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Article Dans Une Revue EBioMedicine Année : 2022

Erythrocytosis associated with IgA nephropathy

Eric Rondeau
  • Fonction : Auteur
Thao Nguyen-Khoa

Résumé

Background Erythrocytosis is a hematological disorder usually related to hematopoietic stem cell somatic muta-tions. However, unexplained erythrocytosis remains frequent. In this study, we evaluated the involvement of IgA1, a regulator of erythropoiesis also implicated in IgA nephropathy (IgAN) pathophysiology, in unexplained polycythe-mia/erythrocytosis (PE) of IgAN patients.Methods IgAN-PE patients’ serum was collected, analyzed and used to study IgA1 effect on proliferation and differ-entiation of erythroid progenitors. Hematological parameters of transgenic mice for human alpha1 heavy chain were studied. Multicentric observational cohorts of chronic kidney disease (CKD) patients, including both native kidney diseases and renal transplants, were studied to analyze patient hemoglobin levels.Findings We retrospectively identified 6 patients with IgAN and unexplained PE. In large CKD cohorts, IgAN was associated with PE in 3.5% of patients (p<0.001 compared to other nephropathies). IgAN was an independent factor associated with higher hemoglobin levels (13.1g/dL vs 12.2 g/dL, p=0.01). During post-transplant anemia, anemia recovery was faster in IgAN patients. Elevated polymeric/monomeric IgA1 ratio as well as high Gd-IgA1 rate were observed in circulating IgA1 of the 6 IgAN-PE patients as compared with control or IgAN patients without PE. IgA1 from these patients increased the sensitivity of erythroid progenitors to Epo. In mice, we also observed an elevation of hematocrit in alpha1 knock-in mice compared to wild type controls.Interpretation These data identify a new etiology of erythrocytosis and demonstrate the role of pIgA1 in human erythropoiesis. This syndrome of IgA-related erythrocytosis should be investigated in case of unexplained erythrocy-tosis and renal disease.
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hal-03887035 , version 1 (08-01-2024)

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Paternité - Pas d'utilisation commerciale

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Camille Cohen, Séverine Coulon, Kanit Bhukhai, Antoine Neuraz, Michael Dussiot, et al.. Erythrocytosis associated with IgA nephropathy. EBioMedicine, 2022, 75, pp.103785. ⟨10.1016/j.ebiom.2021.103785⟩. ⟨hal-03887035⟩
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