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Erythrocytosis associated with IgA nephropathy.

Erythrocytosis associated with IgA nephropathy.

Authors :
Cohen C
Coulon S
Bhukhai K
Neuraz A
Dussiot M
Fouquet G
Stang ML
Flamant M
Vrtovsnik F
Hummel A
Knebelmann B
Mesnard L
Rondeau E
Maciel TT
Favale F
Casadevall N
Nguyen-Khoa T
Moutereau S
Legendre C
Benhamou M
Monteiro RC
Hermine O
El Karoui K
Moura IC
Source :
EBioMedicine [EBioMedicine] 2022 Jan; Vol. 75, pp. 103785. Date of Electronic Publication: 2021 Dec 24.
Publication Year :
2022

Abstract

Background: Erythrocytosis is a hematological disorder usually related to hematopoietic stem cell somatic mutations. 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 polycythemia/erythrocytosis (PE) of IgAN patients.<br />Methods: IgAN-PE patients' serum was collected, analyzed and used to study IgA1 effect on proliferation and differentiation 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.<br />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.<br />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 erythrocytosis and renal disease.<br />Funding: This work was supported by INSERM (French national institute for health and medical research), Labex GRex and Imagine Institute (Paris, France).<br />Competing Interests: Declaration of interests No conflict of interest to disclose<br /> (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
2352-3964
Volume :
75
Database :
MEDLINE
Journal :
EBioMedicine
Publication Type :
Academic Journal
Accession number :
34959131
Full Text :
https://doi.org/10.1016/j.ebiom.2021.103785