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Immune Complex Glomerulonephritis in a Patient with Myelodysplastic Syndrome with Ring Sideroblasts Treated with Luspatercept

Myelodysplastic syndromes (MDS) are a group of clonal myeloid disorders distinguished by dysplastic bone marrow and peripheral blood cells, ineffective hematopoiesis, and an increased risk of developing acute myeloid leukemia (AML). MDS with ring sideroblasts (MDS-RS) is a favorable outcome subtype...

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Autores principales: Delanghe, Sigurd, Nguyen, Tri Q., Mazure, Dominiek, Dendooven, Amélie, Speeckaert, Marijn M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818993/
https://www.ncbi.nlm.nih.gov/pubmed/36611303
http://dx.doi.org/10.3390/diagnostics13010011
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author Delanghe, Sigurd
Nguyen, Tri Q.
Mazure, Dominiek
Dendooven, Amélie
Speeckaert, Marijn M.
author_facet Delanghe, Sigurd
Nguyen, Tri Q.
Mazure, Dominiek
Dendooven, Amélie
Speeckaert, Marijn M.
author_sort Delanghe, Sigurd
collection PubMed
description Myelodysplastic syndromes (MDS) are a group of clonal myeloid disorders distinguished by dysplastic bone marrow and peripheral blood cells, ineffective hematopoiesis, and an increased risk of developing acute myeloid leukemia (AML). MDS with ring sideroblasts (MDS-RS) is a favorable outcome subtype with a lower frequency of AML transformation. The FDA recently approved luspatercept for the treatment of patients with very-low-, low-, and intermediate-risk MDS-RS who have failed to correct anemia with an erythropoiesis-stimulating agent (ESA) and require two units of red blood cells over an eight-week period. This drug’s pharmacology is based on the critical role of the transforming growth factor-beta (TGF-β) pathway in regulating erythropoiesis. In this case report, we describe for the first time an acute kidney injury caused by membranoproliferative glomerulonephritis (MPGN) in a patient with MDS-RS who was treated with luspatercept. We propose that a multi-hit hypothesis could explain the immunopathogenesis. A first unknown hit may stimulate IgA immune complex production, whereas luspatercept administration acts as a second hit, causing Smad1-5-8 phosphorylation. This intriguing case report on immune-complex-mediated proliferative glomerulonephritis following luspatercept treatment generates hypotheses and stimulates further research in this area.
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spelling pubmed-98189932023-01-07 Immune Complex Glomerulonephritis in a Patient with Myelodysplastic Syndrome with Ring Sideroblasts Treated with Luspatercept Delanghe, Sigurd Nguyen, Tri Q. Mazure, Dominiek Dendooven, Amélie Speeckaert, Marijn M. Diagnostics (Basel) Case Report Myelodysplastic syndromes (MDS) are a group of clonal myeloid disorders distinguished by dysplastic bone marrow and peripheral blood cells, ineffective hematopoiesis, and an increased risk of developing acute myeloid leukemia (AML). MDS with ring sideroblasts (MDS-RS) is a favorable outcome subtype with a lower frequency of AML transformation. The FDA recently approved luspatercept for the treatment of patients with very-low-, low-, and intermediate-risk MDS-RS who have failed to correct anemia with an erythropoiesis-stimulating agent (ESA) and require two units of red blood cells over an eight-week period. This drug’s pharmacology is based on the critical role of the transforming growth factor-beta (TGF-β) pathway in regulating erythropoiesis. In this case report, we describe for the first time an acute kidney injury caused by membranoproliferative glomerulonephritis (MPGN) in a patient with MDS-RS who was treated with luspatercept. We propose that a multi-hit hypothesis could explain the immunopathogenesis. A first unknown hit may stimulate IgA immune complex production, whereas luspatercept administration acts as a second hit, causing Smad1-5-8 phosphorylation. This intriguing case report on immune-complex-mediated proliferative glomerulonephritis following luspatercept treatment generates hypotheses and stimulates further research in this area. MDPI 2022-12-21 /pmc/articles/PMC9818993/ /pubmed/36611303 http://dx.doi.org/10.3390/diagnostics13010011 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Delanghe, Sigurd
Nguyen, Tri Q.
Mazure, Dominiek
Dendooven, Amélie
Speeckaert, Marijn M.
Immune Complex Glomerulonephritis in a Patient with Myelodysplastic Syndrome with Ring Sideroblasts Treated with Luspatercept
title Immune Complex Glomerulonephritis in a Patient with Myelodysplastic Syndrome with Ring Sideroblasts Treated with Luspatercept
title_full Immune Complex Glomerulonephritis in a Patient with Myelodysplastic Syndrome with Ring Sideroblasts Treated with Luspatercept
title_fullStr Immune Complex Glomerulonephritis in a Patient with Myelodysplastic Syndrome with Ring Sideroblasts Treated with Luspatercept
title_full_unstemmed Immune Complex Glomerulonephritis in a Patient with Myelodysplastic Syndrome with Ring Sideroblasts Treated with Luspatercept
title_short Immune Complex Glomerulonephritis in a Patient with Myelodysplastic Syndrome with Ring Sideroblasts Treated with Luspatercept
title_sort immune complex glomerulonephritis in a patient with myelodysplastic syndrome with ring sideroblasts treated with luspatercept
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818993/
https://www.ncbi.nlm.nih.gov/pubmed/36611303
http://dx.doi.org/10.3390/diagnostics13010011
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