RESUMEN
Defective glycosylation and immune complex (IC) formation may be of primary importance in immunoglobulin A nephropathy (IgAN) pathogenesis. The aim of this study was to determine whether defective IgA1 glycosylation might support renal deposition of IgA and disease activity. IgA was isolated from the serum of 44 IgAN patients and 46 controls and glycosylation analysed by ELISA using glycan-specific lectins. IgA was measured by immunodiffusion and immune complexes by ELISA. IgA subclasses in IC deposits in kidney glomeruli were identified by immunohistochemical methods. A significant increase in N-acetylgalactosamine (GalNAc) in terminal position (p = 0.02) observed in some of the IgAN patients, became more pronounced when sialic acid was removed from IgA1, indicating enhanced expression of α-2,6-sialyltransferase in patients compared with controls (p < 0.0001). Patients with defective galactosylation had lower serum IgA than other IgAN patients (p = 0.003). IgAN patients with both IgA1 and IgA2 glomerular deposits (21.7%) had increased GalNAc in terminal position (p = 0.003). Taken together, our results show that increased IgA glycosylation in IgAN associates with low levels of IgA, concomitant IgA1 and IgA2 glomerular deposits and poor clinical outcome.
Asunto(s)
Glomerulonefritis por IGA/sangre , Inmunoglobulina A/sangre , Acetilgalactosamina/sangre , Acetilgalactosamina/inmunología , Adolescente , Adulto , Anciano , Complejo Antígeno-Anticuerpo/sangre , Complejo Antígeno-Anticuerpo/inmunología , Estudios de Casos y Controles , Femenino , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/patología , Glicosilación , Humanos , Inmunoglobulina A/inmunología , Glomérulos Renales/inmunología , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Lectinas , Masculino , Persona de Mediana Edad , Sialiltransferasas/sangre , Sialiltransferasas/inmunología , beta-D-Galactósido alfa 2-6-SialiltransferasaRESUMEN
Kidney stone disease is a common condition. To search for sequence variants conferring risk of kidney stones, we conducted a genome-wide association study in 3,773 cases and 42,510 controls from Iceland and The Netherlands. We discovered common, synonymous variants in the CLDN14 gene that associate with kidney stones (OR = 1.25 and P = 4.0 x 10(-12) for rs219780[C]). Approximately 62% of the general population is homozygous for rs219780[C] and is estimated to have 1.64 times greater risk of developing the disease compared to noncarriers. The CLDN14 gene is expressed in the kidney and regulates paracellular permeability at epithelial tight junctions. The same variants were also found to associate with reduced bone mineral density at the hip (P = 0.00039) and spine (P = 0.0077).