Tetsunori Seki, Jeanette Selby, Thomas Haupl, and Robert Winchester 1356

Delineation of the genes comprising the distinctive phenotype of cultured rheumatoid arthritis fibroblastoid synoviocytes should contribute to the understanding of the biologic basis of this type of synoviocyte, the relationship of these cells to lining cell hyperplasia in chronic synovitis, and the physiologic pathways that are involved in synovial membrane histogenesis. Characteristics of the genes identified suggest several mechanisms for how fibroblast-lineage cells interact with monocytoid cells, and how an autoimmune response might be localized to the joint through these properties.

Yoshiya Tanaka, Koichi Fujii, Stefen Hubscher, Megumi Aso, Akiko Takazawa, Kazuyoshi Saito, Toshiyuki Ota, and Sumiya Eto 1365

This study found that endothelial cells in RA synovium characteristically express heparan sulfate proteoglycan, which is involved in T cell integrin-triggering by ``posting'' chemokines, which are produced by synovial T cells, and ``relaying'' them to their receptors on T cells, which activate G-protein-dependent phosphoinositide 3-kinase and actin-dependent integrin-triggering. Thus, heparan sulfate proteoglycan on synovial endothelium plays a pivotal role in the T cell adhesion to the endothelial cells by binding chemokines. These findings are relevant to the inflammatory processes of RA synovitis characterized by T cell accumulation.

Gernot Keyszer, Angela Redlich, Thomas Haupl, Josef Zacher, Martin Sparmann, Ute Ungethum, Steffen Gay, and Gerd R. Burmester 1378

The balance of the cysteine proteinases cathepsins L and B and their specific inhibitor, cystatin C was investigated in inflammatory joint diseases by semiquantitative PCR and immunohistochemistry. The data were compared with the expression of MMP-1, MMP-3, and TIMP-1. In RA, a disturbed balance between both cathepsins and cystatin C was detected on the protein level, but not on the mRNA level, supporting the idea of a specific contribution of cysteine proteinases to joint destruction.

Josef A. Hermann, Mark A. Hall, Ravinder N. Maini, Marc Feldmann, and Fionula M. Brennan 1388

This study is the first to demonstrate the presence and function of IL-11 in RA synovial tissue. IL-11 protein was found in abundance in RA joints, and neutralization of this cytokine resulted in an increase in TNF[alpha] production, particularly if the antiinflammatory cytokine IL-10 was also neutralized. These data suggest that in inflammatory tissue, important immunoregulatory processes still occur, and that IL-11 may have therapeutic potential.

Ruth Carter Borghaei, P. Lyle Rawlings, Jr., and Eugene Mochan 1398

It has been hypothesized that chronic inflammation in RA is perpetuated by an imbalance between proinflammatory (IL-1, TNF) and antiinflammatory (IL-4, IL-10) cytokines, and that the joint destruction might be curtailed if the cytokine balance could be restored. This study provides further evidence to support this hypothesis by demonstrating that coincubation of human synovial fibroblasts with IL-4 and IL-1 results in significant inhibition of the IL-1 induction of both collagenase (MMP-1) and stromelysin (MMP-3). This inhibition 1) takes place, at least in part, at the level of transcription, 2) is accompanied by decreased production of prostaglandin E2 (PGE2), but is not reversed by exogenous addition of PGE2, and 3) does not involve inhibition of transcription factor AP-1 binding, raising the possibility that other, less well-characterized, transcription factors may be involved.

Joseph E. Baggott, Sarah L. Morgan, and William J. Koopman 1407

This study investigated the efficacy, toxicity, and antifolate activity of low-dose MTX compared with its metabolite, 7-OH-MTX. The results indicate that 7-OH-MTX is less effective than MTX in suppressing rat adjuvant arthritis, that prolonged low-dose treatment with 7-OH-MTX is not toxic, and that 7-OH-MTX has variable, but generally reduced, antifolate activity compared with MTX in this animal model. These findings may help to explain why some rheumatoid arthritis patients do not respond well to MTX; these patients may have a relatively increased ability to metabolize MTX to 7-OH-MTX and/or their folate-dependent enzymes may be less sensitive to 7-OH-MTX inhibition.

Geraldine Chow, J. Jaap Nietfeld, Cheryl B. Knudson, and Warren Knudson 1411

The glycoprotein CD44 is expressed on the plasma membrane of articular cartilage chondrocytes and serves as the primary receptor for the matrix macromolecule hyaluronan. The inhibition of CD44 expression by antisense oligonucleotides was used to examine several of the important functions of this receptor, many of which are thought to become altered in osteoarthritis. The results indicate that CD44 expression is required for the maintenance of cartilage homeostasis.

Joan-Carles Reverter, Dolors Tassies, Josep Font, Munther A. Khamashta, Kenji Ichikawa, Ricard Cervera, Gines Escolar, Graham R. V. Hughes, Miguel Ingelmo, and Antoni Ordinas 1420

Patients with autoimmune diseases frequently have clinical manifestations of the antiphospholipid syndrome, but its pathophysiology remains unknown. The present study investigates the effect of 3 well-characterized monoclonal anticardiolipin antibodies on 2 of the proposed prothrombotic mechanisms. The effects of monoclonal antibodies on platelet function under flow conditions and on tissue factor expression on normal monocytes may be important in the pathophysiology of thrombosis in the antiphospholipid syndrome.

Rick Brouwer, Wilma Vree Egberts, Peter H. Jongen, Baziel G. M. van Engelen, and Walther J. van Venrooij 1428

This report describes a frequently occurring and novel autoantibody activity, directed to deproteinized tRNAHis, in the sera of myositis patients. Autoantibodies directed to nucleic acids have been detected previously in patients with autoimmune diseases, and in most cases this response strongly correlates with disease activity, as is the case with the anti-U1 RNA and anti-double-stranded DNA reactions. It is not unlikely that the anti-tRNAHis response might also be a serologic parameter that could be helpful in the followup of patients with myositis.

John H. Stone, William J. C. Amend, and Lindsey A. Criswell 1438

Glomerulonephritis is one of the most serious complications of SLE. Many patients with SLE reach end-stage renal disease, and thus become candidates for renal transplantation. The outcome of this procedure has not been well-studied in SLE patients. The present report describes the largest single-center experience with renal transplantation in SLE, and indicates inferior transplantation outcomes among 97 SLE patients who underwent a total of 106 transplantation procedures compared with controls who were matched for age, sex, race, type of allograft (cadaveric versus living-related), number of previous transplants, and year of transplantation.

Georg Schett, Gunter Steiner, and Josef S. Smolen 1446

The present investigation consisted of a series of immunoprecipitation and immunoblotting studies as well as blocking experiments of the LE cell phenomenon. The data obtained reveal that histone H1 is the major monomeric proteinaceous autoantigen reactive with the LE cell factor.

Ming Pang, Tohru Abe, Tsutomu Fujihara, Shigehisa Mori, Kensei Tsuzaka, Kouichi Amano, Jun Koide, and Tsutomu Takeuchi 1456

This study demonstrates that expression and function of a novel integrin, [alpha]E[beta]7, are up-regulated on activated CD8+ T cells from SLE patients, especially those with oral ulcers and serositis. These findings suggest a possible pathogenic role of this molecule in SLE with epithelial inflammation.

Rosemarie Hirsch, Jing-Ping Lin, William W. Scott, Jr., Loralie D. Ma, Stanley R. Pillemer, Daniel L. Kastner, Lennart T. H. Jacobsson, Daniel A. Bloch, William C. Knowler, Peter H. Bennett, and Sherri J. Bale 1464

The clinical features and familial distribution of RA in the Pima Indians are reported. The findings demonstrate how population-based genealogic, epidemiologic, and demographic data can be used to characterize a complex disorder and to understand potential genetic contributions to RA.

Niels A. Graudal, Anne Grethe Jurik, Anselmo de Carvalho, and Hans K. Graudal 1470

The present study shows that the progression of radiographic damage in individual patients with RA can be described by mathematical functions. Consequently, it may be possible to use a single cross-sectional evaluation of radiographic joint damage as an outcome estimate, if the duration of RA at the time of evaluation is known. Practical methods to optimize the use of the R-score statistic are suggested, especially for the prognostic evaluation of patients with RA.

Maarten C. Kraan, Hans Versendaal, Margreet Jonker, Barry Bresnihan, Wendy J. Post, Bert A. `t Hart, Ferdinand C. Breedveld, and Paul P. Tak 1481

This report describes the synovial cellular infiltrate in clinically involved and clinically uninvolved knee joints from both animal models of arthritis and patients with RA. The aim was to provide insight into the pathobiologic events involved in the onset of RA in relation to clinical symptoms. The need for early therapeutic intervention is underscored by the perception that when signs and symptoms of RA occur, the patient is already confronted with longstanding synovitis.

Thomas Hohler, Thomas Schaper, Peter M. Schneider, Karl-H. Meyer zum Buschenfelde, and Elisabeth Marker-Hermann 1489

This study investigated the frequency of the TNF[alpha] promoter alleles in B27-positive patients with ankylosing spondylitis and in 2 control populations. It was found that allelic variations in the TNF[alpha] promoter influence disease susceptibility in B27-positive subjects. This protective effect of variant promoter alleles could be related to differences in TNF[alpha] production or could reflect the association of different B27 haplotypes with ankylosing spondylitis.

Conor J. McCarthy, Susan Sheldon, Charles W. Ross, and W. Joseph McCune 1493

This work stresses the need for continued vigilance in the use of alkylating drugs for the treatment of rheumatic disease, particularly when high cumulative doses have been used. Characteristic chromosomal changes occur in the setting of myelodysplastic syndromes, which may have prognostic significance.

Miguel A. Gonzalez-Gay, Ricardo Blanco, Vicente Rodriguez-Valverde, Victor M. Martinez-Taboada, Miguel Delgado-Rodriguez, Manuel Figueroa, and Esther Uriarte 1497

Permanent visual loss (VL) and cerebrovascular accidents (CVA) are the most dreaded complications of GCA. This study established the predictors of permanent VL in GCA: transient VL (amaurosis fugax), jaw claudication, normal liver enzyme levels, and absence of constitutional syndrome (fever and or/weight loss). In patients with transient VL, although a temporal artery biopsy should be performed to confirm the diagnosis, high-dose corticosteroid therapy should be started immediately. Once VL develops, treatment may be partially effective if started within the first 24 hours. CVA usually occurred despite appropriate corticosteroid therapy; its predictors were permanent VL and jaw claudication.