Organ Transplantation: How to Find Your Organs’ Doppelgangers

You just stopped by the DMV to renew your license, and you see that you can sign up to be an organ donor. You are hesitant. You have questions. You have concerns. For instance, you may have heard from a neighbor that the process is unfair, and celebrities get priority when it comes to receiving organ transplants. Is this true? You may wonder many things about how the organ donor and transplant process works. In this article, we’ll explore the science behind it. Let’s see if this insight will convince you to sign up to be an organ donor! 

If someone needs a new organ, it is nearly impossible to find an exact match in someone else, unless they have an identical twin. (If you do have an identical twin, now is the time to be nice to them.) The reason is that an organ from someone else’s body looks foreign to yours, which can trigger your immune system. Our immune systems, which have evolved to fight foreign agents such as bacteria and viruses think that this new organ is a threat, just like a virus may be, and that it needs to be eliminated.

How does the immune system recognize an organ as foreign? 

Now is a good time to learn about histo-compatability antigens, or HLAs. First off, an antigen is a type of molecule that is capable of activating the immune system and alerting it to an intruder, sort of like a security system announcing an intruder into your home. Do molecules activate the immune system all the time? The good news is that the immune system is trained not to attack molecules that come from your own body, a phenomenon called self-tolerance. The cells of the immune system are literally taught to distinguish between self vs non-self, mainly in the bone marrow and thymus. This keeps them from launching an attack against our own organs. However, when they encounter a foreign molecule, such as one on a virus or a bacteria, they get activated and begin the process of eliminating the intruder. 

organ donor matching
Figure 1. Immune cells spring into action when they encounter cells with HLA complexes that are different then theirs, such as the cells of a transplanted organ. Adapted from Immense Immunology Insight.

Let’s come back to the histocompatibility part. “Histo” refers to tissue (a.k.a the organization of cells in the human body). Now add compatibility to that, and you’ll find that what these antigens are detecting is whether this (perhaps foreign) tissue is compatible with your own body tissues. If your HLAs are compatible, then all is well. If your HLAs are not compatible, then you may end up like the transplanted cell in Figure 1, who is unrecognized and may get rejected.  

HLAs are proteins that come in many different versions among the human population.  Almost all cells in your body have these HLA proteins. While all of these different versions have the same function, their composition is very different from person to person, just like our genome. In a transplant recipient, these differences can trigger the immune system to  falsely think that there is an intruder for it to eliminate, eventually leading to organ rejection.

organ donor match
Figure 2. Someone you’re not related to can have completely different HLA proteins on their cells than you have on yours. Adapted from stanford.edu.
Why are HLA’s so different between people? 

During organ matching, doctors are looking for one’s closest match in terms of the HLA structure. Your closest match is very likely to be in your family, and here’s why:

Your genetic code carries all the information about your hair color, shoe size, and even disease risk, and it gets passed on from parents to children through DNA, which is grouped into chromosomes. Each cell in our body has these chromosomes. In fact, each cell has two sets of 23: one set we inheret from our mother and one set we inheret from our father. On a chromosome, certain genes may tend to be inherited together, and scientists refer to these groupings as haplotypes. See how inheritance of the HLA haplotype works in the diagram below:

organ donor matching
Figure 3. One example of inheritance of HLA haplotypes. From labtestsonline.au.

Have you decided to be nice to your identical twin or that sibling who is a close match to your HLA genes yet? 

While there are thousands of proteins in the body, you may wonder why we worry only about the HLA proteins. Remember that HLA proteins are the most diverse set of proteins across different people. They’re so diverse because of how they help the immune system.

HLA proteins bind to regions of pathogens, such as viruses and bacteria, and displaying them as red flags to the immune system. Their genetic diversity is very important to our survival because they make humans adaptable to threats to our population. If a new disease comes by, the diversity of HLA proteins means at least some of us are likely to survive it and live to produce a new generation. So, the whole HLA system is thought to have evolved based on the distribution of infectious agents in different parts of the world. These kinds of differences are thought to be protective by avoiding the risk of a new microorganism wiping out the entire human race. Nature is very smart, you guys!

But this genetic diversity, as you now know, makes it harder to find an organ match.

How is a donor matched with a recipient?

HLA typing is a process by which doctors assess the similarity between donor and recipient HLAs. They perform a genetic test using a blood or saliva sample. They compare the genetic sequence that codes for the HLA proteins between the donor and the recipient to determine the extent of the match, which they measure as the number of similar HLA proteins (Figure 2) or haplotypes (Figure 3). Does this remind you of the ABO blood group matching? While HLA typing and ABO blood group matching are looking at different types of proteins, the principle behind the two processes is the same. 

Because of the dearth of available donor organs, a lot of times, a mismatched organ is the only choice. In this case, the recipient of the organ takes drugs that reduce the immune response to the received organ. Patients can end up taking drugs like prednisone, cyclosporine, and rapamycin, for the rest of their lives.

One organ donor can save up to eight people through organ donation or heal up to 75 people through tissue donation. From Donor Network West

One way to improve the odds of finding a donor is by increasing the pool of donors available.  Everyday, 22 people die waiting for an organ, and one organ donor can help save multiple lives. Hopefully, the next time you renew your license, you will consider checking that little box that asks if you want to be a donor. It is as easy as that!

Anugraha Rajagopalan, Ph.D. is a postdoctoral scientist at Rush University specializing in Cancer Immunology