Cargando…
Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis
Background: Pentraxin3 (PTX3) is overexpressed in kidneys of patients developing lupus nephritis (LN). Active LN is associated with reduced anti-PTX3 antibodies. However, abnormalities of B cell differentiation against PTX3 have not been characterized in systemic lupus erythematosus (SLE). Objective...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355680/ https://www.ncbi.nlm.nih.gov/pubmed/30740098 http://dx.doi.org/10.3389/fimmu.2019.00029 |
_version_ | 1783391362231566336 |
---|---|
author | Gatto, Mariele Wiedemann, Annika Nomovi, Nadja Reiter, Karin Schrezenmeier, Eva Rose, Thomas Szelinski, Franziska Lino, Andreia C. Valentino, Sonia Ghirardello, Anna Dörner, Thomas Doria, Andrea |
author_facet | Gatto, Mariele Wiedemann, Annika Nomovi, Nadja Reiter, Karin Schrezenmeier, Eva Rose, Thomas Szelinski, Franziska Lino, Andreia C. Valentino, Sonia Ghirardello, Anna Dörner, Thomas Doria, Andrea |
author_sort | Gatto, Mariele |
collection | PubMed |
description | Background: Pentraxin3 (PTX3) is overexpressed in kidneys of patients developing lupus nephritis (LN). Active LN is associated with reduced anti-PTX3 antibodies. However, abnormalities of B cell differentiation against PTX3 have not been characterized in systemic lupus erythematosus (SLE). Objective: Characterization of PTX3-specific (PTX3(+)) B cells in peripheral blood of SLE patients with or without LN and healthy donors (HD). Patients and Methods: SLE patients without LN, biopsy-proven LN and matched HD were analyzed. Active LN was defined as proteinuria>0.5 g/day or CrCl<60 ml/min/1.73 m(2) with active urinary sediment. Peripheral B cells were analyzed for direct PTX3 binding by flow cytometry using PTX3 labeled with cyanine 5 (Cy5) and phycoerythrin (PE). Results: Initially, a flow cytometry based assay to identify PTX3(+) B cells was developed by demonstrating simultaneous binding of PTX3-Cy5 and PTX3-PE. Specificity of B cells was validated by blocking experiments using unlabeled PTX3. We could identify circulating PTX3(+) B-cells in HD and patients. Notably, LN patients showed a significantly diminished number of PTX3(+) B cells (SLE vs. LN p = 0.033; HD vs. LN p = 0.008). This decrease was identified in naïve and memory B cell compartments (naïve: SLE vs. LN p = 0.028; HD vs. LN p = 0.0001; memory: SLE vs. LN p = 0.038, HD vs. LN p = 0.011). Conclusions: Decreased PTX3(+) B cells in LN within the naïve and memory compartment suggest their negative selection at early stages of B cell development potentially related to a decreased regulatory function. PTX3(+) B cells could candidate for autoantigen-defined regulatory B cells as a striking abnormality of LN patients. |
format | Online Article Text |
id | pubmed-6355680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63556802019-02-08 Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis Gatto, Mariele Wiedemann, Annika Nomovi, Nadja Reiter, Karin Schrezenmeier, Eva Rose, Thomas Szelinski, Franziska Lino, Andreia C. Valentino, Sonia Ghirardello, Anna Dörner, Thomas Doria, Andrea Front Immunol Immunology Background: Pentraxin3 (PTX3) is overexpressed in kidneys of patients developing lupus nephritis (LN). Active LN is associated with reduced anti-PTX3 antibodies. However, abnormalities of B cell differentiation against PTX3 have not been characterized in systemic lupus erythematosus (SLE). Objective: Characterization of PTX3-specific (PTX3(+)) B cells in peripheral blood of SLE patients with or without LN and healthy donors (HD). Patients and Methods: SLE patients without LN, biopsy-proven LN and matched HD were analyzed. Active LN was defined as proteinuria>0.5 g/day or CrCl<60 ml/min/1.73 m(2) with active urinary sediment. Peripheral B cells were analyzed for direct PTX3 binding by flow cytometry using PTX3 labeled with cyanine 5 (Cy5) and phycoerythrin (PE). Results: Initially, a flow cytometry based assay to identify PTX3(+) B cells was developed by demonstrating simultaneous binding of PTX3-Cy5 and PTX3-PE. Specificity of B cells was validated by blocking experiments using unlabeled PTX3. We could identify circulating PTX3(+) B-cells in HD and patients. Notably, LN patients showed a significantly diminished number of PTX3(+) B cells (SLE vs. LN p = 0.033; HD vs. LN p = 0.008). This decrease was identified in naïve and memory B cell compartments (naïve: SLE vs. LN p = 0.028; HD vs. LN p = 0.0001; memory: SLE vs. LN p = 0.038, HD vs. LN p = 0.011). Conclusions: Decreased PTX3(+) B cells in LN within the naïve and memory compartment suggest their negative selection at early stages of B cell development potentially related to a decreased regulatory function. PTX3(+) B cells could candidate for autoantigen-defined regulatory B cells as a striking abnormality of LN patients. Frontiers Media S.A. 2019-01-25 /pmc/articles/PMC6355680/ /pubmed/30740098 http://dx.doi.org/10.3389/fimmu.2019.00029 Text en Copyright © 2019 Gatto, Wiedemann, Nomovi, Reiter, Schrezenmeier, Rose, Szelinski, Lino, Valentino, Ghirardello, Dörner and Doria. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Gatto, Mariele Wiedemann, Annika Nomovi, Nadja Reiter, Karin Schrezenmeier, Eva Rose, Thomas Szelinski, Franziska Lino, Andreia C. Valentino, Sonia Ghirardello, Anna Dörner, Thomas Doria, Andrea Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis |
title | Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis |
title_full | Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis |
title_fullStr | Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis |
title_full_unstemmed | Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis |
title_short | Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis |
title_sort | circulating pentraxin3-specific b cells are decreased in lupus nephritis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355680/ https://www.ncbi.nlm.nih.gov/pubmed/30740098 http://dx.doi.org/10.3389/fimmu.2019.00029 |
work_keys_str_mv | AT gattomariele circulatingpentraxin3specificbcellsaredecreasedinlupusnephritis AT wiedemannannika circulatingpentraxin3specificbcellsaredecreasedinlupusnephritis AT nomovinadja circulatingpentraxin3specificbcellsaredecreasedinlupusnephritis AT reiterkarin circulatingpentraxin3specificbcellsaredecreasedinlupusnephritis AT schrezenmeiereva circulatingpentraxin3specificbcellsaredecreasedinlupusnephritis AT rosethomas circulatingpentraxin3specificbcellsaredecreasedinlupusnephritis AT szelinskifranziska circulatingpentraxin3specificbcellsaredecreasedinlupusnephritis AT linoandreiac circulatingpentraxin3specificbcellsaredecreasedinlupusnephritis AT valentinosonia circulatingpentraxin3specificbcellsaredecreasedinlupusnephritis AT ghirardelloanna circulatingpentraxin3specificbcellsaredecreasedinlupusnephritis AT dornerthomas circulatingpentraxin3specificbcellsaredecreasedinlupusnephritis AT doriaandrea circulatingpentraxin3specificbcellsaredecreasedinlupusnephritis |