| Title: | Human CD33 deficiency is associated with mild alteration of circulating white blood cell counts |
| Journal: | PLOS Genetics |
| Published: | 5 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40043053/ |
| DOI: | https://doi.org/10.1371/journal.pgen.1011600 |
Publication 15984
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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.</p>
10 Keywords
- Adult
- Alzheimer Disease
- Female
- Germ-Line Mutation
- Humans
- Leukocyte Count
- Loss of Function Mutation
- Male
- Middle Aged
- Sialic Acid Binding Ig-like Lectin 3
23 Authors
- 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
1 Application
| Application ID | Title |
|---|---|
| 59456 | Using UK Biobank data to support the Novartis drug discovery and development pipeline |
Enabling scientific discoveries that improve human health