HLA-DPB1 genotype variants predict DP molecule cell surface expression and DP donor specific antibody binding...

Area of Science:

• Immunogenetics
• Transplantation Immunology

Background:

• Mismatched HLA-DP alleles contribute to alloresponses in transplantation.
• Understanding HLA-DPB1 allele regulation is crucial for improving transplant success.

Purpose of the Study:

• To investigate the correlation between the rs9277534G/A single nucleotide polymorphism (SNP) and HLA-DPB1 expression.
• To explore the regulatory mechanisms of HLA-DP expression, including the role of long non-coding RNAs (lncRNAs).

Main Methods:

• Genotyping for rs9277534 SNP.
• Quantification of DPB1 mRNA and protein expression in B cells.
• Interleukin-13 (IL-13) treatment to assess DP expression.
• Fluorescence in situ hybridization (FISH) for mRNA localization.
• Correlation analysis between DPB1 expression and lncRNAs.
• Analysis of DP donor-specific antibody (DSA) and B cell flow crossmatch (B-FCXM).

Main Results:

• The rs9277534GG genotype was associated with significantly higher DPB1 mRNA and protein expression compared to the rs9277534AA genotype.
• IL-13 treatment upregulated DP expression in B cells with rs9277534GG-linked DPB1 alleles.
• FISH analysis revealed distinct cytoplasmic and nuclear localization patterns of DPB1 mRNA based on genotype.
• A strong positive correlation was observed between DPB1 expression and the lncRNA lnc-HLA-DPB1-13:1 (r=0.85).
• DP DSA showed a better correlation with GG and AG genotypes than AA, explaining negative B-FCXM in cases of strong DP DSA with low DP expression.

Conclusions:

• The rs9277534 SNP significantly influences HLA-DPB1 expression levels.
• lncRNAs, specifically lnc-HLA-DPB1-13:1, are potentially involved in regulating HLA-DP expression.
• Understanding these regulatory mechanisms is vital for interpreting DP DSA and B-FCXM results in transplantation.