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Published on: July 8, 2020
Erythrocytosis associated with IgA nephropathy
Camille Cohen1, Séverine Coulon2, Kanit Bhukhai3
1INSERM U1151 « mechanisms and therapeutic strategies of chronic kidney diseases », Hôpital Necker, Université de Paris, Paris, France; Service de Néphrologie et Transplantation rénale, AP-HP, Hôpital Necker, Paris, France.
Immunoglobulin A1 (IgA1) plays a role in unexplained erythrocytosis (high red blood cell count) in patients with IgA nephropathy (IgAN). This finding suggests a new cause for erythrocytosis related to IgA1 and kidney disease.
Area of Science:
- Nephrology
- Hematology
- Immunology
Background:
- Erythrocytosis, often linked to stem cell mutations, frequently remains unexplained.
- Immunoglobulin A1 (IgA1) is implicated in IgA nephropathy (IgAN) and erythropoiesis regulation.
Purpose of the Study:
- To investigate the role of IgA1 in unexplained polycythemia/erythrocytosis (PE) among IgA nephropathy patients.
Main Methods:
- Serum analysis of IgAN-PE patients to assess IgA1's effect on erythroid progenitors.
- Hematological evaluation of transgenic mice expressing human alpha1 heavy chain.
- Analysis of hemoglobin levels in large cohorts of chronic kidney disease (CKD) patients.
Main Results:
- Identified 6 IgAN patients with unexplained PE; IgAN associated with PE in 3.5% of CKD patients (p<0.001).
- IgAN independently correlated with higher hemoglobin (13.1g/dL vs 12.2 g/dL, p=0.01) and faster anemia recovery post-transplant.
- Elevated polymeric/monomeric IgA1 ratio and high Gd-IgA1 were found in IgAN-PE patients; their IgA1 increased erythroid progenitor sensitivity to Epo. Alpha1 knock-in mice showed elevated hematocrit.
Conclusions:
- Identified a novel etiology of erythrocytosis linked to IgA1.
- Demonstrated pIgA1's role in human erythropoiesis, suggesting investigation of IgA-related erythrocytosis in unexplained erythrocytosis with renal disease.
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