The Vel blood group system: a review

Area of Science:

• Immunohematology
• Molecular Biology
• Genetics

Background:

• The Vel blood group antigen presented challenges in immunohematology due to variable antigen strength, potent anti-Vel activity, and difficulties in finding Vel- blood donors.
• The identification of small integral membrane protein 1 (SMIM1) on red blood cells (RBCs) in 2013 provided a breakthrough.

Purpose of the Study:

• To elucidate the genetic basis of the Vel blood group antigen.
• To understand the molecular mechanisms underlying Vel antigen expression and variability.
• To improve screening methods for Vel- blood donors.

Main Methods:

• Genetic analysis of SMIM1 in individuals with varying Vel antigen expression.
• Correlation of SMIM1 expression levels with Vel antigen presence and strength.
• Investigation of SMIM1 gene polymorphisms, particularly in intron 2, affecting transcription.

Main Results:

• Vel- RBCs were found to lack SMIM1, correlating with homozygosity for the c.64_60del deletion in SMIM1.
• Polymorphisms in SMIM1 intron 2 were identified as the cause of variable Vel antigen strength.
• A universal method for screening Vel- blood donors was established.

Conclusions:

• The identification and genetic characterization of SMIM1 have resolved key aspects of the Vel blood group enigma, particularly for donor screening.
• While SMIM1's role in Vel antigen expression is understood, its precise biological function remains unknown.
• Anti-Vel antibodies can cause severe transfusion reactions, highlighting the clinical significance of Vel antigen research.