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1. Coencapsulation of Immunosuppressive Drug with Anti-Inflammatory Molecule in Pickering Emulsions as an Innovative Therapeutic Approach for Inflammatory Dermatoses

Author

Maxime Sintès, Petra Kovjenic, Liasmine Haine (Hablal), Kevin Serror, Mohamed Beladjine, Véronique Parietti (Montcuquet), Marine Delagrange, Bertrand Ducos, Jean-David Bouaziz, David Boccara, Maurice Mimoun, Armand Bensussan, Martine Bagot, Nicolas Huang, and Laurence Michel

Subjects
Coencapsulation, Inflammatory dermatoses, Nanoparticles, Pickering emulsions, Psoriasis, Dermatology, RL1-803
Abstract

Psoriasis is an inflammatory skin disease characterized by epidermal and immune dysfunctions. Although efficient, current topical treatments display adverse effects, including skin atrophy and burning sensation, leading to poor patient adherence. To overcome these downsides, pickering emulsions were formulated in which the calcitriol-containing dispersed phase was stabilized with either cyclosporin A– or tacrolimus-loaded poly(lactic-co-glycolic) acid nanoparticles. This study aimed to investigate their biological effects on lymphocytes and epidermal cells and their effectiveness in an imiquimod-induced psoriasis-like mouse model. Results showed that both emulsions significantly inhibited nuclear factor of activated T cell translocation in T lymphocytes as well as their IL-2 production, cell activation, and proliferation. In keratinocytes, inhibition of nuclear factor of activated T cell translocation decreased the production of IL-8 and TNF-α. Topical application of emulsions over skin biopsies ex vivo showed accumulation of rhodamin B–coupled poly(lactic-co-glycolic) acid nanoparticles throughout the epidermis by immunofluorescence and significantly decreased the antigen-presenting capacity of Langerhans cells in relation to a reduced expression of activation markers CD40, CD86, and HLA-DR. Using an imiquimod-induced psoriasis model in vivo, pickering emulsions significantly alleviated psoriasiform lesions potentially attributed to the decreased cutaneous expression of T-cell markers, proinflammatory cytokines, chemokines, and specific epidermal cell genes. Altogether, pickering emulsion might be a very efficient formulation for treating inflammatory dermatoses.

Published
2024
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2. Beyond 40 fluorescent probes for deep phenotyping of blood mononuclear cells, using spectral technology

Author

Sandrine Schmutz, Pierre-Henri Commere, Nicolas Montcuquet, Ana Cumano, Cédric Ait-Mansour, Sophie Novault, and Milena Hasan

Subjects
spectral cytometry, autofluorescence, high-dimension, unsupervised analysis, immunophenotyping, Immunologic diseases. Allergy, RC581-607
Abstract

The analytical capability of flow cytometry is crucial for differentiating the growing number of cell subsets found in human blood. This is important for accurate immunophenotyping of patients with few cells and a large number of parameters to monitor. Here, we present a 43-parameter panel to analyze peripheral blood mononuclear cells from healthy individuals using 41 fluorescence-labelled monoclonal antibodies, an autofluorescent channel, and a viability dye. We demonstrate minimal population distortions that lead to optimized population identification and reproducible results. We have applied an advanced approach in panel design, in selection of sample acquisition parameters and in data analysis. Appropriate autofluorescence identification and integration in the unmixing matrix, allowed for resolution of unspecific signals and increased dimensionality. Addition of one laser without assigned fluorochrome resulted in decreased fluorescence spill over and improved discrimination of cell subsets. It also increased the staining index when autofluorescence was integrated in the matrix. We conclude that spectral flow cytometry is a highly valuable tool for high-end immunophenotyping, and that fine-tuning of major experimental steps is key for taking advantage of its full capacity.

Published
2024
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3. Responsiveness of EORTC QLQ-C30, QLQ-CR38 and FACT-C quality of life questionnaires in patients with colorectal cancer

Author

Kaminsky Marie-Christine, Miny Joëlle, Guillemin Francis, Rotonda Christine, Uwer Lionel, Mercier Mariette, Tournier-Rangeard Laetitia, Leonard Isabelle, Montcuquet Philippe, Rauch Philippe, and Conroy Thierry

Subjects
Colorectal cancer, Quality of life, EORTC QLQ-C30, EORTC QLQ-CR38, FACT-C, Responsiveness, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background The aim of this study was to compare the responsiveness of the European Organization for Research and Treatment (EORTC) quality of life questionnaires (QLQ-C30, QLQ-CR38) and the Functional Assessment of Cancer Therapy-colorectal version 4 questionnaire (FACT-C). Method This prospective study included 127 patients with colorectal cancer: 71 undergoing chemotherapy and 56 radiation therapy. Responsiveness statistics included the Standardized Response Mean (SRM) and the Effect Size (ES). The patient's overall assessment of his/her change in state of health status was the reference criterion to evaluate the responsiveness of the QoL questionnaires. Results 34 patients perceived their health as stable and 17 as improved between the first and the fourth courses of chemotherapy. 21 patients perceived their health as stable and 22 as improved between before and the last week of radiotherapy. The responsiveness of the 3 questionnaires differed according to treatments. The EORTC QLQ-C30 questionnaire was more responsive in patients receiving chemotherapy, particulary functional scales (SRM > 0.55). The QLQ-CR38 and the FACT-C questionnaires provided little clinically relevant information during chemotherapy or radiotherapy. Conclusion The EORTC QLQ-C30 questionnaire appears to be more responsive in patients receiving chemotherapy.

Published
2011
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5. Comparative Effectiveness of Natalizumab Versus Anti-CD20 in Highly Active Relapsing–Remitting Multiple Sclerosis After Fingolimod Withdrawal

Author

Rollot, Fabien, Couturier, Justine, Casey, Romain, Wiertlewski, Sandrine, Debouverie, Marc, Pelletier, Jean, De Sèze, Jérôme, Labauge, Pierre, Ruet, Aurélie, Thouvenot, Eric, Ciron, Jonathan, Berger, Eric, Gout, Olivier, Clavelou, Pierre, Stankoff, Bruno, Casez, Olivier, Bourre, Bertrand, Zephir, Hélène, Moreau, Thibault, Lebrun-Frenay, Christine, Maillart, Elisabeth, Edan, Gilles, Neau, Jean-Philippe, Montcuquet, Alexis, Cabre, Philippe, Camdessanché, Jean-Philippe, Defer, Gilles, Nasr, Haifa Ben, Maurousset, Aude, Hankiewicz, Karolina, Pottier, Corinne, Leray, Emmanuelle, Vukusic, Sandra, and Laplaud, David-Axel

Published
2022
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6. Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis

Author

Lefort, M., Sharmin, S., Andersen, J. B., Vukusic, S., Casey, R., Debouverie, M., Edan, G., Ciron, J., Ruet, A., De Sèze, J., Maillart, E., Zephir, H., Labauge, P., Defer, G., Lebrun-Frenay, C., Moreau, T., Berger, E., Clavelou, P., Pelletier, J., Stankoff, B., Gout, O., Thouvenot, E., Heinzlef, O., Al-Khedr, A., Bourre, B., Casez, O., Cabre, P., Montcuquet, A., Wahab, A., Camdessanché, J. P., Maurousset, A., Ben Nasr, H., Hankiewicz, K., Pottier, C., Maubeuge, N., Dimitri-Boulos, D., Nifle, C., Laplaud, D. A., Horakova, D., Havrdova, E. K., Alroughani, R., Izquierdo, G., Eichau, S., Ozakbas, S., Patti, F., Onofrj, M., Lugaresi, A., Terzi, M., Grammond, P., Grand’Maison, F., Yamout, B., Prat, A., Girard, M., Duquette, P., Boz, C., Trojano, M., McCombe, P., Slee, M., Lechner-Scott, J., Turkoglu, R., Sola, P., Ferraro, D., Granella, F., Shaygannejad, V., Prevost, J., Maimone, D., Skibina, O., Buzzard, K., Van der Walt, A., Karabudak, R., Van Wijmeersch, B., Csepany, T., Spitaleri, D., Vucic, S., Koch-Henriksen, N., Sellebjerg, F., Soerensen, P. S., Hilt Christensen, C. C., Rasmussen, P. V., Jensen, M. B., Frederiksen, J. L., Bramow, S., Mathiesen, H. K., Schreiber, K. I., Butzkueven, H., Magyari, M., Kalincik, T., and Leray, E.

Published
2022
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7. Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis

Author

M. Lefort, S. Sharmin, J. B. Andersen, S. Vukusic, R. Casey, M. Debouverie, G. Edan, J. Ciron, A. Ruet, J. De Sèze, E. Maillart, H. Zephir, P. Labauge, G. Defer, C. Lebrun-Frenay, T. Moreau, E. Berger, P. Clavelou, J. Pelletier, B. Stankoff, O. Gout, E. Thouvenot, O. Heinzlef, A. Al-Khedr, B. Bourre, O. Casez, P. Cabre, A. Montcuquet, A. Wahab, J. P. Camdessanché, A. Maurousset, H. Ben Nasr, K. Hankiewicz, C. Pottier, N. Maubeuge, D. Dimitri-Boulos, C. Nifle, D. A. Laplaud, D. Horakova, E. K. Havrdova, R. Alroughani, G. Izquierdo, S. Eichau, S. Ozakbas, F. Patti, M. Onofrj, A. Lugaresi, M. Terzi, P. Grammond, F. Grand’Maison, B. Yamout, A. Prat, M. Girard, P. Duquette, C. Boz, M. Trojano, P. McCombe, M. Slee, J. Lechner-Scott, R. Turkoglu, P. Sola, D. Ferraro, F. Granella, V. Shaygannejad, J. Prevost, D. Maimone, O. Skibina, K. Buzzard, A. Van der Walt, R. Karabudak, B. Van Wijmeersch, T. Csepany, D. Spitaleri, S. Vucic, N. Koch-Henriksen, F. Sellebjerg, P. S. Soerensen, C. C. Hilt Christensen, P. V. Rasmussen, M. B. Jensen, J. L. Frederiksen, S. Bramow, H. K. Mathiesen, K. I. Schreiber, H. Butzkueven, M. Magyari, T. Kalincik, and E. Leray

Subjects
Effectiveness, Multiple sclerosis, Propensity score, Indication bias, Causal contrasts, Censoring, Medicine (General), R5-920
Abstract

Abstract Background Natalizumab and fingolimod are used as high-efficacy treatments in relapsing–remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. Methods Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. Results Overall, 5,148 relapsing–remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. Conclusions This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

Published
2022
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9. Usefulness of MOG-antibody titres at first episode to predict the future clinical course in adults

Author

Cobo-Calvo, Alvaro, Sepúlveda, María, d’Indy, Hyacintha, Armangué, Thais, Ruiz, Anne, Maillart, Elisabeth, Papeix, Caroline, Audoin, Bertrand, Zephir, Helene, Biotti, Damien, Ciron, Jonathan, Durand-Dubief, Francoise, Collongues, Nicolas, Ayrignac, Xavier, Labauge, Pierre, Thouvenot, Eric, Montcuquet, Alexis, Deschamps, Romain, Solà-Valls, Nuria, Llufriu, Sara, Blanco, Yolanda, de Seze, Jerome, Vukusic, Sandra, Saiz, Albert, Marignier, Romain, The OFSEP Group, and The REEM Group

Published
2019
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13. Correction to: Usefulness of MOG-antibody titres at first episode to predict the future clinical course in adults

Author

Cobo-Calvo, Alvaro, Sepúlveda, María, d’Indy, Hyacintha, Armangué, Thais, Ruiz, Anne, Maillart, Elisabeth, Papeix, Caroline, Audoin, Bertrand, Zephir, Helene, Biotti, Damien, Ciron, Jonathan, Durand-Dubief, Francoise, Collongues, Nicolas, Ayrignac, Xavier, Labauge, Pierre, Thouvenot, Eric, Montcuquet, Alexis, Deschamps, Romain, Solà-Valls, Nuria, Llufriu, Sara, Blanco, Yolanda, de Seze, Jerome, Vukusic, Sandra, Saiz, Albert, Marignier, Romain, The OFSEP Group, and The REEM Group

Published
2019
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17. Combined NADPH oxidase 1 and interleukin 10 deficiency induces chronic endoplasmic reticulum stress and causes ulcerative colitis-like disease in mice.

Author

Xavier Tréton, Eric Pedruzzi, Cécile Guichard, Yannick Ladeiro, Shirin Sedghi, Mélissa Vallée, Neike Fernandez, Emilie Bruyère, Paul-Louis Woerther, Robert Ducroc, Nicolas Montcuquet, Jean-Noel Freund, Isabelle Van Seuningen, Frédérick Barreau, Assiya Marah, Jean-Pierre Hugot, Dominique Cazals-Hatem, Yoram Bouhnik, Fanny Daniel, and Eric Ogier-Denis

Subjects
Medicine, Science
Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the rectum which progressively extents. Its etiology remains unknown and the number of treatments available is limited. Studies of UC patients have identified an unbalanced endoplasmic reticulum (ER) stress in the non-inflamed colonic mucosa. Animal models with impaired ER stress are sensitive to intestinal inflammation, suggesting that an unbalanced ER stress could cause inflammation. However, there are no ER stress-regulating strategies proposed in the management of UC partly because of the lack of relevant preclinical model mimicking the disease. Here we generated the IL10/Nox1dKO mouse model which combines immune dysfunction (IL-10 deficiency) and abnormal epithelium (NADPH oxidase 1 (Nox1) deficiency) and spontaneously develops a UC-like phenotype with similar complications (colorectal cancer) than UC. Our data identified an unanticipated combined role of IL10 and Nox1 in the fine-tuning of ER stress responses in goblet cells. As in humans, the ER stress was unbalanced in mice with decreased eIF2α phosphorylation preceding inflammation. In IL10/Nox1dKO mice, salubrinal preserved eIF2α phosphorylation through inhibition of the regulatory subunit of the protein phosphatase 1 PP1R15A/GADD34 and prevented colitis. Thus, this new experimental model highlighted the central role of epithelial ER stress abnormalities in the development of colitis and defined the defective eIF2α pathway as a key pathophysiological target for UC. Therefore, specific regulators able to restore the defective eIF2α pathway could lead to the molecular remission needed to treat UC.

Published
2014
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20. Time to steroids impacts visual outcome of optic neuritis in MOGAD

Author

Rode, Julie, Pique, Julie, Maarouf, Adil, Ayrignac, Xavier, Bourre, Bertrand, Ciron, Jonathan, Cohen, Mikael, Collongues, Nicolas, Deschamps, Romain, Maillart, Elisabeth, Montcuquet, Alexis, Papeix, Caroline, Ruet, Aurelie, Wiertlewski, Sandrine, Zephir, Helene, Marignier, Romain, and Audoin, Bertrand

Abstract

BackgroundTo characterise the response to treatment of inaugural optic neuritis (ON) in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).MethodsWe searched the French MOGAD database for adults with inaugural ON with a detailed report of acute treatment modalities and measures of high-contrast best-corrected visual acuity (BCVA) at nadir and after 3 months. Predictors of visual outcomes were assessed by multivariable analysis.ResultsAmong 245 patients with at least one episode of ON, 82 fulfilled all criteria, and data on the peripapillary retinal nerve fibre layer (pRNFL) were available for 44. All patients received methylprednisolone (MP), combined with plasma exchange in 18. After 3 months, 75 of 82 (91%) patients retained full BCVA recovery, and median (range) pRNFL of the affected eye was 72 µm (40–102). Failure to regain 0.0 logarithmic minimum angle of resolution vision (Snellen 20/20) at 3 months was associated with time to first MP treatment ≥10 days (OR 16, 95% CI 1.14 to 213, p=0.01). pRNFL thickness after 3 months was related to better BCVA at nadir and time to first MP treatment <10 days (r2=19%, p=0.004 and r2=11%, p=0.03, respectively).ConclusionsTime to MP affects functional but also structural visual outcomes of ON in MOGAD.

Published
2023
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21. Safety and Efficacy of Cabazitaxel in the Docetaxel-Treated Patients with Hormone-Refractory Prostate Cancer

Author

Fabien Calcagno, Thierry Nguyen, Erion Dobi, Cristian Villanueva, Elsa Curtit, Stefano Kim, Philippe Montcuquet, François Kleinclauss, Xavier Pivot, and Antoine Thiery-Vuillemin

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Prostate cancer (PC) is one of the most common cancers and is a leading cause of death. Its initial growth is dependent on androgens; most patients show an initial response to hormonal therapy but will experience disease progression when PC becomes resistant to castration. In 2004, two key randomized controlled trials demonstrated a benefit for docetaxel-based regimens in the treatment of men with castration-resistant prostate cancer (CRPC). Cabazitaxel (XRP6258, TXD258, and RPR116258A), a tubulin-binding taxane drug as potent as docetaxel in cell lines, was the first treatment able to prolong survival for metastatic CRPC in the post-docetaxel setting. This review describes pharmacologic parameters of this agent followed by a review of clinical trials involving cabazitaxel. Other available treatments and the place of cabazitaxel in metastatic CRPC setting are discussed.

Published
2013
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29. Gynaecological follow-up for women of reproductive age with multiple sclerosis: The GYNESEP study.

Author

Renaud, Juliette, Buissonnière, Pauline, Dulau, Cécile, Deloire, Mathilde, Hontarrede, Florian, Montcuquet, Alexis, Chansel-Debordeaux, Lucie, Hocké, Claude, Ouallet, Jean-Christophe, Ruet, Aurélie, and Bernard, Valérie

Abstract

• Women with multiple sclerosis require more information on reproductive health and prevention of cervical cancer. • Better contraceptive advice would reduce the number of unplanned pregnancies and avoid foetal exposure to potentially teratogenic treatment. • Long acting reversible contraceptives should be strongly encouraged. • Human papillomavirus vaccination should be promoted. • Close cervical screening should be recommended for patients on immunosuppressive treatments. The gynaecological care of women with Multiple Sclerosis has received little attention; most reports focussed on pregnancy or sexuality. The objective of the present study was to evaluate if gynaecological follow-up for women of reproductive age with Multiple Sclerosis was adequate. We performed a cross-sectional study on a large cohort of women with Multiple Sclerosis aged 18–40 years. All participants completed online questionnaires on general health status, gynaecological follow-up, and sexuality. Expanded Disability Status Scale (EDSS) scores were extracted from medical records. The study was registered in clinicaltrials.gov with the number NCT05248438, and in the European database ID-RCB with the number 2021-A02912–39. Of the 192 patients who completed questionnaires, 157 (82.2%) reported gynaecological follow-up. Of the 155 patients on immunosuppressive treatments, only 31 (20%) underwent annual cervical screening. Of the 140 patients who met the French papillomavirus vaccination age recommendations, only 50 (35.7%) were vaccinated. A total of 128 (66.7%) patients used contraception. However, 16 (8.3%) patients reported unplanned pregnancies since the time of diagnosis. Women with Multiple Sclerosis require more information on reproductive health and prevention of cancer. Better contraceptive advice would reduce the number of unplanned pregnancies and avoid foetal exposure to potentially teratogenic treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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30. 6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial

Author

Pivot, Xavier, primary, Romieu, Gilles, additional, Debled, Marc, additional, Pierga, Jean-Yves, additional, Kerbrat, Pierre, additional, Bachelot, Thomas, additional, Lortholary, Alain, additional, Espié, Marc, additional, Fumoleau, Pierre, additional, Serin, Daniel, additional, Jacquin, Jean-Philippe, additional, Jouannaud, Christelle, additional, Rios, Maria, additional, Abadie-Lacourtoisie, Sophie, additional, Venat-Bouvet, Laurence, additional, Cany, Laurent, additional, Catala, Stéphanie, additional, Khayat, David, additional, Gambotti, Laetitia, additional, Pauporté, Iris, additional, Faure-Mercier, Celine, additional, Paget-Bailly, Sophie, additional, Henriques, Julie, additional, Grouin, Jean Marie, additional, Piprot, C, additional, Cals, L, additional, Chaigneau, L, additional, Demarchi, F, additional, N'Guyen, T, additional, Stein, U, additional, Villanueva, C, additional, Bréau, JL, additional, Chouahnia, AK, additional, Saintigny, P, additional, Boué, F, additional, deSaint-Hilaire, P, additional, Guimont, I, additional, Grossat, N, additional, Valenza, B, additional, Lévy, E, additional, Médioni, J, additional, Delbaldo, C, additional, Grenier, J, additional, Pouessel, D, additional, Lavau-Denès, S, additional, Falandry, C, additional, Fournel-Fédérico, C, additional, Freyer, G, additional, Tartas, S, additional, Trillet-Lenoir, V, additional, Bons, F, additional, Auclerc, G, additional, Chièze, S, additional, Raban, N, additional, Tournigand, C, additional, Trager-Maury, S, additional, Bousquet, G, additional, Cuvier, C, additional, Giacchetti, S, additional, Hocini, A, additional, LeMaignan, C, additional, Misset, JL, additional, Avenin, D, additional, Beerblock, C, additional, Gligorov, J, additional, Rivera, P, additional, Roché, H, additional, Bougnoux, P, additional, Hajjaji, N, additional, Capitain, O, additional, Delva, R, additional, Maillart, P, additional, Soulié, P, additional, Bonnefoi, H, additional, Durand, M, additional, Madranges, N, additional, Mauriac, L, additional, Chollet, P, additional, Dillies, AF, additional, Durando, X, additional, Ferrière, JP, additional, Mouret-Reynier, C, additional, Nabholtz, JM, additional, Van Praagh, I, additional, Cottu, P, additional, Diéras, V, additional, Durieux, A, additional, Galotte, M, additional, Girre, V, additional, Henry, S, additional, Iurisci, I, additional, Jouve, M, additional, Laurence, V, additional, Mignot, L, additional, Piperno-Neumann, S, additional, Tresca, P, additional, Coudert, B, additional, Ferrant, E, additional, Mayer, F, additional, Vanneuville, AC, additional, Bonneterre, J, additional, Servent, V, additional, Vanlemmens, L, additional, Vennin, P, additional, Guastalla, JP, additional, Biron, P, additional, Dupuy-Brousseau, L, additional, Lancry, L, additional, Ray-Coquard, I, additional, Rebattu, P, additional, Trédan, O, additional, Extra, JM, additional, Rousseau, F, additional, Tarpin, C, additional, Fabbro, M, additional, Luporsi, E, additional, Uwer, L, additional, Weber, B, additional, Berton-Rigaud, D, additional, Bourbouloux, E, additional, Campone, M, additional, Ferrero, JM, additional, Follana, P, additional, Largillier, R, additional, Mari, V, additional, Costa, B, additional, Curé, H, additional, Eymard, JC, additional, Jovenin, N, additional, Lebrun, D, additional, Meunier, J, additional, Yazbek, G, additional, Gedoin, D, additional, Laguerre, B, additional, Lefeuvre, C, additional, Vauléon, E, additional, Chevrier, A, additional, Guillemet, C, additional, Leheurteur, M, additional, Rigal, O, additional, Tennevet, I, additional, Veyret, C, additional, Brain, E, additional, Guiterrez, M, additional, Mefti-Lacheraf, F, additional, Petit, T, additional, Dalenc, F, additional, Gladieff, L, additional, André, F, additional, Delaloge, S, additional, Domont, J, additional, Ezenfis, J, additional, Spielmann, M, additional, Guillet, P, additional, Boulanger, V, additional, Provençal, J, additional, Stefani, L, additional, Alliot, C, additional, Ré, D, additional, Bellaiche-Miccio, C, additional, Boutan-Laroze, G, additional, Vanica, R, additional, Dion, P, additional, Sadki-Benaoudia, G, additional, Marti, A, additional, Villing, AL, additional, Slama, B, additional, Dutel, JL, additional, Nguyen, S, additional, Saad, R, additional, Arsène, O, additional, Merad-Boudia, Z, additional, Orfeuvre, H, additional, Egreteau, J, additional, Goudier, MJ, additional, Lamy, R, additional, Leduc, B, additional, Sarda, C, additional, Salles, B, additional, Agostini, C, additional, Cauvin, I, additional, Dufresne, A, additional, Mangold, M, additional, Lebouvier-Sadot, S, additional, Audhuy, B, additional, Barats, JC, additional, Cluet-Dennetière, S, additional, Zylberait, D, additional, Netter, G, additional, Gautier-Felizot, L, additional, Cojean-Zelek, I, additional, Plantade, A, additional, Vignot, S, additional, Guardiola, E, additional, Marti, P, additional, deHartingh, I, additional, Diab, R, additional, Dietmann, A, additional, Ruck, S, additional, Portois, C, additional, Oddou-Lagranière, S, additional, Campos-Gazeau, F, additional, Bourcier, A, additional, Priou, F, additional, Geay, JF, additional, Mayeur, D, additional, Gabez, P, additional, ElAmarti, R, additional, Combe, M, additional, Raichon-Patru, P, additional, Amsalhem, P, additional, Dauba, J, additional, Paraiso, D, additional, Guinet, F, additional, Duvert, B, additional, Litor, M, additional, Kara-Slimane, F, additional, Bichoffe, A, additional, Denizon, N, additional, Soyer, P, additional, Morvan, F, additional, Van-Hulst, S, additional, Vincent, L, additional, Alleaume, C, additional, Ibanez-Martin, P, additional, Youssef, A, additional, Tadrist, Z, additional, Carola, E, additional, Pourny, C, additional, Toccanier, JF, additional, Al-Aukla, N, additional, Mahour-Bacha, K, additional, Salvat, J, additional, Nouyrigat, P, additional, Clippe, S, additional, Gouttebel, MC, additional, Vedrine, L, additional, Clavreul, G, additional, Collard, O, additional, Mille, D, additional, Goubely, Y, additional, Hervé, R, additional, Kirscher, S, additional, Plat, F, additional, Delecroix, V, additional, Ligeza-Poisson, V, additional, Coeffic, D, additional, Fric, D, additional, Garnier, C, additional, Leyronnas, C, additional, Kreitman, T, additional, Teissier, E, additional, Martin, P, additional, Rohart deCordoue, S, additional, ElKouri, C, additional, Ramée, JF, additional, Laporte, C, additional, Bernard, O, additional, Altwegg, T, additional, Darut-Jouve, A, additional, Dujols, JP, additional, Darloy, F, additional, Giraud, C, additional, Pottier-Kyndt, V, additional, Achour, N, additional, Drony, S, additional, Moriceau, M, additional, Sarrazin, C, additional, Legueul, JC, additional, Mandet, J, additional, Besson, D, additional, Hardy-Bessard, AC, additional, Cretin, J, additional, Houyau, P, additional, Achille, E, additional, Genêt, D, additional, Thévenot, H, additional, Moran-Ribon, A, additional, Pavlovitch, JM, additional, Ardisson, P, additional, Moullet, I, additional, Couderc, B, additional, Fichet, V, additional, Burki, F, additional, Auliard, A, additional, Levaché, CB, additional, Cailleux, P, additional, Schaeffer, F, additional, Albin, N, additional, Sévin-Robiche, D, additional, Domas, J, additional, Ellis, S, additional, Montcuquet, P, additional, Baumont, GA, additional, Bégue, M, additional, Gréget, S, additional, Ratoanina, JL, additional, Vanoli, A, additional, Bielsa, C, additional, Bonichon-Lamichhane, M, additional, Jaubert, D, additional, Laharie-Mineur, H, additional, Alcaraz, L, additional, Legouffe, E, additional, Bourgeois, H, additional, Cartron, G, additional, Denis, F, additional, Dupuis, O, additional, Ganem, G, additional, Roche-Forestier, S, additional, Delzenne, L, additional, Chirat, E, additional, Baticle, JL, additional, Béguier, E, additional, Jacquot, S, additional, Janssen, E, additional, Lauché, H, additional, LeRol, A, additional, Chantelard, JP, additional, L'Helgoualc'h, GA, additional, Antoine, EC, additional, Kanoui, A, additional, Llory, JF, additional, Vannetzel, JM, additional, Vignoud, J, additional, Bruna, C, additional, Facchini, T, additional, Moutel-Corviole, K, additional, Voloch, A, additional, Ghoul, A, additional, Loiseau, D, additional, Barbet, N, additional, Dohollou, N, additional, and Yakendji, K, additional

Published
2019
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31. Infections and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society

Author

Papeix, C., Donze, C., Lebrun-Frénay, C., Papeix, C., Donzé, C., Lebrun-Frénay, C., Laplaud, D., Thouvenot, E., Ayrignac, X., Pourcher-Martinez, V., Zéphir, H., de Seze, J., Michel, L., Bensa, C., Cara-Dalliere, C., Guen-noc, A.M., Casez, O., Maarouf, A., Bourre, B., Kwiatkowski, A., Cohen, M., Maillart, E., Collongues, N., Louapre, C., Androdias, G., Guegen, A., Audoin, B., Mattey, G., Bernady, P., Faucheux, J.M., Labauge, P., Meckies, C., Stankoff, B., Tourniaire, P., Dinh, A., Guennoc, A.M., Durnad-Dubief, F., Wiertlewski, S., Derache, N., Le page, E., Pittion, S., Vukusic, S., Clavelou, P., Heinzlef, O., Colamarino, R., Planque, E., Rico, A., Sheiber nogueira, C., de Seze, M., Ciron, J., Alchaar, H., Bensmail, D., Biotti, D., Branger, P., Brochet, B., Castan, B., Creange, A., Creisson, E., DeBroucker, T., Depaz, R., Douay, X., Dulau, C., Faucher, M., Fournier, M., Fromont, A., Gallien, P., Gout, O., Grimaud, J., Hervé, Y., Kerbrat, A., Kremer, L., Lanotte, L., Magy, L., Mania, A., Maurousset, A., Moisset, X., Montcuquet, A., Moreau, T., Morel, N., Patry, I., Peaureaux, D., Pouget, M.C., Ruet, A., Saint-Val, C., Stahl, J.P., Taithe, F., Tattevin, P., Vaillant, M., and Vuoto, F.

Abstract

Viral, bacterial, or fungal infections are suspected of triggering multiple sclerosis (MS) and promoting relapses of the disease and are likely to be promoted by immune-active treatments. This raises questions about the infectious workup and preventive treatment of these infections prior to their initiation.

Published
2021
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32. Suivi gynécologique chez les patientes en âge de procréer atteintes de sclérose en plaques : étude GYNESEP

Author

Renaud, Juliette, Buissonnière, Pauline, Dulau, Cécile, Montcuquet, Alexis, Ouallet, Jean-Christophe, Ruet, Aurélie, and Bernard, Valérie

Abstract

Il existe peu de données concernant le suivi gynécologique des patientes atteintes de sclérose en plaques (SEP), la plupart des études portant sur la grossesse ou la sexualité.

Published
2024
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33. Étude descriptive des myélites aiguës en Guyane

Author

Grimont, Prune, Montcuquet, Alexis, Deschamps, Nathalie, Quet, Fabrice, and De Toffol, Bertrand

Abstract

Les myélites sont une entité relativement rare posant souvent la problématique de l’étiologie. La Guyane est une région où les étiologies infectieuses sont multiples et les pathologies immunes semblent émergentes.

Published
2024
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34. Description des neuropathies périphériques en territoire amazonien

Author

Deschamps, Nathalie, Takam, Valérie, Montcuquet, Alexis, Montagnac, Clémentine, Nacher, Mathieu, and De Toffol, Bertrand

Abstract

Les neuropathies périphériques concernent 2,4 % de la population générale. À ce jour, il n’y a pas eu de travaux réalisés sur le territoire amazonien, un territoire cosmopolite à forte biodiversité des pathogènes.

Published
2024
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35. Final report of the French Multicenter Phase II Study of the Nitrosourea Fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases

Author

Jacquillat, C., Khayat, D., Banzet, P., Weil, M., Fumoleau, P., Avril, M.-F., Namer, M., Bonneterre, J., Kerbrat, P., Bonerandi, J.J., Bugat, R., Montcuquet, P., Cupissol, D., Lauvin, R., Vilmer, C., Prache, C., and Bizzari, J.P.

Subjects
Melanoma -- Drug therapy, Chemotherapy -- Physiological aspects, Health
Abstract

The effectiveness of nitrosourea fotemustine in treating malignant melanoma, which is an aggressive tumor of melanocytes, pigmented skin cells, was assessed in 169 afflicted patients. The cancer was disseminated throughout the body, including the brain. Nitrosourea fotemustine was given in a dose of 100 milligrams per square meter of body area by intravenous infusion over a one-hour period, every week for three weeks. This was followed by a rest period of four to five weeks. Therapy was maintained at the same dose every three weeks in patients who responded or were stabilized by initial treatment, until their disease progressed. Of 169 patients treated, 153 were assessed for complete response, as indicated by the elimination of the tumor. Treatment with nitrosourea fotemustine resulted in complete responses in three cases and partial responses in 34 patients, thereby producing a response rate of 24.2 percent. The response rates at specific sites were 25 percent within the brain; 19.2 percent in the viscera (or abdominal region); and 31.8 percent at nonvisceral sites. In most cases, the duration of response was 22 weeks, and the response rate in previously untreated patients was 30.7 percent. The main toxic effects of nitrosourea fotemustine were blood-related, and included leukopenia (an abnormal decrease in white blood cells) and thrombocytopenia (an abnormal decrease in platelets, cells involved in blood clotting). These findings suggest that nitrosourea fotemustine is effective and relatively safe in treating disseminated malignant melanoma. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1990

36. Nod2 Protects the Gut From Experimental Colitis Spreading to Small Intestine.

Author

Nabhani, Ziad Al, Berrebi, Dominique, Martinez-Vinson, Christine, Montcuquet, Nicolas, Madre, Chrystele, Roy, Maryline, Ogier-Denis, Eric, Dussaillant, Monique, Cerf-Bensussan, Nadine, Zouali, Habib, Daniel, Fanny, Barreau, Frédérick, and Hugot, Jean-Pierre

Abstract

Background and Aims Nucleotide oligomerization domain 2 [ NOD2] mutations are key risk factors for Crohn's disease [CD]. NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the exact roles of NOD2 in CD and other NOD2-associated disorders remain poorly known. Methods We initially observed that NOD2 expression was increased in epithelial cells away from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation, and cytokines expression were examined in the small bowel of wild-type [WT], Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulphonic acid [TNBS]. Results In WT mice, Nod2 upregulation upstream to rectal injury was associated with pro-inflammatory cytokine expression but no overt histological inflammatory lesions. Conversely, in Nod2-deficient mice the inflammation spread from colitis to ileum and duodenum. Conclusions Nod2 protects the gut from colitis spreading to small intestine. [ABSTRACT FROM AUTHOR]

Published
2020
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37. Prolonged overall survival for patients with bone-only metastases at presentation of metastatic breast cancer

Author

Curtit, E., primary, Bazan, F., additional, Chaigneau, L., additional, Mouillet, G., additional, Dobi, E., additional, Mansi, L., additional, Meneveau, N., additional, Paillard, M.-J., additional, Meynard, G., additional, Klajer, E., additional, Villanueva, C., additional, Montcuquet, P., additional, Pivot, X., additional, and Cals, L., additional

Published
2018
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38. Impact of BRCA status on outcomes and survival in high-risk early breast cancers

Author

Klajer, E., primary, Paget-Bailly, S., additional, Meynard, G., additional, Meurisse, A., additional, Bazan, F., additional, Chaigneau, L., additional, Dobi, E., additional, Meneveau, N., additional, Montcuquet, P., additional, Villanueva, C., additional, Thiery-Vuillemin, A., additional, Kalbacher, E., additional, Populaire, C., additional, Collonge-Rame, M.-A., additional, Gligorov, J., additional, Curtit, E., additional, Pivot, X., additional, and Mansi, L., additional

Published
2018
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39. Real-life study of BRCA genetic screening in metastatic breast cancer

Author

Meynard, G., primary, Villanueva, C., additional, Thiery-Vuillemin, A., additional, Mansi, L., additional, Montcuquet, P., additional, Meneveau, N., additional, Chaigneau, L., additional, Bazan, F., additional, Almotlak, H., additional, Dobi, E., additional, Nguyen Tan Hon, T., additional, Klajer, E., additional, Fagnoni-Legat, C., additional, Paget-Bailly, S., additional, Meurisse, A., additional, Collonge-Rame, M-A., additional, Populaire-Ventron, C., additional, Pivot, X., additional, and Curtit, E., additional

Published
2017
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40. New OFSEP recommendations for MRI assessment of multiple sclerosis patients: Special consideration for gadolinium deposition and frequent acquisitions

Author

Brisset, Jean-Christophe, Kremer, Stephane, Hannoun, Salem, Bonneville, Fabrice, Durand-Dubief, Francoise, Tourdias, Thomas, Barillot, Christian, Guttmann, Charles, Vukusic, Sandra, Dousset, Vincent, Cotton, Francois, Ameli, R., Anxionnat, R., Audoin, B., Attye, A., Bannier, E., Barillot, C., Ben Salem, D., Boncoeur-Martel, M.-P., Bonhomme, G., Bonneville, F., Boutet, C., Brisset, J.C., Cervenanski, F., Claise, B., Commowick, O., Constans, J.-M., Cotton, F., Dardel, P., Desal, H., Dousset, V., Durand-Dubief, F., Ferre, J.-C., Gaultier, A., Gerardin, E., Glattard, T., Grand, S., Grenier, T., Guillevin, R., Guttmann, C., Krainik, A., Kremer, S., Lion, S., Champfleur, N. Menjot De, Mondot, L., Outteryck, O., Pyatigorskaya, N., Pruvo, J.-P., Rabaste, S., Ranjeva, J.-P., Roch, J.-A., Sadik, J.-C., Sappey-Marinier, D., Savatovsky, J., Stankoff, B., Tanguy, J.-Y., Tourbah, A., Tourdias, T., Brochet, B., Casey, R., Cotton, F., De Sèze, J., Douek, P., Guillemin, F., Laplaud, D., Lebrun-Frenay, C., Mansuy, L., Moreau, T., Olaiz, J., Pelletier, J., Rigaud-Bully, C., Stankoff, B., Vukusic, S., Debouverie, M., Edan, G., Ciron, J., Lubetzki, C., Vermersch, P., Labauge, P., Defer, G., Berger, E., Clavelou, P., Gout, O., Thouvenot, E., Heinzlef, O., Al-Khedr, A., Bourre, B., Casez, O., Cabre, P., Montcuquet, A., Créange, A., Camdessanché, J.-P., Bakchine, S., Maurousset, A., Patry, I., De Broucker, T., Pottier, C., Neau, J.-P., Labeyrie, C., and Nifle, C.

Abstract

New multiple sclerosis (MS) disease-modifying therapies (DMTs), which exert beneficial effects through prevention of relapse, limitation of disability progression, and improvement of patients’ quality of life, have recently emerged. Nonetheless, these DMTs are not without associated complications (severe adverse events like. progressive multifocal leukoencephalopathy). Patient follow-up requires regular clinical evaluations and close monitoring with magnetic resonance imaging (MRI). Detection of new T2 lesions and potential brain atrophy measurements contribute to the evaluation of treatment effectiveness. Current MRI protocols for MS recommend the acquisition of an annual gadolinium (Gd) enhanced MRI, resulting in administration of high volume of contrast agents over time and Gd accumulation in the brain.

Published
2020
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41. Progressive Multifocal Leukoencephalopathy Incidence and Risk Stratification Among Natalizumab Users in France

Author

Vukusic, Sandra, Rollot, Fabien, Casey, Romain, Pique, Julie, Marignier, Romain, Mathey, Guillaume, Edan, Gilles, Brassat, David, Ruet, Aurélie, De Sèze, Jérôme, Maillart, Elisabeth, Zéphir, Hélène, Labauge, Pierre, Derache, Nathalie, Lebrun-Frenay, Christine, Moreau, Thibault, Wiertlewski, Sandrine, Berger, Eric, Moisset, Xavier, Rico-Lamy, Audrey, Stankoff, Bruno, Bensa, Caroline, Thouvenot, Eric, Heinzlef, Olivier, Al-Khedr, Abdullatif, Bourre, Bertrand, Vaillant, Mathieu, Cabre, Philippe, Montcuquet, Alexis, Wahab, Abir, Camdessanché, Jean-Philippe, Tourbah, Ayman, Guennoc, Anne-Marie, Hankiewicz, Karolina, Patry, Ivania, Nifle, Chantal, Maubeuge, Nicolas, Labeyrie, Céline, Vermersch, Patrick, and Laplaud, David-Axel

Abstract

IMPORTANCE: Risk of developing progressive multifocal leukoencephalopathy (PML) is the major barrier to using natalizumab for patients with multiple sclerosis (MS). To date, the association of risk stratification with PML incidence has not been evaluated. OBJECTIVE: To describe the temporal evolution of PML incidence in France before and after introduction of risk minimization recommendations in 2013. DESIGN, SETTING, AND PARTICIPANTS: This observational study used data in the MS registry OFSEP (Observatoire Français de la Sclérose en Plaques) collected between April 15, 2007, and December 31, 2016, by participating MS expert centers and MS-dedicated networks of neurologists in France. Patients with an MS diagnosis according to current criteria, regardless of age, were eligible, and those exposed to at least 1 natalizumab infusion (n = 6318) were included in the at-risk population. A questionnaire was sent to all centers, asking for a description of their practice regarding PML risk stratification. Data were analyzed in July 2018. EXPOSURES: Time from the first natalizumab infusion to the occurrence of PML, natalizumab discontinuation plus 6 months, or the last clinical evaluation. MAIN OUTCOMES AND MEASURES: Incidence was the number of PML cases reported relative to the person-years exposed to natalizumab. A Poisson regression model for the 2007 to 2016 period estimated the annual variation in incidence and incidence rate ratio (IRR), adjusted for sex and age at treatment initiation and stratified by period (2007-2013 and 2013-2016). RESULTS: In total, 6318 patients were exposed to natalizumab during the study period, of whom 4682 (74.1%) were female, with a mean (SD [range]) age at MS onset of 28.5 (9.1 [1.1-72.4]) years; 45 confirmed incident cases of PML were diagnosed in 22 414 person-years of exposure. The crude incidence rate for the whole 2007 to 2016 period was 2.00 (95% CI, 1.46-2.69) per 1000 patient-years. Incidence significantly increased by 45.3% (IRR, 1.45; 95% CI, 1.15-1.83; P = .001) each year before 2013 and decreased by 23.0% (IRR, 0.77; 95% CI, 0.61-0.97; P = .03) each year from 2013 to 2016. CONCLUSIONS AND RELEVANCE: The results of this study suggest, for the first time, a decrease in natalizumab-associated PML incidence since 2013 in France that may be associated with a generalized use of John Cunningham virus serologic test results; this finding appears to support the continuation and reinforcement of educational activities and risk-minimization strategies in the management of disease-modifying therapies for multiple sclerosis.

Published
2020
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42. “Co-encapsulation of Immunosuppressive Drug with Anti-inflammatory Molecule in Pickering Emulsions as a Novel Therapeutic Approach for Inflammatory Dermatoses”

Author

Sintès, Maxime, Kovjenic, Petra, Haine (Hablal), Liasmine, Serror, Kevin, Beladjine, Mohamed, Parietti (Montcuquet), Véronique, Delagrange, Marine, Ducos, Bertrand, Bouaziz, Jean-David, Boccara, David, Mimoun, Maurice, Bensussan, Armand, Bagot, Martine, Huang, Nicolas, and Michel, Laurence

Abstract

Psoriasis is an inflammatory skin disease characterized by epidermal and immune dysfunctions. Although efficient, current topical treatments display adverse effects, including skin atrophy and burning sensation, leading to poor patient adherence. To overcome these downsides, Pickering emulsions were formulated in which the calcitriol-containing dispersed phase was stabilized with either cyclosporin A- or tacrolimus-loaded PLGA nanoparticles. This study aimed to investigate their biological effects on lymphocytes and epidermal cells and their effectiveness in an imiquimod-induce psoriasis-like mouse model. Results showed that both emulsions significantly inhibited NFAT translocation in T lymphocytes as well as their IL-2 production, cell activation and proliferation. In keratinocytes, inhibition of NFAT translocation decreased the production of IL-8 and TNF-α. Topical application of emulsions over skin biopsies ex vivoshowed accumulation of rhodamin B-coupled PLGA nanoparticles throughout the epidermis by immunofluorescence and significantly decreased the antigen-presenting capacity of Langerhans cells in relation with a reduced expression of activation markers CD40, CD86 and HLA-DR. Using an imiquimod-induced psoriasis model in vivo, Pickering emulsions significantly alleviated psoriasiform lesions potentially attributed to the decreased cutaneous expression of T cell markers, pro-inflammatory cytokines, chemokines and specific epidermal cell genes. Altogether, Pickering emulsions might be a very efficient formulation for treating inflammatory dermatoses.

Published
2024
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43. Surf: Open label, randomized multi-centre phase II study to assess the efficacy and tolerability of sunitinib by dose administration regimen (dose modification or dose interruptions) in patients with advanced or metastatic renal cell carcinoma (mRCC)

Author

Mouillet, G., primary, Maurina, T., additional, Paillard, M.-J., additional, Montcuquet, P., additional, Hon, T. Nguyen Tan, additional, Almotlak, H., additional, Stein, U., additional, Berthod, D., additional, Robert, E., additional, Meurisse, A., additional, Bonnetain, F., additional, and Thiery-Vuillemin, A., additional

Published
2016
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46. Immunization and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society

Author

Lebrun, C., Vukusic, S., Abadie, V., Achour, C., Ader, F., Alchaar, H., Alkhedr, A., Andreux, F., Androdias, G., Arjmand, R., Audoin, B., Audry, D., Aufauvre, D., Autreaux, C., Ayrignac, X., Bailbe, M., Benazet, M., Bensa, C., Bensmail, D., Berger, E., Bernady, P., Bertagna, Y., Biotti, D., Blanchard-Dauphin, A., Bonenfant, J., Bonnan, M., Bonnemain, B., Borgel, F., Botelho-Nevers, E., Boucly, S., Bourre, B., Boutière, C., Branger, P., Brassat, D., Bresch, S., Breuil, V., Brochet, B., Brugeilles, H., Bugnon, P., Cabre, P., Camdessanché, J.-P., Carra-Dalière, C., Casez, O., Chamouard, J.-M., Chassande, B., Chataignier, P., Chbicheb, M., Chenet, A., Ciron, J., Clavelou, P., Cohen, M., Colamarino, R., Collongues, N., Coman, I., Corail, P.-R., Courtois, S., Coustans, M., Creange, A., Creisson, E., Daluzeau, N., Davenas, C., De Seze, J., Debouverie, M., Depaz, R., Derache, N., Divio, L., Douay, X., Dulau, C., Durand-Dubief, F., Edan, G., Elias, Z., Fagniez, O., Faucher, M., Faucheux, J.-M., Fournier, M., Gagneux-Brunon, A., Gaida, P., Galli, P., Gallien, P., Gaudelus, J., Gault, D., Gayou, A., Genevray, M., Gentil, A., Gere, J., Gignoux, L., Giroux, M., Givron, P., Gout, O., Grimaud, J., Guennoc, A.-M., Hadhoum, N., Hautecoeur, P., Heinzlef, O., Jaeger, M., Jeannin, S., Kremer, L., Kwiatkowski, A., Labauge, P., Labeyrie, C., Lachaud, S., Laffont, I., Lanctin-Garcia, C., Lannoy, J., Lanotte, L., Laplaud, D., Latombe, D., Lauxerois, M., Le Page, E., Lebrun-Frenay, C., Lejeune, P., Lejoyeux, P., Lemonnier, B., Leray, E., Loche, C.-M., Louapre, C., Lubetzki, C., Maarouf, A., Mada, B., Magy, L., Maillart, E., Manchon, E., Marignier, R., Marque, P., Mathey, G., Maurousset, A., Mekies, C., Merienne, M., Michel, L., Milor, A.-M., Moisset, X., Montcuquet, A., Moreau, T., Morel, N., Moussa, M., Naudillon, J.-P., Normand, M., Olive, P., Ouallet, J.-C., Outteryck, O., Pacault, C., Papeix, C., Patry, I., Peaureaux, D., Pelletier, J., Pichon, B., Pittion, S., Planque, E., Pouget, M.-C., Pourcher, V., Radot, C., Robert, I., Rocher, F., Ruet, A., Ruet, A., Saint-Val, C., Salle, J.-Y., Salmon, A., Sartori, E., Schaeffer, S., Stankhof, B., Taithe, F., Thouvenot, E., Tizon, C., Tourbah, A., Tourniaire, P., Vaillant, M., Vermersch, P., Vidil, S., Wahab, A., Warter, M.-H., Wiertlewski, S., Wiplosz, B., Wittwer, B., Zaenker, C., and Zephir, H.

Abstract

To establish recommendations on immunization for patients with multiple sclerosis (MS).

Published
2019
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48. Nod2 Deficiency Leads to a Specific and Transmissible Mucosa-associated Microbial Dysbiosis Which Is Independent of the Mucosal Barrier Defect.

Author

Al Nabhani, Ziad, Lepage, Patricia, Mauny, Pascal, Montcuquet, Nicolas, Roy, Maryline, Le Roux, Karine, Dussaillant, Monique, Berrebi, Dominique, Hugot, Jean-Pierre, and Barreau, Frédérick

Abstract

Background and Aims: Crohn’s disease [CD] is a complex disorder characterised by an inappropriate immune response, impaired barrier function and microbial dysbiosis. Mutations in nucleotide oligomeriation domain 2 [NOD2] are CD risk factors. Increase of intestinal permeability, CD4+ T cell infiltration, and bacterial dysbiosis are also seen in Nod2-knockout [Nod2KO] mice. However, the specificity and relationship between these Nod2-associated abnormalities remain largely unexplored. Methods: Wild-type [WT], Nod1-knockout [Nod1KO] and Nod2KO mice were analysed in parallel. Microbial composition was defined by 454-pyrosequencing of bacterial 16S rRNA genes. Mucin and antimicrobial peptide expression was assessed by RT-PCR. Cell populations from Peyer’s patches were determined by flow cytometry. Ussing chambers were used to measure intestinal permeability and bacterial translocation. Finally, to explore the impact of colonisation with mother’s microbiota at birth, analyses were also performed in Nod2KO and WT mice born from WT surrogate mothers after embryo transfer. Results: Nod2KO mice exhibited colonic bacterial dysbiosis different from WT and Nod1KO mice. Altered expression of antimicrobial peptides and mucins in ileum and colon was associated with the microbial composition. Bacterial composition of Nod2KO and WT mice obtained by embryo transfer was similar to that observed in Nod2KO mice, arguing for a dominant effect of Nod2KOassociated dysbiosis. In contrast, increased levels of CD4+ T cells and gut barrier defects across Peyer’s patches were specific to Nod2 deficiency and independent of Microbial dysbiosis. Conclusions: Nod2 deficiency is associated with a specific dominant dysbiosis which does not drive mucosal tissue and immune alterations. [ABSTRACT FROM AUTHOR]

Published
2016
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