RESUMEN
BACKGROUND: IgA nephropathy (IgAN) is characterised by the production of galactose-deficient IgA1 (GdIgA1) antibodies. As the source of pathogenic antibodies, B cells are central to IgAN pathogenesis, but the B cell activation pathways as well as the potential B cell source of dysregulated IgA-secretion remain unknown. METHODS: We carried out flow cytometry analysis of peripheral blood B cells in patients with IgA nephropathy and control subjects with a focus on IgA-expressing B cells to uncover the pathways of B cell activation in IgAN and how these could give rise to pathogenic GdIgA1 antibodies. RESULTS: In addition to global changes in the B cell landscape - expansion of naive and reduction in memory B cells - IgAN patients present with an increased frequency of IgA-expressing B cells that lack the classical memory marker CD27, but are CD21pos. IgAN patients further have an expanded population of IgApos antibody-secreting cells, which correlate with serum IgA levels. Both IgApos plasmabalsts and CD27neg B cells co-express GdIgA1. Implicating dysregulation at mucosal surfaces as the driver of such B cell differentiation, we found a correlation between lipopolysaccharide (LPS) in the serum and IgAposCD27neg B cell frequency. CONCLUSION: We propose that dysregulated immunity in the mucosa may drive de novo B cell activation within germinal centres, giving rise to IgAposCD27neg B cells and subsequently IgA-producing plasmablasts. These data integrate B cells into the paradigm of IgAN pathogenesis and allow to further investigate this pathway to uncover biomarkers and develop therapeutic interventions.
RESUMEN
BACKGROUND Kidney transplantation is the treatment of choice for most patients with end-stage renal disease. To improve patient and transplant survival, non-invasive diagnostic methods for different pathologies are important. Leucine-rich alpha-2-glycoprotein (LRG-1) is an innovative biomarker that is elevated in cases of angiogenesis, inflammation, and kidney injury. However, there are limited data about the diagnostic role of LRG-1 in kidney transplant recipients. The aim of this study was to evaluate the association between serum LRG-1, urine LRG-1, and kidney transplant function and injury. MATERIAL AND METHODS We enrolled 35 kidney transplant recipients in the study. LRG-1 in the serum and urine was detected using ELISA. We evaluated the correlation of serum and urine LRG-1 with traditional serum and urine kidney injury markers. RESULTS A higher level of serum LRG-1 correlates with a higher level of urine LRG-1. Serum LRG-1 has a positive correlation with transplant age, serum urea, serum creatinine, serum cystatin C, proteinuria, and fractional excretion of sodium (FENa) and a negative correlation with hemoglobin and estimated glomerular filtration rate (eGFR). Urine LRG-1 has a positive correlation with serum cystatin C, proteinuria, and urine neutrophil gelatinase-associated lipocalin (NGAL). CONCLUSIONS Higher levels of serum and urine LRG-1 are associated with kidney transplant injury and functional deterioration. Thus, LRG-1 might be also as a biomarker for tubular dysfunction in patients after kidney transplantation.