Unveiling molecular determinants and developmental niches for GdIgA+ B cell differentiation in IgA nephropathy

IgA nephropathy (IgAN) is an autoimmune disease with an incompletely understood aetiology. The pathogenesis of IgAN is conceptualised by the multi-hit model. Observations studies from IgAN patients show increased production of aberrantly glycosylated galactose-deficient IgA1 (GdIgA1, hit 1), the generation of antibodies against it (hit 2), immune complex formation (hit 3), and the mechanisms of immune-complex-mediated kidney injury (hit 4). As the source of the pathogenic antibodies B cells are central, yet are absent from the multi-hit model. Recently, we identified and characterised a GdIgA1+ B cell population that is increased in the peripheral blood of IgAN patients; these B cells are the putative precursors of GdIgA1-antibody-secreting cells (ASCs). We aim to provide mechanistic insight into the pathogenesis of IgAN by unravelling the molecular determinants and developmental niches for the differentiation of these GdIgA+ B cells. We combine flow cytometry, single cell transcriptional profiling and confocal microscopy of mucosa-associated lymphoid tissue (MALT), specifically the Peyer\'s patches (PPs), to uncover the determinants of altered B cell activation in IgAN. To mechanistically interrogate the factors that lead to GdIgA1+ B cell and ASC differentiation we will use cultures of sorted B cells and in vitro PP modelling. Together this will address a major gap in knowledge with regards to the B cell source and differentiation pathways in the pathogenesis of IgAN. 

Outcomes

• Original scientific articles published, submitted or accepted for publication in the Q1 or Q2 quartile publications included in Web of Science Core Collection or SCOPUS databases - 2;
• Scientific databases and datasets developed within the project and prepared according to FAIR principles -1;
• Project proposal submitted in a Latvian call for research and development projects - 1;
• Other project results according to the specific nature of the project complementary to those listed above (including pre-prints) - 1;
• BA thesis - 1;
• Theses in international conferences - 4.

Media

New Therapeutic Options for Patients with IgA Nephropathy, Doctus magazine (in Latvian), A. Dobele, K. Rācenis, I. Ziediņa (19 May 2026)

Podcast in Latvian Kas notiek medicīnā? (What is happening in medicine?) – What is happening in Nephrology (27 January 2025)
Project researcher Kārlis Rācenis participated in the podcast, discussing recent developments in nephrology, treatment options for kidney diseases, and current research initiatives in the field.

Project-related activities

• B Cell Profiling in Peripheral Blood and Peyer's Patches in IgA Nephropathy. At the RSU 12th International Student Conference in Health and Social Sciences (ISC 2026), the study received First Prize in the Internal Medicine poster presentation category (26–27 March 2026) 
  Book of abstracts
• Poster presentation "Spectral Flow Cytometry-Based Profiling of B Cells in Peripheral Blood and Peyer's Patches in IgA Nephropathy" at the Second Baltic Flow Cytometry Society Conference (BFCS 2026), presenting the immunophenotyping platform developed within the project (19–20 March 2026) 
  Book of abstracts
• First Baltic Scientific Meeting on IgA Nephropathy. The meeting brought together leading experts in nephrology, immunology and pathology from the Baltic States and across Europe and established a new annual platform for scientific collaboration in IgA nephropathy research within the Baltic region (2–3 February 2026)
• Doctoral thesis defence of Anna Popova: The Role of B-Cell Differentiation and Gut Microbiome in the Pathogenesis and Progression of IgA Nephropathy. The thesis provides an important scientific foundation for the further development of the current project. Supervisors: Prof. Viktorija Kuzema and Prof. Juta Kroiča (2 February 2026)
• IgA Nephropathy: Current Advances in Pathogenesis and Pharmacological Treatment. Theoretical session of the RSU Nephrology Student Scientific Interest Group (29 October 2025)
• Gut Microbiome Features in IgA Nephropathy Patients with Favourable and Unfavourable Prognosis. Presentation at the 18th International Symposium on IgA Nephropathy, Prague, Czech Republic (17–20 September 2025) 
  Book of abstracts
• During the second quarter of 2025, the project remained in its preparatory phase. Following the initial feedback from the Central Medical Ethics Committee, the study documentation was revised while patient recruitment procedures and protocols for biological sample collection and processing were further refined. These activities established the organisational and methodological framework required to initiate the project's clinical research following receipt of ethics approval
• Three oral presentations on IgA nephropathy progression, gut microbiome alterations and GdIgA1-positive B-cell differentiation at the RSU International Research Conference on Medical and Health Care Sciences (26–28 March 2025)
  Book of abstracts
• Disease-Modifying Therapy in IgA Nephropathy and Clinical Case Analysis, scientific presentations by project researchers at the clinicopathological meeting of the Latvian Association of Nephrologists (30 January 2025)
• IgA Nephropathy and the Implementation of Kinpeygo in Clinical Practice, national expert meeting for nephrologists, clinicians and other stakeholders involved in IgA nephropathy management (28 January 2025)

Project Research Team

• Lead Researcher: Viktorija Kuzema
• Kristīne Oļeinika
• Kārlis Rācenis

Project Partner

Pauls Stradiņš Clinical University Hospital Research Institute