| Summary: | Introduction: Anion exchanger 1 (AE1) (SLC4A1 gene product) is a membrane protein expressed in both kidney and red blood cells (RBCs): it exchanges extracellular bicarbonate (HCO3–) for intracellular chloride (Cl–) and participates in acid−base homeostasis. AE1 mutations in kidney α-intercalated cells can lead to distal renal tubular acidosis (dRTA). In RBC, AE1 (known as band 3) is also implicated in membrane stability: deletions can cause South Asian ovalocytosis (SAO). Methods: We retrospectively collected clinical and biological data from patients harboring dRTA due to a SLC4A1 mutation and analyzed HCO3– and Cl– transports (by stopped-flow spectrophotometry) and expression (by flow cytometry, fluorescence activated cell sorting, and Coomassie blue staining) in RBCs, as well as RBC membrane stability (ektacytometry). Results: Fifteen patients were included. All experience nephrolithiasis and/or nephrocalcinosis, 2 had SAO and dRTA (dRTA SAO+), 13 dominant dRTA (dRTA SAO−). The latter did not exert specific RBC membrane anomalies. Both HCO3– and Cl– transports were lower in patients with dRTA SAO+ than in those with dRTA SAO− or controls. Using 3 different extracellular probes, we report a decreased expression (by 52%, P < 0.05) in dRTA SAO+ patients by fluorescence activated cell sorting, whereas total amount of protein was not affected. Conclusion: Band 3 transport function and expression in RBCs from dRTA SAO− patients is normal. However, in SAO RBCs, impaired conformation of AE1/band 3 corresponds to an impaired function. Thus, the driver of acid−base defect during dominant dRTA is probably an impaired membrane expression. Keywords: acidosis, renal tubular, anion exchange protein 1, erythrocyte, hematologic diseases, nephrocalcinosis, nephrolithiasis
|
|---|
