title: Generation of Catalytic Antibodies Is an Intrinsic Property of an Individual's Immune System: A Study on a Large Cohort of Renal Transplant Patients.
abstract: Renal transplant is the treatment of choice for patients with terminal end-stage renal disease. We have previously identified low levels of catalytic IgG as a potential prognosis marker for chronic allograft rejection. The origin and physiopathological relevance of catalytic Abs is not well understood, owing to the fact that catalytic Abs have been studied in relatively small cohorts of patients with rare diseases and/or without systematic follow-up. In the current study, we have followed the evolution of the levels of catalytic IgG in a large cohort of renal transplant patients over a 2-y period. Our results demonstrate that, prior to transplant, patients with renal failure present with heterogeneous levels of IgG hydrolyzing the generic proline-phenylalanine-arginine-methylcoumarinamide (PFR-MCA) substrate. PFR-MCA hydrolysis was greater for patients' IgG than for a therapeutic preparation of pooled IgG from healthy donors. Renal transplant was marked by a drastic decrease in levels of catalytic IgG over 3 mo followed by a steady increase during the next 21 mo. Patients who displayed high levels of catalytic IgG pretransplant recovered high levels of catalytic Abs 2 y posttransplant. Interestingly, IgG-mediated hydrolysis of a model protein substrate, procoagulant factor VIII, did not correlate with that of PFR-MCA prior transplantation, whereas it did 12 mo posttransplant. Taken together, our results suggest that the level of circulating catalytic IgG under pathological conditions is an intrinsic property of each individual's immune system and that recovery of pretransplant levels of catalytic IgG is accompanied by changes in the repertoire of target Ags.
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France;
authors.forename: Ankit
authors.identifier: 0000-0002-6664-5974
authors.initials: A
authors.lastname: Mahendra
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France;
authors.forename: Ivan
authors.identifier: 0000-0002-3843-642X
authors.initials: I
authors.lastname: Peyron
authors.affiliation: INSERM, U1111, F-69007 Lyon, France; Service de Transplantation, Néphrologie et Immunologie Clinique, Hospices Civils de Lyon, Hôpital Edouard Herriot, F-69003 Lyon, France; Université de Lyon, F-69007 Lyon, France;
authors.forename: Olivier
authors.initials: O
authors.lastname: Thaunat
authors.affiliation: INSERM, U1111, F-69007 Lyon, France;
authors.forename: Cécile
authors.initials: C
authors.lastname: Dollinger
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France;
authors.forename: Laurent
authors.initials: L
authors.lastname: Gilardin
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France;
authors.forename: Meenu
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905;
authors.forename: Bharath
authors.identifier: 0000-0001-7522-1121
authors.initials: B
authors.lastname: Wootla
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India;
authors.forename: Desirazu N
authors.initials: DN
authors.lastname: Rao
authors.affiliation: Génie Enzymatique et Cellulaire, Formation de Recherche en Evolution 3580 Centre National de la Recherche Scientifique, Université de Technologie de Compiègne, F-60203 Compiègne, France;
authors.forename: Séverine
authors.identifier: 0000-0002-5475-1358
authors.initials: S
authors.lastname: Padiolleau-Lefevre
authors.affiliation: Service de Pharmacologie et d'Immunoanalyse, Laboratoire d'Ingénierie des Anticorps pour la Santé, Commissariat a l'Énergie Atomique, Institut de Biologie et de Technologies de Saclay, Saclay, F-91191 Gif-sur-Yvette, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Boquet
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX 77204; Department of Biology and Biochemistry, University of Houston, Houston, TX 77204;
authors.forename: Abhijit
authors.initials: A
authors.lastname: More
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX 77204; Department of Biology and Biochemistry, University of Houston, Houston, TX 77204;
authors.forename: Navin
authors.identifier: 0000-0001-7524-8228
authors.initials: N
authors.lastname: Varadarajan
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Laboratoire International Associé INSERM, F-75013 Paris, France; Indian Council of Medical Research, New Delhi 110029, India; and.
authors.forename: Srini V
authors.identifier: 0000-0002-0837-4053
authors.initials: SV
authors.lastname: Kaveri
authors.affiliation: Service de Néphrologie-Transplantation, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, F-75015 Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Laboratoire International Associé INSERM, F-75013 Paris, France; Indian Council of Medical Research, New Delhi 110029, India; and sebastien.lacroix-desmazes@crc.jussieu.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017151:Antibodies, Catalytic; D001323:Autoantibodies / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D001777:Blood Coagulation; D002908:Chronic Disease; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007107:Immune System; D007074:Immunoglobulin G / Q000378:metabolism*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D066027:Transplant Recipients; D055815:Young Adult
chemical_list: D017151:Antibodies, Catalytic; D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D005169:Factor VIII