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7. Unmet needs, health policies, and actions during the COVID-19 pandemic: a report from six European countries

Author

Miralles, Oriol, Sanchez-Rodriguez, Dolores, Marco, Esther, Annweiler, Cédric, Baztan, Ainhoa, Betancor, Évora, Cambra, Alicia, Cesari, Matteo, Fontecha, Benito J., Gąsowski, Jerzy, Gillain, Sophie, Hope, Suzy, Phillips, Katie, Piotrowicz, Karolina, Piro, Niccolò, Sacco, Guillaume, Saporiti, Edoardo, Surquin, Murielle, and Vall-llosera, Estel

Published
2021
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9. Which treatment to prevent an imminent fracture?

Author

Iconaru Laura, Baleanu Felicia, Charles Alexia, Mugisha Aude, Benoit Florence, Surquin Murielle, Karmali Rafik, Body Jean-Jacques, and Bergmann Pierre

Subjects
Imminent fracture, Osteoporosis, Bisphosphonate, Denosumab, Anabolic, Diseases of the musculoskeletal system, RC925-935
Abstract

Purpose: To provide a summarized state of the art of the relative efficacy and rapidity of action of pharmacological treatments to prevent imminent osteoporotic fractures. Methods: We reviewed metanalyses (MA) and network metaanalyses (NMA) published during the last 10 years concerning the pharmacological treatment of osteoporosis. We compared the anti-fracture efficacy and the rapidity of action of various agents versus placebo and versus risedronate. Results: All bisphosphonates decrease the incidence of vertebral fractures compared with placebo. Ibandronate is the only one without demonstrated efficacy against non-vertebral and hip fractures. Zoledronate, denosumab and anabolic therapy are associated with a higher fracture risk reduction than oral bisphosphonates. Compared with risedronate, which significantly reduces the rate of hip fractures, zoledronate, denosumab, teriparatide, abaloparatide and romosozumab are more efficient for vertebral fractures but not for non-vertebral or hip fractures reduction. No studies have compared bone anabolic treatments with zoledronate or denosumab. Oral bisphosphonates significantly reduce fracture risk only after more than one year of therapy. A faster reduction of fracture risk is observed with zoledronate and denosumab, or with anabolic agents. For denosumab and anabolic agents, a sequential treatment is required to keep gains after treatment withdrawal. Conclusions: In patients at high risk of imminent fracture, starting therapy with potent antiresorptive agents or with an anabolic agent seems most appropriate to promptly reduce the fracture risk. Available NMA/MA suggest that, compared to zoledronate and denosumab, anabolic agents have a higher efficacy for vertebral fractures but head-to-head studies are lacking.

Published
2021
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16. Correction to: Unmet needs, health policies, and actions during the COVID-19 pandemic: a report from six European countries

Author

Miralles, Oriol, Sanchez-Rodriguez, Dolores, Marco, Esther, Annweiler, Cédric, Baztan, Ainhoa, Betancor, Évora, Cambra, Alicia, Cesari, Matteo, Fontecha, Benito J., Gąsowski, Jerzy, Gillain, Sophie, Hope, Suzy, Phillips, Katie, Piotrowicz, Karolina, Piro, Niccolò, Sacco, Guillaume, Saporiti, Edoardo, Surquin, Murielle, and Vall-llosera, Estel

Published
2021
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17. Fragility Fractures in Postmenopausal Women: Development of 5-Year Prediction Models Using the FRISBEE Study

Author

Iconaru Laura, Bergmann Pierre, Mugisha Aude, Baleanu Felicia, Benoit Florence, Rubinstein Michel, Charles Alexia, Moreau Michel, Surquin Murielle, Rozenberg Serge, Karmali Rafik, Paesmans Marianne, and Jacques Body Jean

Subjects
Gerontology, Postmenopausal women, business.industry, Femur Neck, Hip Fractures, Endocrinology, Diabetes and Metabolism, Biochemistry (medical), Clinical Biochemistry, Risk Assessment, Biochemistry, Postmenopause, Fragility, Endocrinology, Bone Density, Risk Factors, Medicine, Humans, Osteoporosis, Female, Orthopedics and Sports Medicine, business, Predictive modelling, Osteoporotic Fractures
Abstract

Context Individualized fracture risk may help to select patients requiring a pharmacological treatment for osteoporosis. FRAX and the Garvan fracture risk calculators are the most used tools, although their external validation has shown significant differences in their risk prediction ability. Objective and Methods Using data from the Fracture Risk Brussels Epidemiological Enquiry study, a cohort of 3560 postmenopausal women aged 60 to 85 years, we aimed to construct original 5-year fracture risk prediction models using validated clinical risk factors (CRFs). Three models of competing risk analysis were developed to predict major osteoporotic fractures (MOFs), all fractures, and central fractures (femoral neck, shoulder, clinical spine, pelvis, ribs, scapula, clavicle, sternum). Results Age, a history of fracture, and hip or spine BMD were predictors common to the 3 models. Excessive alcohol intake and the presence of comorbidities were specific additional CRFs for MOFs, a history of fall for all fractures, and rheumatoid arthritis for central fractures. Our models predicted the fracture probability at 5 years with an acceptable accuracy (Brier scores ≤ 0.1) and had a good discrimination power (area under the receiver operating curve of 0.73 for MOFs and 0.72 for central fractures) when internally validated by bootstrap. Three simple nomograms, integrating significant CRFs and the mortality risk, were constructed for different fracture sites. In conclusion, we derived 3 models predicting fractures with an acceptable accuracy, particularly for MOFs and central fractures. The models are based on a limited number of CRFs, and we constructed nomograms for use in clinical practice.

Published
2022

18. External validation of FRISBEE 5-year fracture prediction models: a registry-based cohort study

Author

Agarwal, Arnav, primary, Baleanu, Felicia, additional, Moreau, Michel, additional, Charles, Alexia, additional, Iconaru, Laura, additional, Surquin, Murielle, additional, Benoit, Florence, additional, Paesmans, Marianne, additional, Karmali, Rafik, additional, Bergmann, Pierre, additional, Body, Jean-Jacques, additional, and Leslie, William D., additional

Published
2022
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20. Prediction of an imminent fracture after an index fracture – models derived from the Frisbee cohort

Author

Iconaru, Laura, primary, Charles, Alexia, additional, Baleanu, Felicia, additional, Surquin, Murielle, additional, Benoit, Florence, additional, Mugisha, Aude, additional, Moreau, Michel, additional, Paesmans, Marianne, additional, Karmali, Rafik, additional, Rubinstein, Michel, additional, Rozenberg, Serge, additional, Body, Jean-Jacques, additional, and Bergmann, Pierre, additional

Published
2022
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21. Fragility fractures in postmenopausal women: development of 5-year prediction models using the FRISBEE study

Author

Baleanu, Felicia, primary, Moreau, Michel, additional, Charles, Alexia, additional, Iconaru, Laura, additional, Karmali, Rafik, additional, Surquin, Murielle, additional, Benoit, Florence, additional, Mugisha, Aude, additional, Paesmans, Marianne, additional, Rubinstein, Michel, additional, Rozenberg, Serge, additional, Bergmann, Pierre, additional, and Body, Jean-Jacques, additional

Published
2022
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23. Which treatment to prevent an imminent fracture?

Author

Body Jean-Jacques, Mugisha Aude, Bergmann Pierre, Baleanu Felicia, Benoit Florence, Karmali Rafik, Iconaru Laura, Surquin Murielle, and Charles Alexia

Subjects
medicine.medical_specialty, Anabolic, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Abaloparatide, Osteoporosis, Romosozumab, Urology, Diseases of the musculoskeletal system, Placebo, Anabolic Agents, Imminent fracture, medicine, Teriparatide, Bisphosphonate, Orthopedics and Sports Medicine, business.industry, Mini-Review, medicine.disease, Denosumab, RC925-935, business, medicine.drug
Abstract

Purpose To provide a summarized state of the art of the relative efficacy and rapidity of action of pharmacological treatments to prevent imminent osteoporotic fractures. Methods We reviewed metanalyses (MA) and network metaanalyses (NMA) published during the last 10 years concerning the pharmacological treatment of osteoporosis. We compared the anti-fracture efficacy and the rapidity of action of various agents versus placebo and versus risedronate. Results All bisphosphonates decrease the incidence of vertebral fractures compared with placebo. Ibandronate is the only one without demonstrated efficacy against non-vertebral and hip fractures. Zoledronate, denosumab and anabolic therapy are associated with a higher fracture risk reduction than oral bisphosphonates. Compared with risedronate, which significantly reduces the rate of hip fractures, zoledronate, denosumab, teriparatide, abaloparatide and romosozumab are more efficient for vertebral fractures but not for non-vertebral or hip fractures reduction. No studies have compared bone anabolic treatments with zoledronate or denosumab. Oral bisphosphonates significantly reduce fracture risk only after more than one year of therapy. A faster reduction of fracture risk is observed with zoledronate and denosumab, or with anabolic agents. For denosumab and anabolic agents, a sequential treatment is required to keep gains after treatment withdrawal. Conclusions In patients at high risk of imminent fracture, starting therapy with potent antiresorptive agents or with an anabolic agent seems most appropriate to promptly reduce the fracture risk. Available NMA/MA suggest that, compared to zoledronate and denosumab, anabolic agents have a higher efficacy for vertebral fractures but head-to-head studies are lacking., Highlights • The concept of imminent fracture has implications for the choice of therapy • We reviewed metanalyses and network metaanalyses published in the last 10 years • We compared the efficacy and rapidity of treatments to prevent imminent fractures • Potent antiresorptive and anabolic agents are most appropriate to promptly reduce fracture risk • Anabolic agents seem to be more efficient to reduce vertebral fracture risk

Published
2021

24. Prediction of an Imminent Fracture After an Index Fracture – Models Derived From the Frisbee Cohort

Author

Iconaru, Laura, primary, Charles, Alexia, additional, Baleanu, Felicia, additional, Surquin, Murielle, additional, Benoit, Florence, additional, Mugisha, Aude, additional, Moreau, Michel, additional, Paesmans, Mairanne, additional, Karmali, Rafix, additional, Rubinstein, Michel, additional, Rozenberg, Serge, additional, Body, Jean‐Jacques, additional, and Bergmann, Pierre, additional

Published
2021
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25. Acute sarcopenia changes following hospitalization: influence of pre-admission care dependency level

Author

De Spiegeleer, Anton, primary, Kahya, Hasan, additional, Sanchez-Rodriguez, Dolores, additional, Piotrowicz, Karolina, additional, Surquin, Murielle, additional, Marco, Ester, additional, Detremerie, Celine, additional, Hussein, Dhurgham, additional, Hope, Suzy, additional, Dallmeier, Dhayana, additional, Decker, Genia, additional, Hrnciarikova, Dana, additional, Czesak, Joanna, additional, Toscano-Rico, Miguel, additional, Meza-Valderrama, Delky, additional, Bahat, Gülistan, additional, Descamps, Amélie, additional, Wynendaele, Evelien, additional, Elewaut, Dirk, additional, Vankova, Hana, additional, Landi, Francesco, additional, Benoit, Florence, additional, Gasowski, Jerzy, additional, and Van Den Noortgate, Nele, additional

Published
2021
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26. Independent External Validation of FRAX and Garvan Fracture Risk Calculators: A Sub‐Study of the FRISBEE Cohort

Author

Baleanu, Felicia, primary, Iconaru, Laura, additional, Charles, Alexia, additional, Kinnard, Virginie, additional, Fils, Jean‐François, additional, Moreau, Michel, additional, Karmali, Rafik, additional, Surquin, Murielle, additional, Benoit, Florence, additional, Mugisha, Aude, additional, Paesmans, Marianne, additional, Laurent, Michaël R, additional, Bergmann, Pierre, additional, and Body, Jean‐Jacques, additional

Published
2021
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28. Fracture distribution in elderly women: A FRISBEE sub-study

Author

Mugisha, Aude, primary, Body, Jean-Jacques, additional, Kinnard, Virginie, additional, Iconaru, Laura, additional, Baleanu, Felicia, additional, Charles, Alexia, additional, Surquin, Murielle, additional, Karmali, Rafik, additional, Bergmann, Pierre, additional, and Benoit, Florence, additional

Published
2021
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29. Risk factors for imminent fractures: A substudy of the Frisbee cohort

Author

Iconaru, Laura, primary, Moreau, Michel, additional, Baleanu, Felicia, additional, Kinnard, Virginie, additional, Charles, Alexia, additional, Mugisha, Aude, additional, Surquin, Murielle, additional, Benoit, Florence, additional, Karmali, Rafik, additional, Paesmans, Marianne, additional, Body, Jean-Jacques, additional, and Bergmann, Pierre, additional

Published
2021
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30. Fragility Fractures in Postmenopausal Women: Development of 5-Year Prediction Models Using the FRISBEE Study.

Author

Baleanu, Felicia, Moreau, Michel, Charles, Alexia, Iconaru, Laura, Karmali, Rafik, Surquin, Murielle, Benoit, Florence, Mugisha, Aude, Paesmans, Marianne, Rubinstein, Michel, Rozenberg, Serge, Bergmann, Pierre, and Body, Jean-Jacques

Subjects
OSTEOPOROSIS, POSTMENOPAUSE, CLAVICLE
Abstract

Context: Individualized fracture risk may help to select patients requiring a pharmacological treatment for osteoporosis. FRAX and the Garvan fracture risk calculators are the most used tools, although their external validation has shown significant differences in their risk prediction ability. Objective and Methods: Using data from the Fracture Risk Brussels Epidemiological Enquiry study, a cohort of 3560 postmenopausal women aged 60 to 85 years, we aimed to construct original 5-year fracture risk prediction models using validated clinical risk factors (CRFs). Three models of competing risk analysis were developed to predict major osteoporotic fractures (MOFs), all fractures, and central fractures (femoral neck, shoulder, clinical spine, pelvis, ribs, scapula, clavicle, sternum). Results: Age, a history of fracture, and hip or spine BMD were predictors common to the 3 models. Excessive alcohol intake and the presence of comorbidities were specific additional CRFs for MOFs, a history of fall for all fractures, and rheumatoid arthritis for central fractures. Our models predicted the fracture probability at 5 years with an acceptable accuracy (Brier scores ≤ 0.1) and had a good discrimination power (area under the receiver operating curve of 0.73 for MOFs and 0.72 for central fractures) when internally validated by bootstrap. Three simple nomograms, integrating significant CRFs and the mortality risk, were constructed for different fracture sites. In conclusion, we derived 3 models predicting fractures with an acceptable accuracy, particularly for MOFs and central fractures. The models are based on a limited number of CRFs, and we constructed nomograms for use in clinical practice. [ABSTRACT FROM AUTHOR]

Published
2022
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31. Sarcopenia in Acute Care Patients: Protocol for the European Collaboration of Geriatric Surveys: Sarcopenia 9+ EAMA Project

Author

Sanchez-Rodriguez, Dolores, Hope, Suzy, Piotrowicz, Karolina, Benoit, Florence, Czesak, Joanna, Dallmeier, Dhayana, Decker, Genia, De Spiegeleer, Anton, Højmann, Anette Hansen, Hrnciarikova, Dana, Marco, Ester, Mendes, Diana, Meza, Delky, Nascimento, Paula, Rodrigues, Afonso, Surquin, Murielle, Toscano-Rico, Miguel, Vankova, Hana, Vetrano, Davide L., Gąsowski, Jerzy, Van Den Noortgate, Nele, and Landi, Francesco

Published
2019
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32. Unmet needs, health policies, and actions during the COVID-19 pandemic: a report from six European countries

Author

Miralles, Oriol, primary, Sanchez-Rodriguez, Dolores, additional, Marco, Esther, additional, Annweiler, Cédric, additional, Baztan, Ainhoa, additional, Betancor, Évora, additional, Cambra, Alicia, additional, Cesari, Matteo, additional, Fontecha, Benito J., additional, Gąsowski, Jerzy, additional, Gillain, Sophie, additional, Hope, Suzy, additional, Phillips, Katie, additional, Piotrowicz, Karolina, additional, Piro, Niccolò, additional, Sacco, Guillaume, additional, Saporiti, Edoardo, additional, Surquin, Murielle, additional, and Vall-llosera, Estel, additional

Published
2020
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33. Osteoporosis treatment gap in the FRISBEE cohort

Author

Iconaru, Laura, primary, Smeys, Celeste, additional, Baleanu, Felicia, additional, Kinnard, Virginie, additional, Moreau, Michel, additional, Cappelle, Silvie, additional, Surquin, Murielle, additional, Rubinstein, Michel, additional, Rozemberg, Serge, additional, Paesmans, Marianne, additional, Karmali, Rafik, additional, Bergmann, Pierre, additional, and Body, Jean-Jacques, additional

Published
2020
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35. Prediction of an Imminent Fracture After an Index Fracture – Models Derived From the Frisbee Cohort.

Author

Iconaru, Laura, Charles, Alexia, Baleanu, Felicia, Surquin, Murielle, Benoit, Florence, Mugisha, Aude, Moreau, Michel, Paesmans, Mairanne, Karmali, Rafix, Rubinstein, Michel, Rozenberg, Serge, Body, Jean‐Jacques, and Bergmann, Pierre

Abstract

Patients who sustain a fracture are at greatest risk of recurrent fracture during the next 2 years. We propose three models to identify subjects most at risk of an imminent fracture, according to fracture site (any fracture, major osteoporotic fracture [MOF] or central). They were constructed using data of the prospective Frisbee cohort, which includes 3560 postmenopausal women aged 60 to 85 years who were followed for at least 5 years. A total of 881 subjects had a first incident validated fragility fracture before December 2018. Among these, we validated 130 imminent fractures occurring within the next 2 years; 79 were MOFs, and 88 were central fractures. Clinical risk factors were re‐evaluated at the time of the index fracture. Fine and Gray proportional hazard models were derived separately for each group of fractures. The following risk factors were significantly associated with the risk of any imminent fracture: total hip bone mineral density (BMD) (p < 0.001), a fall history (p < 0.001), and comorbidities (p = 0.03). Age (p = 0.05 and p = 0.03, respectively) and a central fracture as the index fracture (p = 0.04 and p = 0.005, respectively) were additional predictors of MOFs and central fractures. The three prediction models are presented as nomograms. The calibration curves and the Brier scores based on bootstrap resampling showed calibration scores of 0.089 for MOF, 0.094 for central fractures, and 0.132 for any fractures. The predictive accuracy of the models expressed as area under the receiver operating characteristic (AUROC) curve (AUC) were 0.74 for central fractures, 0.72 for MOFs, and 0.66 for all fractures, respectively. These AUCs compare well with those of FRAX and Garvan to predict the 5‐ or 10‐year fracture probability. In summary, five predictors (BMD, age, comorbidities, falls, and central fracture as the incident fracture) allow the calculation with a reasonable accuracy of the imminent risk of fracture at different sites (MOF, central fracture, and any fracture) after a recent sentinel fracture. © 2021 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Published
2022
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39. European Academy for medicine of ageing session participants' report on malnutrition assessment and diagnostic methods; an international survey

Author

Sanchez-Rodriguez, Dolores, primary, Annweiler, Cédric, additional, Marco, Ester, additional, Hope, Suzy, additional, Piotrowicz, Karolina, additional, Surquin, Murielle, additional, Ranhoff, Annette, additional, Van Den Noortgate, Nele, additional, Andersen-Ranberg, Karen, additional, Bonin-Guillaume, Sylvie, additional, Conroy, Simon, additional, Gordon, Adam, additional, Grodziki, Tomasz, additional, Landi, Francesco, additional, Martínez-Velilla, Nicolás, additional, Münzer, Thomas, additional, Ranhoff, Anette Hylen, additional, Roller-Wirnsberger, Regina, additional, Singler, Katrin, additional, Al Hamad, Hanadi Khamis, additional, Beuscart, Jean-Baptiste, additional, Blanc, Frédéric, additional, Ciurea, Annette, additional, Cobbaert, Katrien, additional, Dallmeier, Dhayana, additional, Dinan, Pascale, additional, Engvig, Andreas, additional, Højmann, Anette Hansen, additional, Hosia, Helka, additional, Kerminen, Hanna-Maria, additional, Knapskog, Anne-Brita, additional, Koutsouri, Anastasia, additional, Laurent, Marie, additional, Lilamand, Matthieu, additional, Marien, Sophie, additional, Mellingsaeter, Marte, additional, Mendes, Aline, additional, Nguyen, Sylvain, additional, Ogugua, Chile, additional, Ommundsen, Nina, additional, Périvier, Samuel, additional, Rapo-Pylkkö, Susanna, additional, Roitto, Hanna-Maria, additional, Roubaud-Baudron, Claire, additional, Saka, Bülent, additional, Sanchez-Rodriguez, Dolores, additional, Tarazona, Francisco, additional, Toscano-Rico, Miguel, additional, Tschurr, Gaudenz, additional, Vande Walle, Natalie, additional, Vetrano, Davide, additional, and Yavuz, Burcu-Balam, additional

Published
2020
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44. Acute sarcopenia changes following hospitalization: influence of pre-admission care dependency level.

Author

Spiegeleer, Anton De, Kahya, Hasan, Sanchez-Rodriguez, Dolores, Piotrowicz, Karolina, Surquin, Murielle, Marco, Ester, Detremerie, Celine, Hussein, Dhurgham, Hope, Suzy, Dallmeier, Dhayana, Decker, Genia, Hrnciarikova, Dana, Czesak, Joanna, Toscano-Rico, Miguel, Meza-Valderrama, Delky, Bahat, Gülistan, Descamps, Amélie, Wynendaele, Evelien, Elewaut, Dirk, and Vankova, Hana

Subjects
GRIP strength, WALKING speed, CONFIDENCE intervals, SARCOPENIA, REGRESSION analysis, CONGREGATE housing, HOSPITAL care of older people, CALF muscles, INDEPENDENT living, DESCRIPTIVE statistics, DEPENDENCY (Psychology)
Abstract

Introduction Hospitalization is associated with acute changes in sarcopenia status in older people, but the influencing factors are not fully understood. Pre-admission care dependency level as a risk factor has not yet been investigated. Objective Evaluate if pre-admission care dependency level is an independent predictor of sarcopenia changes following hospitalization. Setting and subjects Data came from the Sarcopenia 9+ EAMA Project, a European prospective multi-centre study. For this study, 227 hospitalised older people were included from four different hospitals in Belgium, Spain and Poland, between 18 February 2019 and 5 September 2020. Methods Sarcopenia status at admission and discharge were calculated using a combined score (desirability value) based on muscle mass (calf circumference), strength (grip) and function (walking speed). Ratio of admission to discharge status was the outcome (desirability ratio; 1.00 meaning no difference). Predictor variable was the pre-admission care dependency level, classified into three groups: independent older people living at home, dependent older people living at home and older people living in a care home. Linear regression models were applied, considering potential confounders. Results Mean desirability ratio for dependent older people living at home ('middle dependent group') was lower (0.89) compared to independent older people (0.98; regression coefficient −0.09 [95% CI −0.16, −0.02]) and care home patients (1.05; −0.16 [95% CI −0.01, −0.31]). Adjusting for potential confounders or using another statistical approach did not affect the main results. Conclusion Dependent older people living at home were at higher risk of deterioration in sarcopenia status following hospitalization. In-depth studies investigating causes and potential interventions of these findings are needed. [ABSTRACT FROM AUTHOR]

Published
2021
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47. Role of Th2 cytokines and polymorphonuclear cells in allograft rejection in mice

Author

Surquin, Murielle, Abramowicz, Daniel, Devière, Jacques, Bruyns, Catherine, Eizirik, Decio L., Donckier De Donceel, Vincent, Saoudi, Abdelhadi A., and Cuturi, Maria-Cristina

Subjects
Neutrophils, Mice as laboratory animals, Neutrophiles, Médecine pathologie humaine, souris, Rejet (Biologie), Transplantation of organs, tissues, etc, Graft rejection, Cytokines, Souris (Animaux de laboratoire), Greffe (Chirurgie), Homogreffes, Th2 cytokines, Homografts, transplantation
Abstract

Acute allograft rejection remains a major problem in solid organ transplantation, because rejection may lead to acute or chronic loss of graft function. The failure of certain anti-rejection prophylactic treatments suggests that several unexpected pathways might be involved in the rejection process.The aim of our experiments was to investigate the effector mechanisms responsible for skin graft rejection in mice. To adress this question, we took advantage of the possibility to restrict the alloimmune response to isolated allogeneic MHC class II molecules or to isolated minor transplantation antigens, combined with the possibility to study separately the response of CD4+ or CD8+ T cells in mice deficient for Th1 or Th2 cytokines or cytotoxic molecules. We used the bm12 skin graft combination (C57BL/6 H2Kbm12 grafted on C57BL/6 H2Kb) as a model of single MHC class II disparity and the b2microglobulin skin graft model (C57BL/6 b2m+/+ grafted on C57BL/6 b2m-/-) as a model of minor transplantation antigen disparity. Our goal was to engage a limited number of effectors, trying in a second time to block each rejection pathway selectively. We showed that Fas/FasL-mediated CD4+ T cells cytotoxicity, eosinophil recruitment, activation and degranulation induced by Th2 derived cytokines, and CD4-derived IFN-g production are involved in the rejection of grafts bearing either a single MHC class II disparity or b2m-derived minor histocompatibilty antigens. In addition, rejection of MHC class II disparate skin grafts also includes the participation of neutrophils, in particular conditions where the occurrence of the Th2/eosinophil pathway was prevented. Altogether, our data show a multiplicity and a redundancy of the effector pathways participating in allograft rejection. Among the different effectors pathways identified, including effectors from both innate and adaptive immune systems, some act synergistically, whereas others act as alternative pathways, depending of the degree of donor-recipient mismatch., Doctorat en Sciences médicales, info:eu-repo/semantics/nonPublished

Published
2007

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