Human neutrophil antigen 2 sequence-based typing: Joining the hunt for the CD177 answer

Area of Science:

• Immunogenetics
• Molecular diagnostics
• Hematology

Background:

• Isoantibodies to human neutrophil antigen 2 (CD177) are linked to clinical conditions.
• The molecular basis of CD177 altered or null expression remains undetermined.
• Current phenotyping methods are resource-intensive and inconvenient for patients.

Purpose of the Study:

• To introduce a molecular approach for investigating CD177 null expression.
• To identify genetic mutations responsible for CD177 null expression.
• To improve diagnostic efficiency and patient care in neutropenic cases.

Main Methods:

• Sequence-based typing of DNA from 100 blood donors and 18 CD177 null individuals.
• Analysis of DNA from two families with neonatal alloimmune neutropenia due to CD177.
• Recording of observed polymorphisms and identification of mutations.

Main Results:

• A known exon 7 single-nucleotide polymorphism was associated with CD177 null expression in 16/21 cases.
• Two additional mutations, one potentially novel, were identified as causes of null expression.
• Identified mutations were confirmed in maternal DNA samples from investigated families.

Conclusions:

• CD177 genotyping can identify null expression in over 75% of associated cases.
• Routine CD177 genotyping can reduce the need for supplementary testing and patient inconvenience.
• This approach enhances laboratory efficiency and may reveal other clinically relevant mutations.