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Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis.
- Source :
-
Frontiers in immunology [Front Immunol] 2019 Jan 25; Vol. 10, pp. 29. Date of Electronic Publication: 2019 Jan 25 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- 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 <superscript>+</superscript> ) 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 <superscript>2</superscript> 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 <superscript>+</superscript> 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 <superscript>+</superscript> B-cells in HD and patients. Notably, LN patients showed a significantly diminished number of PTX3 <superscript>+</superscript> 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 <superscript>+</superscript> 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 <superscript>+</superscript> B cells could candidate for autoantigen-defined regulatory B cells as a striking abnormality of LN patients.
- Subjects :
- Adult
Autoantibodies blood
Autoantigens metabolism
Biomarkers metabolism
C-Reactive Protein chemistry
C-Reactive Protein immunology
Carbocyanines chemistry
Female
Flow Cytometry methods
Humans
Male
Middle Aged
Phycoerythrin chemistry
Serum Amyloid P-Component chemistry
Serum Amyloid P-Component immunology
Staining and Labeling
B-Lymphocytes metabolism
C-Reactive Protein metabolism
Lupus Erythematosus, Systemic blood
Lupus Nephritis blood
Serum Amyloid P-Component metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 30740098
- Full Text :
- https://doi.org/10.3389/fimmu.2019.00029