Diagnosing Lyme disease, especially the chronic variant, can be a long and delicate process. The number of misdiagnoses is high; while this has a lot to do with the poor education and recognition of the disease and the doctors treating it, it also speaks to the insidious nature of the condition. Lyme disease often mimics the symptoms of other, more prominent degenerative disorders, leading to constant misidentification. In addition, the disease affects patients in different ways, as the prevalent symptoms are often caused by a patient’s individual immune response, not the bacteria itself. Anything that can help diagnose Lyme successfully is much appreciated by doctors on the frontline. Recently, help has been identified in the form of T-cells, specifically the IFN-gamma (also called type II interferon) and IL-2 (also called interleukin-2) molecules.
So what role do these important molecules play in the clinical diagnosis of Lyme disease? While it all sounds highly scientific, the actual mechanism is easy to understand once it’s put into context. It’s also important to the future of Lyme treatment, so worth getting to grips with. We’ll break it down piece by piece.
For starters, let’s define what T-cells are. T-cells are a form of lymphocytes or white blood cells and are basically our natural defense against viruses and bacteria (known as pathogens), forming a crucial component of our immune system. Most infections are stopped by the epithelium (which refers to part of our exterior skin) and innate immune cells that are recruited to site of infection. This system is our first line of defense against foreign invaders. Inevitably, however, some pathogens slip through the cracks. When this occurs, we become sick, as our adaptive or learned immune system kicks in and our body has to work hard to eradicate the threat. This eradication duty is performed by T-cells and other white blood cells, which are dispatched through the blood to the infection site. Their mission is to attack and destroy any unfamiliar cells they encounter.
T-cells are defined through a molecule on their surface: the so-called “T-cell receptor.” This molecule makes them specific to certain diseases; they are activated if they see the antigen they are specifically for. T-cells come in many subsets, which all have different missions in an immune response. One subset of T-cells is known as “T-helper” cells. They play an important role in our immune system, as they “identify” invaders that the body is dealing with in a current infection. They talk to B-cells, another cell type of the lymphocytes, which produce antibodies against the invaders. They can also travel to the site of infection and organize the fight against the invaders. They produce a specific molecule, called interferon gamma (IFN-gamma), to communicate the threat to our body.
Another subset of T-cells is the memory T-cells. These are produced during the end of an infection, or once the pathogen is retreating. Once formed, they travel through the body, most specifically to the site where the infection occurred originally. Their role is to help prevent another infection of the same kind; they “memorize” the pathogen that invaded and patrol the entry point of the pathogen. The so-called “effector memory cells” that we find in the blood produce a cytokine called interleukin-2 (IL-2).
As you might be able to work out, fighter cells are instrumental in attacking pathogens that have antigens on their surface. The memory cells kick in once the fighter cells figure out exactly how to eradicate the antigen-bearing invaders, recording the information for future use. They reroute and ultimately reside in the lymph nodes, as well as the tissue where the infection originated. If the same pathogen manages to break through the epithelium again, the memory cells will trigger the immune system to mount a swift and effective attack to eradicate the disease.
The T-cells formed during an infection are all classified as antigen-specific T-cells. The role or type of antigen-specific T-cell they will be depends on the time and signals they receive during an infection – they will form T-helper cells, memory cells, or one of the other possible subsets. The effectiveness of this mechanism can be observed with diseases like chicken pox and measles, which humans can only catch once. It’s also why people talk about different strains of flu; each time a person comes down with the flu, it’s a different variant of the same pathogen, meaning that the immune system must learn to how to fight it all over again.
IFN-gamma molecules are produced by the attacking antigen-specific T-cells traveling through the blood, while IL-2 molecules are produced by the antigen-specific effector memory cells. So how do these T-cells, and more specifically the IFN-gamma and IL-2 molecules found in them, help in the clinical diagnoses of Lyme disease?
Previous diagnostic tests were based on the presence of antibodies, which is traditionally a very good way to tell if a person has suffered an infection or not. However, antibodies don’t tell the whole story of the infection. This has been particularly troublesome with Lyme disease, as it has two wildly different stages: acute and chronic. Both stages affect the body in totally different ways, and merely knowing a Lyme infection existed isn’t specific enough for successful treatment.
Essentially, the presence (or lack thereof) of these two important molecules is able to tell doctors what state the patient is at with regards to Lyme disease. It is particularly useful when it comes to chronic Lyme, which is notoriously difficult to both diagnose and treat. Lyme specialists like BCA-clinic in Germany and Infectolab in the U.S. will conduct a test known as an ELISpot, which is a specific type of blood test. If the Lyme infection is successfully cleared and has not developed into any kind of chronic form, doctors would expect to see only IL-2 producing T-cells in the blood sample. As these are only the effector memory cells, it would indicate that no active infection is ongoing, and the cells are merely there to provide defense if the infection arises again.
If the blood test finds evidence of both IL-2 and IFN-gamma molecules, this would indicate that the infection is chronic controlled, and that the body is continuing to fight the infection. Treatment plans can be accurately decided upon once this critical information is known.
This is an important step forward for chronic Lyme disease diagnosis. The investigation into the process and role of T-cells in the fight against chronic diseases such as Lyme is a crucial area of study for both doctors and scientists alike. An important consideration is that many chronic Lyme symptoms are caused by inflammation response, which is essentially the natural immune system going haywire. By investigating the immune system’s natural response further, we might be able to discern more about how the body reacts to long-term Lyme disease infection, and forge a successful treatment path for hundreds of thousands of patients around the world.
