CD36 Deficiency and Its Implications in Hematological Conditions

CD36 is a multifunctional class B scavenger receptor expressed on platelets, monocytes, adipocytes and, as newly appreciated, on erythroid cells. It binds diverse ligands including thrombospondin, oxidised low-density lipoprotein and parasitised erythrocytes, mediating roles in lipid metabolism, immune recognition and cell adhesion. Inherited CD36 deficiency arises when CD36 is absent on both platelets and monocytes (type I) or platelets alone (type II). This deficiency alters platelet reactivity, compromises lipid handling and can provoke alloimmune responses during transfusion or pregnancy, notably foetal/neonatal alloimmune thrombocytopenia and foetal anaemia. Prevalence varies by population, with higher rates in certain Asian and African cohorts. Molecular mechanisms encompass point mutations, deletions affecting transcript stability, alternative splicing and aberrant protein folding. Clinically, CD36 deficiency influences bleeding risk, cardiovascular disease susceptibility and malaria severity. Recognition of CD36’s broader expression on reticulocytes and mature red cells has prompted its classification as a novel blood group system, with implications for pre-transfusion screening and management of affected pregnancies. Emerging biomarkers such as soluble CD36 (sCD36) offer further avenues for risk stratification and therapeutic monitoring. Understanding the genetic and functional landscape of CD36 deficiency is critical for improving diagnostic accuracy, guiding personalised transfusion strategies and mitigating immune-mediated complications in diverse patient populations.

Research from Nature Portfolio

Recent studies have characterised CD36 genetic variants in healthy platelet donors, revealing a spectrum of novel and known mutations that alter protein stability and expression. High-throughput sequencing identified several deletions and single-nucleotide changes in the extracellular domain, with the most prevalent allele reducing membrane CD36 by more than 50%. Flow cytometry and ELISA analyses correlated specific genotypes with markedly lower platelet CD36 levels and diminished soluble CD36 in plasma, particularly in individuals with type II deficiency. RNA quantification demonstrated that transcript reduction underpins many cases of deficient expression on platelets, whereas monocyte RNA remains relatively preserved. These findings highlight the interplay between gene variant, RNA transcript abundance and receptor presentation, and suggest that circulating sCD36 could serve as a surrogate marker for immune-reaction risk in CD36-deficient individuals.

CD36 Deficiency and Its Implications in Hematological Conditions publication trend

The graph below shows the total number of articles in cd36 deficiency and its implications in hematological conditions across all publications each year (not limited to Nature Index journals).

Technical terms

CD36: A class B scavenger receptor glycoprotein involved in lipid uptake, cell adhesion and immune recognition.

Type I deficiency: Absence of CD36 on both platelets and monocytes, often due to homozygous or compound heterozygous mutations.

Type II deficiency: Absence of CD36 on platelets only, typically resulting from platelet-specific transcript or protein defects.

Polymorphism: Genetic variation in DNA sequence among individuals, including single-nucleotide changes and small insertions/deletions.

Foetal/neonatal alloimmune thrombocytopenia (FNAIT): A condition in which maternal anti-platelet antibodies cross the placenta and destroy foetal platelets.

Alternative splicing: The process by which pre-mRNA exons are variably joined or skipped to produce multiple transcript isoforms.

References

1. The polymorphism analysis for CD36 among platelet donors. Scientific Reports (2024).
2. Structural organization of the gene for human CD36 glycoprotein.. Journal of Biological Chemistry (1994).
3. Identification of a human CD36 isoform produced by exon skipping. Conservation of exon organization and pre-mRNA splicing patterns with a CD36 gene family member, CLA-1.. Journal of Biological Chemistry (1994).
4. Frequency and molecular basis of CD36 deficiency among platelet donors in Kunming, China. Platelets (2023).
5. Evidence that CD36 is expressed on red blood cells and constitutes a novel blood group system of clinical importance. Vox Sanguinis (2024).