clinic, and followup of ≥ 10 years, were analyzed retrospectively with regard to features of disease found 6 months, 12 months, and 10 years after onset. Results. At 6 months, various features appeared more frequently in the juvenile-onset AS group than in the JRA group, i.e., pauciarthritis (54.3% versus 30.7%; P = 0.03, odds ratio [OR] = 2.7), enthesopathy (82.9% versus 0%; P < 0.0001, OR = 321.4), tarsal disease (71.4% versus 1.3%; P < 0.0001, OR = 185.0), and lumbar/sacroiliac symptoms (11.4% versus 0%; P = 0.02, OR = 11.9). At 12 months, the features found more frequently among juvenile-onset AS patients than JRA patients were enthesopathy (88.6% versus 4.0%; P < 0.0001, OR = 186.0), tarsal disease (85.7% versus 10.7%; P < 0.0001, OR = 50.3), and knee disease (100.0% versus 82.7%; P = 0.04, OR = 8.0). Involvement of the upper extremities (especially the hands) was found in significantly fewer juvenile-onset AS patients compared with the JRA group. Definite involvement of the spine and sacroiliitis in juvenile-onset AS occurred after a mean ± SD of 7.3 ± 2.0 years. Conclusion. Regardless of axial disease, enthes opathy and tarsal disease in children who have arthritis of the lower, but not of the upper extremities differentiate juvenile-onset AS from JRA within 1 year of symptoms. The discriminative value of these parameters approaches that of axial disease (the gold standard) throughout the followup period.     

Cross-cultural adaptation and validation of an argentine Spanish version of the Stanford childhood health assessment questionnaire

Objectives . To translate into Argentine Spanish and cross-culturally adapt the Childhood Health Assessment Questionnaire (CHAQ) and validate the adapted instrument in Argentine patients with juvenile rheumatoid arthritis (JRA). Methods . Five bilingual Argentine pediatric rheumatologists translated into Argentine Spanish and cross-culturally adapted the United States English CHAQ. Pretesting was done in a sample of 23 parents using a probe question technique. Parents of 70 patients with JRA and 21 healthy children (controls) participated in the validation phase. All were from Argentina. Results . The mean disability index (DI) scores for patients with systemic, polyarticular, or pauciarticular onset JRA were 0.64, 0.32, and 0.1, respectively. Healthy controls averaged 0.2. Intercomponent correlations were between 0.4 and 0.9, suggesting internal consistency, but also some redundancy. Test-retest reliability, studied at a 1-week interval, was moderate (mean DI 0.44 [in clinic] and 0.29 [one week later], Pearson's correlation = 0.82). We compared CHAQ scores from 15 parents with those of their children >10 years of age. Significantly higher DI scores were given by patients than their respective parents (P > 0.019), but the pairwise scores (parent–patient) were highly correlated (r = 0.986). Conclusions . Cross-cultural adaptation of the US CHAQ to Argentina required few changes. Although DI scores for all patient subgroups were higher than for controls subjects, the scores were low, particularly for those with pauciarticular disease. Prospective studies designed to examine the sensitivity to change and predictive validity will help to assess further the usefulness of the adapted CHAQ in the Argentine population.     

Health status of patients with juvenile rheumatoid arthritis at 1 and 5 years after diagnosis

OBJECTIVE: To describe the health and functional status of children with juvenile rheumatoid arthritis (JRA) diagnosed in the early 1990s. METHODS: Patients were obtained from the Pediatric Rheumatology Disease Registry, a database of patients seen in pediatric rheumatology centers across the United States. Questionnaires designed to be filled out after retrospective chart review were sent to pediatric rheumatologists caring for children diagnosed with JRA between 1992 and 1997. RESULTS: We studied 703 patients -- 376 with pauciarticular onset (pauci), 232 with polyarticular onset (poly), and 95 with systemic onset JRA (systemic). At 1 year after diagnosis, half of the pauci and systemic patients no longer required medication, compared to 78% of the poly patients; 98% of the patients functioned in Steinbrocker classes I and II. Six percent of pauci, 27% of poly, and 11% of systemic patients had limitations in school function. Nearly 1/3 of poly patients already had joint space narrowing on radiograph. By 5 years after diagnosis, all pauci, 88% of poly, and 70% of systemic patients were in Steinbrocker classes I and II; but 6% of pauci, 28% of poly, and 44% of systemic patients had limitations in school function. Nearly 2/3 of poly and systemic patients had joint space narrowing. CONCLUSION: In these children treated prior to the era of biologic therapy, at 5 years after onset, > 25% of poly and nearly half of systemic patients had functional limitations that required modifications in their school schedule. Radiographically evident joint space damage was seen within a year of onset in poly patients, and by 5 years 2/3 of poly and systemic patients had damage.     

A descriptive study of foot problems in children with juvenile rheumatoid arthritis (JRA)

In this study, we evaluated the feet of 144 consecutive children with juvenile rheumatoid arthritis (JRA) during a routine outpatient visit to discover patterns of foot problems. We found that all but nine subjects had at least 1 of 21 foot problems, categorized as inflammation, limitation of motion, and abnormal alignment. Overall, pronated rearfoot and midfoot were observed in 73% and 72% of JRA patients, respectively. Additionally, 36% had splayfoot, whereas 35% of subjects had ankle limitation of motion. Other common foot problems included pronated forefoot, rearfoot and forefoot synovitis, forefoot limitation of motion, and toe valgus. Significant differences in the occurrence of various foot problems were observed among JRA onset/course subgroups and were influenced by both age and disease duration. Specifically, subjects with polyarticular JRA had more forefoot limitation and toe valgus, whereas subjects with pauciarticular JRA had pronated forefoot more often. Ankle limitation of motion, although unrelated to the JRA subgroup, was related to the duration of JRA. Subjects with longer disease histories also had toe valgus more often. Conversely, forefoot limitation of motion seemed to be more a function of age than of disease duration. These results indicate that foot problems are common in the JRA population, and they underscore the need for thorough evaluation and physical therapy management.     

The Immunologic and Clinical Associations of the Split Products of C3 in Plasma in Juvenile Rheumatoid Arthritis

A qualitative counterimmunoelectrophoretic assay for the complement activation products C3c and C3d was used to study plasma from children with juvenile rheumatoid arthritis (JRA) and other rheumatic diseases. Positive tests for C3c,d were found in all patients with active systemic lupus erythematosus (SLE), 7 of 10 patients with active systemic JRA, 16 of 29 with active polyarticular JRA, 7 of 20 with active pauciarticular JRA, and in only 2 of 20 with inactive joint disease. The incidence of positive assays for C3c,d in JRA was increased in the presence of positive latex fixation tests, antinuclear antibody tests, or elevated values for antiglobulins as determined by affinity chromatography, but these associations were not statistically significant. Three joint fluids from children with pauciarticular JRA were negative for C3c,d. These studies show that the subgroups of JRA defined by clinical criteria are heterogeneous by current laboratory parameters and that evidence implicating antigen-antibody complexes in the pathogenesis of JRA is lacking in many patients.     

The immunologic and clinical associations of the split products of C3 in plasma in juvenile rheumatoid arthritis.

A qualitative counterimmunoelectrophoretic assay for the complement activation products C3c and C3d was used to study plasma from children with juvenile rheumatoid arthritis (JRA) and other rheumatic diseases. Positive tests for C3c,d were found in all patients with active systemic lupus erythematosus (SLE), 7 of 10 patients with active systemic JRA, 16 of 29 with active polyarticular JRA, 7 of 20 with active pauciarticular JRA, and in only 2 of 20 with inactive joint disease. The incidence of positive assays for C3c,d in JRA was increased in the presence of positive latex fixation tests, antinuclear antibody tests, or elevated values for antiglobulins as determined by affinity chromatography, but these associations were not statistically significant. Three joint fluids from children with pauciarticular JRA were negative for C3c,d. These studies show that the subgroups of JRA defined by clinical criteria are heterogeneous by current laboratory parameters and that evidence implicating antigen-antibody complexes in the pathogenesis of JRA is lacking in many patients.     

Polymorphism in the MHC-encoded LMP7 gene: association with JRA without functional significance for immunoproteasome assembly.

OBJECTIVE: To determine if a polymorphism in the immunoproteasome subunit LMP7 was associated with juvenile rheumatoid arthritis (JRA) and had functional significance. METHODS: The frequency of LMP7QQ+ vs QQ- (QK and KK genotypes) among 207 patients with JRA and 50 controls was determined. JRA subtypes were pauciarticular (53%), polyarticular (33%), and systemic (14%). Onset was before age 6 (early onset) in 60% of patients. The functional significance of the LMP7 polymorphism was determined by comparing incorporation of LMP7Q vs LMP7K into proteasomes. RESULTS: There was an increased frequency of LMP7QQ in patients vs controls (73 vs 56%; p = 0.016), mainly due to the pauciarticular and systemic JRA subtypes (p = 0.037), and more pronounced in early onset disease (77 vs 56%; p = 0.006). The association persisted with stratification for HLA-DR5(11) and -DPB 1 *0201 (p = 0.002 and 0.013). We found no difference in the relative incorporation of LMP7Q and LMP7K into proteasomes. CONCLUSIONS: These results support an association between LMP7QQ homozygosity and JRA, particularly early onset disease. The difference persists with stratification, at least for DR5(11) and DPB1*0201, suggesting that this effect is unlikely to be due to linkage disequilibrium with HLA alleles known to be associated with early onset pauciarticular JRA. Importantly, as there does not appear to be functional significance associated with the LMP7 polymorphism, this may be a marker for another as yet unidentified susceptibility locus.     

Expression of the rheumatoid factor cross-reactive idiotype in JRA: association with disease onset subtype, disease activity and disease severity.

We previously reported that approximately one-third of patients with juvenile rheumatoid arthritis (JRA) express high concentrations of antibodies marked by the rheumatoid factor cross reactive idiotype (RCRI) in their sera (6). In order to determine if an expression of RCRI is associated with certain clinical features of the disease, we prospectively studied 49 patients with JRA over a six month period, and determined serum RCRI concentrations by inhibition ELISA. RCRI concentrations correlated significantly with the duration of morning stiffness (r = .3866, p less than .01), and the functional class (p less than .001), but not with the number of active joints. Expression of RCRI was higher in patients with systemic onset disease (p less than .03), compared to patients with pauciarticular or polyarticular disease. In patients studied on more than one occasion, the RCRI expression was relatively constant despite changes in disease activity. A subset of JRA patients with systemic onset disease, higher serum concentrations of the RCRI.     

Use of the HEp-2 cell substrate in the detection of antinuclear antibodies in juvenile rheumatoid arthritis

Presence and titer of antinuclear antibodies (ANA) were determined in 217 juvenile rheumatoid arthritis (JRA) patients, by indirect immunofluorescence using HEp-2 cells as substrate. Positive ANA titers (greater than or equal to 1:40) were present in 131 (60%) of the JRA patients. All 3 JRA onset types demonstrated increased percentages of ANA positivity compared with healthy children. Sixty-seven percent of the patients in the polyarticular onset group had positive titers; titers were positive in 62% of the pauciarticular onset group and in 32% of the systemic onset group. ANA were also found in 45% of control patients with other connective tissue diseases. In JRA patients, the speckled pattern occurred most commonly (72%). Fourteen patients (8 with pauciarticular onset and 6 with polyarticular onset) had iridocyclitis; all of them had high titers (greater than or equal to 1:80) of ANA. The use of HEp-2 cells provided a sensitive substrate for detecting ANA in JRA. It proved to be of value in differentiating JRA patients from healthy controls, but not from patients with other connective tissue diseases.     

Autoantibodies to chromatin: prevalence and clinical significance in juvenile rheumatoid arthritis

OBJECTIVE: To determine the prevalence of anti-chromatin antibodies (Abs) in juvenile rheumatoid arthritis (JRA) and to assess any association between the presence of anti-chromatin Abs and clinical subsets of the disease. METHODS: IgG anti-chromatin Abs and anti-extractable nuclear antigens (ENA) Abs were detected by an enzyme-linked immunosorbent assay (ELISA), and antinuclear Abs (ANA) by indirect immunofluorescence in sera of 89 children with JRA. Ten children with systemic, 32 with polyarticular and 47 with pauciarticular disease onset (uveitis occurred in 17/47 children) were studied. As a control group, 12 sera of patients suffering from idiopathic uveitis and 31 age- and-sex-matched healthy children (HC) were examined. RESULTS: Abs to chromatin were detected in 14/47 (29.8%) of children suffering from pauciarticular onset JRA and in this group the higher prevalence of anti-chromatin Abs has been found in children with chronic uveitis (p = 0.002). Anti-chromatin positivity was observed in 2/10 (20%) of systemic and in 3/32 (9.3%) of polyarticular onset JRA. Furthermore, none of the patients with idiopathic uveitis and HC had Abs to chromatin. anti-chromatin Abs titers remained relatively stable over a 6-month control period. CONCLUSION: Our results confirm previous data about the presence of circulating anti-chromatin Abs in juvenile arthritis. Interestingly, anti-chromatin Abs were significantly higher in the group of patients with pauciarticular onset with past or present history of uveitis, than in patients without ocular involvement. A long-term follow-up study could be useful to demonstrate the potential utility of these autoantibodies in diagnosing, classifying and treating children affected.