Gerald N. Smith, Jr., Stephen L. Myers, Kenneth D. Brandt, and Elizabeth A. Mickler 976

Intraarticular hyaluronan injection is currently in use as a palliative treatment of knee OA. The possibility that this treatment might also have a disease-modifying effect was examined in experimental canine OA. It was found that intraarticular hyaluronan injection did not alter the progression of early OA, but, 7 weeks after the last hyaluronan injection, the proteoglycan concentration in articular cartilage from the hyaluronan-injected knee was lower than that in the contralateral knee or in saline-injected control knees.

L. Hambach, D. Neureiter, G. Zeiler, T. Kirchner, and T. Aigner 986

This comparative in situ analysis of the expression and distribution patterns of type VI collagen chains, the major type of pericellular collagen, demonstrates a severe disturbance of the pericellular microenvironment of chondrocytes in OA cartilage as well as the attempts of the cells to counteract this disturbance by increasing their synthetic activity. These results provide evidence that increased degradation and remodeling of the pericellular matrix is a key factor in OA cartilage destruction.

Anneliese D. Recklies, Linon Baillargeon, and Chantal White 997

Increased serum and synovial fluid levels of COMP have been associated with accelerated joint erosion in arthritis. This study demonstrates that COMP is synthesized in synovial tissue as well as in cartilage. The finding that synovial cells can contribute to the pool of COMP released into the circulation indicates that increased COMP levels may be indicative of active synovitis, which could directly or indirecly contribute to accelerated joint damage.

Tibor T. Glant, Gabriella Cs-Szab6, Hideaki Nagase, Joshua J. Jacobs, and Katalin Mikecz 1007

Immunization with high-density cartilage proteoglycan (aggrecan) induces progressive polyarthritis in genetically susceptible BALB/c mice. This arthritis model shares similarities with human RA. This report describes a simple method of arthritis induction using proteoglycans from normal or OA cartilage samples.

Alexei Guerassimov, Yping Zhang, Subhashis Banerjee, Annie Cartman, Jean-Yves Leroux, Lawrence C. Rosenberg, John Esdaile, Mary-Ann Fitzcharles, and A. Robin Poole 1019

The results of this study demonstrate that patients with RA exhibit increased cellular immunity to the Nterminal G1 globular domain of cartilage PG. Thus, the G1 domain may be a candidate autoantigen in RA.

Wataru Ikematsu, Fu-Lung Luan, Luigi La Rosa, Barbara Beltrami, Ferdinando Nicoletti Jill P. Buyon, Pier Luigi Meroni Genesio Balestrieri, and Paolo Casali 1026

Anticardiolipin antibodies are closely associated with recurrent thrombosis and fetal loss. It has been shown that the presence of ,B2-glycoprotein I is necessary in order for autoimmune aCL to be detected in a solidphase assay, and this I32-glycoprotein I dependence has been suggested to represent a characteristic that differentiates autoimmune aCL from aCL occurring secondary to infection. This study demonstrates that human anticardiolipin IgG monoclonal antibodies that are ,l32-glycoprotein I independent and that utilize minimally mutated VHDJH and KKJK gene segments are able to induce fetal loss and placental necrosis in a passive-transfer murine model.

Hisashi Hasegawa, Toshio Uchiumi Takehiro Sato, Masaoki Arakawa, and Ryo Kominami 1040

This study demonstrates that some anti-Sin antibodies cross-react with ribosomal protein S10 at the carboxyl-terminal region, and shows that the Gly-Arg-Gly sequence motif shared by the S10 protein and the Sm proteins B/B' and D is involved in constructing a cross-reactive epitope. The S10 ribosomal protein can be used as a tool for studying the nature of the epitope, and also for screening of this type of autoantibody in sera from patients with systemic lupus erythematosus

Erik J. Peterson, Kevin M. Latinis, and Gary A. Koretzky 1047

CD95 (Fas/APO-1) is a "death receptor" known to be defective in murine models of autoimmune disease such as Ipr and gld mice, as well as in the human disorder autoimmune Iymphoproliferative syndrome. Intracellular signaling events associated with ligation of the CD95 receptor are incompletely understood. Data presented in this report suggest that a mutant form of the receptor can impair apoptosis signaling in human T Iymphocytes, and suggest a means whereby activated Iymphocytes might evade apoptosis and persist to cause autoimmunity.

Juha Kirveskari, Sirpa Jalkanen, Outi Maki-lkola, and Kaisa Granfors 1054

Reactive arthritis develops as a complication of certain mucosal infections, and components of the causative bacteria found in inflamed joints are thought to be triggering factors for the arthritis. However, the mechanisms by which these antigens are relocated to the joints are unclear. This study provides the first direct evidence that mucosal infection increases the capacity of PBMC to bind to vascular endothelium in inflamed synovium, and that bacterial antigens can be transported within these cells to inflamed joints. Since there is usually a lag period of 1-4 weeks between the infection and the appearance of arthritis, blocking the adhesion of PBMC can be useful for preventing arthritis in susceptible individuals or for treatment during joint inflammation.

David T. Felson, Nat N. Couropmitree, Christine E. Chaisson, Marian T. Hannan, Yuqing Zhang, Timothy E. McAlindon, Michael LaValley, Daniel Levy, and Richard H. Myers 1064

Data were obtained from the Framingham Study to investigate the inheritance of generalized OA among 337 nuclear families with 2 parents and at least 1 biologic offspring. The presence of OA was defined according to the findings on serial hand and knee radiographs. Segregation analyses indicated that generalized OA is inherited, with the most likely pattern of inheritance being that of a major Mendelian gene with a residual multifactorial component.

Frederick Wolfe and Samuel H. Zwillich 1072

It is estimated that total joint arthroplasty is performed in 25% of RA patients within 21.8 years of disease onset, a duration which is within the lifespan of the average RA patient. Almost all disease severity and activity variables are important predictors of TJA. Data from this study suggest that the course of RA can be largely identified within the first 2 years. and that some patients with poor prognoses can be identified even at the first clinic visit.

Patricia Jouvenne, Edouard Cannier, Charles A. Dinarello, and Pierre Miossec 1083

In this study, levels of circulating IL-1 receptor antagonist correlated positively with all indices of disease activity and joint destruction in patients with chronic arthritis. Conversely, levels of soluble IL-1 receptor type II correlated negatively with indices of joint destruction and were higher in patients with nondestructive arthritis than in those with destructive arthritis. Correlations with disease indices were not observed for soluble IL-1 receptor type I. These results indicate a possible therapeutic value of soluble IL-1 receptor type II in rheumatoid arthritis.

Chi Chiu Mod Jerry S. Lanchbury, David Wai Chan, and Chak Sing Lau 1090

IL-10 is a cytokine that is relevant to the pathogenesis of SLE. The recent description of the polymorphisms in the promoter region of the IL-10 gene and their possible influence on IL-10 production has prompted the present study on the role of these polymorphisms in susceptibility to SLE. Identification of subsets of patients who are at risk of developing certain manifestations of the disease allows close monitoring of disease activity in various organs.

Salman Ahmed, Elia M. Ayoub, Juan C Scornik Cong-Yi Wang, and Jin-Xiong She 1096

Poststreptococcal ReA is a recently described clinical entity. Its manifestations are not well recognized and its pathogenesis remains unknown. This article reemphasizes the clinical characteristics of poststreptococcal ReA and provides insight into its pathogenesis, which should facilitate recognition of the disease in patients.

Dacha D. Gladman, Demon T. Farewell, Katy Hong, and Janice Husted 1103

This study shows that patients with psoriatic arthritis are at increased risk for death compared with the general population. Prognostic indicators for death among these patients include evidence of previously active and severe disease as manifested by prior use of medications and by radiologic changes, as well as an elevated ESR at presentation. The presence of nail changes appears to be protective in the context of previously active and severe disease.

Paul J. Nietert, Susan E. Sutherland, Richard M. Silver, Janardan P. Pandey, Rebecca G. Knapp, David G. Hoel, and Mustafa Dosemeci 1111

The primary objective of this study was to determine whether occupational organic solvent exposure is related to an increased risk of SSc. Exposure-disease associations were determined among men and women, among diffuse and limited cutaneous Scleroderma patients, and among those testing positive or negative for anti-Scl-70 autoantibodies. Significant associations with occupational solvent exposure were found among the SSc patients.

Andrew L. Taylor, C. Balakrishnan, and Andrei Calin 1119

The management of ankylosing spondylitis has been hampered by a lack of process and outcome measures. Newly developed outcome measures have improved disease assessment in the research setting. This report documents the construction of reference centile charts for measures of ankylosing spondylitis disease activity, functional impairment, and metrology that will have applications in both research and clinical practice.