Dysregulated B Cell Responses in IgA Nephropathy

Activity: Talk or presentation types › Oral presentation

Description

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide with an incompletely understood aetiology and mechanisms of pathogenesis. Despite characteristic deposition of IgA-containing immune complexes in the kidney that indicates aberrant B cell function, an in-depth characterisation of B cell activation and its association with renal function is yet to be carried out; here we address this gap in knowledge.. We recruited individuals with renal biopsy-confirmed IgAN (n=68) at the Nephrology Centre of Pauls Stradins Clinical University Hospital; collectively these patients had a range of renal function – from normal to severe kidney damage. Age- and sex-matched healthy individuals (n=23) were recruited as controls. Peripheral blood mononuclear cells were isolated by density gradient centrifugation and analysed with fluorescently-labelled antibodies against surface markers CD19, CD27, IgD, CD38, CD24. These markers allowed us to determine the peripheral blood frequencies of antigen-inexperienced B cells (IgD+CD27-), including transitional (CD24intCD38int) and mature naïve (CD24intCD38int) B cells. We also determined the composition of the antigen-experienced B cell compartment – unswitched (IgD+CD27+), switched (IgD-CD27+) and double negative (IgD-CD27-) B cell subpopulations. IgA, CXCR5, CD11c, CD43 and CD1d surface markers were used to gain further functional insight of the subsets. Data analysis was done with FlowJo and GraphPad Prism software version 9.2.0. . Unique B cell profile characterises patients with IgAN. We observe a marked increase of naïve (IgD+CD27-) and a reduction of unswitched memory (IgD+CD27+) B cells; this dysregulation in the B cell compartment is particularly pronounced in individuals with more severely impaired renal function. Of note, we did not observe an expansion of double negative (IgD-CD27-) B cells previously associated with pathogenic antibody production in systemic autoimmunity.. IgAN is associated with aberrant B cell activation, future studies will address the mechanisms that enable this dysregulation, including importantly microbiota-derived signals. Funded by Latvian Council of Science (lzp-2019/1-0139).
Period29 Mar 2023
Event titleRSU International Research Conference 2023: Knowledge for Use in Practice
Event typeConference
OrganiserRīga Stradiņš University
LocationRiga, LatviaShow on map
Degree of RecognitionInternational

Related content