Gold sodium thiomalate and D-penicillamine. A controlled, comparative study in patients with pauciarticular and polyarticular juvenile rheumatoid arthritis

Seventy-seven consecutive patients with pauciarticular or polyarticular juvenile rheumatoid arthritis were randomized to treatment with either gold sodium thiomalate (GSTM) or D-penicillamine (PEN) in a parallel 50-week clinical trial. Adverse reactions were reported by or observed in 9 GSTM-treated and 15 PEN-treated patients. Of these, 5 and 7 respectively were withdrawn from the study. Most disease activity measurements were changed in favour of the GSTM group, compared with the PEN group, but significant differences between the treatment regimens were observed for only a few measurements. This possible advantage of GSTM with regard to efficacy was only seen in patients with the polyarticular disease type.     

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.     

Antibodies to histones H1 and H5 in sera of patients with juvenile rheumatoid arthritis

The specificity of juvenile rheumatoid arthritis (JRA) sera for histone subclasses was examined by immunoblotting. Antibodies to H1 alone were found in 4 of 21 pauciarticular-onset JRA sera, 4 of 19 polyarticular-onset JRA sera, and 2 of 11 systemic-onset JRA sera. Antibodies to H5 alone were found in 1 of 21 pauciarticular JRA sera, 1 of 19 polyarticular JRA sera, and 3 of 11 systemic JRA sera. Antibodies to both H1 and H5 were found in 4 of 21 pauciarticular JRA sera, 4 of 19 polyarticular JRA sera, and 1 of 11 systemic JRA sera. Antibodies to the core histones (H2A and H2B) were found in 1 of 21 pauciarticular JRA sera, 1 of 19 polyarticular JRA sera, and no systemic JRA sera. No reactivity to histones was observed in 30 sera from age-matched children with nonrheumatic diseases. The presence of H1 and H5 antibodies did not correlate with antinuclear antibody titers or with a homogeneous pattern of immunofluorescence. The predominance of H1 and H5 antibodies and relative absence of antibodies binding to core histones in JRA contrast with findings in adult systemic lupus erythematosus. Further, the presence of antibodies to H5 alone in some of the JRA patients indicates that the immune response in these patients is directed to determinants that are not shared by sequences of mammalian proteins.     

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.     

Clonal analysis of joint fluid T lymphocytes in patients with juvenile rheumatoid arthritis

Synovial fluid (SF) lymphocytes from 4 patients with pauciarticular juvenile rheumatoid arthritis (JRA) and 4 patients with polyarticular JRA were examined for their phenotypic and functional characteristics. In all 8 patients there was a high proportion of activated SF T cells, together with an increased proportion of CD2+CD3- and the presence of CD3+CD4-CD8-WT31- lymphocytes. The functional analysis at the clonal level in 5 patients (427 clones) showed a relevant proportion of cytotoxic T cell clones, which were not confined to typically cytolytic phenotypes, but were also present among CD3+CD4+CD8- cultures. Compared to those with pauciarticular JRA, patients with polyarticular disease had a significantly higher proportion of T cell clones with cytotoxic activity. Although derived from a limited number of patients, our data suggest a direct involvement of T cells in the pathogenetic mechanisms that originate and maintain the articular damage, and the possibility of different or more pronounced T cell reactivities in the clinically more diffuse JRA types.     

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.     

Antibody to streptococcal cell wall peptidoglycan-polysaccharide polymers in sera of patients with juvenile rheumatoid arthritis but absent in isolated immune complexes

Sera of 88 children with juvenile rheumatoid arthritis (JRA) (10 seropositive, polyarticular onset, 29 seronegative, polyarticular onset, 32 pauciarticular onset, and 17 systemic onset) were evaluated for the presence of serum antibodies to streptococcal cell wall peptidoglycan-polysaccharide polymers (PG-PSP). Immune complexes (IC) isolated by the antihuman IgM (HIgM) affinity column method were also evaluated for the presence of antibodies to PG-PSP. Forty-one of 88 patients with JRA (7 of 10 seropositive, polyarticular onset, 11 of 29 seronegative, polyarticular onset, 16 of 32 pauciarticular onset, and 7 of 17 systemic onset) showed elevated levels of antibodies to PG-PSP in their sera. IgM rheumatoid factors (RF) were demonstrated in 70/88 isolated IC fractions of patients with JRA and IgG RF in 7; however, none of the patients demonstrated the presence of antibodies to PG-PSP in their isolated IC fractions from the anti-HIgM affinity column. These data indicate that antibodies are produced to PG-PSP in all JRA onset types, but they are not constituents of isolated IC by the anti-HIgM affinity column method.     

Increased circulating vascular endothelial growth factor is correlated with disease activity in polyarticular juvenile rheumatoid arthritis.

OBJECTIVE: To investigate the relevance of vascular endothelial growth factor (VEGF) in the pathogenesis of juvenile rheumatoid arthritis (JRA). METHODS: Serum VEGF levels in 58 patients with JRA (systemic in 17, polyarticular in 29, pauciarticular in 12) were measured by ELISA and compared with those of 21 patients with infectious diseases and 50 healthy children. Correlations of VEGF levels with number of joints with active arthritis, erythrocyte sedimentation rate (ESR), and hyaluronic acid (HA) were examined. RESULTS: Serum levels of VEGF in patients with JRA were significantly higher than in healthy controls. Patients with systemic and polyarticular JRA showed statistically higher levels of VEGF than those with infectious diseases. VEGF levels correlated statistically with C-reactive protein (CRP) in patients with both infectious diseases and polyarticular JRA, but the regression slope (VEGF/CRP) was much steeper in polyarticular JRA than in infectious diseases. Serum VEGF levels correlated with disease activity variables such as the number of joints with active arthritis, ESR, and serum HA levels in polyarticular JRA. CONCLUSION: The correlation of serum VEGF levels and disease activity in polyarticular JRA suggests that VEGF may take an active part in joint inflammation.     

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.     

Analysis of the HLA-DR gene frequencies in Japanese cases of juveniles rheumatoid arthritis and rheumatoid arthritis by oligonucleotide DNA typing

Summary HLA-DR gene frequencies in 59 Japanese children with juvenile rheumatoid arthritis (JRA) and 62 Japanese adults with rheumatoid arthritis (RA) were analyzed by oligonucleotide DNA typing. As in other studies, the frequency of DRB1*0405 in RA patients was significantly higher than in the Japanese controls. In a comparison of non-calssified JRA patients with Japanese controls, no significant differences were observed in the frequency of DR types. However, when the JRA patients were classified into four clinical types, i.e., a rheumatoid factor-positive [RF(+)] polyarticular type, a rheumatoid factor-negative [RF(-)] polyarticular type, a pauciarticular type, and a systemic onset type, DRB1*0405 was found to be significantly higher in the RF(+) polyarticular JRA patients than in the controls (P>0.05). Thus, the RF(+) polyarticular type of JRA had the same HLA association as RA. This result is consistent with the fact that both RF(+) polyarticular JRA and RA cases have a similar clinical course.     

Differences in the profiles of circulating levels of soluble tumor necrosis factor receptors and interleukin 1 receptor antagonist reflect the heterogeneity of the subgroups of juvenile rheumatoid arthritis

OBJECTIVE: To determine whether levels of soluble tumor necrosis factor receptor 55 (sTNFR55), sTNFR75, and interleukin 1 receptor antagonist (IL-1Ra) can differentiate different subtypes of juvenile rheumatoid arthritis (JRA), and to determine if the levels of these proteins correlate with disease activity. METHODS: Serum sTNFR (55 and 75) and IL-1Ra levels were measured by ELISA in 34 patients with JRA and these values were correlated with disease subtype and activity. RESULTS: Serum sTNFR55 levels were significantly elevated in patients with systemic onset JRA (SoJRA) (mean +/- 2 SD, 2.9 +/- 1.8 ng/ml) (p < or = 0.05) compared to rheumatoid factor positive (RF+) polyarticular JRA (2.1 +/- 0.6), RF-polyarticular JRA (1.5 +/- 0.6), and pauciarticular JRA (1.4 +/- 0.4). There was a trend for elevation of sTNFR75 levels in patients with SoJRA compared to other subtypes (p = 0.08). More patients had elevated levels of sTNFR75 than sTNFR55 (15 vs 7). This was true for all subsets (SoJRA 7 vs 5; polyarticular JRA 4 vs 2; and pauciarticular JRA 4 vs 0). In contrast to sTNFR, IL-1Ra levels were significantly elevated in RF+ polyarticular JRA compared to the other subgroups (p < or = 0.001). We found statistically significant Pearson correlations between (1) sTNFR75 and hemoglobin concentration: and (2) IL-1Ra and number of active joints and number of joints with effusions. CONCLUSION: The increased serum level of sTNF receptors in SoJRA suggests that TNF is likely more important than IL-1 in systemic inflammation and in particular in SoJRA. Conversely, IL-1 is likely more important in the inflammatory arthritis of JRA and in particular in the pathogenesis of RF+ polyarticular JRA. Our results suggest that cytokines have differing roles in JRA subtypes and likely reflect JRA subtype heterogeneity.     

Antibodies against cyclic citrullinated peptide are associated with HLA–DR4 in simplex and multiplex polyarticular‐onset juvenile rheumatoid arthritis

Objective

Anti–cyclic citrullinated peptide (anti‐CCP) antibodies have been detected in patients with juvenile rheumatoid arthritis (JRA), particularly in those with polyarticular, rheumatoid factor (RF)‐positive JRA. Our objectives were to determine whether anti‐CCP antibodies are associated with HLA–DR4 in children with polyarticular JRA, whether anti‐CCP antibodies are associated with clinical features of disease, and whether affected sibling pairs (ASPs) with JRA are concordant for this antibody.

Methods

Stored serum samples obtained from 230 HLA‐typed patients with JRA (77 with polyarticular‐onset disease and 153 with pauciarticular‐ or systemic‐onset disease), 100 JRA ASPs, and 688 healthy children were tested for anti‐CCP antibodies and RF.

Results

Thirteen percent of the patients with polyarticular‐onset JRA and 2% of the other JRA patients exhibited anti‐CCP antibodies, compared with only 0.6% of the controls. Fifty‐seven percent of RF‐positive patients with polyarticular‐onset JRA had anti‐CCP antibodies. HLA–DR4–positive patients with polyarticular‐onset JRA were more likely to have anti‐CCP antibodies than were those without HLA–DR4 alleles (odds ratio [OR] 5.20, 95% confidence interval [95% CI] 1.30–20.9). Anti‐CCP antibodies were associated with polyarticular onset (OR 7.46, 95% CI 1.99–28.0), a polyarticular disease course (OR 9.78, 95% CI 1.25–76.7), and erosive disease (OR 14.3, 95% CI 3.01–67.9). Concordance rates for anti‐CCP antibodies among ASPs were statistically significant.

Conclusion

These data demonstrate increased anti‐CCP antibody formation in HLA–DR4–positive patients with polyarticular‐onset JRA. The overall prevalence of anti‐CCP antibodies in JRA is low, but a substantial proportion of RF‐positive patients with polyarticular‐onset JRA have these antibodies. Anti‐CCP antibodies in JRA are associated with polyarticular onset, a polyarticular course, and erosive disease.

     

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.     

High prevalence of iga rheumatoid factor in severe polyarticular-onset juvenile rheumatoid arthritis,but not in systemic-onset or pauciarticular-onset disease

The presence of IgA rheumatoid factor (IgA-RF) has been correlated with severe joint disease in adult rheumatoid arthritis (RA), but IgA-RF has not been reported in juvenile rheumatoid arthritis (JRA). In the present study, IgA-RF was assayed by an enzyme-linked immunosorbent assay and was found in the sera of 14 of 24 children (58%) with active polyarticular JRA. The presence of IgA-RF correlated with the degree of functional disability. In contrast, IgA-RF was not found in the sera of systemic-onset disease patients, regardless of the degree of dysfunction. IgA-RF was detected in only 1 patient with pauciarticular disease, despite the fact that several patients in this group had severe disease. The presence of IgA-RF in polyarticular JRA did not correlate with serum IgA levels, but did correlate with the presence and the level of serum IgM-RF. Thus, the presence of IgA-RF appears to be specific for polyarticular JRA, and shows a correlation with severe disease in this group.     

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.     

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.     

Juvenile rheumatoid arthritis: linkage to HLA demonstrated by allele sharing in affected sibpairs

OBJECTIVE: To test for linkage between the HLA region and juvenile rheumatoid arthritis (JRA), with stratification by onset and course types, in a cohort of affected sibling pairs (ASPs). METHODS: Eighty pairs of siblings with JRA who were registered with the Research Registry for JRA ASPs (sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases) were typed for HLA-DR. The observed ratio of sharing of none, one, or both parental DR alleles was compared against the expected ratio of 1:2:1 by goodness-of-fit chi-square tests. A group of 265 unrelated control subjects served as a comparison population for HLA-DR allele frequencies among patients, by Fisher's exact test. RESULTS: Overall, there was excess sharing of 2 DR alleles among ASPs with JRA. The observed ratio of sharing 0, 1, or 2 DR alleles was 8:40:32, instead of the expected ratio of 20:40:20 (P < 0.001). When stratified by JRA onset type, excess allele sharing was demonstrated among ASPs who were concordant for onset type (P = 0.002). This was true for both pauciarticular and polyarticular onset. When stratified by disease course, excess allele sharing was also demonstrated among ASPs who were concordant for disease course (P < 0.001). This was true for both the pauciarticular and the polyarticular course. Among the 32 ASPs who shared two DR alleles, 5 pairs had both DR8 and DR11, which was significantly more frequent (P < 0.0001) than the incidence in the control group (n = 0). CONCLUSION: This study of an independent cohort of multiplex families confirms the previously reported linkage between pauciarticular JRA and the HLA-DR region that was identified using a different analytic method in a cohort of simplex families. Additionally, this study establishes evidence for linkage between polyarticular JRA and the HLA-DR region.     

Longitudinal growth attainments of Indian boys with Juvenile Rheumatoid Arthritis

The objective is to study the pattern of distance and velocity growth in terms of weight and height in adolescent boys with Juvenile Rheumatoid Arthritis (JRA). This study was conducted on children diagnosed to have JRA (Cassidy and Petty in Juvenile Rheumatoid Arthritis, WB Saunders Co., Philadelphia, 2005) at the Pediatric Rheumatology and Immunology Clinic of Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh. A total of 203 observations made on 70 boys with JRA, between 9 and 17 years of age, comprised the sample for this prospective mixed-longitudinal growth study. Each subject was measured for body weight and standing height using standardized anthropometric techniques (Eveleth and Tanner in Worldwide variation in human growth, Cambridge University Press, New York, 1990) at half yearly age intervals. All anthropometric measurements were carried out in the Growth Laboratory of Advanced Pediatrics Centre. Boys with polyarticular and systemic onset types of JRA in general measured lighter than their pauciarticular counterparts throughout the period of study. Height attainments in boys with polyarticular and systemic onset JRA measured shorter than their pauciarticular counterparts till 15 years and 12 years, respectively, where-after they became comparable to boys with pauciarticular JRA. As compared to normal Indian (Bhalla and Kumar in Int J Anthropol 18:113–125, 2003; Aggarwal et al. in Indian Pediatr 29:1203–1282, 1992) and American (Ogden et al. in Pediatrics 109:45–60, 2002) counterparts boys representing all categories of JRA remained lighter and shorter. Onset of Peak Height Velocity (PHV) in boys with polyarticular JRA (i.e. 12.5 years) was delayed by 1 year as compared to boys with pauciarticular JRA (i.e. 11.5 years). Attainment of Peak Weight Velocity (PWV) in boys with polyarticular JRA (i.e. 13.5 years) was also delayed by 1 year when compared to those with pauciarticular type (i.e. 12.5 years). In conclusion, weight and height growth attainments in Indian adolescent boys afflicted with different categories of JRA in general remained impaired as compared to their normal counterparts. However, the magnitude of growth deficit experienced by them appears to be a disease severity related phenomenon. This is the first study of its kind from a developing country.     

Complement C3b receptors on erythrocytes in patients with juvenile rheumatoid arthritis

Forty patients with juvenile rheumatoid arthritis (JRA) were examined for C3b receptor (CR1) levels on erythrocytes (by an enzyme-linked immunosorbent assay), levels of circulating immune complexes (IC) (by a polyethylene glycol precipitation-complement consumption method), C3d split products (by intermediate gel rocket immunoelectrophoresis), and HLA-A, B, and C (by microdroplet lymphocytotoxicity test). Lower CR1 levels were found predominantly among patients with JRA (mean 57%) compared with 40 age-matched controls (mean 68%) (P = 0.008). The CR1 levels differed when the JRA patients were grouped by mode of disease onset and by clinical state at the time of testing (levels in patients with pauciarticular disease were higher than those in patients with polyarticular disease, and levels in patients with polyarticular disease were higher than those in patients with systemic disease) or by sex (girls had higher levels than boys; P = 0.01). The levels of circulating IC and C3d were elevated in 25% and 40% of JRA patients, respectively, and were mutually correlated (P less than 0.05, tau = 0.20). A negative correlation was found between levels of C3d and the numbers of CR1 (P less than 0.01, tau = -0.28), but concentrations of circulating IC did not correlate with CR1 values. CR1 levels were the same in 6 HLA-B27 positive and 25 HLA-B27 negative patients. These findings do not represent conclusive evidence that the number of CR1 on erythrocytes serves as a predictor of disease severity or as an indicator of disease activity in patients with JRA.