Larry W. Moreland, Elizabeth E. Morgan, Thomas C Adamson, III, Zdenka Fronek Leonard H. Calabrese,Joseph M. Cash, Joseph A. Markenson, Alan K Matsumoto, Joan Bathon, Eric L. Matteson,Kristine M. Uramoto, Comelia M. Weyand, William J. Koopman, Louis W Heck Vibeke Strand,Jocelyn P. Diveley, Dennis J. Carlo, Christopher J. Nardo, Steven P. Richien, and Steven W Brostoff 1919

As pathogenetic mechanisms that are operative in RA are better defined, better therapies can be providedfor patients. There is significant evidence that T cells are involved in the pathogenesis of RA. This placebocontrolled trial provides information on the safety and efficacy of vaccination with T cell receptor peptidesVb33, V~14, and Vb17. Further clinical trials are planned to confirm and extend these initial observations.

B. E E. M. van den Borne, R. B. M. Landewe, I. Houkes, F. Schild, P. C. W. van der Heyden,J. M. W Hazes, J. P. Vandenbroucke, A. H. Zwinderman, H. S. Goei The, F. C. Breedveld,H. J. Bemelot Moens, P. M. Kluin, and B. A. C. Dijkmans 1930

The use of the immunosuppressive drug CSA has been associated with an increased risk of malignant Iymphoproliferative diseases (LPDs) and skin cancers in organ transplant patients. In this study, patients with RA who were being treated with CSA did not exhibit an increased risk of malignancies in general or malignant LPDs or skin cancers in particular. Moreover, the incidence of mortality in CSA-treated RA patients was comparable with that in matched control RA patients.

Christof Zimmermann, Gunter Steiner, Karl Skriner, Wolfgang Hassfeld, Peter Petera, and Josef S. Smolen 1938

This report describes 3 patients with longstanding RA in whom limited systemic sclerosis evolved late in the course of RA. Comparison with control groups of patients with RA or with limited systemic sclerosis, and observations on the autoantibody profiles in the 3 patients, led to the conclusion that these patients had a novel, benign type of overlap syndrome.

J. Aerssens, J. Dequeker, J. Peeters, S. Breernans, and S. Boonen 1946

Association studies have the potential to identify genetic markers associated with increased susceptibility to OA. Because an association between early knee OA and a polymorphism at the vitamin D receptor (VDR) gene was recently suggested, this study was undertaken to examine the possibility of such an association between hip OA and polymorphisms at 3 candidate genes, including the VDR gene. In the white postmenopausal female population studied, no significant contribution of these polymorphisms to hip OA was found.

Charles Slemenda, Douglas K Heilman, Kenneth D. Brandt, Barry P. Katz, Steven A. Mazzuca, Ethan M. Braunstein, and Donna Byrd 1951

The present study showed that baseline quadriceps strength, adjusted for lower extremity muscle mass or for body weight, was lower in women who developed incident radiographic OA during a 2-3 year followup than in female controls whose knee radiographs remained normal during this interval. No such relationship between decreased quadriceps strength relative to body weight and incident OA was apparent in men, and no relationship between hamstring strength and OA was noted in either sex. Furthermore, there was a strong inverse relationship between body weight and quadriceps strength relative to weight in women who developed incident OA; i.e., the heavier the subject, the greater the quadriceps weakness. These results suggest that quadriceps weakness may be a risk factor for the pathologic changes of knee OA in women, and quadriceps strengthening exercises may be a valid recommendation for women in this age group, particularly for those who are obese.

Pierre Duhaut, Laurent Pinede, Sylvie Demolombe-Rague, Robert Loire, Dominique Seydoux, Jacques Ninet, and Jean Pasquier, on Behalf of the Groupe de Recherche Sur l'Arterite a Cellules Geantes 1960

As an important step in understanding the etiology of GCA, cardiovascular risk factors were determined separately for each sex. No significant risk factors were identified among the men at disease onset. Among the women, smoking and a preexistent peripheral vascular disease appeared to be independently associated with GCA.

Manuel Martinez-Lavin, Antonio G. Hermosillo, Martin Rosas, and Maria-Elena Soto : 1966

Dysautonomia has been proposed as a pathogenetic factor in fibromyalgia. In this study, heart rate variability was assessed in fibromyalgia patients and controls, and variability was found to be diminished in the patients. Analysis of heart rate variability is a useful, noninvasive tool to study the function of the autonomic nervous system.

Yukiko Ohyama, Seiji Nakamura, Hideo Hara, Masanori Shinohara, Masanori Sasaki Akiko Ikebe-Hiroki, Takefumi Mouri, Shizuka Tsunawaki, Kihachiro Abe, Kanemitsu Shirasuna, and Kikno Nomoto 1972

This study addressed the involvement of HTLV-I in the pathogenesis of SS. HTLV-I proviral DNA in the labial salivary glands of HTLV-I-seropositive patients with SS was mainly detected in the nucleus of the infiltrating T cells. Quantitative detection of HTLV-I proviral DNA indicated the viral loads in the salivary glands to be substantially higher than those in the peripheral blood mononuclear cells. Thus, an accumulation of HTLV-I-infected T cells in the salivary glands may play an important role in the pathogenesis of HTLV-I-associated SS.

Fumiaki Imamura, Hiroyuki Aono, Tomoko Hasunuma, Takayuki Sumida, Hiroomi Tateishi, Souji Maruo, and Kusuki Nishioka 1979

The exact etiology of RA is not yet clear. This is the first report to suggest that the presence of synoviocytes with high proliferative activity plays a role in the development of RA, and that these synoviocytes are likely to be of monoclonal origin, especially synoviocytes found in pannus lesions. These cells may be responsible for the destruction of joint cartilage and bone in RA.

Matthew P. Vincenti, Charles I. Coon, and Constance E. Brinckerhoff 1987

The cartilage degradation observed in rheumatoid arthritis is due in part to IL-1-induced MMP-1 expression by synovial fibroblasts. Results of the present study show that transcriptional activation of the MMP-1 promoter in IL-1-stimulated synovial fibroblasts requires a binding site for dorsal, the Drosophila homolog of nuclear factor KB (NF-KB) (nucleotide -3,029), as well as an activator protein 1 site (nucleotide -77). The transcription factor NF-KB/p50 binds to the dorsal-like site in response to IL-1, thus demonstrating a novel role for NF-KB/p50 in cartilage degradation.

Hiroyuki Aono, sushi Fujisawa, Tomoko Hasunuma, Susan J. Marriott, and Kusuki Nishioka 1995

This is the first report that extracellular HTLV-I Tax protein stimulates cytokine production and the proliferation of Synovial cells. Proliferation of these cells correlated with HTLV-I Tax protein-induced activation of transcription factor NF-KB in the same cells.

Takemine Mino, Eiji Sugiyama, Hirofumi Taki, Arihiko Kuroda, Nachiro Yamashita, Muneharu Marayama, and Masashi Kobayashi 2004

IL-11, an IL-6-type cytokine, has several biologic activities related to inflammatory events in rheumatoid joints. This study shows that IL-1a and TNFa synergistically stimulate the production of IL-11 in rheumatoid Synovial fibroblasts, and that atypical protein kinase C-mediated signaling is involved in the induction of IL-11 by these cytokines. These results provide new insights into the pathophysiology of joint destruction in rheumatoid arthritis.

H. Matsuno, T. Sawai T. Nezaka, M. UZuki H. Tsuji N. Nishimoto, and K Yoshizaki 2014

In this study, a murine model of human RA was developed using SCID mice implanted with RA Synovial tissue. In further studies in which this model was used to examine the effect of anti-reshaping human IL-6 receptor monoclonal antibody on RA synovitis, the anti-reshaping IL-6 receptor antibody appeared to have an antiinflammatory effect. This monoclonal antibody might represent a potential new therapeutic strategy for use in patients with RA.

Paul H. Wooley, Sudha Sud, Janey D. Whalen, and Sam Nasser 2022

Rheumatoid arthritis (RA) is an autoimmune disease that is hypothesized to be T cell mediated. However, the pathologically relevant immunologic event that activates T cells in RA has not been identified, and early immunologic events are difficult to study in RA patients. Pristane-induced arthritis is a unique murine model of seropositive RA that is elicited via a nonantigenic specific mechanism. The resulting arthritis and broad spectrum of autoantibodies in pristane-induced arthritis are dependent on an intact T cell response. In this study, pristane was shown to cause a polyclonal expansion of T cells within the lymph node, but a restricted T cell population infiltrating the arthritic joint. These insights may strengthen T cell-targeted immunotherapy for rheumatoid disease.

Michael Seitz, Marianne Zwicker, and Pius Loetscher 2032

This study may help to improve our understanding of the mode of action of MTX in inflammatory diseasessuch as rheumatoid arthritis. Knowledge of the exact mechanisms of the antiinflammatory action of MTXon monocytes should facilitate its use in combination with complementary drugs such as disease-modifyingantirheumatic drugs or biologic agents, for therapeutic intervention in rheumatoid arthritis and otherchronic inflammatory diseases.

Carlo Chizzolini Roger Rezzonico, Clio Ribbens, Danielle Burger, Frank A. Wollheim, and Jean-Michel Dayer 2039

This report describes the effect of Iymphocyte-to-fibroblast contact on collagen synthesis, as determined in an in vitro study prompted by the observation that early active skin lesions in SSc are characterized by lymphocyte infiltration next to areas of increased extracellular matrix deposition. The results show that activated T cells specifically down-regulate collagen production, that interferon-y associated with membranes of activated T cells is, at least in part, responsible for the inhibitory activity, and that SSc skin Fibroblasts are more resistant to inhibition than are fibroblasts from normal controls.

Elena G. Hitraya, John Varga, Carol M Artlett, and Sergio A. Jimenez 2048

This study demonstrates that a short region in the proximal promoter of COLIAI containing 2 tandem NF1/Spl elements displays up-regulated transcriptional activity in SSc fibroblasts and that SSc fibroblastscontain 3.4-fold greater DNA binding activity recognizing these elements than normal cells. Identification ofthe elements in COLlA1 involved in the up-regulated expression of this gene in SSc fibroblasts may opennew avenues for the development of novel therapeutic interventions for controlling tissue fibrosis in SSc andother fibrogenic processes.

Yoshihiko Takeda, Kim S. Wise, Grace Wang, Giuua Grady, Evelyn V. Hess, Gordon C. Sharp, William S. Dynan, and John A. Hardin 2059

This study provides information about the presence of new autoantibodies that recognize native structures of the particle containing Sm-core proteins, which are not distinguishable from classic anti-Sin antibodies by conventional assays for antinuclear antibodies. Furthermore, these antibodies are common in classic antiSm-positive sera. With respect to mechanisms of autoantibody production, these findings support the possibility that the native U snRNP particle itself is available to the immune system in systemic rheumatic diseases.

Ivan G. Ottemess, James D. Eskra, Marcia L. Bliven, Anne K Shay, Jean-Pierre Pelletier, and A. J. Milici 2068

This study demonstrates that cartilage degeneration in the hamster can result from a sedentary lifestyle. Exercise maintains the proteoglycan content of young articular cartilage and the synovial fluid volume of the younger animal; exercise also prevents cartilage fibrillation, pitting, and fissuring. These results indicate that joint disuse may be a factor in cartilage degeneration.