Childhood Arthritis and Rheumatic Diseases Unit, Department of Rheumatology, University of Birmingham, Birmingham B15 2TT

ity if the host immune response to infectious antigens cross-reacted with host antigens. Proposed antigens include heat shock proteins (HSP), which are highly conserved between some bacteria and man. Data from groups in the Netherlands, USA, Italy and UK demonstrated significantly elevated T and B cell mediated immune responses to HSP in children with arthritis. Importantly, the group from the Netherlands (who have published their findings in the Lancet 337, 1368— 1372, 1991) also demonstrated that HSP were expressed in synovial membrane from patients but not controls. A group from Toronto questioned whether synovial T cells from children with arthritis were of oligoclonal origin (suggesting selective recruitment of antigen-driven proliferation within the joint), or of polyclonal origin. They analysed T cell receptor gene usage using PCR, with somewhat equivocal results. Nevertheless, there appeared to be decreased use of variable gamma 2 region genes in synovial T cells with respect to peripheral blood, raising the possibility of oligoclonality. Using flow cytometry, the same group also reported that over 90% of synovial CD4 positive ('helper') T cells were of the 'memory' phenotype (CD45RA-), and numbers of synovial B cells were reduced compared to peripheral blood. Cytokines were investigated by groups from Canada, UK/France and USA. In patients with inflammatory arthritis, serum levels of IL-1 a and p\ IL-2, IL-6, TNF a and p were elevated, and synovial mononuclear cells appeared to be more active producers than their peripheral blood counterparts. An attempt was made to correlate serum levels of TNF a with serum keratan sulphate (KS) and osteocalcin (OC) levels, two indices of skeletal metabolism, in children with JCA. Systemic JCA was the only subgroup in which the TNF a levels correlated with disease activity. Taking JCA as a whole, there was no correlation between TNF a levels and disease activity, ESR, KS or OC. When the same group measured bone mineral density (BMD) by photon absorbitometry, they found that there was significant repair of osteopaenia as disease severity improved. Further work on antinuclear antibodies (ANA) was presented by a group from Saskatoon, Canada. Using cells in mitosis and at other stages of cycling as substrates, they demonstrated that autoantibodies were often directed against constituents of chromatin, and in further work suggested that the antigen could be one of the high mobility group (HMG) proteins. The recent interest in IgG glycosylation in adult rheumatoid arthritis patients was reflected in one study of paediatric patients in which serum levels were measured using an ELISA technique. Except for systemic JCA, all JCA subgroups and some other juvenile connective tissue diseases had elevated levels of agalactosyl IgG

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UNDER the chill late November sun, the John B. Hynes Veterans' Memorial Convention Center threw open its doors to over 4000 registrants for the 55th Annual Scientific Meeting of the American College of Rheumatology. The warmth of the paediatric rheumatologists' reunion was undiminished, though only 8 months had elapsed since the previous meeting at the Park City III conference, Utah. Much of the paediatric rheumatology research presented in that rarefied atmosphere was re-presented in Boston. It was probably just as well! There were more than 60 abstracts specifically concerned with paediatric rheumatic diseases, of which seven were presented orally at the only paediatric concurrent session. The rest were presented as posters scattered through the four poster sessions (the ratio of paediatric to adult posters was 1:13!). The paediatric rheumatology study group dealt with cell adhesion molecules and treatment of arthritis with biologic agents, but as virtually no paediatric data was presented, this session will not be referred to further in this report. There were only a few abstracts devoted to childhood connective tissue diseases other than the chronic arthritides, so the remainder of the report will summarize presented information on juvenile chronic arthritis (JCA), which has been judiciously substituted for juvenile rheumatoid arthritis (JRA) as appropriate! The genetic background conferring susceptibility to childhood arthritis or its complications received only scant attention, which was surprising in view of recent interest in this field. A group from Cincinnati investigated the HLA-DR5 association with chronic iridocyclitis of early onset pauciarticular JCA in 61 patients. Five splits of DR5 were defined by oligonucleotide probes on polymerase chain reaction (PCR) amplified DNA. Only the DRB1*11O4 split was significantly associated with iridocyclitis. Of 13 patients who expressed DRB1*11O4 and DPB1*0201, 11 had iridocyclitis, suggesting that additional susceptibility may be conferred independently by genes at the DP locus. A report from the UK indicated that children with arthritis who were HLA-B27 positive had increased immune responses to infectious agents including Yersinia, Salmonella and influenza A, compared with B27 negative patients, but the mechanism underlying this association was not clear. The possibility that nonMHC genes contribute to disease susceptibility was supported by the Cincinnati group, who found an association between a specific polymorphism in the T cell receptor variable region germline genes (defined by the gene probe TCRb V6.1) and pauciarticular JCA. The involvement of infectious agents in childhood arthritis was the subject of several posters. It has been hypothesized that infection could trigger autoimmun-


tive treatment of JCA were reported. Methotrexate continued to receive good press, with results of the USA-USSR randomized controlled trial indicating that 10 mg/m2/week was significantly more effective (72% improvement in physicians global assessment) that half the dose, or placebo (41% improvement). The safety profile was very encouraging, with only three of approximately 80 patients given methotrexate having significant adverse effects. A meta-analysis revealed that, of hydroxychloroquine, penicillamine, auranofin and methotrexate, only methotrexate was better than placebo for the treatment of JCA. Other reports showed that soluble IL-2 receptor levels decreased, and radiological progression of disease slowed, in association with clinical response to methotrexate. There was a wide variation in plasma methotrexate levels taken at 1,2,3 and 24h after administration, and only the 2h level was significantly correlated with the dose given. In summary, the meeting was enjoyable and perhaps the most important advances were made in terms of international collaboration, through progress towards a standardized nomenclature for JCA and initiating an international database for the rheumatic disease of childhood. The most interesting new information on JCA was in the fields of genetics and pathogenesis, but even here no major breakthroughs had occurred. If it didn't happen in the USA, perhaps it is up to us Europeans to lead the way!

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which correlated with disease activity. The significance of this finding was not clear but it adds further evidence that systemic JCA is a disease distinct from other forms ofJCA. ' The behavioural, social and economic complications of arthritis were extensively reported. In a study from Stanford, patients were reported as feeling less popular and less attractive than siblings, although they had similar levels of self-confidence. The most significant predictors of poor psychosocial status were maternal depression and family stressors (home moves, deaths). In follow up studies from the UK, over 20 per cent of JCA patients were shown to be clinically depressed during early adult life, despite having equivalent educational achievements to their peers. Depression correlated directly with severity of disability. A second group from Stanford measured the functional status of patients using the Childhood Health Assessment Questionnaire (CHAQ), and found it to be a more sensitive measure than the more conventional parameters of early morning joint stiffness or joint counts. However, their comparisons were with the 'gold standard' of parental global assessment, so comparisons with other techniques (e.g. the juvenile arthritis functional assessment score (JAFAS) from Cincinnati) might be more useful. The financial impact of JCA on US families were estimated to be over $2000 per year (6% of mean family income); this figure did not include direct hospital inpatient and outpatient costs. Unfortunately, no startling new drugs for the effec-


Advances in paediatric rheumatology: report of the American College of Rheumatology meeting, Boston 1991.

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