Circulating plasmablasts and high level of BAFF are hallmarks of minimal change nephrotic syndrome in adults

Author:

Oniszczuk Julie12,Beldi-Ferchiou Asma34,Audureau Etienne5,Azzaoui Imane6,Molinier-Frenkel Valérie34,Frontera Vincent2,Karras Alexandre78,Moktefi Anissa29,Pillebout Evangeline10,Zaidan Mohamad11,El Karoui Khalil12,Delfau-Larue Marie-Hélène312,Hénique Carole2,Ollero Mario2,Sahali Dil12,Mahévas Matthieu613,Audard Vincent12

Affiliation:

1. Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Service de Néphrologie et Transplantation, Centre de Référence Maladie Rare « Syndrome Néphrotique Idiopathique », Fédération Hospitalo-Universitaire « Innovative Therapy for Immune Disorders », Créteil, France

2. Univ Paris Est Créteil, Institut National de la Santé et de la Recherche Médicale (INSERM) U955, Institut Mondor de Recherche Biomédicale (IMRB), Equipe 21, Créteil, France

3. AP-HP, Hôpitaux Universitaires Henri Mondor, Département d’Hématologie et Immunologie Biologiques, Créteil, France

4. Univ Paris Est Créteil, INSERM U955, IMRB, Equipe Immunorégulation et Biothérapie, Créteil, France

5. AP-HP, Hôpitaux Universitaires Henri Mondor, Service de Santé Publique, Unité de Recherche Clinique, Université Paris Est Créteil, INSERM U955, IMRB, Equipe CEPIA, Créteil, France

6. Univ Paris Est Créteil, INSERM U955, IMRB, Equipe 2, Créteil, France

7. AP-HP, Hôpital Européen Georges Pompidou, Service de Néphrologie, Paris, France

8. Faculté de Médecine Paris-Descartes, Université de Paris, Paris, France

9. AP-HP, Hôpitaux Universitaires Henri Mondor, Département de Pathologie, Créteil, France

10. Service de Néphrologie et Transplantation, AP-HP, Hôpital Saint Louis, Paris, France

11. AP-HP, Hôpitaux Universitaires du Kremlin Bicêtre, Service de Néphrologie-Dialyse-Transplantation, Le Kremlin-Bicêtre, France

12. Univ Paris Est Créteil, INSERM U955, IMRB, Equipe 9, Créteil, France

13. AP-HP, Hôpitaux Universitaires Henri Mondor, Service de Médecine interne, Centre de Référence Maladie Rare « Cytopénies Auto-immunes », Créteil, France

Abstract

Abstract Background The recent success achieved with the use of B cell-depleting agents in some patients with minimal change nephrotic syndrome (MCNS) suggests an unexpected role for B lymphocytes in the pathogenesis of this immune-mediated glomerular disease. Nevertheless, no extensive B-cell phenotyping analysis has ever been performed in untreated adult patients soon after MCNS diagnosis. Methods We investigated the distribution of the different B-cell subpopulations in 22 untreated adult patients with biopsy-proven MCNS [MCNS relapse (MCNS-Rel)]. We compared these data with those for 24 healthy controls, 13 MCNS patients in remission (with no specific treatment) and 19 patients with idiopathic membranous nephropathy (IMN). Results Patients with MCNS-Rel or IMN had higher proteinuria and lower serum albumin and gammaglobulin levels (P < 0.0001 for all comparisons) than MCNS patients in remission. Plasmablasts were the only B-cell subsets present at significantly higher levels in MCNS-Rel patients than in the patients of the other three groups (P < 0.05 for all comparisons). The lower albumin levels and higher proteinuria levels were positively correlated with the percentage of circulating plasmablasts (Spearman test’s ρ = −0.54, P = 0.01 and ρ = 0.65, P = 0.002, respectively). Similarly, the increase of immunoglobulin M (IgM) and the decrease of IgG levels were significantly associated with the percentage of plasmablasts in MCNS-Rel patients (Spearman’s ρ = 0.36, P = 0.01 and Spearman’s ρ = −0.60, P = 0.01, respectively). Increased production of interleukin (IL)-21, IL-6 and B-cell activating factor (BAFF) in the serum of MCNS-Rel patients was found significantly correlated with the percentage of plasmablasts (ρ = 0.72, P = 0.0002, ρ = 0.49, P = 0.04 and ρ = 0.62, P = 0.009, respectively). Conclusions An increase in the proportion of circulating plasmablasts seems to be a hallmark of untreated MCNS in adult patients. Further studies are required to more precisely determine the phenotype and functions of these cells.

Funder

French Kidney Foundation

University Paris Est Créteil

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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