Simon J. Bowman, Margaret A. Hall, Gabriel S. Panayi, and Jerry S. Lanchbury 615

This study demonstrates the involvement of antigen-specific expansions of CD3+,CD8+,CD57+ cells in patients with RA and neutropenia. This may ultimately lead to the development of novel therapies for this condition.

Gordon Starkebaum, Thomas P. Loughran, Jr., Lakshmi K. Gaur, Paul Davis, and Barbara S. Nepom 624

Discovering why large granular lymphocytes are occasionally markedly expanded in a clonal manner in patients with rheumatoid arthritis may provide important clues about the cause of rheumatoid arthritis. The findings of this study suggest that Felty's syndrome and large granular lymphocyte leukemia plus rheumatoid arthritis are parts of a single disease spectrum rather than two separate disorders.

Kaku Nakagawa, Vladimir Brusic, Geoffrey McColl, and Leonard C. Harrison 627

This study demonstrates directly that certain endogenous retrovirus genes are differentially expressed in the synovial compartment in RA. These findings support a proposed role for endogenous retroviruses in the pathogenesis of RA.

Hendrik Schulze-Koops, Laurie S. Davis, Arthur F. Kavanaugh, and Peter E. Lipsky 639

Monocyte-derived proinflammatory cytokines are particularly prominent in the rheumatoid synovium and are thought to contribute to the pathogenesis of the disease. However, it has not been determined whether monocytes in RA are activated to produce proinflammatory cytokines in the peripheral circulation before entering the synovium and whether the pattern of cytokines that is expressed correlates with disease activity. Cytokine mRNA levels in freshly isolated PBMC from patients with active RA were assessed by RT-PCR. The findings indicate that myeloid precursor cells become activated to produce cytokines before they enter the synovium, which emphasizes the systemic nature of rheumatoid inflammation.

Dan Yu, Peter M. Rumore, Qingli Liu, and Charles R. Steinman 648

Evaluation of the mechanism by which synovial inflammation is perpetuated is of central importance for understanding the chronic arthritides. The present study shows that inflamed synovial fluids contain oligonucleosomal complexes in concentrations sufficient to have biologic activity in vitro. A hypothesized mechanism is suggested to explain how such complexes could contribute to the chronicity of rheumatoid synovitis.

Jill P. Buyon, Chung-E Tseng, Francis Di Donato, William Rashbaum, Allan Morris, and Edward K. L. Chan 655

Although neonatal lupus is rare, its discussion is an integral part of pregnancy counseling for all women with systemic lupus erythematosus, Sjogren's syndrome, or undifferentiated autoimmune syndromes. This study provides evidence that cardiac expression of an alternative transcript of 52-kd SS-A/Ro encoding 52β, an antigenic target of the autoimmune response in mothers whose children have congenital heart block, during the second trimester may be a factor contributing to selective vulnerability of the fetal and not the adult heart.

Elli Neu, Peter H. Hemmerich, Hans-Hartmut Peter, Ulrich Krawinkel, and Anna H. von Mikecz 661

This report gives insight into the understanding of the production of anti-L7 autoantibodies in autoimmune arthritis. It describes a disease-specific epitope-recognition pattern that may help to discriminate between clinical subsets and overlap syndromes, thereby providing a more precise diagnosis and prognosis for the patient.

Hero Brahms, Veronica A. Raker, Walther J. van Venrooij, and Reinhard Luhrmann 672

This study demonstrates that the Sm protein E-F-G complex provides a major and highly specific antigen for the detection of anti-Sm autoantibodies in SLE patient sera. All 30 anti-Sm patient sera tested immunoprecipitated the E-F-G complex, whereas none of the patient sera with other serotypes, such as anti-RNP from MCTD patients, did. Furthermore, the individual proteins, while not often recognized on immunoblots by SLE patient sera, were immunoprecipitated by 50-70% of the anti-Sm patient sera tested. This recognition of the E-F-G complex and its constituents is therefore highly dependent on the conformational state of these polypeptides.

Ralph C. Williams, Jr., Christine C. Malone, Gentry Fry, and Franco Silvestris 683

Treatment of patients with active systemic lupus erythematosus, particularly those with potentially progressive renal disease, represents a difficult challenge. This report presents observations from studies attempting to assay specific anti-DNA idiotypic activity within individual lots of intravenous gamma globulins. This approach may offer a new strategy to tailor individual gamma globulin preparations for therapeutic use.

Feng Huang, Akihiro Yamaguchi, Naoyuki Tsuchiya, Takashi Ikawa, Naoto Tamura, Mika M. K. Virtala, Kaisa Granfors, Parvin Yasaei, and David Tak Yan Yu 694

HLA-B27 is a key to the pathogenesis of reactive arthritis. The question of how B27 mediates arthritis has been unresolved; the solution will be important both for diagnosis and for therapy. The results of this study contribute to our understanding of how arthritis-causing bacteria and HLA-B27 are associated, by demonstrating that bacterial invasion amplifies alternative splicing of B27.

Frank H. Buttner, Susan Chubinskaya, Daniel Margerie, Klaus Huch, Johannes Flechtenmacher, Ada A. Cole, Klaus E. Kuettner, and Eckart Bartnik 704

This study demonstrates the expression of an additional member of the matrix metalloproteinase family in articular cartilage. Identification of this MMP with a transmembrane domain is significant because it has been shown to be an activator of gelatinase A. Gelatinase A is constitutively produced by chondrocytes within the cartilage and is capable of producing the proteolytic destruction of cartilage associated with OA. Therefore, the activator of gelatinase A may play a role in the OA process as well.

Anu Mustila, Markku Korpela, Jukka Mustonen, Heikki Helin, Heini Huhtala, Esa Soppi, Amos Pasternack, and Ari Miettinen 710

This study demonstrates that the presence of pANCA in RA indicates severe disease with increased inflammatory activity. There is an especially strong and independent association between pANCA and RA-associated nephropathy.

Ronenn Roubenoff, Paul Dellaripa, Marie R. Nadeau, Leslie W. Abad, Bernadette A. Muldoon, Jacob Selhub, and Irwin H. Rosenberg 718

In this study, patients with RA who were not taking methotrexate had higher fasting and post-methionine levels of tHcy, indicating an increased risk of atherosclerosis. However, patients with RA taking methotrexate had normal tHcy levels. These findings may explain some of the increased cardiovascular mortality among patients with RA, and suggest the effectiveness of vitamin B6 in conjuction with folate and vitamin B12 as a nutritional supplement in a subgroup of patients with RA.

T. D. Spector, D. J. Hart, D. Nandra, D. V. Doyle, N. Mackillop, J. R. Gallimore, and M. B. Pepys 723

This study shows that CRP levels are modestly but significantly increased in women with early knee OA, and that higher levels predict those whose disease will progress over 4 years. This suggests that low-grade inflammation may be a significant aspect of early OA and may be amenable to therapeutic intervention and secondary prevention.

David T. Felson, Yuqing Zhang, Marian T. Hannan, Allan Naimark, Barbara Weissman, Piran Aliabadi, and Daniel Levy 728

This longitudinal study assessed the risk factors for the development of radiographic knee OA in an elderly cohort derived from the Framingham Heart Study. Female sex, weight, nonsmoking, and physical activity were all found to increase the risk of developing OA.

Timothy J. Laing, Brenda W. Gillespie, Mary B. Toth, Maureen D. Mayes, Robert H. Gallavan, Jr., Carol J. Burns, Jewel R. Johanns, Brenda C. Cooper, Brian J. Keroack, Mary Chester M. Wasko, James V. Lacey, Jr., and David Schottenfeld 734

This study characterizes the clinical manifestations of a large, racially diverse cohort of women with scleroderma in the state of Michigan. Black and white women with scleroderma were compared with regard to disease severity and age at diagnosis. The results suggest that among black women, diffuse scleroderma is much more common, there is a higher incidence of inflammatory features, and, after adjusting for age, survival is lower than among white women with scleroderma.

Marcy B. Bolster, Anna Ludwicka, Susan E. Sutherland, Charlie Strange, and Richard M. Silver 743

This study demonstrates the presence of chemotactic and growth factors in the bronchoalveolar lavage fluid of patients with scleroderma. Lung disease is a major cause of morbidity and mortality in scleroderma and is a very difficult manifestation to treat. Increased understanding of the early inflammatory changes in the pathogenesis of lung disease, before the development of pulmonary fibrosis, may lead to the development of more effective therapeutic interventions.

Graham J. Reid, Bianca A. Lang, and Patrick J. McGrath 752

Compared with children with JRA and with pain-free controls, depression, anxiety, and family dysfunction were not more common in children with fibromyalgia, nor in their parents, thus indicating that neither psychological nor family factors appear to play a role in the pathogenesis of the disease. Several of these variables showed an association with functional disability. These findings have implications for the development of new treatment strategies in juvenile fibromyalgia.

Lene Mellemkjaer, Vagn Andersen, Martha S. Linet, Gloria Gridley, Robert Hoover, and J\orgen H. Olsen 761

This study shows an increase in the risk of non-Hodgkin's lymphoma among patients with SLE. Determination of the increased risk of cancer in specific sites among patients with SLE is important for the surveillance and early diagnosis of such cancers in these patients.

Vedat Hamuryudan, Yilmaz Ozyazgan, Nail Hizli, Cem Mat, Sebahattin Yurdakul, Yalcin Tuzun, Mustafa Senocak, and Hasan Yazici 769

This study reevaluates patients involved in a previous double-blind, placebo-controlled trial of azathioprine for the treatment of Behcet's syndrome, after an average of 8 years. The results suggest that not only is the beneficial effect of azathioprine sustained long term, but the prognosis is also better the earlier during the disease course azathioprine is started.