DISCLAIMER: The information presented in this article, as well as the usage and classification of “race” and “ethnicity,” is based on scientific findings as of 2/2/2022. Future research may further clarify this information, especially the role of race and ethnicity in HLA typing and the definitions of race and ethnicity as presented.
In the 2009 National Marrow Donor Program (NMDP) registry, people of European descent had a 93% chance of finding a bone marrow donor, while African Americans had a 58% chance. A decade later in the 2019 NMDP registry, the discrepancy only increased with Caucasians having a 77% chance of finding a matching donor and African Americans having a 23% likelihood.
The barriers to equitable regenerative medicine treatments for all races remain a concern due to the limitations posed by HLA typing — a process to match patients and donors for bone marrow or cord blood transplants. HLA typing often relies on finding donors with similar ethnic backgrounds, since they are more likely to have matching HLA alleles. This matching system helps minimize rejection of foreign tissue but comes with its own set of barriers, especially for minority groups searching for treatment.
What is HLA typing?
With any transplant, there is a chance of rejection of the transplanted organ. HLA typing helps find donors and recipients with matching HLA gene combinations to characterize a person’s immune system for transplantations, minimizing the chance of rejection issues — the more similar the HLA type, the lower the chance for rejection.
The likelihood of HLA markers matching is increased between family members as well as members of the same ethnic group. However, a person being of the same family or ethnic group as a recipient does not always mean they can donate because donor potential for organ transplantations is ultimately evaluated based on three tests — compatible HLA blood type, crossmatch and HLA testing.
How does HLA typing work?
The human major histocompatibility complex (MHC) is a group of genes that code for cell surface proteins — such as HLA class I and class II. After attaching to cells in the body, these proteins form the HLA complex — which is used to present processed peptide antigens, or foreign substances — that the immune system can respond to.
In HLA typing, variations in a person’s immune system are identified to determine whether or not they can donate blood, bone marrow, organs and stem cells. Donors that have matching HLA patterns as recipients are more likely to provide compatible transplants, where the recipient’s body does not make antibodies that fight against the transplanted HLA proteins. Without antibodies to recognize the foreign pathogens and attack them, the transplanted proteins are much more likely to be accepted by the recipient’s immune system, therefore allowing for more successful transplantations with fewer complications.
The different HLA gene combinations that a person inherits determine their specific HLA type and make their cells unique. Since there are more possible HLA types than blood types, finding an HLA match is significantly harder than finding a blood type match.
Furthermore, each HLA marker has a name with a unique combination of letters and numbers with some HLA types being more or less common than others across ethnic groups. For example, the A*02:06 allele is more frequent in Native American, Asian and Oceanian groups but less common in European and African populations, and the C*14:03 allele is common in the Korean population but less recurrent in the Chinese and Taiwanese populations.
Since HLA markers used in matching are inherited, and some ethnic groups have tissue types that are more complex than others, a patient has a higher chance of finding a donor within the same ethnic group.
HLA genes are located in close proximity to each other on DNA strands, so they are often inherited together with little to no recombination. Recombination is a process by which genetic diversity is created due to pieces of DNA being broken and recombined to produce new allele combinations. Due to the decreased amount of recombination, 50% of the HLA genes come from the mother and 50% from the father. Thus, siblings have a 25% chance of being a perfect match, and family members are the best donors.
However, if family members are unable to donate, donors with similar genetic makeup — usually those of the same ethnicity — are preferred for HLA type matching because different HLA markers are prevalent in different ethnic frequencies. Due to the higher percentage of shared HLA gene variations within the same ethnic group, there is a smaller chance that the recipient will reject the donation and the transplant is more likely to be successful.
Why is HLA typing important, and how does it prevent rejection issues?
Despite HLA typing helping better assess donor-recipient immune compatibility based on tissues or organs being transplanted, transplantation issues can still occur. The recipient’s immune system may mistakenly attack the transplanted cells or organs, thinking they are harmful foreign substances.
Graft-versus-host disease (GVHD) arises when a recipient’s cells get attacked by the donor’s transplanted stem cells. GVHD affects about 5,500 patients each year, and approximately 35 to 50% of hematopoietic stem cell transplant recipients are expected to develop GVHD as a result of the reaction of donor immune cells against host tissues. Hematopoietic stem cell transplants involve the infusion of stem cells to reset hematopoietic function — which is the production of all blood components, including immune cells — in patients with damaged immune systems.
Data from the Center for International Blood and Marrow Transplant Research on allogeneic hematopoietic cell transplants — which involve the transfer of stem cells from a healthy, related or unrelated donor to a recipient’s body after high-intensity radiation — reports varying occurrences of acute GVHD based on donor sources from 1999 to 2005. It was 39% with sibling donors and 59% with unrelated donors.
A study published in Biology of Blood and Marrow Transplantation examined the risk of GVHD for individuals of the same or different ethnicity and found that the chance of grades II-IV GVHD was 50% in African American pairs but 60% in patients of mismatched ethnicities.
Essentially, increased genetic similarity between two individuals decreases the likelihood of rejection issues during a transplantation.
Why are minority groups less likely to find compatible blood?
Though traditional concepts of race aren’t nearly defined based on clear genetic markers or biological characteristics that definitely distinguish one race from another, some HLA gene versions are more common in people of particular ethnicities.
African Americans also tend to have more diverse genetic makeup than Caucasians because they are likely to carry gene combinations from different parts of the world, making it harder for them to find a matching HLA gene version to successfully donate or receive transplants.
A 2009 study by the Washington Post found that historical migrations and genetic mixing across Africa resulted in Africans being the most genetically diverse group of all. Thus, even if the barriers to African American donations are alleviated, the chances of finding an adequate HLA match are lower for African Americans due to the genetic diversity caused by the years of colonization, intermarriage and slave-rape that make up African American history.
When trying to find transplants for people with sickle-cell disease, African American patients are disproportionately disadvantaged due to low donor eligibility which hinders access to regenerative disease treatments.
Due to African Americans having a higher risk for developing cancer, hypertension, sickle-cell disease, iron-deficiency anemia and other conditions as well as the average hemoglobin value of African Americans being 0.5-0.7 g/dl lower than that of whites, African Americans are less often able to meet the donor eligibility criteria.
Consequently, the FDA’s Code of Federal Regulations and the AABB Standards for Blood Banks and Transfusion Services is less likely to permit them from donating. In fact, only 39.33% of all African Americans are eligible to donate blood compared to 51.32% of Caucasians.
Why are minority groups less likely to donate to healthcare institutions?
“Minority groups are limited in their awareness regarding the need to sign up for voluntary participation in the donor programs,” said Dr. Ashish Gupta, a pediatric blood and bone marrow transplant physician at University of Minnesota Masonic Children’s Hospital. “This involves donating either a buccal swab or blood testing for one’s immune makeup, and because there is genetic information that can be extracted from it, it may further discourage people from opting for it.”
In addition to fear surrounding the general donation process, many minority groups are unaware of the specifics of blood or stem cell donations and how they differ from organ donations.
A lot of minorities may have misconceptions with stem cell donations, thinking they are similar to kidney donations where the donor comes out negatively, explains Emilee Moeke, a bone marrow transplants coordinator at Rush University Medical Center. “Stem cells, on the other hand, regenerate within six to eight weeks and won’t take much from the donor.”
In addition to a lack of awareness, there is a lack of trust in healthcare institutions. Because minorities have historically been subjected to inequitable practices in scientific trials, many are less likely to trust healthcare institutions to ethically provide them what they need.
A study from the Journal of American Association of Blood Banks asked participants whether or not they trusted hospitals and found that 55% of respondents trusted hospitals, 17% distrusted hospitals and 28% were not sure. Participants who trusted hospitals were more informed of the shortage of blood supply and less hesitant to provide the necessary blood, indicating that fostering trust between donation centers and the African American community, as well as ensuring donation safety, may be vital in improving African American blood donation rates.
Another reason for the unwillingness of minority groups to donate blood or organs is religious values, according to a 2002 study from the Johns Hopkins School of Medicine. This study found that African American females are the least willing to donate blood and that African American males are the least willing to become cadaveric donors.
This study also found a large reason for the unwillingness of many minority groups to donate blood is institutional distrust, while unwillingness to donate cadaveric organs came from differences in religious beliefs. For example, the religious belief of Jehovah’s Witnesses that blood products should not be accepted across humans, can make transplants more challenging, as does the stigma in Judaism associated with desecration of the cadaver.
What efforts are being made to increase donations from minority communities?
According to Moeke, a substantial part of increasing access to these treatments for minority groups comes from increasing the number of donations by donors of minority races.
Dr. Kyle Mack, a pediatric hematologist at Lurie’s Children’s Hospital, is trying to foster trust among the African American community by reaching out to South Side churches and ensuring that their blood donations would be given to those who need it: patients with sickle cell disease at Lurie Children’s Hospital.
Due to his efforts, the donations of African American donors have blue tags attached to help flag them down for use in sickle cell patients. Because sickle cell anemia mainly affects African Americans, flagging down the donations and directing them towards sickle cell patients may improve the chance of African Americans patients getting the donations they need.
The National Marrow Donor Program in Minneapolis, Minnesota was founded in 1981 to serve as a registry for the volunteer hematopoietic stem cell transplants and umbilical cord units at Be the Match, a nonprofit organization for bone marrow transplantation.
“[The National Marrow Done Program has] created a campaign to go to minority neighborhoods […] and historically black colleges to do outreach there, especially because younger donors are who they prefer,” said Moeke. By working on informing minority groups of the donation process, they can reduce fear or hesitancy among minority groups. “Sometimes, minority groups will get typed, but the follow-through with those groups is much lower when they get called to donate because they do not think they will actually get called in to donate,” explained Moeke. As a result, having minority group keynote speakers instill confidence and awareness with minority groups of the whole process, from getting typed to finally donating, can be highly beneficial.
A 2001 study funded by the Medical University of South Carolina found that the most effective ways to increase donation are to provide educational programs before the bone marrow drives as well as more opportunities to donate. The results of this method show that the number of African American donors increased from 768 to 1,977 in less than two years.
“[Be the Match is] also communicating and educating people on myths or at least concerns with things that have happened in the past, and how is it different now,” said Gift Matemba-Mutasa, the director of donor recruitment at Be the Match.
By hiring interns at historically black universities to give classroom presentations about the bone marrow donation process and set up information tables at popular events, Be the Match hopes to recruit more donors of underrepresented groups — which can increase the HLA subtype diversity in public banks so that various ethnic groups can obtain the remedies they require.
A 2006 study found that African Americans were more supportive of incentives for donation, such as helping with the funeral expenses of the donor. Although the Food and Drug Administration (FDA) fears that paying blood donors can jeopardize the safety of the blood supply, lower-income individuals are often more willing to make the donations for this incentive.
Apart from material incentives, other incentives such as education about advances in treatment that could occur because of the research, emphasis on altruism, and inclusion of African Americans in the research process as study personnel can improve research participation among minorities. Monetary or not, given that the reimbursements remain ethical and donors are honest about their health, incentivizing donations could play a large role in increasing the number of donations from minority groups.
“Erasing decades of distrust won’t be easy,” Mack said. “What I have learned as a physician who cares for a myriad of patients, is that we are all more similar than we think. As humans, we are all a match.”