High Levels of Intestinal-Activated IgA<sup>+ </sup> B Lymphocytes Support the Pathogenic Role of Intestinal Mucosal Hyper-Responsiveness in IgA Nephropathy (IgAN) Patients
November 08, 2019 | 10:00 AM - 12:00 PM
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High Levels of Intestinal-Activated IgA+ B Lymphocytes Support the Pathogenic Role of Intestinal Mucosal Hyper-Responsiveness in IgA Nephropathy (IgAN) Patients
Glomerular Diseases: Immunology, Inflammation - I
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
- Sallustio, Fabio, University of Bari, Bari, Italy
- Curci, Claudia, University of Bari, Bari, Italy
- Chaoul, Nada, University of Bari, Bari, Italy
- Lauriero, Gabriella, University of Bari "Aldo Moro", Altamura, Italy
- Divella, Chiara, University of Bari, Bari, Italy
- Di leo, Vincenzo, University of Bari, Bari, Italy
- Ben mkaddem, Sanae, Inserm U1149-, Paris, France
- Monteiro, Renato C., Bichat Medical School, Paris, France
- Gallone, Anna, University of Bari, Bari, Italy
- Pesce, Francesco, University of Bari, Bari, Italy
- Gesualdo, Loreto, University of Bari, Bari, Italy
Vincenzo Di leo,
Sanae Ben mkaddem,
Renato C. Monteiro,
In the last years, the role of mucosal immunity in IgAN, together with that of the gut microbiota in the activation of innate and adaptive immune cells, has gained importance. Particularly interesting is the role of the microbiota and intestinal immunity in IgAN, due to the activity of secretory IgA in the intestinal mucosa. Here we studied the intestinal-renal axis connections analyzing levels of BAFF, April and intestinal-activated B cells in patients and healthy subjects (HS).
Serum and fecal samples were collected from 44 IgAN patients and 23 HS. BAFF and APRIL serum levels were measured by ELISA assay. Metabolomic analysis of fecal microbiome was performed by mass spectrometry. B cell subsets were identified by FACS. We used anti-IgA, anti-Integrin β7 and anti-CCR9 antibodies to identify B cell subsets producing IgA and B cells from intestinal mucosa.
IgAN patients had increased levels of Baff correlating to higher amounts of 5 specific microbiota metabolites (p=.012). We found also high April levels in IgAN patients. BAFF and APRIL can be produced by the intestinal epithelium, in response to signals triggered by TLRs activated by the commensal bacteria in the intestinal lumen. In addition, we found that IgAN patients have a higher proportion of circulating Breg activated at the intestinal level (CCR9+/INTB7+) compared to HS (p=0.02). Moreover, IgAN patients had also high levels of CCR9+/INTB7+ memory Bcells (p=.006) and of intestinal IgA-producing memory Bcells (CCR9+/INTB7+/IgA+ p=.03). Interestingly, they were significantly increased in IgAN patients but not in non-IgA glomerulonephritis. Finally, we found that IgAN patients had high levels both of total plasmablasts (p=.001) and of intestinal-activated plasmablasts (p=.01).
The results of our study showed for the first time an important difference in the amount of intestinal-activated B lymphocytes among patients with IgAN and HS, confirming the hypothesis of the pathogenic role of intestinal mucosal hyperresponsiveness in the IgAN patients. Therefore, this represents an important area of research for new targeted therapies aiming to stop the evolution towards end stage renal disease.