PMID- 33102969
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220417
IS  - 2468-0249 (Electronic)
IS  - 2468-0249 (Linking)
VI  - 5
IP  - 10
DP  - 2020 Oct
TI  - A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating 
      Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy 
      Patients.
PG  - 1764-1776
LID - 10.1016/j.ekir.2020.07.028 [doi]
AB  - INTRODUCTION: Primary membranous nephropathy (MN) is characterized by the 
      presence of antipodocyte antibodies, but studies describing phenotypic and 
      functional abnormalities in circulating lymphocytes are limited. METHODS: We 
      analyzed 68 different B- and T-cell subsets using flow cytometry in 30 MN 
      patients (before initiating immunosuppression) compared with 31 patients with 
      non-immune-mediated chronic kidney disease (CKD) and 12 healthy individuals. We 
      also measured 19 serum cytokines in MN patients and in healthy controls. Lastly, 
      we quantified the ex vivo production of phospholipase A2 receptor 
      (PLA2R)-specific IgG by plasmablasts (measuring antibodies in culture 
      supernatants and by the newly developed FluoroSpot assay [AutoImmun Diagnostika, 
      Strasberg, Germany]) and assessed the circulating antibody repertoire by phage 
      immunoprecipitation sequencing (PhIP-Seq). RESULTS: After adjusting for multiple 
      testing, plasma cells and regulatory B cells (B(REG)) were significantly higher 
      (P < 0.05) in MN patients compared with both control groups. The percentages of 
      circulating plasma cells correlated with serum anti-PLA2R antibody levels (P = 
      0.042) and were associated with disease activity. Ex vivo-expanded PLA2R-specific 
      IgG-producing plasmablasts generated from circulating PLA2R-specific memory B 
      cells (mBCs) correlated with serum anti-PLA2R IgG antibodies (P < 0.001) in MN 
      patients. Tumor necrosis factor-alpha (TNF-alpha) was the only significantly increased 
      cytokine in MN patients (P < 0.05), whereas there was no significant difference 
      across study groups in the autoantibody and antiviral antibody repertoire. 
      CONCLUSION: This extensive phenotypic and functional immune characterization 
      shows that autoreactive plasma cells are present in the circulation of MN 
      patients, providing a new therapeutic target and a candidate biomarker of disease 
      activity.
CI  - (c) 2020 International Society of Nephrology. Published by Elsevier Inc.
FAU - Cantarelli, Chiara
AU  - Cantarelli C
AD  - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New 
      York, USA.
AD  - Dipartimento di Medicina e Chirurgia Universita di Parma, Unita' Operativa 
      Nefrologia, Azienda Ospedaliera-Universitaria Parma, Parma, Italy.
FAU - Jarque, Marta
AU  - Jarque M
AD  - Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, 
      Barcelona University, Biomedical Research Institute of Bellvitge, Barcelona, 
      Spain.
FAU - Angeletti, Andrea
AU  - Angeletti A
AD  - Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Policlinico 
      Sant'Orsola-Malpighi, Bologna, Italy.
FAU - Manrique, Joaquin
AU  - Manrique J
AD  - Nephrology Service, Complejo Hospitalario de Navarra, Pamplona, Spain.
FAU - Hartzell, Susan
AU  - Hartzell S
AD  - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New 
      York, USA.
FAU - O'Donnell, Timothy
AU  - O'Donnell T
AD  - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount 
      Sinai, New York, New York, USA.
FAU - Merritt, Elliot
AU  - Merritt E
AD  - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount 
      Sinai, New York, New York, USA.
FAU - Laserson, Uri
AU  - Laserson U
AD  - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount 
      Sinai, New York, New York, USA.
FAU - Perin, Laura
AU  - Perin L
AD  - Department of Urology, Keck School of Medicine, University of Southern 
      California, Los Angeles, California, USA.
FAU - Donadei, Chiara
AU  - Donadei C
AD  - Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Policlinico 
      Sant'Orsola-Malpighi, Bologna, Italy.
FAU - Anderson, Lisa
AU  - Anderson L
AD  - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New 
      York, USA.
FAU - Fischman, Clara
AU  - Fischman C
AD  - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New 
      York, USA.
FAU - Chan, Emilie
AU  - Chan E
AD  - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New 
      York, USA.
FAU - Draibe, Juliana
AU  - Draibe J
AD  - Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, 
      Barcelona University, Biomedical Research Institute of Bellvitge, Barcelona, 
      Spain.
FAU - Fulladosa, Xavier
AU  - Fulladosa X
AD  - Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, 
      Barcelona University, Biomedical Research Institute of Bellvitge, Barcelona, 
      Spain.
FAU - Torras, Joan
AU  - Torras J
AD  - Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, 
      Barcelona University, Biomedical Research Institute of Bellvitge, Barcelona, 
      Spain.
FAU - Riella, Leonardo V
AU  - Riella LV
AD  - Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, 
      Boston, Massachusetts, USA.
AD  - Center for Transplantation Sciences, Department of Surgery, Massachusetts General 
      Hospital, Boston, Massachusetts, USA.
FAU - La Manna, Gaetano
AU  - La Manna G
AD  - Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Policlinico 
      Sant'Orsola-Malpighi, Bologna, Italy.
FAU - Fiaccadori, Enrico
AU  - Fiaccadori E
AD  - Dipartimento di Medicina e Chirurgia Universita di Parma, Unita' Operativa 
      Nefrologia, Azienda Ospedaliera-Universitaria Parma, Parma, Italy.
FAU - Maggiore, Umberto
AU  - Maggiore U
AD  - Dipartimento di Medicina e Chirurgia Universita di Parma, Unita' Operativa 
      Nefrologia, Azienda Ospedaliera-Universitaria Parma, Parma, Italy.
FAU - Bestard, Oriol
AU  - Bestard O
AD  - Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, 
      Barcelona University, Biomedical Research Institute of Bellvitge, Barcelona, 
      Spain.
FAU - Cravedi, Paolo
AU  - Cravedi P
AD  - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New 
      York, USA.
LA  - eng
GR  - R01 DK119431/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20200801
PL  - United States
TA  - Kidney Int Rep
JT  - Kidney international reports
JID - 101684752
PMC - PMC7569696
OTO - NOTNLM
OT  - membranous nephropathy
OT  - phospholipase A2 receptor
OT  - plasma cells
OT  - regulatory B cells
OT  - regulatory T cells
EDAT- 2020/10/27 06:00
MHDA- 2020/10/27 06:01
PMCR- 2020/08/01
CRDT- 2020/10/26 05:28
PHST- 2020/05/28 00:00 [received]
PHST- 2020/07/20 00:00 [revised]
PHST- 2020/07/24 00:00 [accepted]
PHST- 2020/10/26 05:28 [entrez]
PHST- 2020/10/27 06:00 [pubmed]
PHST- 2020/10/27 06:01 [medline]
PHST- 2020/08/01 00:00 [pmc-release]
AID - S2468-0249(20)31427-3 [pii]
AID - 10.1016/j.ekir.2020.07.028 [doi]
PST - epublish
SO  - Kidney Int Rep. 2020 Aug 1;5(10):1764-1776. doi: 10.1016/j.ekir.2020.07.028. 
      eCollection 2020 Oct.