Antihistone antibodies in antinuclear antibody-positive juvenile arthritis

The binding of antinuclear antibody-positive juvenile arthritis (JA) sera to bovine thymus histones H1, H2A, H2B, H3, and H4 was studied by an enzyme-linked immunosorbent assay. Seventy-five percent of the JA patients tested positive for at least 1 antibody specificity. Antihistone antibodies were predominantly IgM, while IgG antibodies were less common and were restricted to histones H1 or H3. In the group of patients with JA of pauciarticular onset, antihistone antibodies were significantly more elevated in patients with past or present uveitis than in patients without a history of uveitis. Anti-H1 antibodies in JA patients were found to react mostly with determinants located in the carboxyl-terminal domain of the H1 molecule. Sera were also reactive with human histone H1(0) or chicken histone H5, which are H1 variants found only in nondividing cells.     

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.     

Course of joint disease in patients with antinuclear antibody-positive juvenile idiopathic arthritis

OBJECTIVE: To describe the patterns and time course of arthritis in patients with antinuclear antibody (ANA)-positive juvenile idiopathic arthritis (JIA). METHODS: We identified patients followed during a 16-year period who had JIA by ILAR criteria, were ANA-positive (i.e., had >or= 2 positive ANA test results at titer >or= 1:160), and had a disease duration >or= 2 years. Demographic and clinical features, including ILAR category and cumulative number and type of joints affected over time, were recorded. RESULTS: A total of 195 patients were studied. The ILAR category was oligoarthritis in 159 patients and rheumatoid factor-negative polyarthritis in 36 patients. The cumulative rate of polyarticular extension in patients with oligoarticular onset was 26%, 38%, 45%, 49%, and 51% at 1, 2, 3, 4, and 5 years, respectively. At disease onset, most patients had monoarthritis and 95% had 相似文献   

Anti-keratin antibodies in patients with juvenile idiopathic arthritis

OBJECTIVE: We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA). METHODS: An indirect immunofluorescence test with rat oesophagus substrate was used for the detection and quantification of AKA antibodies in patients'sera. RESULTS: Overall 30/60 patients with JIA had sera positiveforAKA (50%, p=0.0005) ranging from 1:20 to 1:160 dilutions. Using the classification criteria for childhood idiopathic arthritis, AKA occurred in 2/7 patients with systemic disease (28.6%), in 13/30 patients with RF negative polyarthritis (43.3%, p=0.008) and in 12/18 RF positive polyarthritis (66.7%, p=0.002). AKA were also found in a small cohort of patients with oligoarthritis (1/3) and psoriatic arthritis (2/2). AKA positivity occurred in 3/26 healthy controls at a 1:20 dilution. The presence ofAKA was correlated as well as with the severity of the disease. Our study revealed that AKA was present overall in 16/29 patients (55.2%) with severe JIA and in 11/26 patients (42.3%) with non-severe disease. We also observed that AKA remained positive regardless of disease activity. AKA were detectable in 44.4% patients with active JIA and in 45.9% patients in the complete or near remission. CONCLUSION: Our data suggest that AKA are present in patients with JIA. However no correlation with severity or disease activity was observed.     

Anticyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

Abstract

Anticyclic citrullinated peptide (anti-CCP) antibodies have been detected in patients with juvenile idiopathic arthritis (JRA), particularly in those with polyarticular JIA. We analyzed the presence of anti-CCP antibodies of the IgG class in sera of patients with defined juvenile idiopathic arthritis (JIA) of various subgroups. One hundred and fifty-nine serum samples were investigated. Forty-five patients were diagnosed with JIA (15 male and 30 female) aged 1.9–17.3 years (median 12.9, mean 11.0). Thirty-eight samples were taken from patients suffering from other autoimmunopathies and 34 patients with other underlying diseases were taken at different time points in their disease course. Under 42 samples were taken from patients with noninflammatory diseases. Enzyme-linked immunosorbent assay (ELISA) was used for the detection of anti-CCP antibodies. Anti-CCP antibodies were found in 6.9% of all samples and in 4.4% patients with JIA. Disease duration and medication did not differ significantly between anti-CCP positive and negative patients. A review of the literature and our own results shows that anti-CCP antibodies can be detected in the sera of only some patients with JIA. Routine determination of anti-CCP cannot be recommended.     

Anticyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

Anticyclic citrullinated peptide (anti-CCP) antibodies have been detected in patients with juvenile idiopathic arthritis (JRA), particularly in those with polyarticular JIA. We analyzed the presence of anti-CCP antibodies of the IgG class in sera of patients with defined juvenile idiopathic arthritis (JIA) of various subgroups. One hundred and fifty-nine serum samples were investigated. Forty-five patients were diagnosed with JIA (15 male and 30 female) aged 1.9–17.3 years (median 12.9, mean 11.0). Thirty-eight samples were taken from patients suffering from other autoimmunopathies and 34 patients with other underlying diseases were taken at different time points in their disease course. Under 42 samples were taken from patients with noninflammatory diseases. Enzyme-linked immunosorbent assay (ELISA) was used for the detection of anti-CCP antibodies. Anti-CCP antibodies were found in 6.9% of all samples and in 4.4% patients with JIA. Disease duration and medication did not differ significantly between anti-CCP positive and negative patients. A review of the literature and our own results shows that anti-CCP antibodies can be detected in the sera of only some patients with JIA. Routine determination of anti-CCP cannot be recommended.     

Reactivity of antinuclear antibodies with histones and other antigens in juvenile rheumatoid arthritis

Antinuclear antibodies are found in serum samples from most children with juvenile rheumatoid arthritis (JRA), but the antigenic specificities of these antibodies are not known. Using an immunoblot technique, we found that JRA patients' sera react with a variety of proteins in the nuclei of HEp-2 cells. Antibody to histone H1 was found in 42% of the JRA serum samples. An IgG antibody to a 45-kd protein was found in serum samples from some patients without uveitis, but it was not found in any sample from patients with uveitis. The immunoblot reactivity patterns do not appear to be useful in distinguishing between disease onset types or disease course types in patients with JRA.     

Clinical significance of anticardiolipin antibodies in juvenile idiopathic arthritis.

OBJECTIVE: Anticardiolipin antibodies (aCL) have been demonstrated in a large spectrum of autoimmune diseases. However, its occurrence in childhood, in particular in juvenile idiopathic arthritis (JIA), is not well established. The present study addressed the frequency and clinical significance of aCL in a group of JIA patients. METHODS: aCL (IgG and IgM isotypes), antinuclear antibodies (ANA), and rheumatoid factor (RF) were determined in 86 children with JIA (33 systemic, 31 polyarticular and 22 oligoarticular onset type). Thirty-two juvenile systemic erythematosus lupus patients (JSLE) and 52 healthy children formed the control groups. The disease activity and functional status of the JIA patients were scored to study their possible associations with the presence of aCL. RESULTS: Serum aCL levels above the normal range were detected in 28/86 JIA patients (32.5%), 12/32 JSLE patients (37.5%), and 3/52 healthy children (6%). Positive aCL levels were slightly or moderately elevated (usually below 30 GPL and 20 MPL). The presence of aCL was not associated with the presence of ANA or RF. Associations between aCL and clinical parameters, such as disease onset, duration, activity or severity could not be established. No JIA patient had vascular thrombosis, thrombocytopenia or "livedo reticularis". CONCLUSION: aCL occurred in low titers in JIA children, in a similar frequency to that observed in JSLE. No association with JIA clinical parameters or the clinical features classically linked to the antiphospholipid antibody syndrome were observed.     

Use of ELISA to measure antinuclear antibodies in children with juvenile rheumatoid arthritis.

OBJECTIVE: To compare a series of commercial ELISA tests with an indirect immunofluorescent antibody (IFA) test for the detection of antinuclear antibodies (ANA) in children with juvenile rheumatoid arthritis (JRA). METHODS: Sera from 178 patients with JRA (88 pauciarticular, 68 polyarticular, 22 systemic) were compared with 26 healthy pediatric subjects. Twenty-one samples from patients with systemic lupus erythematosus (SLE) were also tested. All samples were analyzed by IFA and by 3 commercial ELISA methods. Concordance of ELISA results with IFA results (selected standard) were used as a measure of performance. Sensitivity and specificity were calculated for each test and likelihood ratios (LR) were established for IFA and ELISA in pauciarticular and polyarticular JRA sera. The increment in pretest probability was then obtained for each test as an additional measure of test performance. RESULTS: IFA rendered positive results on 18-77% of the JRA sera depending upon the subset, 100% of SLE sera, and 15% of normal patient sera. Using IFA as the standard, correspondence with positive results among patients with JRA ranged from 0 to 74% for the 3 ELISA tests, while it ranged from 5 to 73% in IFA negative sera. IFA tests showed intermediate range likelihood ratios (0.3, 0.5, 3.5, and 5) and increments in pretest probability ranging from 25 to 45%. While one of the ELISA tests attained 50% of increment in pretest probability for the positive test, it showed 0% increment as a negative test. The other 2 ELISA tests incremented the pretest probability from 0 to 25%. CONCLUSION: Our findings indicate that in JRA, the lack of correspondence with the historic standard IFA precludes the use of ELISA tests for detection of ANA. In addition, IFA out-performs ELISA by a substantial degree when "clinical utility" analysis of test performance is utilized. Detection of ANA in children with JRA should either continue to rely on IFA or be based on a different set of antigens if an ELISA format is chosen.     

Diagnostic accuracy of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

OBJECTIVE: To correlate serum anti-cyclic citrullinated peptide antibodies (anti-CCP) levels with juvenile idiopathic arthritis (JIA) subtypes and with an erosive disease course. METHODS: The study group comprised 122 children with JIA; 16 were evaluated during both active disease and remission. Nineteen children with systemic lupus erythematosus (SLE), 27 with rheumatoid arthritis (RA), and 15 healthy children were also included in the study. Twelve children with JIA were rheumatoid factor (RF) positive, and 34 patients had persistent erosive joint disease. Anti-CCP antibody levels were determined by ELISA; values above 5 relative units were regarded as positive. RESULTS: Three girls with seropositive polyarticular JIA and erosive joint disease had positive anti-CCP values. Children evaluated during active disease and remission, patients with SLE, and healthy children all had negative anti-CCP antibody levels. However, 19/27 (70%) adult patients with RA had positive anti-CCP antibody values. CONCLUSIONS: In contrast with RA, anti-CCP positivity is only rarely found in patients with JIA. In patients with RF positivity and/or in patients with erosive joint disease, anti-CCP can be detected.     

Studies of antinuclear antibodies in rheumatoid arthritis

Antinuclear antibodies (ANA) by the indirect immunofluorescence method and their immunospecificities were investigated in 60 patients with rheumatoid arthritis using HEp-2 cells as substrates. ANA were detected in 35% of the patients. The patterns of nuclear staining observed included: diffuse or patchy homogeneous (20%), speckled (8.3%), centromere (3.3%), nucleolar (1.6%) and in 1 patient a mixed pattern (1.6%). The presence of antihistone antibodies (20%) correlated with the presence of an homogeneous pattern on the HEp-2 cells.     

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 in juvenile idiopathic arthritis: glucose-6-phosphate isomerase is not a specific target

OBJECTIVE: Antibodies recognizing the ubiquitous cytosolic enzyme glucose-6-phosphate isomerase (GPI) cause arthritis in the K/BxN mouse model. Studies have shown that these antibodies are not specific for rheumatoid arthritis (RA) in humans. We evaluated GPI as a target of autoantibodies in juvenile idiopathic arthritis (JIA). METHODS: We studied 324 serum and 48 synovial fluid (SF) samples from 103 patients with JIA, 36 with RA, and 8 with arthralgia and 11 controls. Anti-GPI antibodies were assessed by densitometrically evaluating immunoblots and ELISA using native and recombinant GPI. We determined the GPI activity of the soluble antigen in serum and SF. RESULTS: Although several samples contained anti-GPI-IgG antibodies, this was not specific for JIA or its subgroups, or for RA. Other proteins in the GPI preparation were also frequently recognized by antibodies. Additionally, we observed increased GPI activity in patients with the systemic manifestation of JIA, but not in other patients. Neither anti-GPI concentrations nor GPI activity were associated with disease activity. CONCLUSION: In addition to the findings in RA, our results indicate that GPI is not a general target of autoantibodies in JIA.     

Anti-CCP antibodies in Brazilian children and adults with juvenile idiopathic arthritis

Patients with juvenile idiopathic arthritis (JIA) may need further care in the adult clinic as this disease frequently has continuous inflammatory activity during adult life. To identify which pediatric JIA patients will need continuing care into adulthood. We compared the clinical, serological, and demographic data of 45 JIA patients followed up by the pediatric clinic to those of 49 JIA patients in the adult rheumatology clinic. Patients in the adult clinic have older age at disease onset (p?<?0.0001) and higher prevalence of positive anti-cyclic citrullinated peptide (CCP) (p?=?0.05). No differences were observed in JIA form, presence of rheumatoid factor (RF), uveitis, and gender. Anti-CCP and older age at disease onset may identify pediatric JIA patients that will need further care in the adult clinic.     

Osteoporosis in juvenile idiopathic arthritis

Osteoporosis is characterized by loss of both bone mass and microarchitectural integrity, resulting in an increased risk of fractures with associated morbidity and mortality. Awareness of this condition is increasing in pediatrics, including pediatric rheumatology. Reduced bone mineral density is now well recognized in children and young adults with juvenile idiopathic arthritis and is multifactorial in origin. The problems of interpretation of bone analysis techniques during childhood and adolescence are highlighted. Recent studies have reported on the use of newer methods of imaging, including quantitative ultrasound and bone single photon emission computed tomography techniques. Attempting to disentangle the relative effects of disease activity, corticosteroids, nutrition, and physical activity in the development of osteoporosis in juvenile idiopathic arthritis is the focus of several studies. Finally, early optimistic reports of the use of bisphosphonates in juvenile idiopathic arthritis are welcome additions to the growing body of literature in this area.