DNA strand transforming into a tree, symbolizing genetic discovery and improved health.

Decoding the DRB502:21 Allele: What It Means for Transplants

Soraya Malik in Health & Wellness December 2025 • 4 min read.

"A newly identified gene variant could improve outcomes in kidney and stem cell transplantation."

The world of transplant medicine is constantly evolving, with researchers working to refine the matching process between donors and recipients. A critical aspect of this is understanding the subtle variations in human leukocyte antigen (HLA) genes, which play a vital role in the immune system's ability to distinguish between self and non-self.

Recently, a team of scientists identified a novel HLA-DRB502 allele, named DRB502:21. This new allele carries a single nucleotide substitution compared to the more common DRB502:02:01 allele. The discovery, made during the HLA typing of two patients awaiting transplants, highlights the ongoing refinement of our understanding of genetic diversity and its implications for transplantation.

This article breaks down what the DRB502:21 allele is, why its identification is important, and what it could mean for individuals awaiting kidney or hematopoietic stem cell transplants.

DRB502:21: A Tiny Change with Big Implications

DNA strand transforming into a tree, symbolizing genetic discovery and improved health.

The HLA-DRB5 gene is part of the major histocompatibility complex (MHC), a region of the human genome that is highly variable. This variability is crucial for the immune system, allowing it to recognize a wide range of foreign invaders. However, it also means that matching donors and recipients for transplantation can be challenging.

The newly identified DRB502:21 allele differs from the DRB502:02:01 allele by a single nucleotide substitution in exon 4, the region of the gene that codes for a critical part of the HLA-DRB5 protein. Specifically, at codon 203, an A (adenine) is replaced by a G (guanine). This seemingly small change leads to a different amino acid in the protein sequence: isoleucine is replaced by valine.

The difference: The DRB502:21 allele has one nucleotide substitution compared to DRB502:02:01.
Location of change: This substitution occurs at codon 203 in exon 4 of the HLA-DRB5 gene.
Protein alteration: The change results in an isoleucine to valine substitution in the HLA-DRB5 protein.

This subtle change could affect how the HLA-DRB5 protein interacts with other molecules, potentially influencing the success of a transplant. Precise HLA typing is essential to minimize the risk of rejection and improve long-term outcomes for transplant recipients. Identifying and characterizing new alleles like DRB502:21 contributes to this precision.

Looking Ahead: The Importance of Precise HLA Typing

The identification of the DRB502:21 allele underscores the importance of continuous refinement in HLA typing methods. As technology advances, researchers can identify increasingly subtle genetic variations that may impact transplant outcomes.

The nucleotide sequence of the exons 2 to 5 of the new allele has been submitted to the GenBank database (Accession No. MH645229) and to the IPD-IMGT/HLA Database (Submission No. HWS10052823 and HWS10053373), ensuring this information is available to the broader scientific community.

For patients awaiting transplants, this discovery highlights the ongoing efforts to improve matching and minimize the risk of rejection. While the clinical significance of this specific allele remains to be fully elucidated, its identification represents another step forward in the quest for personalized and successful transplantation.

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Everything You Need To Know

What exactly is the DRB5*02:21 allele, and how does it differ from other alleles?

The DRB5*02:21 allele is a newly identified variant of the HLA-DRB5 gene, differing from the more common DRB5*02:02:01 allele by a single nucleotide substitution. This substitution occurs in exon 4, specifically at codon 203, where an adenine (A) is replaced by a guanine (G). This leads to a change in the protein sequence, with isoleucine being replaced by valine. This seemingly minor change may have significant implications for transplant outcomes.

Why is the identification of the DRB5*02:21 allele considered important in the field of transplant medicine?

The identification of the DRB5*02:21 allele is important because it highlights the ongoing refinement of HLA typing. Precise HLA typing is essential for minimizing the risk of transplant rejection and improving long-term outcomes for transplant recipients. Identifying new alleles contributes to a more accurate matching process between donors and recipients. This ultimately leads to better patient outcomes, especially in kidney and stem cell transplantation where HLA matching is critical.

Where does the nucleotide substitution occur in the DRB5*02:21 allele, and what specific change does it cause?

The nucleotide substitution in the DRB5*02:21 allele occurs at codon 203 in exon 4 of the HLA-DRB5 gene. Specifically, an adenine (A) is replaced by a guanine (G). This change results in the substitution of isoleucine with valine in the HLA-DRB5 protein. While seemingly small, this alteration has the potential to affect how the HLA-DRB5 protein interacts with other molecules, which could impact transplant success.

How does the DRB5*02:21 allele potentially affect transplant outcomes for individuals needing kidney or stem cell transplants?

The DRB5*02:21 allele affects transplant outcomes because the HLA-DRB5 protein plays a crucial role in the immune system's ability to distinguish between self and non-self. The subtle change in the protein structure, caused by the nucleotide substitution, could alter how the HLA-DRB5 protein interacts with immune cells. This could lead to a higher or lower risk of transplant rejection, depending on the specific interaction. Understanding these nuances is essential for improving transplant success rates.

Can you explain the role of HLA typing in transplant matching and why identifying alleles like DRB5*02:21 are crucial?

HLA typing is used to match organ and stem cell donors with recipients. The process involves identifying the specific HLA alleles present in both the donor and recipient. The goal is to find the closest possible match to minimize the risk of the recipient's immune system attacking the donated organ or cells. The discovery of the DRB5*02:21 allele underscores the importance of refining HLA typing methods to identify even the most subtle genetic variations that may impact transplant outcomes, such as single nucleotide polymorphisms, which might affect protein folding and presentation of antigens.