Human CD33 deficiency is associated with mild alteration of circulating white blood cell counts.

IF 4 2区 生物学 Q1 GENETICS & HEREDITY
PLoS Genetics Pub Date : 2025-03-05 eCollection Date: 2025-03-01 DOI:10.1371/journal.pgen.1011600
John Dominy, Jirong Bai, Christopher Koch, Maleeha Zaman Khan, Shareef Khalid, Jonathan H Chung, Madhura Panditrao, Lulu Liu, Qi Zhang, Muhammad Jahanzaib, Muhammad Rehan Mian, Muhammad Bilal Liaqat, Syed Shahzaib Raza, Riffat Sultana, Anjum Jalal, Muhammad Hamid Saeed, Shahid Abbas, Fazal Rehman Memon, Mohammad Ishaq, Kashif Saleheen, Asif Rasheed, Allan Gurtan, Danish Saleheen
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引用次数: 0

Abstract

The single pass transmembrane protein CD33 is enriched in phagocytic and hematopoietic cell types, such as monocytes. CD33 is thought to be associated with immune cell function, susceptibility to Alzheimer's disease, and rare leukemias. Antagonism or genetic ablation of CD33 has been proposed to treat Alzheimer's disease, hematological cancers, and as a selection mechanism for enriching genetically altered blood cells. To understand the impact of chronic CD33 loss or ablation, we describe individuals who we confirmed to be missing CD33 due to germline loss of function variants. Through PheWAS-based approaches using existing whole exome biobanks and bespoke phenotyping using recall-by-genotype (RBG) studies, we show that CD33 loss of function alters circulating white blood cell counts and distributions, albeit mildly and with no overt clinical pathology. These findings indicate that chronic CD33 antagonism/ablation is likely to be safe in humans.

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来源期刊
PLoS Genetics
PLoS Genetics GENETICS & HEREDITY-
自引率
2.20%
发文量
438
期刊介绍: PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.
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