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:...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00029/full |
| _version_ | 1828769462432563200 |
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| author | Mariele Gatto Mariele Gatto Annika Wiedemann Nadja Nomovi Karin Reiter Eva Schrezenmeier Thomas Rose Franziska Szelinski Andreia C. Lino Sonia Valentino Anna Ghirardello Thomas Dörner Andrea Doria |
| author_facet | Mariele Gatto Mariele Gatto Annika Wiedemann Nadja Nomovi Karin Reiter Eva Schrezenmeier Thomas Rose Franziska Szelinski Andreia C. Lino Sonia Valentino Anna Ghirardello Thomas Dörner Andrea Doria |
| author_sort | Mariele Gatto |
| collection | DOAJ |
| 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 m2 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. |
| first_indexed | 2024-12-11T13:48:32Z |
| format | Article |
| id | doaj.art-9cf005332572471abdd500599e8ffda5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T13:48:32Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9cf005332572471abdd500599e8ffda52022-12-22T01:04:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-01-011010.3389/fimmu.2019.00029428457Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus NephritisMariele Gatto0Mariele Gatto1Annika Wiedemann2Nadja Nomovi3Karin Reiter4Eva Schrezenmeier5Thomas Rose6Franziska Szelinski7Andreia C. Lino8Sonia Valentino9Anna Ghirardello10Thomas Dörner11Andrea Doria12Unit of Rheumatology, Department of Medicine, University of Padova, Padua, ItalyDepartment Medicine, Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, GermanyDepartment Medicine, Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, GermanyDepartment Medicine, Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, GermanyDepartment Medicine, Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, GermanyDepartment of Medicine, Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, GermanyDepartment Medicine, Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, GermanyDepartment Medicine, Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, GermanyDeutsches Rheuma-Forschungszentrum (DRFZ), Berlin, GermanyHumanitas Clinical and Research Center, Milan, ItalyUnit of Rheumatology, Department of Medicine, University of Padova, Padua, ItalyDepartment Medicine, Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, GermanyUnit of Rheumatology, Department of Medicine, University of Padova, Padua, ItalyBackground: 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 m2 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00029/fullSLEPTX3+ B cellslupus nephritisbiomarkersflow-cytometry |
| spellingShingle | Mariele Gatto Mariele Gatto Annika Wiedemann Nadja Nomovi Karin Reiter Eva Schrezenmeier Thomas Rose Franziska Szelinski Andreia C. Lino Sonia Valentino Anna Ghirardello Thomas Dörner Andrea Doria Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis Frontiers in Immunology SLE PTX3+ B cells lupus nephritis biomarkers flow-cytometry |
| 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 | SLE PTX3+ B cells lupus nephritis biomarkers flow-cytometry |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00029/full |
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