No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34295/1/2_ftp.pd

Akizuki, M.

Andrade, Luiz Eduardo Coelho

Dong, X. W.

Fujii, T.

Kabir, F. N.

Miller, M. L.

Pachman, L. M.

Reed, A. M.

Reeves, W. H.

Satoh, M.

Shaw, M.

Stein, L.

Trevisani, Virgínia Fernandes Moça

Wang, J. S.

Arthritis & Rheumatism

PubMed

Objective, To investigate the in vitro ability of antiphospholipid antibodies (aPL) to bind human trophoblast cells and to affect gonadotropin secretion and invasiveness. Methods, Antiphospholipid antibody IgG from women with recurrent miscarriages, beta(2)-glycoprotein I (beta(2)GPI)-independent IgG aPL human monoclonal antibody (mAb) (519), and IgM anti-beta(2)GPI human mAb (TM1G2) were investigated for their binding to trophoblasts cultured for various amounts of time, their ability to affect invasiveness of Matrigel-coated filters, and their release of human chorionic gonadotropin (hCG), Results, Polyclonal IgG aPL, as well as mAb 519 and TM1G2, bound to trophoblasts, the highest binding being found when cells displayed the greatest amount of syncytium formation. TM1G2 binding was found to be beta(2)GPI dependent. Both polyclonal and monoclonal aPL, but not the controls, significantly reduced hCG release and Matrigel invasiveness. Conclusion. These findings suggest that aPL recognition of both anionic PL and adhered beta(2)GPI on trophoblast cell structures might represent a potential pathogenetic mechanism for defective placentation in women with the antiphospholipid syndrome

Di Simone, N

Meroni, P L

Del Papa, N

Raschi, E

Caliandro, D

De Carolis, S

Khamashta, M A

Atsumi, T

Hughes, G R V

Balestrieri, G

Tincani, A

Casali, P

Caruso, A

King's Research Portal

Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered beta(2)-glycoprotein I

OBJECTIVE: To verify the hypothesis that in rheumatoid arthritis (RA), tumor necrosis factor alpha (TNFalpha) plays a critical role in regulating leukocyte trafficking and chemokine levels. METHODS: Ten patients with longstanding RA received a single 10 mg/kg infusion of anti-TNFalpha monoclonal antibody (cA2). The articular localization of autologous granulocytes, separated in vitro and labeled with 111In, was studied by analysis of gamma-camera images both before and 2 weeks after treatment. At the same sequential time points, synovial biopsy samples were assessed for infiltrating CD3+ T cells, CD22+ B cells, and CD68+ macrophages. Synovial tissue expression of the chemokines interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, Groalpha, and RANTES was also determined. Serum IL-8 and MCP-1 concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: Anti-TNFalpha therapy in RA significantly reduced 111In-labeled granulocyte migration into affected joints. There was a simultaneous and significant reduction in the numbers of infiltrating synovial CD3+ T cells, CD22+ B cells, and CD68+ macrophages and in the expression of IL-8 and MCP-1, with a trend toward a reduction in serum concentrations of these chemokines. CONCLUSION: TNFalpha blockade reduces synovial expression of the chemokines IL-8 and MCP-1 and diminishes inflammatory cell migration into RA joints

Taylor, Peter

Peters, AM

Paleolog, E

Chapman, PT

Elliott, MJ

McCloskey, R

Feldmann, Marc

Maini, RN

ORA - Oxford University Research Archive

Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the in vitro ability of antiphospholipid antibodies (aPL) to bind human trophoblast cells and to affect gonadotropin secretion and invasiveness.

METHODS: Antiphospholipid antibody IgG from women with recurrent miscarriages, beta2-glycoprotein I (beta2GPI)-independent IgG aPL human monoclonal antibody (mAb) (519), and IgM anti-beta2GPI human mAb (TMIG2) were investigated for their binding to trophoblasts cultured for various amounts of time, their ability to affect invasiveness of Matrigel-coated filters, and their release of human chorionic gonadotropin (hCG).

RESULTS: Polyclonal IgG aPL, as well as mAb 519 and TMIG2, bound to trophoblasts, the highest binding being found when cells displayed the greatest amount of syncytium formation. TM1G2 binding was found to be betaGPI dependent. Both polyclonal and monoclonal aPL, but not the controls, significantly reduced hCG release and Matrigel invasiveness.

CONCLUSION: These findings suggest that aPL recognition of both anionic PL and adhered beta2GPI on trophoblast cell structures might represent a potential pathogenetic mechanism for defective placentation in women with the antiphospholipid syndrome

N. Di Simone

N. de Papa

E. Raschi

D. Caliandro

C. S. De Carolis

M. A. Khamashta

T. Atsumi

G. R. Hughes

G. Balestrieri

A. Tincani

P. Casali

A. Caruso

P. L. Meroni

AIR Universita degli studi di Milano

Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered beta2-glycoprotein I

Schmidt

Mallya

Kushner

Crossref

Acute-phase response and the risk of developing ischemic complications in giant cell arteritis: Comment on the article by Cid et al

Taylor, PC

Feldmann, M

Oxford University Research Archive (ORA)

Objective. To evaluate the specificity of anti-DEK antibodies for juvenile rheumatoid arthritis (JRA),Methods. Anti-DEK autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA) using affinity-purified his6-DEK fusion protein. Sera from 639 subjects (417 patients with systemic autoimmune disease, 13 with sarcoidosis, 44 with pulmonary tuberculosis, 125 with uveitis, and 6 with scleritis, and 34 healthy control subjects) were screened. Reactivity was verified by immunoblotting and immunoprecipitation Studies using baculovirus-expressed human DEK.Results. Anti-DEK activity was found at the following frequencies: JRA 39.4% (n = 71), systemic lupus erythematosus (SLE) 25.1% (n = 216), sarcoidosis 46.2% (n = 13), rheumatoid arthritis 15.5% (n = 71), systemic sclerosis 36.0% (n = 22), polymyositis 6.2% (n = 16), and adult Still's disease 0% (n = 21), Autoantibodies also were detected in 9.1% of tuberculosis sera (n = 44), but were undetectable in sera from the 34 healthy controls. Western blot and immunoprecipitation assay results correlated well with the ELISA findings. in general, levels of anti-DEK autoantibodies were higher in SLE than in other patient subsets, including JRA.Conclusion. Anti-DEK autoantibodies are less specific for JRA than previously believed. They are produced in association with a variety of inflammatory conditions, many of which are associated with granuloma formation and/or predominant Th1 cytokine production. Anti-DEK antibodies may be a marker for a subset of autoimmunity associated with interferon-gamma production rather than a particular disease subset.Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC USAUniv N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USAUniversidade Federal de São Paulo, São Paulo, BrazilNorthwestern Univ, Sch Med, Chicago, IL USAKeio Univ Hosp, Tokyo, JapanUniversidade Federal de São Paulo, EPM, São Paulo, BrazilWeb of Scienc

Andrade, Luiz Eduardo Coelho [UNIFESP]

Trevisani, Virgínia Fernandes Moça [UNIFESP]

Repositório Institucional UNIFESP

Autoantibodies to DEK oncoprotein in human inflammatory disease

Objective. Type II mixed cryoglobulinemia (type II MC) is often characterized by features of indolent B cell lymphoma (IBCL) found on pathologic examination of bone marrow, whereas the clinical evidence does not indicate a neoplastic disorder. To better address the issue of indolent malignant versus nonmalignant bone marrow lymphoproliferation underlying type II MC, molecular analyses of B cell clonality were performed in the present study, in conjunction with clinical and pathologic characterization. Methods. Polymerase chain reaction DNA amplification of immunoglobulin heavy chain genes was performed in bone marrow biopsy specimens obtained from 15 selected patients with type II MC, all infected with hepatitis C virus. Five of them had also developed overt B cell lymphoma (OBCL) during followup. Bone marrow features were consistent with IBCL in 9 of the 15 patients (group 1) and with reactive lymphoplasmacytosis in 6 of the 15 (group 2). Results. An oligoclonal B cell expansion was detected in 6 of 9 baseline bone marrow lesions from group 1 patients (biclonal or monoclonal expansion in the remaining 3 cases), and in 6 of 6 from group 2 patients. OBCL was always monoclonal. Selected lesions were analyzed by clonospecific hybridization and by cloning and sequence analysis in patients who had developed OBCL at followup. In 4 of 5 cases, OBCL did not originate from the dominant B cell clones that were overexpanded in the putative neoplastic baseline bone marrow lesions. OBCL clones showed significant homology with rheumatoid factor database sequences. Conclusion. Based on the present results, as well as on evidence from previous studies of liver lesions, oligoclonal non-neoplastic B cell proliferation in the course of chronic infection-related inflammation appears to be the key feature of type II MC. Of note, molecular evidence from target tissues supports the clinical findings both at the time of type II MC diagnosis and in cases of OBCL complication. Bone marrow pathologic findings resembling those of IBCL should thus be considered in the light of clinical and molecular evidence

DE VITA, Salvatore

De Re V

Gasparotto D

Ballarè M

Pivetta B

Ferraccioli G

Pileri S

Boiocchi M

Monteverde A.

Archivio istituzionale della ricerca - Università degli Studi di Udine

Oligoclonal non-neoplastic B cell expansion is the key feature of type II mixed cryoglobulinemia. Clinical and molecular findings do not support a bone marrow pathologic diagnosis of indolent B cell lymphoma

LAReferencia - Red Federada de Repositorios Institucionales de Publicaciones Científicas Latinoamericanas