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Special Articles

Guidelines for the Management of Rheumatoid Arthritis

• American College of Rheumatology Ad Hoc Committee on Clinical Guidelines 713

Guidelines for Monitoring Drug Therapy in Rheumatoid Arthritis

• American College of Rheumatology Ad Hoc Committee on Clinical Guidelines 723

Clinical Science

Cigarette Smoking Increases the Risk of Rheumatoid Arthritis: Results from a Nationwide Study of Disease-Discordant Twins

• Alan J. Silman, Jason Newman, and Alexander J. MacGregor 732
• This study demonstrated that among twin pairs who were discordant for disease, there was a strong association between cigarette smoking and susceptibility to RA. Identification of risk factors such as cigarette smoking is important in understanding the etiology of RA.

Detection of Borrelia burgdorferi by DNA Amplification in Synovial Tissue Samples from Patients with Lyme Arthritis

• Benoit Jaulhac, Isabelle Chary-Valckenaere, Jean Sibilia, Rose-Marie Javier, Yves Piemont, Jean-Louis Kuntz, Henri Monteil, and Jacques Pourel 736
• This prospective study shows that in some cases of Lyme arthritis in which PCR of synovial fluid is negative for B burgdorferi, the spirochete can be detected in synovial tissue. Therefore, negative PCR results must be interpreted cautiously when evaluating a suspected case of Lyme arthritis. Moreover, when using a chromosomal target, B burgdorferi DNA can be detected more easily from synovium than from joint fluid.

Bone Mineralization and Bone Mineral Metabolism in Children with Juvenile Rheumatoid Arthritis

• Peri Hickman Pepmueller, James T. Cassidy, Susan H. Allen, and Laura S. Hillman 746
• Concurrent development of osteopenia and a chronic disease such as juvenile rheumatoid arthritis results in an increased frequency of skeletal growth abnormalities and fractures in the child, and a failure to achieve peak bone mass in the early adult years. The present study investigates the magnitude and pathogenic mechanisms of this osteopenia. Based on the results, proposed therapeutic interventions are discussed.

Anti-Endothelial Cell IgG Antibodies from Patients with Wegener's Granulomatosis Bind to Human Endothelial Cells In Vitro and Induce Adhesion Molecule Expression and Cytokine Secretion

• Nicoletta Del Papa, Luisa Guidali, Marina Sironi, Yehuda Shoenfeld, Alberto Mantovani, Angela Tincani, Genesio Balestrieri, Antonella Radice, R. Alberto Sinico, and Pier Luigi Meroni 758
• Wegener's granulomatosis is a prototype of primary autoimmune vasculitis in which the exact pathogenetic mechanism(s) is still a matter of debate. Wegener's vasculitis is frequently a life-threatening disease; a better knowledge of its pathogenesis could help us determine the best therapeutic approach. Anti-endothelial antibodies are relatively new antibodies frequently found in patients with autoimmune vasculitis; studies on their potential pathogenetic effects offer new insights into their diagnostic and/or prognostic value.

Mixed Monoclonal Cryoglobulinemia and Monoclonal Rheumatoid Factor Cross-Reactive Idiotypes as Predictive Factors for the Development of Lymphoma in Primary Sjogren's Syndrome

• Athanasios G. Tzioufas, Dimitra S. Boumba, Fotini N. Skopouli, and Haralampos M. Moutsopoulos 767
• Patients with Sjogren's syndrome are at increased risk for the development of lymphoma. Previous studies have shown that lymphadenopathy and parotid gland enlargement are associated with lymphoma development. This study demonstrates that mixed monoclonal cryoglobulinemia and monoclonal rheumatoid factor cross-reactive idiotypes may also serve as predictive factors for lymphoma development in Sjogren syndrome patients.

Increased Expression of Human Thioredoxin/Adult T Cell Leukemia-Derived Factor in Sjogren's Syndrome

• Ichiro Saito, Misa Shimuta, Kumiko Terauchi, Kazuo Tsubota, Junji Yodoi, and Nobuyuki Miyasaka 773
• The coexistence of TRX/ADF, a redox regulator capable of inducing lymphocyte activation, and Epstein-Barr virus was detected in the labial salivary glands of patients with SS. These findings suggest that TRX/ADF expression closely reflects the intracellular event of EBV reactivation in SS and might be etiologically associated with the disease.

Aberrant Expression Pattern of the SS-B/La Antigen in the Labial Salivary Glands of Patients with Sjogren's Syndrome

• P. C. M. de Wilde, L. Kater, C. Bodeutsch, F. H. J. van den Hoogen, L. B. A. van de Putte, and W. J. van Venrooij 783
• This study investigated differences in the localization of SS-B/La in labial salivary glands of Sjogren's syndrome patients versus control patients. The consistently enhanced nuclear immunostaining of SS-B/ La in acinic cells from the labial salivary glands of patients with Sjogren's syndrome seems to be a promising tool to improve the diagnosis of this disease using the lip biopsy.

Elevated Serum Level of Soluble HLA Class I Antigens in Patients with Systemic Lupus Erythematosus

• Naoyuki Tsuchiya, Michiko Shiota, Akihiro Yamaguchi, and Koji Ito 792
• This study demonstrated a markedly elevated serum level of soluble HLA class I antigens in patients with SLE and a small, but significant, rise in patients with rheumatoid arthritis. This information may provide a clue for elucidating the pathogenesis of SLE. In addition, soluble HLA class I might potentially be useful as a laboratory marker for active SLE.

Clinical Images

Subcutaneous Calcinosis in Systemic Sclerosis

• Jean-Luc Senecal 796

Basic Science

Anticytokine Treatment of Established Type II Collagen-Induced Arthritis in DBA/1 Mice: A Comparative Study Using Anti-TNFα, Anti-IL-1α/β, and IL-1Ra

• Leo A. B. Joosten, Monique M. A. Helsen, Fons A. J. van de Loo, and Wim B. van den Berg 797
• In this widely used animal model of polyarthritis, the importance of IL-1 in both the induction and perpetuation of collagen-induced arthritis was confirmed. It was found that TNFα is involved in the induction, but plays a minor role in the later stages of this arthritis. Both TNFα and IL-1 should be considered therapeutic targets in humans with RA.

Cellular Adhesion Molecules in Rat Adjuvant Arthritis

• Margaret M. Halloran, Zoltan Szekanecz, Nora Barquin, G. Kenneth Haines, and Alisa E. Koch 810
• Using an animal model of RA, such as adjuvant-induced arthritis, enables one to study the cellular events involved in the early stages of the disease. CD44 expression on macrophages and lymphocytes was found to be up-regulated during the early development of adjuvant arthritis, whereas LFA-1 expression was up-regulated later in the development of the disease. Understanding the interactions between adhesion molecules and endothelium at the earliest stages of adjuvant arthritis could lead to significant advances in the methods used in the treatment of RA.

Direct Gene Delivery to Synovium: An Evaluation of Potential Vectors In Vitro and In Vivo

• I. Nita, S. C. Ghivizzani, J. Galea-Lauri, G. Bandara, H. I. Georgescu, P. D. Robbins, and C. H. Evans 820
• Gene therapy is a promising new approach to the treatment of diseased joints. One way to apply this strategy is to develop methods for the transfer of genes to the synovial lining of joints. This report presents the results of a study in which various vectors have been tested for their ability to deliver a marker gene to the synovia of rabbits' knees.

Prevention and Reversal of Cartilage Degradation in Rheumatoid Arthritis By Interleukin-10 and Interleukin-4

• Joel A. G. van Roon, Johanna L. A. M. van Roy, Frits H. J. Gmelig-Meyling, Floris P. J. G. Lafeber, and Johannes W. J. Bijlsma 829
• IL-10 and IL-4 are important immunoregulatory cytokines which can be produced by type 2 T cells and are capable of down-regulating proinflammatory responses. Furthermore, synergistic activity of IL-10 and IL-4 has been described. The present study shows the ability of IL-10, IL-4, and the combination of the 2 cytokines to control inflammatory responses and subsequently to prevent cartilage damage in RA, which may lead to new treatment strategies.

Accelerated Generation of CD14+ Monocyte-Lineage Cells from the Bone Marrow of Rheumatoid Arthritis Patients

• Shunsei Hirohata, Tamiko Yanagida, Kenji Itoh, Hiroshi Nakamura, Shin'ichi Yoshino, Tetsuya Tomita, and Takahiro Ochi 836
• This study examined the capacity of bone marrow progenitor cells to generate CD14+ cells in patients with RA. The results strongly support the hypothesis that the accelerated generation of CD14+ cells from bone marrow plays a central role in the pathogenesis of RA, possibly through continuous recruitment of inherently abnormal monocytes into the synovium.

Enrichment of Differentiated CD45RBdim,CD27[minus] Memory T Cells in the Peripheral Blood, Synovial Fluid, and Synovial Tissue of Patients with Rheumatoid Arthritis

• Charles L. Kohem, Ruth I. Brezinschek, Heather Wisbey, Cosimo Tortorella, Peter E. Lipsky, and Nancy Oppenheimer-Marks 844
• This study further defines the phenotypic characteristics and differentiation status of T cells present in the peripheral blood and synovium of RA patients. These findings provide insights into the pathogenesis of this immune-mediated disease, and may thus permit a better understanding of the specific T cell subset involved in RA.

An Epitope on Ki Antigen Recognized by Autoantibodies from Lupus Patients Shows Homology with the SV40 Large T Antigen Nuclear Localization Signal

• Yoshinari Takasaki, Tetsuro Yano, Kaoru Hirokawa, Ken Takeuchi, Soichiro Ando, Toshimitsu Takahashi, Kohichiro Shimada, and Hiroshi Hashimoto 855
• Molecular cloning of Ki cDNA revealed that the Ki antigen contained an amino acid sequence that was homologous to the SV40 large T antigen nuclear localization signal (SV40 T NLS). Using a 16-mer Ki synthetic peptide with an amino acid sequence homologous to that of SV40 T NLS, the reactivity of 49 anti-Ki-positive sera to KILT was tested by enzyme-linked immunosorbent assay. The results revealed that the sequence homologous to SV40 T NLS on the Ki antigen is one of the antigenic epitopes recognized by autoantibodies to the Ki antigen in lupus sera.

Detection of Anticentromere Antibodies Using Recombinant Human CENP-A Protein

• Dongxu Sun, Antigona Martinez, Kevin F. Sullivan, Gordon C. Sharp, and Sallie O. Hoch 863
• Anticentromere antibodies are associated with the milder manifestation of scleroderma called limited systemic sclerosis. This report describes the development of a quantitative assay for one of the major centromere antigens, CENP-A, using recombinant protein. This assay has obvious implications for helping to diagnose a major clinical subgroup of patients (with the attendant implications as to treatment) and allowing investigators to explore specific questions about the utility of ACA in predicting disease progression.

Strong Association of Dermatomyositis-Specific Mi-2 Autoantibodies with a Tryptophan at Position 9 of the HLA-DRβ Chain

• Rudolf Mierau, Thomas Dick, Peter Bartz-Bazzanella, Elisabeth Keller, Ekkehard D. Albert, and Ekkehard Genth 868
• Mi-2 autoantibodies are rare but highly specific for dermatomyositis. In 17 Mi-2 antibody-positive dermatomyositis patients, signs of scleroderma, lung involvement, and arthritis were rare or absent. Strong associations with HLA-DR7 and with a tryptophan residue at position 9 of the HLA-DRβ chain are evidence for a common immunogenetic background of Mi-2 antibody production.

Case Report

Chronic Intestinal Pseudoobstruction Associated with Autoantibodies Against Proliferating Cell Nuclear Antigen

• Yoshihisa Nojima, Toshihide Mimura, Ken Hamasaki, Hiroko Furuya, Go Tanaka, Atsushi Nakajima, Nobuyuki Matsuhashi, and Yoshio Yazaki 877

Concise Communications

Prevalence of Human Parvovirus B19 Infection in Children with Henoch-Schonlein Purpura

• Polly J. Ferguson, Frank T. Saulsbury, Scott F. Dowell, Thomas J. Torok, Dean D. Erdman, and Larry J. Anderson 880

Mycobacterium kansasii Septic Arthritis in a Patient with Acquired Immunodeficiency Syndrome

• Maria Luz Garcia Vivar, Santiago Gonzalez de Etxabarri, Eva Galindez Agirregoikoa, and Juan Miguel Santamaria 881

Letters

Tumor Necrosis Factor Receptor p75 Correlates Better than p55 with Disease Activity in Juvenile Rheumatoid Arthritis: Comment on the Article by Mangge et al

• Marco Gattorno, Paolo Picco, Antonella Buoncompagni, Franca Stalla, and Vito Pistoia 883

Reply

• Harald Mangge 884

Serum Pro-Matrix Metalloproteinase 3 in Rheumatoid Arthritis: A Reflection of Local or Systemic Inflammation?

• Nap T. Cheung, Derek L. Mattey, Peter T. Dawes, and David J. Taylor 884

Reply

• Daniel-Henri Manicourt, Noboru Fujimoto, Ken'ichi Obata, and Eugene J.-M. A. Thonar 885

ACR Announcements 7A