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

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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Publication Details

Journal
PLoS Genetics
Published
2025-03-05
DOI
https://doi.org/10.1371/journal.pgen.1011600
Citations
2
Primary Topic
Blood groups and transfusion
Type
article
Field-Weighted Citation Impact
3.54

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article

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

Fazal Rehman Memon, Madhura Panditrao, Asif Rasheed, Jirong Bai et al.
2 citations
PLoS Genetics
Blood groups and transfusion
3.54
article

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

Fazal Rehman Memon, Madhura Panditrao, Asif Rasheed, Jirong Bai, Jonathan H. Chung, Danish Saleheen, Allan Gurtan, Qí Zhāng, Muhammad Rehan Mian, Riffat Sultana, Muhammad Jahanzaib, Anjum Jalal, Christopher Koch, John Dominy, Mohammad Ishaq, Maleeha Khan, Lulu Liu, Muhammad Hamid Saeed, Shareef Khalid, Shahid Abbas, Syed Shahzaib Raza, Muhammad Bilal Liaqat, Kashif Saleheen
article en
2 citations

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.

PLoS GeneticsVol. 21(3)
Punjab Institute of Cardiology (PK), Columbia University Irving Medical Center (US), Karachi Institute of Heart Diseases (PK), Novartis (United States) (US), University of Faisalabad (PK), Center for Non-Communicable Diseases (PK)
Novartis
Openalex Percentile: Top 9%
Blood groups and transfusion
3.54
DOIOpen Access PDFOpenAlex
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