Filemon K. Tan, David N. Stivers, Morris W. Foster, Ranajit Chakraborty, Robert F. Howard, Dianna M. Milewicz, and Frank C. Arnett 1729

This study utilized microsatellite markers together with genetic epidemiology methods to identify genetic loci associated with a high prevalence of scleroderma among Oklahoma Choctaw Native Americans. The genotyping data implicated fibrillin 1 as a possible susceptibility gene. An abnormality in fibrillin 1, an extracellular matrix protein, is also responsible for the tight skin 1 mouse phenotype, a model of human scleroderma.

Anne Bordron, Maryvonne Dueymes, Yair Levy, Christophe Jamin, Lea Ziporen, Jean-Charles Piette, Yehuda Shoenfeld, and Pierre Youinou 1738

This is the first study to establish the ability of anti-endothelial cell autoantibodies to initiate the exposure of phosphatidylserine. Anionic phospholipids then become available for binding to β2-glycoprotein I and, subsequently, to aPL. Since independent data indicate that aPL bind to apoptotic cells, the findings in this study contribute to a new field for investigation. The study data provide a mechanism by which these autoantibodies may be pathogenic, and it is proposed that some may have the potential to induce the production of aPL, which is known to be associated with the primary antiphospholipid syndrome.

Danielle Burger, Roger Rezzonico, Jian-Mei Li, Christine Modoux, Richard A. Pierce, Howard G. Welgus, and Jean-Michel Dayer 1748

Synovial tissue T cell clones and peripheral blood T lymphocytes stimulated for long periods of time were shown to trigger the production of prostaglandin E2 and matrix metalloproteinase 1, but not TIMP-1, in synoviocytes and dermal fibroblasts, thus inducing an imbalance between the metalloenzyme and its inhibitor. This is consistent with a putative role of T lymphocytes in the maintenance of inflammation at the inflammatory site. These results demonstrate that T cells may affect fibroblast and synoviocyte functions directly (i.e., by contact activation) and indirectly (i.e., by activation of cytokine production in monocyte/macrophages, which in turn, trigger stromal cell functions). Since the production of matrix metalloproteinases in monocyte/macrophages is also induced upon contact with stimulated T cells, the results strongly suggest that contact of synovial cells with chronically stimulated T lymphocytes favors matrix catabolism. By analogy, this mechanism may trigger tissue destruction in vivo and, thus, may potentiate tissue destruction in chronic inflammatory diseases such as rheumatoid arthritis.

Jennifer Leigh Cannons, Jacob Karsh, H. Chaim Birnboim, and Rose Goldstein 1772

This study describes a novel approach to studying the specific T cells involved in the rheumatoid arthritis disease process using an assay for somatic gene mutation. Knowledge of the characteristics of the T cells active in rheumatoid arthritis will lead to a better understanding of the biologic mechanisms involved in this clinical entity.

R. Wikaningrum, J. Highton, A. Parker, M. Coleman, P. A. Hessian, P. J. Roberts-Thomson, M. J. Ahern, and M. D. Smith 1783

This study examined the production of cytokines, at the messenger RNA and protein levels, and cell adhesion molecule expression in rheumatoid nodules (a common extraarticular feature of RA) and in paired synovial membrane samples. The similarities in cytokine production between rheumatoid nodules and synovial membranes suggest that there are significant similarities in the pathogenic mechanisms of chronic inflammation in both types of RA lesions.

Yuhe Ma, Sherry Thornton, Gregory P. Boivin, David Hirsh, Raphael Hirsch, and Emmet Hirsch 1798

Rheumatoid arthritis is characterized by an imbalance between proinflammatory and antiinflammatory cytokines. The proinflammatory cytokine IL-1 is a major mediator of inflammation. The present study demonstrates that endogenous overexpression of the gene for IL-1 receptor antagonist, a natural inhibitor of IL-1, protects mice from collagen-induced arthritis, while targeted disruption of IL-1 receptor antagonist renders mice more susceptible to collagen-induced arthritis. These results suggest that IL-1 receptor antagonist may be a useful therapeutic agent in rheumatoid arthritis.

Richard O. Williams, Claudia Mauri, Lesley J. Mason, Lilia Marinova-Mutafchieva, Susan E. Ross, Marc Feldmann, and Ravinder N. Maini 1806

There is a growing need to understand the mechanisms of action of existing or novel therapeutic agents used for treating rheumatoid arthritis. This study helps to elucidate how 2 novel drugs, cyclosporine and anti-TNFα antibody, mediate their therapeutic effects in vivo. In addition, the effects of combined treatment with cyclosporine and anti-TNFα are evaluated.

Harry R. Koene, Marion Kleijer, Anton J. G. Swaak, Kathleen E. Sullivan, Marc Bijl, Michelle A. Petri, Cees G. M. Kallenberg, Dirk Roos, Albert E. G. K. von dem Borne, and Masja de Haas 1813

The FcγRIIIa-158V/F polymorphism influences the affinity of the receptor for IgG. In this study, 70 SLE patients were typed for all known FcγR polymorphisms. Only the FcγRIIIa-158F isoform, which has a relatively low affinity for IgG, was found to be a risk factor for SLE.

Kunio Isshi and Shunsei Hirohata 1819

The results of the present study disclosed the differential roles of antineuronal cell antibodies (anti-N) and anti-ribosomal P protein antibodies (anti-P) in the pathogenesis of lupus psychosis. Anti-P in the serum compartment and anti-N in the cerebrospinal fluid compartment may each play a critical role in neuropsychiatric systemic lupus erythematosus, although anti-N appear to have a more direct effect on disease development than do anti-P antibodies.

Daniel F. Battafarano, Nicholas J. Battafarano, Lawrence Larsen, P. Dennis Dyer, Steven A. Older, S. Muehlbauer, A. Hoyt, J. Lima, David Goodman, Michael Lieberman, and Raymond J. Enzenauer 1828

Infection is a leading cause of morbidity and mortality in SLE. The present results show that immunization of SLE patients is both safe (i.e., does not cause disease flare) and efficacious (i.e., protective serum antibody levels are attained). These findings indicate that SLE patients should be immunized according to the recommendations of the Immunization Practices Advisory Committee.

M. Haubitz, S. Schellong, U. Gobel, H. J. Schurek, D. Schaumann, K. M. Koch, and R. Brunkhorst 1835

This prospective, controlled study shows equal efficacy of IV pulse administration of CYC compared with standard, daily oral CYC administration in patients with ANCA-associated vasculitis and renal involvement. IV pulse CYC therapy led to a significantly reduced short-term toxicity, and possibly to fewer long-term side effects, as a result of a 57% reduction of the total CYC dose. Thus, this treatment approach should be considered in ANCA-associated vasculitis and renal involvement, a group of diseases with a potentially favorable long-term prognosis.

Anke M. van Gestel, Cees J. Haagsma, and Piet L. C. M. van Riel 1845

This validation study of RA response criteria was performed to improve uniformity among researchers measuring treatment effects in groups of RA patients by using standardized and validated measures. It was found that criteria sets that include 28-joint counts are as valid as those that include more comprehensive joint counts.

Judith Fifield, Howard Tennen, Susan Reisine, and Julia McQuillan 1851

In this study, it was found that a prior episode of major depression leaves rheumatoid arthritis patients at risk for higher levels of pain long after the depressive episode. These findings illustrate the importance of assessing whether past episodes of distress meet criteria for lifetime major depression, even when caring for patients who do not currently meet criteria for a depressive disorder.

Jan N. Stolk, Agnes M. T. Boerbooms, Ronney A. de Abreu, Diana G. M. de Koning, Henk J. van Beusekom, Wim Hissink Muller, and Leo B. A. van de Putte 1858

Thirty-three RA patients beginning AZA treatment and 66 controls were studied to assess whether thiopurine enzyme activities have prognostic value for predicting the development of AZA-related toxicity in RA. The results show that inherited intermediate thiopurine methyltransferase activity seems predictive for the development of severe, predominantly nonhematologic side effects (relative risk 3.1). This implies that in clinical practice, thiopurine methyltransferase activity should be measured prior to the initiation of AZA treatment in order to prevent severe side effects.

Yuqing Zhang, Timothy E. McAlindon, Marian T. Hannan, Christine E. Chaisson, Ray Klein, Peter W. F. Wilson, and David T. Felson 1867

In this population-based, prospective cohort study, current estrogen replacement therapy had a moderate, but not statistically significant, protective effect against worsening of radiographic knee osteoarthritis among elderly white women. The findings corroborate those of cross-sectional studies and point further to a potential benefit of female hormones in osteoarthritis.

Isabelle Marie, Herve Levesque, Philippe Ducrotte, Philippe Denis, Jacques Benichou, Marie-France Hellot, Nicole Cailleux, Xavier Le Loet, Pascal Joly, Philippe Lauret, and Hubert Courtois 1874

The findings of this study suggest that manometry of the upper intestinal tract may be useful in SSc patients with clinical manifestations in the small bowel (i.e., malabsorption syndrome or pseudoobstruction) in that it can be used to accurately evaluate both the nature and the severity of motor disturbances. Furthermore, this procedure can be used to assist in the selection of patients who may require octreotide therapy.