Frequency of CD36 deficiency in Thais analyzed by quantification of CD36 on cell surfaces and in plasma

Abstract

BACKGROUND Anti‐CD36s, developing after transfusion or during pregnancy, play an important role in immune‐mediated bleeding disorders among Asian populations. Currently, little is known about the clinical relevance of anti‐CD36. Here, we aimed to determine the frequency of CD36 deficiency in Thais by analyzing CD36 expression on cell surfaces and in plasma. STUDY DESIGN AND METHODS The expression and deficiency of CD36 on platelets and monocytes were determined by flow cytometry. Mutations in the CD36 gene were analyzed by nucleotide sequencing. Soluble CD36 (sCD36) in plasma was quantified with enzyme‐linked immunosorbent assay. RESULTS Fifteen of 700 blood donors (2.14%) were identified as CD36 deficient. The frequencies of Type I and II CD36 deficiency were 0.43% and 1.71%, respectively. Type I individuals exhibited c.1163A > T, c.429 + 4insG, and c.1156C > T. Type II individuals exhibited c.879 T > C, c.329‐330delAC, c.818 + 108delAACT, c.1125 + 13C > A, and c.1163A > T. CD36 on donor platelets (n = 685) showed a wide distribution of expression levels (mean fluorescence intensity, 16.71 ± 8.68). In the normal phenotype (n = 14), sCD36 concentration was 58.84 ± 11.68 ng/mL, which was significantly correlated with platelet CD36 expression (r2 = 0.8551). In Type II–deficient individuals (n = 6), a similar sCD36 concentration was detected (53.67 ± 8.17 ng/mL). However, sCD36 could not be detected in Type I individuals (n = 3). CONCLUSION CD36 Type I deficiency was found, indicating the potential for immune‐mediated platelet disorders in Thais. However, the underlying mutations differed from those reported in Japan and China. Interestingly, sCD36 could not be detected in plasma of Type I–deficient individuals. This finding may lead to the use of plasma to identify individuals at risk and to allow screening of large cohorts.

Platelet CD36 deficiency is present in 2.6% of Arabian individuals and can cause NAIT and platelet refractoriness

“…Frequently observed were CD36*c.268C > T , c.329_330delAC, c.ins949A, c.1228‐1239del12 , and others. Most mutations observed in this study differ from the reported variations, except for CD36*c.975 T > G (p.Y325X), 30 c.1079 T > G (p.L360X), 31 c.1156C > T (p.R386W), 15,17 and IVS12, 1200‐53_‐5inv49 26 indicating that CD36 variation in individuals from Arabian countries seems to have developed largely independent from those in Eastern Asia. The CD36*c.1079 T > G variation has been described before as a very rare mutation in a Caucasian pedigree presenting with autosomal dominant diabetes 31 .…”

“…Different mutations within the coding region, 5'UTR and an unusual complex molecular regulation of CD36 in different tissues have been addressed as basis of this peculiar expression. Since the first descriptions, a high number of different mutations associated with a negative or weak phenotype has been reported, most of them in Eastern Asians 11,15–18,26,28,29 . Frequently observed were CD36*c.268C > T , c.329_330delAC, c.ins949A, c.1228‐1239del12 , and others.…”

“…The molecular basis of CD36 deficiency is complex with type I deficiency lacking CD36 expression on both monocytes and platelets, and type II deficiency characterized by a selective deficiency on platelets 12,13 . Alternative promoter usage in different cells and tissues seems to contribute to CD36 cellular expression as well as a variety of different genomic mutations 6,14–17 . Whereas nonsense and non‐synonymous mutations on both CD36 alleles, either homozygous or in compound heterozygosity, account for type 1 deficiency, the molecular background of type 2 deficiency still remains a matter of debate 18 .…”