Rheumatoid Arthritis: Sawaki T

Umehara H, Sawaki T, Kawanami T, Masaki Y, Fukushima T. · Division of Hematology and Immunology, Kanazawa Medical University. · Nippon Rinsho. · Pubmed #19280925 No free full text.

Abstract: Sjögren's syndrome (SS) is chronic autoimmune disease characterized by destructive lymphocyte infiltration of salivary and lacrimal glands, which results in dry eyes and dry mouth. Despite extensive study of the underlying cause of SS, the pathogenesis remains obscure. The Sjögren's International Collaborative Clinical Alliance (SICCA) by five Research Groups located in Argentina, China, Denmark, the United States and Japan, is the first registry and clinical data-specimen repository to establish the International Standard Criteria for diagnosing SS. Patients with SS have a relative increased risk for development of B cell lymphoma compared with other autoimmune rheumatic diseases. We discuss the possible mechanisms for lymphoma development. The topics concerning SS is IgG4-related lymphoproliferative diseases, such as Mikulicz's disease and autoimmune pancreatitis. Based on the analysis of patients registered from all over Japan, we propose a new clinical entity IgG4-positive multi-organ lymphoproliferative syndrome (IgG4+ MOLPS).

Dong L, Masaki Y, Takegami T, Jin ZX, Huang CR, Fukushima T, Sawaki T, Kawanami T, Saeki T, Kitagawa K, Sugai S, Okazaki T, Hirose Y, Umehara H. · Department of Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan. · Clin Exp Immunol. · Pubmed #17937678 links to  free full text

Abstract: The aim of this study was to clarify the nature of the clonal lymphocyte infiltration in Sjögren's syndrome (SS) patients associated with lymphoproliferative disorders. We examined B cell clonality in lymphoproliferative tissues from six primary SS patients associated with lymphoproliferative disorders or lymphoma by cloning and sequencing of the gene rearrangement of the immunoglobulin heavy chain complementarity determining region 3 (IgVH-CDR3). Three patients with sequential observation showed progressional clonal expansion with the presence of the same subclone in different tissues during the course of disease. Among them, one patient developed mucosa-associated lymphoid tissue (MALT) lymphoma in glandular parotid. The other three SS patients concomitant with malignant B cells lymphomas showed different clonal expansion of B cells between nodal sites and salivary glands. The cloanality analysis indicated that monoclonal B cell population could spread from one glandular site to another site during the course of SS, suggesting that the malignant clone may arise from the general abnormal microenvironment, not restricted to the glandular tissue, in some SS patients.

Umehara H, Tanaka M, Sawaki T, Jin ZX, Huang CR, Dong L, Kawanami T, Karasawa H, Masaki Y, Fukushima T, Hirose Y, Okazaki T. · Division of Hematology and Immunology, Department of Internal Medicine, Kanazawa Medical University, Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa, 920-0293, Japan. · Mod Rheumatol. · Pubmed #16767549 No free full text.

Abstract: Leukocyte adhesion and trafficking at the endothelium requires both adhesion molecules and chemotactic factors. Fractalkine (CX3C) is a unique chemokine, and is expressed on tumor necrosis factor-alpha- and interleukin-1-activated endothelial cells (ECs). Fractalkine receptor, CX3CR1, is expressed on NK cells, monocytes, and some portion of CD4- and CD8-positive T cells. Interactions between fractalkine and CX3CR1 can mediate not only chemotaxis, but also cell adhesion in the absence of substrates for other adhesion molecules. Furthermore, fractalkine activates NK cells, leading to increased cytotoxicity and interferon-gamma production. Recently, accumulating evidence has shown that fractalkine is involved in the pathogenesis of rheumatoid arthritis and allied conditions. This review examines new concepts underlying fractalkine-mediated leukocyte migration and tissue damage, focusing primarily on the pathophysiological roles of fractalkine in rheumatic diseases.

Shimoyama K, Ogawa N, Sakai T, Sawaki T, Kawanami T, Karasawa H, Masaki Y, Tanaka M, Fukushima T, Hirose Y, Umehara H. · The third Department of Internal Medicine, Hamamatsu University School of Medicine. · Nihon Rinsho Meneki Gakkai Kaishi. · Pubmed #17984582 links to  free full text

Abstract: OBJECTIVE: To examine clinical significance of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) in RA. METHODS: Hundred fifteen patients with polyarthralgia (89 females, 26 males) were recruited, and subjected for the study. We studied anti-CCP antibody, ESR, CRP, IgM-RF, IgG-RF, RAPA, MMP-3, CARF, C1q-IC, Stage, Class, Joint score, Sharp score, KL-6, SP-D, chest CT. RESULTS: Anti-CCP antibody test had high specificity (93.5%). In RA with positive anti-CCP antibody, Sharp score (10.9+/-22.4) was higher than those with negative anti-CCP (1.7+/-1.8), and may serve as a prognostic marker of joint destruction (P<0.05). Anti-CCP antibody in RA with interstitial pneumonia is higher (84.5+/-36.4 U/mL) than those without interstitial pneumonia (52.6+/-44.7 U/mL) (P<0.05). CONCLUSION: Anti-CCP antibody is useful for diagnosis of RA, and could be a specific marker of joint destruction. Further investigation is necessary to clarify the relation of anti-CCP antibody with organ involvement and activity of RA.

Dong L, Masaki Y, Takegami T, Kawanami T, Itoh K, Jin ZX, Huang CR, Tong XP, Fukushima T, Tanaka M, Sawaki T, Sakai T, Sugai S, Okazaki T, Hirose Y, Umehara H. · Department of Hematology and Immunology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. · Int Immunol. · Pubmed #17272286 links to  free full text

Abstract: Serum titers of antibody to Epstein-Barr virus (EBV) viral capsid antigen (VCA) have been positively correlated with malignancies of lymphoid proliferation, such as Burkitt's lymphoma and Hodgkin's lymphoma. We have constructed a phage display combinatorial antibody Fab library from a patient with marginal zone B cell lymphoma associated with Sjögren's syndrome and carrying high serum anti-EBV-VCA IgG titer. Fab fragments were selected by panning against EBV-VCA protein coated onto ELISA plates, and selected Fab clones were characterized by ELISA, western blotting (WB), indirect immunofluorescence assay and immunohistochemistry. We have established two Fab clones, Fab-aVCA1 and Fab-aVCA21, which specifically recognize EBV-VCA by ELISA and WB. Inhibition ELISA competition showed that both clones could significantly reduce the binding of specific anti-EBV-VCA mAb to its relevant proteins. Furthermore, these two Fab clones could localize VCA protein in the EBV-positive P3HR1 and Daudi cell lines, as well as in tissue samples from patients with EBV-infected lymphoid malignancies. These results indicate that our two Fab clones are novel human mAbs specific for EBV-VCA protein and may have potential benefits for development of novel diagnostic and therapeutic approaches in EBV-related lymphoid malignancies.