Dissecting the interplay between intestinal dysbiosis and B cell function in the pathogenesis of immunoglobulin A nephropathy

Immunoglobulin A nephropathy (IgAN) is an autoimmune disease and the most common form of primary glomerulonephritis. Patients present with heterogeneous clinicopathological manifestations and variable prognosis. The mechanisms of IgAN pathogenesis remain poorly defined but both B cells and microbiota are implicated. Our study will be the first to characterise the peripheral B cell subsets and function and explore possible interplay with intestinal microbiome diversity in IgAN patients. It is likely that intestinal dysbiosis in IgAN leads to aberrant B cell activation and differentiation towards antibody-producing plasma cells as opposed to regulatory B cells. This is in turn associated with a break in tolerance in IgAN pathogenesis. We will investigate peripheral B cell phenotype by flow cytometry and function in vitro, sequence the fecal microbiome, assess bacterial translocation markers and gut-derived uremic toxins in patients with histologically proven IgAN selected from renal biopsy registry at Pauls Stradiņš Clinical University Hospital compared to healthy individuals. The findings of this study will significantly contribute to understanding IgAN pathogenesis, and may enable patient subtyping for disease management and limit disease progression, and ultimately to the discovery of non-invasive disease-specific biomarkers for earlier diagnosis and development of new therapies.

Project working group meeting. From the right: Viktorija Kuzema, dr. Kārlis Rācenis, dr. Baiba Šlisere, lead researcher Kristīne Oļeiņika, dr. Anna Popova, dr. Aiga Vasiļvolfa

Project results achieved by project mid-term (during 18 months)

Scientific publications

In peer-reviewed open-access journal Proceedings of the Latvian Academy of Sciences (Cite score - 0,7, indexed in Web of Science and Scopus):

• Kučāne, L., Popova, A., Kuzema, V., Lejnieks, A.,  Pētersons, A. (2020). "Epidemiological, Clinical and Morphological Characteristics of Immunoglobulin a Nephropathy in Latvia, Proceedings of the Latvian Academy of Sciences." Section B. Natural, Exact, and Applied Sciences, 74(4), 227-231. doi: https://doi.org/10.2478/prolas-2020-0036. Published.
• Saulīte, A. J., Popova, A., Erts, R., Rācenis, K., Kučāne, L., Pētersons, A., Laurinavičius, A., Čerņevskis, H., Kuzema, V. (2021). "Renal Survival and Validation of Novel International Immunoglobulin A Nephropathy Prediction Tool in Latvian Population, Preliminary Data, Proceedings of the Latvian Academy of Sciences." Section B. Natural, Exact, and Applied Sciences, 75. Accepted for publication (acceptance letter available upon request).

Poster abstracts

• Šlisere, B., Popova, A., Rācenis, K., Vasiļvolfa, A., Berga-Švītiņa, E., Kuzema, V.,  Lejnieks, A., Kroiča, J., Pētersons, A., Čerņevskis, H., Oļeiņika, K. "Characterization of peripheral B-cells in IgA nephropathy." XV Baltic Congress in Laboratory Medicine, 2020, Riga. https://www.mitto.me/uploaded/balmriga/files/1252/114677_sl… . Published.
• Šlisere, B., Popova, A., Rācenis, K., Vasiļvolfa, A., Berga-Švītiņa, E., Imša, K., Saulīte, A.J., Kuzema, V., Laurinavicius, A., Lejnieks, A., Kroiča, J., Pētersons, A., Čerņevskis, H., Oleinika, K. "Altered B-cell populations in IgA nephropathy." RSU RW 22-26 March 2021; https://dspace.rsu.lv/jspui/bitstream/123456789/3645/1/KUP_…; 267 p.  Published.
• Popova, A., Saulīte, A.J., Rācenis, K., Vasiļvolfa, A., Kroiča, J., Pētersons, A., Lejnieks, A., Oleinika, K., Čerņevskis, H., Kuzema, V. "Serum complement C3 and C4 levels: prognostic factors in immunoglobulin A nephropathy." RSU RW 22-26 March 2021; https://dspace.rsu.lv/jspui/bitstream/123456789/3645/1/KUP_…; 524 p. Published.
• Kroiča, J., Pētersons, A., Kuzema, V. "LRG-1 as a tubular dysfunction marker in kidney transplant recipients." RSU RW 22-26 March 2021; https://dspace.rsu.lv/jspui/bitstream/123456789/3645/1/KUP_…; 509 p.  Published.
• Saulīte, A.J., Popova, A., Kučāne, L., Kuzema, V., Pētersons, A.  "Kidney survival analysis in immunoglobulin A nephropathy patients." International Scientific Conference of the University of Latvia 12 March 2020. https://medicina.lsmuni.lt/abstracts-of-the-international-s… 171 p. Published.
• Babičeva P., Popova A. "Assessment of dietary habits in patients with immunoglobulin a nephropathy." Warsaw International Medical Congress. 29-30 May, 2021; https://wimc.wum.edu.pl/wp-content/uploads/2017/05/16th_WIM…; 68 p. Published.

Mini-oral presentations

Presented in ERA-EDTA Congress 2021. Berlin, abstracts published in Nephrology Dialysis Transplantation, Volume 36, Issue Supplement (Impact factor 4,5):

• Popova, A., Rācenis, K., Saulite, A.J., Vasiļvolfa, A., Pētersons, A., Čerņevskis, H., Kuzema, V. "Bedside Urine Sediment Examination in Immunoglobulin A Nephropathy Patients Performed by Nephrologists." Nephrology Dialysis Transplantation, Volume 36, Issue Supplement_1, May 2021, gfab104.0077 (MO319), https://doi.org/10.1093/ndt/gfab104.0077 . Published.
• Vasiļvolfa, A., Kroiča, J., Popova, A., Rācenis, K., Šlisere, B., Ziediņa, I., Folkmane, I., Lejnieks, A., Čerņevskis, H., Pētersons, A., Kuzema, V.  "Serum and Urine Leucine Rich Alpha-2-Glycoprotein 1 is Associated with Kidney Transplant Injury and Failure." Nephrology Dialysis Transplantation, Volume 36, Issue Supplement_1, May 2021, gfab110.0024, https://doi.org/10.1093/ndt/gfab110.0024 Published.

Oral presentations

• Bernšteine (Saulīte), A.J., Popova, A., Kučāne, L., Rācenis, K., Kuzema, V., Pētersons, A. "Immunoglobulin A nephropathy prediction tool validation in Latvian population." XV Baltic Nephrology Conference UpToDate in Nephrology, Dialysis and Kidney Transplantation, Abstract book, p.8, 11 Dec.2020, Lithuania. http://balticnephrology2020.com/user/_files/571/Abstract%20… Published.
• Popova, A. "IgA nephropathy research in Latvia - national project." XV Baltic Nephrology Conference “UpToDate in Nephrology, Dialysis and Kidney Transplantation, 12 Dec.2020, Lithuania http://balticnephrology2020.com/user/_files/574/XV%20Nephro…
• Popova, A., Rācenis, K., Šlisere, B., Oleinika, K.,  Vasiļvolfa, A.,  Saulīte, A.J., Kuzema, V., Kroiča, J., Lejnieks, A., Berga-Švītiņa, E., Pētersons, A., Čerņevskis, H. "Dissecting the interplay between intestinal dysbiosis and B cell function in the pathogenesis of immunoglobulin A nephropathy." RSU conference, 22-26 March 2021; Riga, Latvia. https://dspace.rsu.lv/jspui/bitstream/123456789/3645/1/KUP_…; 434 p. Published.

Doctoral thesis

• Anna Popova, RSU PhD student (supervisor and consultant - Juta Kroiča, Prof.; Viktorija Kuzema, MD, PhD). "Dysbiosis characteristics of gut microbiome in immunoglobulin nephropathy a patients" (defence: continues)

Master's theses

• Anna Jana Saulīte, Faculty of Medicine, LU student (supervisor, Anna Popova). "Kidney survival of immunoglobulin a nephropathy patients" (defence: 21.05.2020.)
• Polīna Babičeva, Faculty of Medicine, LU student (supervisor,  Anna Popova). "Assessment of dietary habits in patients with immunoglobulin a nephropathy" (defence: 24.05.2021.)