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Official Journal of the American College of Rheumatology

Special Articles

Review: Presentation of Self Peptides by Dendritic Cells: Possible Implications for the Pathogenesis of Rheumatoid Arthritis

• Ranjeny Thomas and Peter E. Lipsky 183

Viewpoint: Maternal-Fetal Immunology and Autoimmune Disease: Is Some Autoimmune Disease Auto-Alloimmune or Allo-Autoimmune?

• J. Lee Nelson 191

Fifth International Symposium on Sjogren's Syndrome

• Robert I. Fox 195

Basic Science

Activation of Transcription Factor NF-[gk]B in Human Synovial Cells in Response to Tumor Necrosis Factor α

• Koushi Fujisawa, Hiroyuki Aono, Tomoko Hasunuma, Kazuhiko Yamamoto, Shiro Mita, and Kusuki Nishioka 197
• This is the first study to demonstrate activation of transcription factor NF-[gk]B in response to TNFα in synovial cells and to examine the effect of NF-[gk]B inhibitor on TNFα-induced synovial cell proliferation and activation. The results suggest that activation of NF-[gk]B is a possible mechanism of synovial cell proliferation and activation.

Depletion of γ/δ T Cells Does Not Prevent or Ameliorate, but Rather Aggravates, Rat Adjuvant Arthritis

• Carme Pelegri, Petra Kuhnlein, Eberhard Buchner, Carsten B. Schmidt, Angels Franch, Margarida Castell, Thomas Hunig, Frank Emmrich, and Raimund W. Kinne 204
• γ/δ T cells preferentially recognize mycobacterial antigens in humans and mice and are increased in peripheral blood and synovial fluid of patients with rheumatoid arthritis. Treatment of Mycobacterium-induced rat adjuvant arthritis with a monoclonal antibody directed against T cell receptor γ/δ revealed that γ/δ T cells do not promote or perpetuate arthritis, but rather may play a protective role.

Neutrophil Trafficking Into Inflamed Joints in Patients with Rheumatoid Arthritis, and the Effects of Methylprednisolone

• Peter P. Youssef, John Cormack, Charles A. Evill, Daryl T. Peter, Peter J. Roberts-Thomson, Michael J. Ahern, and Malcolm D. Smith 216
• This study investigates the mechanisms of action of pulse corticosteroids, which are potent antiinflammatory agents that are typically prescribed in rheumatology practice. The effects of this treatment on RA, a common rheumatologic condition which may be associated with severe morbidity and mortality, are evaluated.

Inhibition of Lymphocyte Adhesion to Cytokine-Activated Synovial Fibroblasts by Glucocorticoids Involves the Attenuation of Vascular Cell Adhesion Molecule 1 and Intercellular Adhesion Molecule 1 Gene Expression

• Philippe A. Tessier, Paola Cattaruzzi, and Shaun R. McColl 226
• While glucocorticoids are widely used as antiinflammatory agents, their exact mechanism of action is not completely understood. This study shows that glucocorticoids inhibit lymphocyte adhesion to synovial fibroblasts, an effect that is likely mediated, at least in part, by an attenuation of ICAM-1 and VCAM-1 gene expression. Results from this study provide a conceptual basis for the pursuit of new therapeutic avenues such as anti-TNFα and anti-ICAM-1 antibody therapies currently under clinical trials.

Activation of Recombinant Human Neutrophil Procollagenase in the Presence of Doxycycline Results in Fragmentation of the Enzyme and Loss of Enzyme Activity

• Gerald N. Smith, Jr., Kenneth D. Brandt, and Karen A. Hasty 235
• Cartilage destruction in osteoarthritis is due to the action of matrix metalloproteinases (MMP). Doxycycline slows the progression of cartilage destruction in experimental osteoarthritis, presumably by reducing the level of MMP. This study demonstrates, using human recombinant MMP-8 (neutrophil collagenase) as a model, that this reduction may be due in part to enhanced degradation of the enzyme.

Specificity of a Porcine 127-kd Nucleotide Pyrophosphohydrolase for Articular Tissues

• Antonio Cardenal, Ikuko Masuda, Arthur L. Haas, and Daniel J. McCarty 245
• A sedimentable porcine 127-kd nucleotide pyrophosphohydrolase associated with extracellular vesicles was found only in hyaline, fibrous, and elastic cartilage and in ligamentous and tendinous tissues. Since antibodies to this molecule cross-react with a human counterpart, the specificity of this enzyme for cartilage and other joint tissues prompted a search for degradation products in human serum as a potential molecule reflecting connective tissue metabolism.

Identification of a Nucleotide Pyrophosphohydrolase from Articular Tissues in Human Serum

• Antonio Cardenal, Ikuko Masuda, Arthur L. Haas, Wataru Ono, and Daniel J. McCarty 252
• The apparent specificity of a 127-kd NTPPHase for cartilage, ligament, and tendon is described in the accompanying paper. A soluble degradation product of this enzyme is found in normal human serum as well as in serum from patients with joint diseases. The 127-kd enzyme is the only active ecto-NTPPHase in these sera. This human NTPPHase is immunologically and kinetically identical to the porcine enzyme and is immunologically identical to the sedimentable 127-kd protein found in normal and pathologic synovial fluids. Serum levels of this enzyme might reflect changes in the metabolism of connective tissues.

Clinical Science

Recombinant Human Interleukin-1 Receptor Type I in the Treatment of Patients with Active Rheumatoid Arthritis

• Barbara E. Drevlow, Rosa Lovis, Mary Ann Haag, James M. Sinacore, Cindy Jacobs, Consuelo Blosche, Alan Landay, Larry W. Moreland, and Richard M. Pope 257
• An understanding of the immune mechanisms responsible for the initiation and perpetuation of the chronic synovitis of RA is important to all rheumatologists. This study is the first in which soluble IL-1R was administered systemically in an attempt to modulate the chronic inflammation associated with RA.

The Mortality of Rheumatoid Vasculitis Compared with Rheumatoid Arthritis

• Alexandre E. Voskuyl, Aeilko H. Zwinderman, Marie Louise Westedt, Jan P. Vandenbroucke, Ferdinand C. Breedveld, and Johanna M. W. Hazes 266
• In this retrospective cohort study, the first to compare mortality in rheumatoid vasculitis versus rheumatoid arthritis patients, the apparent high mortality rate of RV patients was mainly due to age, male sex, and severity of arthritis. Adjustment for these factors resulted in only a small excess mortality in RV patients when compared with the RA controls. A beneficial effect of prompt immunosuppressive and cytostatic treatment in RV patients with severe organ involvement might have contributed to this favorable outcome of RV.

Pancytopenia Secondary to Methotrexate Therapy in Rheumatoid Arthritis

• Sergio Gutierrez-Urena, Jose F. Molina, Cesar O. Garcia, Marta L. Cuellar, and Luis R. Espinoza 272
• A literature search revealed 70 reports of rheumatoid arthritis patients in whom pancytopenia developed in association with methotrexate treatment. Twelve of the 70 cases were fatal. Serious hematologic toxicity appears to be an underrecognized side effect of methotrexate treatment.

The Systemic Effect of Intraarticular Administration of Corticosteroid on Markers of Bone Formation and Bone Resorption in Patients with Rheumatoid Arthritis

• Ronald D. Emkey, Robert Lindsay, Jane Lyssy, Jerome S. Weisberg, David W. Dempster, and Victor Shen 277
• Intraarticular administration of corticosteroid has only a transient systemic effect on bone turnover markers. This therapeutic mode may be better for bone metabolism than continuous use of orally administered corticosteroid in the treatment of rheumatoid arthritis patients.

Rheumatoid Arthritis in a United States Public Health Service Hospital in Oklahoma: Serologic Manifestations in Rheumatoid Arthritis Vary Among Tribal Groups

• R. Hal Scofield, Mark Fogle, Everett R. Rhoades, and John B. Harley 283
• This work describes the experience with RA in a USPHS hospital serving Native Americans. It was found that the disease is serologically distinct in one group compared with other groups living in the same area. The heterogeneity among patients with RA who are of similar ethnic origin is clinically important to the practicing rheumatologist.

Evaluating Systemic Lupus Erythematosus Disease Activity Using Molecular Markers of Hemostasis

• Masayuki Inoh, Michiaki Tokuda, Hiroyuki Kiuchi, Noriyuki Kurata, and Jiro Takahara 287
• The coagulation-fibrinolysis system is enhanced when disease activity is high. Measuring the sensitive parameters of the coagulation-fibrinolysis system could provide useful information for following the disease activity of SLE.

Sensitivity and Specificity of Anti-Jo-1 Antibodies in Autoimmune Diseases with Myositis

• Dolores Vazquez-Abad and Naomi F. Rothfield 292
• Polymyositis/dermatomyositis and the scleroderma spectrum of diseases are autoimmune diseases characterized by the presence of specific autoantibodies. In both disease groups the autoantibody identifies different clinical subsets and outcomes and may assist in selecting therapeutic strategies. Since myositis is not uncommon in SSc, the presence of SSc was investigated in these patients, and this antibody was found to be absent in this disease group. Thus, anti-Jo-1 does not predict myositis and/or interstitial lung fibrosis in SSc patients, but is highly specific for PM/DM (specificity 100%, sensitivity = 20%).

Long-Term Followup of Patients with Sjogren's Syndrome

• Aike A. Kruize, Ronald J. Hene, Agnes van der Heide, Cliff Bodeutsch, Peter C. M. de Wilde, O. Paul van Bijsterveld, Jan de Jong, T. E. W. Feltkamp, Louis Kater, and Johannes W. J. Bijlsma 297
• In this long-term followup study, primary Sjogren's syndrome generally appeared to be a stable disease with a mild course of glandular and extraglandular manifestations, but with a marked increased risk for development of malignant lymphoma. Since patients with isolated keratoconjunctivitis sicca do not bear this increased risk for the development of malignant lymphoma, the presumptive diagnosis of primary Sjogren's syndrome in these patients should be confirmed.

Polymyalgia Rheumatica in Patients with a Normal Erythrocyte Sedimentation Rate

• Simon M. Helfgott and Raphael I. Kieval 304
• The hallmark laboratory test for the diagnosis of PMR is the elevated ESR. In the present series of 117 patients with PMR, 22% of patients had a normal ESR. Distinguishing features of these patients were a higher incidence of males, normal hemoglobin levels, and a delay in diagnosis. The presence of a normal ESR in a patient with suspected PMR should not necessarily rule out the diagnosis and may not be uncommon.

Numerical Scoring Systems for the Anatomic Evolution of Osteoarthritis of the Finger Joints

• Gust Verbruggen and Eric M. Veys 308
• Systems were developed to score anatomic changes in the finger joints of 46 patients with OA who were followed up for more than 3 years, enabling clinicians to define the rate of progression of OA. From radiographs of the hands, it could be concluded that OA of the finger joints was progressive in nature and went through predictable phases.

Case Reports

Nonsteroidal Antiinflammatory Drug-Induced Enteropathy and Severe Chronic Anemia in a Patient with Rheumatoid Arthritis

• Neal M. Davies, Fakhreddin Jamali, and Kenneth J. Skeith 321

Methotrexate-Associated Lymphoma in Patients with Rheumatoid Arthritis: Report of Two Cases

• Teresa R. Bachman, Allen D. Sawitzke, Sherrie L. Perkins, John H. Ward, and Grant W. Cannon 325

Multiple Myeloma-Associated Systemic Vasculopathy Due to Crystalglobulin or Polyarteritis Nodosa

• Hisashi Hasegawa, Tetsuo Ozawa, Noriyoshi Tada, Youko Taguchi, Koichiro Ohno, Takaaki Chou, Takeshi Watanabe, Takeshi Kuroda, Masaaki Nakano, Hiroyuki Usuda, Iwao Emura, and Masaaki Arakawa 330

Cryocrystalglobulinemia as a Cause of Systemic Vasculopathy and Widespread Erosive Arthropathy

• Thomas Papo, Lucile Musset, Thomas Bardin, Barbara Bucki, Christian Jorgensen, Elisabeth Dion, Alain Quillard, Christian de Gennes, Jacques Sany, Pierre Godeau, and Jean-Charles Piette 335

Gastric Antral Vascular Ectasia (Watermelon Stomach) in Patients with Systemic Sclerosis

• Maria Watson, Robert J. Hally, Peter A. McCue, John Varga, and Sergio A. Jimenez 341

Calcific Constrictive Pericarditis: A Rare Complication of CREST Syndrome

• Prerana Panchal, Elaine Adams, and Annming Hsieh 347

Letters

HLA-DR8 and Susceptibility to Acute Anterior Uveitis in Ankylosing Spondylitis: Comment on the Article by Monowarul Islam et al

• Rafal Ploski, Walter Maksymowych, and Oystein Forre 351

Reply

• S. M. Monowarul Islam, Jiro Numaga, and Hiroo Maeda 351

Fatal postpartum vasculitis in systemic lupus erythematosus

• Osvaldo Hubscher, Alicia Eimon, and Roberto M. Arana 352

Hepatitis C as Another Possible Cause of Porphyria Cutanea Tarda and Systemic Lupus Erythematosus: Comment on the Article by Kutz and Bridges

• Karen Nepveu and Bonita Libman 352

Reply

• Alan J. Bridges 353

Chinese Herbs Can Themselves Be Harmful: Comment on the Article by Gertner et al

• Manuel Macia, Juan Navarro, Victor Garcia-Nieto, and Javier Garcia 354

Reply

• E. Gertner and Peter S. Marshall 355

Book Review 355

ACR Announcements 10A