Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation

Abstract Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. We recently found IgG Fc-glycosylation towards platelet and RBC alloantigens to be skewed towards decreased fucosylatio...

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Autores principales:	Myrthe E. Sonneveld, Masja de Haas, Carolien Koeleman, Noortje de Haan, Sacha S. Zeerleder, Peter C. Ligthart, Manfred Wuhrer, C. Ellen van der Schoot, Gestur Vidarsson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9331eca3284a4261ade0540383c4b35b
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spelling	oai:doaj.org-article:9331eca3284a4261ade0540383c4b35b2021-12-02T12:31:53ZPatients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation10.1038/s41598-017-08654-y2045-2322https://doaj.org/article/9331eca3284a4261ade0540383c4b35b2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08654-yhttps://doaj.org/toc/2045-2322Abstract Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. We recently found IgG Fc-glycosylation towards platelet and RBC alloantigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core-fucosylation increases the affinity of the pathogenic alloantibodies to FcγRIIIa/b, and hence RBC destruction. It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed. We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. In contrast to alloantibodies against RBCs, RBC-bound IgG1 Fc-fucosylation was not different between healthy controls and patients. Analysis of anti-RBC Fc-glycoprofiles suggested that lower bisection and higher galactosylation associate with lower Hb levels.Myrthe E. SonneveldMasja de HaasCarolien KoelemanNoortje de HaanSacha S. ZeerlederPeter C. LigthartManfred WuhrerC. Ellen van der SchootGestur VidarssonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Myrthe E. Sonneveld Masja de Haas Carolien Koeleman Noortje de Haan Sacha S. Zeerleder Peter C. Ligthart Manfred Wuhrer C. Ellen van der Schoot Gestur Vidarsson Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation
description	Abstract Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. We recently found IgG Fc-glycosylation towards platelet and RBC alloantigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core-fucosylation increases the affinity of the pathogenic alloantibodies to FcγRIIIa/b, and hence RBC destruction. It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed. We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. In contrast to alloantibodies against RBCs, RBC-bound IgG1 Fc-fucosylation was not different between healthy controls and patients. Analysis of anti-RBC Fc-glycoprofiles suggested that lower bisection and higher galactosylation associate with lower Hb levels.
format	article
author	Myrthe E. Sonneveld Masja de Haas Carolien Koeleman Noortje de Haan Sacha S. Zeerleder Peter C. Ligthart Manfred Wuhrer C. Ellen van der Schoot Gestur Vidarsson
author_facet	Myrthe E. Sonneveld Masja de Haas Carolien Koeleman Noortje de Haan Sacha S. Zeerleder Peter C. Ligthart Manfred Wuhrer C. Ellen van der Schoot Gestur Vidarsson
author_sort	Myrthe E. Sonneveld
title	Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation
title_short	Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation
title_full	Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation
title_fullStr	Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation
title_full_unstemmed	Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation
title_sort	patients with igg1-anti-red blood cell autoantibodies show aberrant fc-glycosylation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9331eca3284a4261ade0540383c4b35b
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Patients with IgG1-anti-red blood cell autoantibodies show aberrant Fc-glycosylation

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