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2. OP0007 INCIDENCE, PREVALENCE AND CO-OCCURRENCE OF AUTOIMMUNE DISORDERS, TRENDS OVER TIME AND BY AGE, SEX AND SOCIOECONOMIC STATUS. A POPULATION-BASED STUDY IN 22 MILLION INDIVIDUALS.

Author

Conrad, N., primary, Misra, S., additional, Verbakel, J., additional, Verbeke, G., additional, Molenberghs, G., additional, Taylor, P., additional, Mason, J., additional, Sattar, N., additional, Mcmurray, J., additional, Mcinnes, I., additional, Khunti, K., additional, and Cambridge, G., additional

Published
2023
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34. Anti-myeloperoxidase antibodies in patients with rheumatoid arthritis: prevalence, clinical correlates and IgG subclass

Author

Cambridge, G., Williams, M., Leaker, B., Corbett, M., and Smith, C.R.

Subjects
Rheumatoid arthritis -- Complications, Lung diseases -- Risk factors, Autoantibodies -- Measurement, Health
Abstract

Patients with rheumatoid arthritis (RA) who have antibodies to myeloperoxidase (MPO) may have an increased risk of developing lung disease. RA is a chronic systemic disease usually affecting the joints. MPO is a blood protein. Researchers analyzed blood samples from 97 RA patients, 29 patients with systemic vasculitis and 50 healthy people (control group). Vasculitis is the inflammation of a blood vessel. MPO autoantibodies were found in 12% of the RA patients and in none of the control subjects. Three RA patients had RA-associated lung disease. In addition, one patient had vasculitis of the skin. An association between cutaneous vasculitis and MPO autoantibodies could not be established. However, 83% of the patients with systemic vasculitis tested positive for MPO autoantibodies.

Published
1994

35. CD24 Expression and B Cell Maturation Shows a Novel Link With Energy Metabolism: Potential Implications for Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Author

Mensah, FFK, Armstrong, CW, Reddy, V, Bansal, AS, Berkovitz, S, Leandro, MJ, Cambridge, G, Mensah, FFK, Armstrong, CW, Reddy, V, Bansal, AS, Berkovitz, S, Leandro, MJ, and Cambridge, G

Abstract

CD24 expression on pro-B cells plays a role in B cell selection and development in the bone marrow. We previously detected higher CD24 expression and frequency within IgD+ naïve and memory B cells in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) compared with age-matched healthy controls (HC). Here, we investigated the relationship between CD24 expression and B cell maturation. In vitro stimulation of isolated B cells in response to conventional agonists were used to follow the dynamics of CD24 positivity during proliferation and differentiation (or maturation). The relationship between CD24 expression to cycles of proliferation and metabolism in purified B cells from HC was also investigated using phospho-flow (phosphorylation of AMPK-pAMPK), 1proton nuclear magnetic resonance and Mitotracker Far-red (Mitochondrial mass-MM). In vitro, in the absence of stimulation, there was an increased percentage of CD24+ viable B cells in ME/CFS patients compared to HC (p < 0.05) following 5 days culture. Following stimulation with B cell agonists, percentage of CD24+B cells in both naïve and memory B cell populations decreased. P < 0.01). There was a negative relationship between percentage of CD24+B cells with MM (R2 = 0.76; p < 0.01), which was subsequently lost over sequential cycles of proliferation. There was a significant correlation between CD24 expression on B cells and the usage of glucose and secretion of lactate in vitro. Short term ligation of the B cell receptor with anti-IgM antibody significantly reduced the viability of CD24+ memory B cells compared to those cross-linked by anti-IgD or anti-IgG antibody. A clear difference was found between naïve and memory B cells with respect to CD24 expression and pAMPK, most notably a strong positive association in IgD+IgM+ memory B cells. In vitro findings confirmed dysregulation of CD24-expressing B cells from ME/CFS patients previously suggested by immunophenotype studies of B cells from periph

Published
2018

42. Internalization of rituximab and the efficiency of B cell depletion in rheumatoid arthritis and systemic lupus erythematosus

Author

Reddy, V., Cambridge, G., Isenberg, D.A., Glennie, M.J., Cragg, M.S., and Leandro, M.

Subjects
immune system diseases, education
Abstract

Objective: Rituximab, a type I anti-CD20 monoclonal antibody (mAb), induces incomplete B cell depletion in some patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), thus contributing to a poor clinical response. The mechanisms of this resistance remain elusive. The purpose of this study was to determine whether type II mAb are more efficient than type I mAb at depleting B cells from RA and SLE patients, whether internalization influences the efficiency of depletion, and whether Fc? receptor type IIb (Fc?RIIb) and the B cell receptor regulate this internalization process.Methods: We used an in vitro whole blood B cell–depletion assay to assess the efficiency of depletion, flow cytometry to study cell surface protein expression, and surface fluorescence–quenching assays to assess rituximab internalization, in samples from patients with RA and patients with SLE. Paired t-test or Mann-Whitney U test was used to compare groups, and Spearman's rank correlation test was used to assess correlation.Results: We found that type II mAb internalized significantly less rituximab than type I mAb and depleted B cells from patients with RA and SLE at least 2-fold more efficiently than type I mAb. Internalization of rituximab was highly variable between patients, was regulated by Fc?RIIb, and inversely correlated with cytotoxicity in whole blood B cell–depletion assays. The lowest levels of internalization were seen in IgD– B cells, including postswitched (IgD–CD27+) memory cells. Internalization of type I anti-CD20 mAb was also partially inhibited by anti-IgM stimulation.Conclusion: Variability in internalization of rituximab was observed and was correlated with impaired B cell depletion. Therefore, slower-internalizing type II mAb should be considered as alternative B cell–depleting agents for the treatment of RA and SLE.

Published
2015

48. IX Eular Workshop for Rheumatology Research: Molecular biology of autoantigens, autoantibodies and immunopeptides. Vienna, Austria, March 9–12, 1989

Author

Fournier, C., Texier, B., Chiocchia, G., Boissier, M. C., Herbage, D., Brown, C. M. S., Zyberk, C. Plater, Maini, R. N., Palacios, A., Sieper, J., Heinegard, D., Panayi, G. S., Gentric, A., Mackenzie, L., Lydyard, P. M., Youinou, P., Menzel, E. J., Kaik, B., Sykulev, Yu. K., Guschin, A. Je., Vasiljev, V. I., Ostreiko, K. K., Yeronina, T. V., Tumanova, I. A., Moynier, M., Abderrazik, M., Combe, B., Rucheton, M., Brochier, J., Tuomi, T., Palosuo, T., Heliövaara, M., Aho, K., McHugh, N. J., James, I. E., Kallenberg, C. G. M., Tervaert, J. W. Cohen, Goldschmeding, R., Von Dem Borne, A. E. G. K. R., Bouanani, M., Piechaczyk, M., Pau, B., Bastide, M., Le Page, S., Williams, W., Parkhouse, D., Cambridge, G., Isenberg, D. A., Nimmegeers, J., De Keyser, F., Verbruggen, G., Veys, E. M., Walravens M. J. F., Verdeyen I., Vandepol B., Cortens W., Schatteman, L., Goethals, K., Wu, D. -H., Tavoni, A., Neri, R., Garzelli, C., Vitali, C., Bombardieri, S., Logar, D., Kveder, T., Dobovisek, J., Rozman, B., Menard, H. A., Boire, G., Lopez-Longo, F. J., Masson, Ch., Lapointe, S., Clair, E. W. St., Zerva, L., Moutsopoulos, H. M., Keene, J. D., Pisetsky, D. S., Van Dam, A. P., Cuypers, H. T. M., Winkel, I., Smeenk, R. J. T., Taylor, D., Valente, E., Foster, J. P., Williams, D. G., Stocks, M. R., Caporali, R., De Gennaro, F., Cerino, A., Cobianchi, F., Astaldi-Ricotti, G. C. B., Montecucco, C., Habets, W., Sillekens, P. T. G., Hoet, M. H., McAllister, G., Lerner, M. R., Van Venrooij, W. J., Habets, W. J., Van Der Kemp, A., De Jong, B., Scarpa, R., Pucino, A., Di Girolamo, C., della Valle, G., Larizza, G., Casiere, D., Oriente, P., Paimela, L., Palvimo, J., Kurki, P., Hassfeld, W., Steiner, G., Graninger, W., Smolen, J. S., Lopez-Longo, E. J., Larose, A., Hoet, R., Zewald, R., Smeenk, R., Brinkman, K., Van Den Brink, H., Westgeest, A., Huss, R., Krapf, E. F., Herrmann, M., Leitmann, W., Kalden, J. R., Merétey, K., Cebecauer, L., Böhm, U., Kozakova, D., Brózik, M., Temesvári, P., Nagy, L., Bozic, B., Stegnar, M., Vene, N., Peternel, P., Giuggioli, C., Monti, P., Rossi, G., Ferri, C., Chiellini, S., Baboonian, C., Venables, P. J. W., Roffe, L., Booth, J., Krapf, F., Abuljadayel, I., Ebringer, A., Cox, N. L., Brand, S. R., McIntosh, D. P., Bernstein, R. M., Van Den Broek, M. F., Van Bruggen, M. C. J., Smetsers, T., Kuyer, P., Van De Putte, L., Van Den Berg, W. B., Toivanen, A., Jalkanen, S., Lahesmaa-Rantala, R., Isomäki, O., Pekkola-Heino, K., Merilahti-Palo Saario, R., Von Essen, R., Isomäki, H., Granfors, K., Gaston, J. S. H., Life, P. F., Bailey, L., Bacon, P. A., Khalafpour, S., Wilson, C., Awad, J., Toivanen, P., Saario, R., Skurnik, M., Van Der Straeten, C., Mielants, H., Gazic, M., Hartung, K., Riedel, T., Stannat, S., Specker, Ch., Röther, E., Pirner, K., Schendel, D., Baur, M., Corvetta, A., Peter, H. H., Lakomek, H. J., Deicher, H., Andonopoulos, A. P., Papasteriades, C. A., Drosos, A. A., Dimou, G. S., Shattles, W., Venables, P., Charles, P. J., Markwick, J. R., Venables, P. J., Galeazzi, M., Lulli, P., Tuzi, T., Cappellacci, S., Morellini, M., Trabace, S., Cutrupi, F., Sorrentino, R., Botti, S., Iannicola, C., Costanzi, S., Tosi, R., Gospodinoff, A., Eliaou, J. F., Humbert, H., Balaguer, P., Nicolas, J. C., Sany, J., Clot, J., Sakkas, L. I., Bird, H., Welsh, K. I., Pitzalis, C., Kingsley, G., Haskard, D., Vischer, T. L., Bas, S., Werner-Favre, C., Wohlwend, D., Zubler, R. H., Afeltra, A., De Pita, O., Basso, P., Pietrucci, A., Ferri, G. M., Bonomo, L., Gerli, R., Cernetti, C., Bertotto, A., Agea, E., Arcangeli, C., Lanfrancone, L., Rambotti, P., Crupi, S., Baglioni, A., Spinozzi, F., Papazoglou, S., Skoumi, D., Athanasiou, P., Iliopoulos, A., Stavropoulou, A., Kontomerkos, T., Hendrich, G., Kuipers, J. G., Hammer, M., Schmidt, R. E., Manoussakis, M. N., Germandis, G., Zerva, L. V., Siouna-Fatourou, H. J., Katsikis, P. D., Mavridis, A., Toubert, A., Sadouk, M., de la Tour, B., Vaquero, C., Amor, B., Miossec, P., Naviliat, M., Cretien, I., Banchereau, J., Graninger, P., Aschauer, B., Sinski, A., Smolen, J., Krutmann, J., Kirnbauer, R., Köck, A., Schwarz, T., May, L. T., Sehgal, P. B., Luger, T. A., Field, M., Chu, C. Q., Feldmann, M., Wilbrink, B., Nietfeld, J. J., Helle, M., Boeije, L. C. M., Van Roy, J. L. A. M., Den Otter, W., Aarden, L. A., Huber-Bruning, O., Malejczyk, J., Urbanski, A., Malejczyk, M., Karbowski, A., Völker, W., Feige, U., Otter, W. Den, Malfait, A. M., Wieme, N., Gyselbrecht, L., Van de Loo, A. A. J., Van Lent, P. L. E. M., Haskard, D. O., Wellicome, S., Lanchbury, J., Thornhill, M., Krutmann, K., Gschnait, F., Yaron, M., Yaron, I., Dayer, J. -M., Bleiberg, I., Meyer, F. -A., Maury, C. P. J., Teppo, A. -M., Salo, E., Pelkonen, P., Malfait, A., Cochez, Ph., Gruschwitz, M., Müller, P. U., Wick, G., Madhok, R., Wilson, R., Frame, M., Thompson, J., Sturrock, R. D., Partsch, G., Matucci-Cerinic, M., Marabini, S., Jantsch, S., Neumüller, J., Eberl, R., van Beuningen, H. M., Arntz, O. J., Zlabinger, G. J., Steffen, C., Brand, H. S., Van Kampen, G. P. J., De Koning, M. H. M. T., Kiljan, E., Van Der Korst, J. K., Gemmell, C. G., Swaak, A. J. G., Van Rooyen, A., Hall, N. D., Woolf, A. D., Kantharia, B., Maymo, J., Blake, D. R., Goulding, N. J., Maddison, P. J., Munthe, E., Berntzen, H. B., Fagerhol, M., Mathieu, A., Pala, R., Contu, L., Cirillo, R., Garau, P., Nurchis, P., Viberti, G. C., Meyer, O., Zenklusen, C., Le Thi Huong Du, Z., Gaudouen, C., Mery, J. Ph., Ronco, P., Kahn, M. F., Rasmussen, N., Szpirt, W., Thomsen, B., Humbel, R. L., Ter Borg, E. J., Horst, G., Hummel, E., Limburg, P. C., Aeschilmann, A., Bourgeois, P., De Rooij, D. J., Van de Putte, L. B. A., Verbeek, L., Farinaro, C., Infranzi, E., Couret, M., Ackerman, C., De Vlam, K., Carapic, V., Carapic, D., Annefeld, M., Erne, B., Rosenwasser, L. J., Pazoles, C. J., Otterness, I. G., Hanson, D. C., McDonald, B., Loose, L. D., Dougados, M., Machold, K. P., Wiesenberg-Böttcher, I., Wanner, K., Pignat, W., Altmann, H., Tuschl, H., Bröll, H., Balestrieri, G., Tincani, A., Cattaneo, R., Bertoli, M. T., Martinelli, M., Allegro, F., Meroni, P. L., Balesini, G., Aichinger, G., Schlögl, E., Huber, Ch., Shoenfeld, Y., Fleishmaker, E., Mendlovic, S., Mozes, E., Blank, M., Talal, N., Hogervorst, E. J. M., Van Eden, W., Van Der Zee, R., Psychos, D., Dimou, G., Stefanaki-Nikou, S., Papadimitriou, C. S., Settas, L., Alexiou, P., Dimitriadis, G., Mataftsi, E., Soliou, E., Tourkantonis, A., Babic, M., Jeurissen, M. E. C., and Boerbooms, A. MTh

Published
1989
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