Cab4b, the first human platelet antigen carried by glycoprotein IX discovered in a context of severe neonatal thrombocytopenia.
Vincent JalluT BerangerF BianchiC CasaleC ChenetN FerreS PhilippeJ QuesneC MartageixR PetermannPublished in: Journal of thrombosis and haemostasis : JTH (2017)
Background After three miscarriages, a 39-year-old woman gave birth, with a 1-year interval, to two severely thrombocytopenic neonates (4 ×109 L-1 and 33 ×109 L-1 ) with intracranial hemorrhages. Transfusion of platelet concentrates corrected the thrombocytopenia. The outcome was favorable for the first child, but the second one died 10 days after cesarean delivery (31 weeks of gestation + 6 days). Methods Serologic studies were performed with mAb-specific immobilization of platelet antigens and flow cytometry techniques. Human platelet alloantigen (HPA) genotyping was performed with the BioArray HPA BeadChip and PCR-sequence-specific primer techniques. Genomic DNA was studied by direct sequencing of PCR products. The mutant glycoprotein (GP) was expressed in transiently transfected HEK293 cells. Results In MAIPA assay, the maternal serum faintly reacted with GPIbIX from paternal and child 1 platelets, but not with maternal or panel platelets. No maternofetal incompatibility was found in the 22 known HPA systems, tested except for HPA-1b in child 2. A new alloantigen carried by GPIbIX was suspected. Genomic sequencing revealed a paternal GPIX variation (NM_000174.4:c.368C>T). The father and children were heterozygous and incompatible with the mother, who was NM_000174.4:c.368C homozygous. The maternal serum reacted with the GPIX NP_000165.1:p.Leu123 form coexpressed with GPIb in transfected HEK293 cells. The NM_000174.4:c.368T allele (rs202229101) has a minor allele frequency of 0.0002, and was not detected in 120 French subjects (families with fetal and neonatal alloimmune thrombocytopenia [FNAIT]), suggesting that it is rarely implicated in alloimmunization. Conclusion The NP_000165.1:p.Leu123 allele named Cab4b is the first platelet alloantigen described on GPIX. In the absence of other known maternofetal incompatibility, the child 1 case suggests that anti-Cab4b alloantibodies can induce severe thrombocytopenias.
Keyphrases
- mental health
- induced apoptosis
- birth weight
- endothelial cells
- flow cytometry
- gestational age
- photodynamic therapy
- single cell
- pregnancy outcomes
- cell cycle arrest
- early onset
- high throughput
- young adults
- signaling pathway
- induced pluripotent stem cells
- copy number
- cell free
- genome wide
- gene expression
- circulating tumor
- single molecule
- pregnant women
- sars cov
- pulmonary embolism
- acute kidney injury
- cell proliferation
- drug induced
- coronavirus disease
- body mass index
- optical coherence tomography
- real time pcr
- weight gain