Lourdes Villalba Jeanne E. Hicks, Elizabeth M. Adams, Jeffrey B. Sherman, Mark F. Gourley, Richard L. Leff, Bonnie C. Thomton, Suzanne H. Burgess, Paul H. Plotz, and Frederick W. Mille 392

The results of this study suggest that 2 therapies which have not been previously evaluated for the treatment of myositis-combination oral MTX with AZA and IV MTX with leucovorin rescue-benefit some patients with refractory disease in whom conventional treatments have failed. The analysis indicates that more patients improve with the combination oral therapy, which even benefits some patients who previously had inadequate responses to either MTX or AZA alone. Given the prevalence of treatment-resistant disease and the few options available for therapy, these findings increase the options available to rheumatologists for the management of patients with myositis.

Lisa R. Ginn, Jing-Ping Lin, Paul H. Plotz, Sherri J. Bale, Ronald L. Wilder, Angelina Mbauya, and Frederick W. Miller 400

Autoimmune diseases were found to be significantly increased in frequency in first-degree relatives of patients with idiopathic inflammatory myopathy, to affect more women than men, to increase with age, and to be distributed in a pattern similar to that in the general population. Genetic modeling of these data suggests that many autoimmune disorders share genes that, together, act as polygenic risk factors for autoimmunity.

Jane H. Park Phomma Phothimat, Carolyn T. Oates, Marta Hemanz-Schulman, and Nancy J. Olsen 406

Magnetic resonance spectroscopy has clinical utility in the diagnosis and management of patients with muscle dysfunction. Application of this technique to the study of muscles in patients with fibromyalgia demonstrated the presence of metabolic abnormalities which may contribute to clinical symptoms of fatigue and lack of endurance in this syndrome.

Martin Aringer, Josef S. Smolen, and Winfried B. Graninger 414

This study demonstrates an increased risk of serious infections among patients with severely active SLE undergoing long-term plasmapheresis in addition to IV cyclophosphamide. The occurrence of infections and infection-related mortality must be closely monitored when plasmapheresis is used to treat SLE.

Yeong Wook Song, Chang-Wan Han, Seong-Wook Kang, Han-Joo Baek, Eun-Bong Lee,Chang-Ho Shin, Bevra H. Hahn, and Betty P. Tsao 421

Abnormal distribution of FcyRIIa polymorphisms was found to be associated with the development of SLE in this ethnic population. There was a significant decrease of the FcyRIIa-H/H genotype and H131 allele frequency in SLE patients, particularly in those with nephritis. These data add to the findings in other populations, in which associations between FcyRIIa polymorphisms and SLE have been found.

Kristin H. Traustadottir, Bjami 0. Rafnar, Kristjan Steinsson, Helgi Valdimarsson, and Kristjan Erlendsson 427

This work explores the relationship between factor B and a low-grade immune complex transport ability in serum from a C2-deficient SLE patient treated with regular plasma infusions. Between plasma infusions, the decline of factor B levels in the patient's serum correlated with the appearance of and increase in clinical manifestations, suggesting involvement of factor B in immune complex transport. Such a cooperation between the classical and alternative pathways is consistent with a low incidence of disease and less severe symptoms in SLE patients with homozygous C2 deficiency compared with SLE patients who are deficient in other early components of the classical pathway.

Blanca Coll-Vinent, Mireia Cebrian, Maria C Cid, Carme Font, Jordi Esparza, Manel Juan, Jordi Yague, Alvaro Urbano-Marquez, and Josep M. Grau 435

Immunohistochemical studies were performed on muscle and nerve biopsy specimens from a homogeneous group of 30 patients with polyarteritis nodosa. The results indicate that the expression of cell adhesion molecules follows an evolving pattern that corresponds with disease progression. Polyarteritis nodosa might be considered among the autoimmune diseases that could potentially benefit from anti-adhesion therapy.

Wilhelm H. Schmitt, Elena Gemok, Shigeto Kobayashi, Anja Klinkenborg, Eva Reinhold-Keller, and Wolfgang L. Gross 445

CSS is associated with markedly increased levels of sIL-2R and eosinophil catonic protein (ECP) in its active state, indicating T cell and eosinophil activation. Elevated sIL-2R, ECP, and soluble thrombomodulin (sTM) levels correlate with clinical disease activity, and serum levels of sIL-2R, ECP, and sTM can be regarded as reliable serologic indicators of disease activity. Monitoring of serial sIL-2R levels, in particular, appears to be useful in assessing immune activation and may help in the management of complicated cases of CSS.

John A. Snowden, Philip Keamey, Annabel Keamey, Helen M. Cooley, Andrew Grigg, Peter Jacobs, Jack Bergman, Peter M. Brooks, and James C. Biggs 453

Long-term followup of autoimmune disease (rheumatoid arthritis, psoriasis) following allogeneic bone marrow transplantation confirmed cure of the autoimmune disease in some patients but relapse in others. Relapse apparently occurred despite complete donor hemopoietic reconstitution, suggesting de novo as opposed to persistent disease. There may be a relationship between remission of autoimmune disease and graft-versus-host reaction. These findings may have significance with regard to the development of stem cell transplantation therapy for autoimmune disease.

Matthew A. Brown, L. Gail Kennedy, Chris Darke, Kathryn Gibson, Kevin D. Pile, Jane L. Shatford, Andrew Taylor, Andrei Calin, and B. Paul Wordsworth 460

Ankylosing spondylitis is a common and highly familial rheumatic disease whose etiology is incompletely defined. This study investigates the role of HLA-DR genes in susceptibility to, and clinical manifestations of, ankylosingspondylitis. Defining the genetic susceptibility to ankylosing spondylitis may result in improved diagnosis and treatment of this condition.

N. Menon, L. McAlpine, A. J. Peacock and R. Madhok 466

Patients with pulmonary hypertension complicating SSc have a 40% 2-year survival rate. This study shows that prostacyclin infused into the systemic circulation results in a reduction in both pulmonary artery pressure and pulmonary vascular resistance in patients with SSc and pulmonary hypertension. These findings suggest that the vasospastic component of SSc-associated pulmonary hypertension may be amenable to treatment using strategies that have been shown to improve survival in primary pulmonary hypertension.

Sueshige Wakisaka, Noboru Suzuki Nobahiko Saito, Takahiro Ochi, and Tsayoshi Sakane 470

Overexpression of jun D protooncogene was shown to down-regulate the proliferation of, and proinflammatory cytokine and collagenase production by, RA Synovial cells. Thus, transfection of jun D would be a promising candidate for treating dysregulated proliferation and function of RA Synovial cells.

Susan D. Thompson, Kevin J. Murray, Alexei A. Grom, Murray H. Passo, Edmund Choi, and David N. Glass 482

The identification of common features of the T cell receptors present on clonally expanded T cells in the joints of children with juvenile rheumatoid arthritis or spondylarthropathies, as done in this study; may provide the basis for therapeutic interventions such as T cell receptor-specific vaccination. These interventions may be specific for the features of the T cell receptors found in each disease type.

Samuel M. Behar, Chris Roy, James Lederer, Pat Fraser, and Michael B. Brenner 498

Little is known about the remarkable expansions of CD8+ T cells that are found in individuals with RA. This study demonstrated that the clonally expanded population of V12+,CD8+ T cells from a patient with RA were autoreactive and were restricted by class I MHC. This finding is of interest in terms of the role of T cells in RA.

Yasunori Shimozuru, Sumitaka Yamane, Koji Fujimoto, Keiji Terao, Shigeo Honjo, Yutaka Nagai Allen D. Sawitzke, and Kuniaki Terato 507

This study shows that heterologous and homologous CII and even cyanogen bromide-generated peptide fragments of chicken CII can induce a severe form of autoantibody-associated arthritis in cynomologus monkeys, which correlates with the levels of antibody to autologous monkey CII. The reaction against autologous CII results from the cross-reactivity of the anticollagen antibodies used for immunization and varies in individual monkeys, thus indicating the influence of genetic diversity on epitope specificity of autoantibodies in outbred populations.

Fuad Mehraban and Sriram Kastun 515

The inhibition of the IL-1 pathway may constitute a possible therapy for osteoarthritis and rheumatoid arthritis. A soluble type 1 IL-1 receptor expression vector construct was transfected into a rabbit synovial cell line. Gene transfer resulted in a marked down-regulation of stromelysin expression and inflammatory responses. This suggests that the soluble type 1 IL-1 receptor may be a potentially useful gene therapy for inflammatory arthropathies.

L. G. Ratkay, R. K Chowdhary, A. Iamaroon, A. M. Richter, H. C. Neyndorff, E. C. Keystone, J. D. Waterfield, and J. G. Levy 525

In RA, erosive joint changes are the dominating cause of chronic disability, and their prevention is still not resolved. These preclinical results suggest that local transdermal photodynamic therapy (tPDT) could be used to treat arthritis-affected joints, especially by preventing bone and cartilage destruction. Local tPDT treatment of the hands and feet as an adjunct to DMARD therapy can be envisioned. Treatment with tPDT might provide a noninvasive, simultaneous treatment of multiple joints with significantly less systemic side effects than current treatments.

Bert Wilbrink Ineke M. van der Heijden, Leo M. Schouls, Jan D. A. van Embden, Johanna M. W. Hazes, Ferdinand C. Breedveld, and Paul P. Tak 535

Bacteria are implicated in the pathogenesis of various arthritides. This study shows the possibilities of the use of a PCR method that utilizes broad-range primers, which are able to detect all bacterial species. This technique may be used to reveal the presence of bacterial DNA in samples from inflamed joints.

Carina Vingsbo-Lundberg, Tore Saxne, Henric Olsson, and Rikard Holmdahl 544

Serum analyses of cartilage oligomeric matrix protein (COMP) were applied in pristane-induced arthritis, and the serum concentrations correlated closely with the development of arthritis. Serum analyses of COMP offer promise as a novel noninvasive tool for monitoring tissue involvement in arthritis, and the application of such measurements in experimental arthritis makes it possible to verify the utility of this technology in human arthritis (e.g., for monitoring therapy aimed at retarding tissue destruction).

Gary J. Mack, Jennifer Rees, Olof Sandblom, Ronald Balczon, Marvin J. Fritzler, and J. B. Rattner 551

Examination of 21 autoimmune sera with a centrosomal IIF pattern revealed that each contained autoantibodies that reacted with a group of centrosomal proteins, including previously identified centrosomal autoantigens, novel centrosomal proteins, and centrosomal proteins identified by other means and heretofore unknown as human autoantigens. Review of the clinical features of the patients did not disclose any unifying clinical diagnosis or feature. The most common diagnosis or presenting problem was symmetric polyarthritis, although these patients did not have sufficient clinical features to meet criteria for a diagnosis of RA. The complexity of the immune response to the centrosome suggests that the centrosome itself is the immune target, while variations in the frequency of specific autoantibodies may reflect differences in the features of individual antigens.