Stéphanie Malard-Castagnet1, Emilie Dugast2, Nicolas Degauque3, Annaïck Pallier4, Jean Paul Soulillou5, Anne Cesbron6, Magali Giral7, Jean Harb8, Sophie Brouard9. 1. Etablissement Français du sang, Pays de la Loire, HLA Laboratory, 34 Boulevard Jean Monnet, 44011 Nantes, France; Institut National de la Sante Et de la Recherche Médicale INSERM U1064, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, LabEx Transplantex, CHU de Nantes, 30 Boulevard Jean Monnet, 44093 Nantes Cedex 01, France. Electronic address: casteph@live.fr. 2. Institut National de la Sante Et de la Recherche Médicale INSERM U1064, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, LabEx Transplantex, CHU de Nantes, 30 Boulevard Jean Monnet, 44093 Nantes Cedex 01, France; Université de Nantes, Faculté de Médecine, Nantes, France. Electronic address: Emilie.dugast@univ-nantes.fr. 3. Institut National de la Sante Et de la Recherche Médicale INSERM U1064, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, LabEx Transplantex, CHU de Nantes, 30 Boulevard Jean Monnet, 44093 Nantes Cedex 01, France; Université de Nantes, Faculté de Médecine, Nantes, France. Electronic address: Nicolas.degauque@univ-nantes.fr. 4. Institut National de la Sante Et de la Recherche Médicale INSERM U1064, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, LabEx Transplantex, CHU de Nantes, 30 Boulevard Jean Monnet, 44093 Nantes Cedex 01, France. Electronic address: Annaik.pallier@univ-nantes.fr. 5. Institut National de la Sante Et de la Recherche Médicale INSERM U1064, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, LabEx Transplantex, CHU de Nantes, 30 Boulevard Jean Monnet, 44093 Nantes Cedex 01, France; Université de Nantes, Faculté de Médecine, Nantes, France. Electronic address: jean-paul.soulillou@univ-nantes.fr. 6. Etablissement Français du sang, Pays de la Loire, HLA Laboratory, 34 Boulevard Jean Monnet, 44011 Nantes, France. Electronic address: Anne.cesbron@efs.sante.fr. 7. Institut National de la Sante Et de la Recherche Médicale INSERM U1064, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, LabEx Transplantex, CHU de Nantes, 30 Boulevard Jean Monnet, 44093 Nantes Cedex 01, France; Université de Nantes, Faculté de Médecine, Nantes, France; CIC Biothérapie, 5, allée de l'Ile Gloriette, 44093 Nantes Cedex 0144035, Nantes, France; CHU Nantes, CRB, 9 quai Moncousu, 44093 Nantes Cedex 1, Nantes F-44093, France. Electronic address: Magali.giral@chu-nantes.fr. 8. Institut National de la Sante Et de la Recherche Médicale INSERM U1064, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, LabEx Transplantex, CHU de Nantes, 30 Boulevard Jean Monnet, 44093 Nantes Cedex 01, France; Université de Nantes, Faculté de Médecine, Nantes, France. Electronic address: Jean.harb@univ-nantes.fr. 9. Institut National de la Sante Et de la Recherche Médicale INSERM U1064, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, LabEx Transplantex, CHU de Nantes, 30 Boulevard Jean Monnet, 44093 Nantes Cedex 01, France; CIC Biothérapie, 5, allée de l'Ile Gloriette, 44093 Nantes Cedex 0144035, Nantes, France; CHU Nantes, CRB, 9 quai Moncousu, 44093 Nantes Cedex 1, Nantes F-44093, France. Electronic address: sophie.brouard@univ-nantes.fr.
Abstract
BACKGROUND: DSA are associated with reduced long-term transplant function and increased prevalence of chronic rejection in some patients, whereas others do not: our goal was to determine whether the sialylation of IgG and DSA could help to explain in these last cases their "non-aggressive" and/or "protective" biological activity. METHODS: The sialylation level of total IgG in blood from two groups of kidney-transplant patients with de novo DSA, one with an AMR (DSA+AMR+), and the other without were studied. RESULTS: In the DSA+AMR- patients total IgG were more sialylated at time of transplant, and at the first detection of DSA, class I DSA were 2.6-fold more sialylated (mean 9.943±1.801 versus 3.898±2.475, p=0.058); DSA+AMR+ patients exhibited higher levels of class II DSA. CONCLUSIONS: In our study, higher levels of sialylated IgG are detectable on day of transplant in patients who do not develop AMR, they have higher sialylated class I DSA at the initial detection of DSA, whereas class II DSA are significantly higher in patients who develop AMR. This is the first report suggesting that transplant outcome, and particularly AMR, is associated with levels of sialylated IgG antibodies. Our data suggest that DSA are functionally heterogeneous and that further studies with an enlarged cohort may improve our understanding of their clinical impact.
BACKGROUND: DSA are associated with reduced long-term transplant function and increased prevalence of chronic rejection in some patients, whereas others do not: our goal was to determine whether the sialylation of IgG and DSA could help to explain in these last cases their "non-aggressive" and/or "protective" biological activity. METHODS: The sialylation level of total IgG in blood from two groups of kidney-transplant patients with de novo DSA, one with an AMR (DSA+AMR+), and the other without were studied. RESULTS: In the DSA+AMR- patients total IgG were more sialylated at time of transplant, and at the first detection of DSA, class I DSA were 2.6-fold more sialylated (mean 9.943±1.801 versus 3.898±2.475, p=0.058); DSA+AMR+ patients exhibited higher levels of class II DSA. CONCLUSIONS: In our study, higher levels of sialylated IgG are detectable on day of transplant in patients who do not develop AMR, they have higher sialylated class I DSA at the initial detection of DSA, whereas class II DSA are significantly higher in patients who develop AMR. This is the first report suggesting that transplant outcome, and particularly AMR, is associated with levels of sialylated IgG antibodies. Our data suggest that DSA are functionally heterogeneous and that further studies with an enlarged cohort may improve our understanding of their clinical impact.
Authors: Adrien Bosseboeuf; Sophie Allain-Maillet; Nicolas Mennesson; Anne Tallet; Cédric Rossi; Laurent Garderet; Denis Caillot; Philippe Moreau; Eric Piver; François Girodon; Hélène Perreault; Sophie Brouard; Arnaud Nicot; Edith Bigot-Corbel; Sylvie Hermouet; Jean Harb Journal: Front Immunol Date: 2017-10-19 Impact factor: 7.561