John D. Reveille, Graciela S. Alarcon, Sarah E. Fowler, Stanley R. Pillemer, Rosemarie Neuner, Daniel O. Clegg, Isis S. Mikhail, David E. Trentham, James C. C. Leisen, Gilbert Bluhm, Sheldon M. Cooper, Howard Duncan, Marilyn Tuttleman, Stephen P. Heyse, John T. Sharp, and Barbara Tilley, for the MIRA Trial Group 1802

This study examined the effect of alleles encoding the shared epitope/rheumatoid epitope on the severity of RA in patients who participated in the MIRA trial. It was found that DRB1 oligotyping may be useful in predicting the progression of RA in some Caucasian patients. The infrequency of the epitope among African-American patients with RA was corroborated.

Robert B. Zurier, Ronald G. Rossetti, Eric W. Jacobson, Deborah M. DeMarco, Nancy Y. Liu, Joseph E. Temming, Bernadette M. White, and Michael Laposata 1808

This is a controlled clinical trial of an apparently benign substance, Gamma-Linolenic Acid (GLA), in the treatment of RA. It is possible that in the future, GLA will be used by rheumatologists to treat RA, perhaps as a substitute for or an adjunct to more toxic agents. The GLA formulation is being improved, and FDA approval is being sought.

Kenneth G. Saag, Lindsey A. Criswell, Kelly M. Sems, Mary D. Nettleman, and Sheela Kolluri 1818

Despite limited published information on their effectiveness, corticosteroids are widely used for the treatment of RA. This meta-analysis provides the first quantitative appraisal of the effectiveness of corticosteroids.

A. B. J. Prakken, W. van Eden, G. T. Rijkers, W. Kuis, E. A. Toebes, E.R. de Graeff-Meeder, R. van der Zee, and B. J. M. Zegers 1826

This is a prospective followup study of new patients with JRA, showing that T cell reactivity to human hsp60 correlates with a good prognosis in these patients. The findings are also consistent with recent findings in animal models of arthritis. The study gives new insight into the role of this autoreactivity in the pathogenesis of JRA and RA and offers new possibilities for immunologic intervention.

Frank C. Arnett, John D. Reveille, Haralampos M. Moutsopoulos, Liviu Georgescu, and Keith B. Elkon 1833

Studies of antiribosomal P autoantibodies in a large cohort of multiethnic SLE patients revealed frequencies of [approx]15% in most ethnic groups and a striking association with lupus psychosis and depression. Anti-P antibodies were also correlated with an HLA-DR2, DQ6 haplotype and a shared amino acid sequence in HLA-DQB1 molecules, thusindicating a genetic influence on this autoimmune response.

William Stohl, Julie E. Elliott, Ann S. Hamilton, Dennis M. Deapen, Thomas M. Mack, and David A. Horwitz 1840

Despite extensive knowledge regarding immune abnormalities in SLE, the pathogenesis of SLE remains enigmatic. Identification of predisposing factors to SLE susceptibility will enable investigators to focus on these factors, elucidate their nature, and, ultimately, promote development of specific preventive and/or therapeutic modalities to mitigate or counteract the "SLE-promoting" features of such factors. In this report, evidence is presented suggesting that a defect in the number and cytolytic function of CD56+ T cells may be one such predisposing factor for SLE.

Don Goldenberg, Michael Mayskiy, Christopher Mossey, Robin Ruthazer, and Christopher Schmid 1852

This study investigated the efficacy of 2 commonly used medications, fluoxetine and amitriptyline, alone or in combination, in the treatment of fibromyalgia. The results indicate that a combination of the 2 agents is more effective than placebo or either of the medications used alone.

Bruno Stuhlmuller, Ricardo Jerez, Gert Hausdorf, Hans-R. Barthel, Michael Meurer, Eckehard Genth, Joachim R. Kalden, and Gerd R. Burmester 1860

Autoantibodies against intracellular molecules have been demonstrated in the sera of patients with idiopathic inflammatory myopathies. However, the autoantigens recognized thus far have not been specific for muscle-cell structures. In this study, the presence of muscle-cell surface membrane antigen-directed autoantibodies was documented at the highest levels in patients with polymyositis, with a wide variation in antibody binding activity among patients with dermatomyositis and other rheumatic diseases. Since the antigen is localized in the muscle-cell surface membrane, these autoantibodies could play a major role in the pathogenesis of polymyositis.

Joaquin Arenas, Maria R. Gonzalez-Crespo, Yolanda Campos, Miguel A. Martin, Ana Cabello, and Juan J. Gomez-Reino 1869

This study shows abnormal distribution of muscle carnitine and signs of mitochondrial dysfunction in patients with idiopathic inflammatory myopathy. These findings may lead to new means of therapy to be explored in the field of inflammatory myopathies.

Noriyoshi Ogawa, Howard Dang, Liping Kong, Juan-Manuel Anaya, George Tye Liu, and Norman Talal 1875

This study showed that peripheral blood T lymphocytes from patients with Sjogren's syndrome demonstrated accelerated in vitro apoptoxis and increased expression of the death-suppressor gene, bcl-2. However, bcl-2 messenger RNA expression and protein levels decreased with time under in vitro conditions. The rate of decrease was not significantly different than that in normal T cells. These findings suggest that apoptotic abnormalities of lymphocytes are involved in the pathogenesis of Sjogren's syndrome. Agents that modulate apoptosis may be useful in the treatment of autoimmune diseases like Sjogren's syndrome.

Michito Hirakata, Jyotshna Kanungo, Akira Suwa, Yoshihiko Takeda, Joe Craft, and John A. Hardin 1886

Autoantibodies to RNA polymerase II have been found in patients with scleroderma. This study demonstrates that the carboxyl terminal domain of the large subunit of this enzyme is a focal point for autoimmune responses, suggesting that the heptapeptide repeat of this molecular segment constitutes an important autoantigenic epitope. Knowledge of this autoimmunogen is important for understanding the pathogenesis of scleroderma and autoantibodies associated with this disease.

Jens G. Kuipers, Richard B. Raybourne, Kristina M. Williams, Henning Zeidler, and David Tak Yan Yu 1892

In view of the low prevalence of ankylosing spondylitis and reactive arthritis in HLA-B27 positive individuals, additional modifying or susceptibility genes have been purported to act in concert with HLA-B27. The TAP genes are potential candidates, since they are polymorphic and provide antigenic peptides to be loaded in HLA-B27. In this study, it was found that the polymorphism of human TAP does not affect translocation of HLA-B27-binding peptides, and therefore probably does not play a decisive role in the development of these diseases.

Johannes Flechtenmacher, Klaus Huch, Eugene J-M. A. Thonar, Juergen A. Mollenhauer, Sherri R. Davies, Thomas M. Schmid, Wolfhart Puhl, T. Kuber Sampath, Margaret B. Aydelotte, and Klaus E. Kuettner 1896

This report presents evidence that osteogenic protein-1 (OP-1), a bone morphogenetic protein (BMP) also known as BMP-7, is one of the most potent stimulators of cartilage-specific proteoglycans and collagens. This morphogenetic protein does not appear, at least in the short term, to adversely affect the stability of the chondrocyte phenotype. It could thus prove useful in promoting repair of articular cartilage in diseases such as osteoarthritis and in promoting cartilage matrix formation by transplanted chondrocytes.

Sally R. Frenkel, Robert M. Clancy, John L. Ricci, Paul E. Di Cesare, John J. Rediske, and Steven B. Abramson 1905

This study addresses the important issue of chondrocyte repair of damaged cartilage, showing, for the first time, that chondrocytes are capable of directed migration in vitro. The migration of cells of chondrocyte lineage may be important for normal growth and repair. These data also demonstrate that nitric oxide, which is known to be produced by both chondrocytes and synovial cells, inhibits chondrocyte migration and attachment, probably via disruption of actin assembly. These findings suggest that clinical therapeutic strategies could be developed that reduce nitric oxide production in order to promote cartilage repair processes both in acute injury and chronic conditions such as osteoarthritis.

Hani El-Gabalawy, Janice Canvin, Guoping M. Ma, Monica van der Vieren, Patricia Hoffman, Michael Gallatin, and John Wilkins 1913

This report describes the distribution of a new β2-integrin, αd/CD18, in normal and pathologic synovium. This molecule is widely expressed on synovial macrophages and lymphocytes. The only known ligand for αd is ICAM-3, and the presence of large numbers of leukocytes expressing this receptor/ligand pair in inflamed synovium suggests that they may play a role in cellular interactions in the synovium.