SEPTEMBER-OCTOBER REV. HOSP. CLÍN. FAC. MED. S. PAULO 57(5):209-216, 2002 IMMUNOGLOBULIN E-RHEUMATOID FACTOR IN JUVENILE RHEUMATOID ARTHRITIS Rosa Aparecida Ferreira1, Virgínia Paes Leme Ferriani2, Mônica Camargo Sopelete1, Deise Aparecida Oliveira Silva1, José Roberto Mineo1, Maria Helena Bittencourt Kiss3 and Carlos Henrique Martins Silva1 RHCFAP/3095 FERREIRA RA et al. - Immunoglonulin E-rheumatoid factor in juvenile rheumatoid arthritis. Rev. Hosp. Clín. Fac. Med. S. Paulo 57(5): 209-216, 2002. OBJECTIVES: To determine the presence of immunoglobulin E-rheumatoid factor in patients with juvenile rheumatoid arthritis and to correlate it with clinical and laboratory parameters. METHODS: A multicenter prospective study was carried out from January 1993 to January 1999 with the enrollment of 3 centers of pediatric rheumatology. Ninety-one children with juvenile rheumatoid arthritis diagnosed according to the American College of Rheumatology criteria were studied: 38 (42%) with systemic, 28 (31%) with pauciarticular, and 25 (27%) with polyarticular onset. Ages ranged from 2.1 years to 22.6 years (mean 10.5 ± 4.7), with 59 (65%) girls. The control group consisted of 45 healthy children. The detection of immunoglobulin E-rheumatoid factor was carried out utilizing an enzyme-linked immunosorbent assay. Associations of immunoglobulin E-rheumatoid factor with immunoglobulin M- rheumatoid factor (latex agglutination test), total serum immunoglobulin E, erythrocyte sedimentation rate, antinuclear antibody, and functional and radiological classes III or IV were analyzed. RESULTS: Positive immunoglobulin E-rheumatoid factor was found in 15 (16.5%) of the 91 children with juvenile rheumatoid arthritis: 7 (18.5%) with systemic, 5 (18%) with pauciarticular, and 3 (12%) with polyarticular onset. A significant correlation was observed between immunoglobulin E-rheumatoid factor and total serum immunoglobulin E in the juvenile rheumatoid arthritis patients. No correlation was found between immunoglobulin E-rheumatoid factor and positive latex agglutination slide test, erythrocyte sedimentation rate, antinuclear antibody, or the functional and radiological classes III or IV in any disease onset group. In 4 out of 45 control children (8.9%), immunoglobulin E-rheumatoid factor was positive but with no correlation with total serum immunoglobulin E levels. CONCLUSIONS: Immunoglobulin E-rheumatoid factor could be detected in 16.5% of juvenile rheumatoid arthritis patients, particularly in those with high levels of total serum immunoglobulin E, and immunoglobulin E-rheumatoid factor appears not to be associated with disease activity or severity. DESCRIPTORS: Rheumatoid factor. Immunoglobulin E. Juvenile rheumatoid arthritis. ELISA. INTRODUCTION infections2. Several studies have RFs of the IgM immunoglobulin shown that only 5% to 25% of chil- class can be detected by employing Rheumatoid factors (RF) are spe- dren with juvenile rheumatoid arthri- the commonly used agglutination test. cific autoantibodies directed against tis (JRA) have positive latex aggluti- These antibodies directed to IgG are antigenic determinants on the Fc frag- nation tests for RF3. the “classic” RFs that are associated ment of the IgG molecule1. However, with adult-onset rheumatoid arthritis. RFs are not unique to rheumatoid ar- From the School of Medicine, Federal They are found in only a small sub- thritis; they sometimes occur in nor- University of Uberlândia1, School of group of children who have RF-posi- mal elderly individuals, healthy immu- Medicine of Ribeirão Preto, University of São Paulo2 and from the Pediatric tive polyarthritis, the disease that is nized individuals, and patients with Department, Children’s Institute, School of probably the childhood equivalent of 3 other autoimmune diseases or chronic Medicine, University of São Paulo . classic adult rheumatoid arthritis4. 209 3095.p65 209 30/10/02, 10:45 REV. HOSP. CLÍN. FAC. MED. S. PAULO 57(5):209-216, 2002 SEPTEMBER-OCTOBER Children with JRA who are RF posi- ease duration, activity of disease, METHODS tive are likely to be girls, to be older at erythrocyte sedimentation rate, antinu- disease onset, and to have many joints clear antibody, total serum IgE, IgM- Serum was obtained from each pa- involved. It has been suggested that RF (latex agglutination), and func- tient during the first appointment after they have more roentgenographic evi- tional and radiological classes III or IV. obtaining fully informed consent from dence of bony erosion and an overall their parents or relatives. Approval for poorer prognosis than their rheumatoid the study was also obtained from the 3 factor-negative counterparts5. Some PATIENTS AND METHODS Institutional Ethics Committees. Serum clinical and immunogenetic associa- samples were stored at –20°C. tions are well known, such as nodes, Patients The demographic and clinical char- bony erosions, functional incapacities, acteristics of the JRA patients are and HLA Dw4 (DRB1*0401) and A prospective, multicentric study shown in table 1 (sex, age at onset, dis- Dw14 (BRB1*0404) associations5,6. was carried out from January 1993 to ease duration, and activity of disease). In one-third of patients with JRA January 1999. Ninety-one children (59 Serum was obtained from each patient who present idiotypic expression with girls) with JRA diagnosed according to for the following laboratory measure- cross-reaction for RF, classical RF the American College of Rheumatol- ments: erythrocyte sedimentation rate (IgM-RF) is not observed7. It is possi- ogy criteria18,6 were studied. Sera were (by the Wyntrobe method), antinuclear ble that in this group of patients, other randomly obtained from patients who antibody (by the Hep 2 immunoassay RF isotypes are present8. With the use visited one of the following three method), and total serum IgE (measured of ELISA, an increased detection is Centers of Pediatric Rheumatology: by monoclonal antibody-based ELISA observed in JRA, with IgM-RF being Hospital de Clínicas da Universidade modified from a previously described demonstrated in 22% to 35% of pa- de São Paulo, São Paulo (51 cases), radioimmunoassay (RIA) by Pollart19). tients, IgG-RF in 4% to 6%, and IgA- Hospital de Clínicas da Faculdade de Values of total IgE ≥ 300 IU/mL were RF in 30% to 60%, depending on the Medicina de Ribeirão Preto da considered abnormally high (posi- type of disease onset9-11. The presence Universidade de São Paulo, Ribeirão tive)20. IgM-RF was determined by the of IgA-RF and IgM-RF has been ob- Preto, São Paulo (28 cases), and Hos- latex agglutination slide test using a served in a varying percentage of chil- pital de Clínicas da Universidade Fed- commercially available kit (RapiTex dren with JRA, mainly in the polyar- eral de Uberlândia, Minas Gerais (12 RF, Hoechst, Marburg, Germany). Sam- ticular onset type12,13. However, the fre- cases). The age of the patients ranged ples with RF of 20 IU/mL or more were quency and clinical and prognostic from 2.1 to 22.7 years (mean 10.5 ± considered to be positive. roles of the other RF isotypes (IgG and 4.7). The type of disease onset was sys- Active disease was defined by the IgE) in JRA are still unknown14. temic in 38 children, pauciarticular in presence of joint swelling or limitation There is evidence suggesting that 28, and polyarticular in 25. of mobility with warmth, pain, or ten- IgE-RF is associated with extra-articu- Forty-five healthy control children derness in 1 or more joints. Severity lar rheumatoid vasculitis and activity with no symptoms of connective tis- was evaluated according to of the disease in rheumatoid arthri- sue disease or acute or chronic infec- Steinbrocker’s functional and radio- tis15,16. We found 1 study about IgE-RF tions were selected from the pediatric logical classes21with classes III and IV in JRA in the literature17. These inves- outpatient clinic. The mean age of denoting major dysfunction. tigators observed that sera from 11/26 controls was 5.5 ± 3.3 years. children with JRA had low concentra- Quantitative determination of the tions of IgE-RF detected by the indi- Inclusion criteria IGE rheumatoid factor by ELISA rect immunofluorescence technique and suggested that IgE-RF may be in- All patients included had no clini- IgE-RF was determined by a stand- volved in the pathogenesis of JRA and cal symptoms suggestive of allergic ard ELISA technique according to rheumatoid arthritis by eliciting type rhynitis, asthma, or atopic dermatitis. SILVA22, with some modifications. The I and III reactions17. In addition, they had 3 samples of samples were always analyzed in du- The aims of the present study were feces examined for helminths with plicate. to determine the presence and the lev- negative results. None of the JRA pa- Briefly, polystyrene microtiter els of IgE rheumatoid factor (IgE-RF) tients were receiving or had received plates were coated with 10 µg/mL of in children with JRA and to correlate gold salts or D-penicilamine. mouse IgG in 0.06 M carbonate buffer, its presence with sex, age at onset, dis- pH 9.6, overnight at 4ºC. Plates were 210 3095.p65 210 30/10/02, 10:45 SEPTEMBER-OCTOBER REV. HOSP. CLÍN. FAC. MED. S. PAULO 57(5):209-216, 2002 Table 1 - Clinical and laboratory features of the children with juvenile rheumatoid arthritis (n= 91) according to disease onset (systemic, pauciarticular, or polyarticular). Clinical and Laboratory Features JUVENILE RHEUMATOID ARTHRITIS Total Systemic Pauciarticular Polyartycular (n = 91) (n = 38) (n = 28) (n = 25) Females 59 (64.4%) 21 (55,3%)