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The mysterious role of Epstein-Barr virus: Why are immunosuppressed people more likely to develop lymphoma?
After organ transplantation, patients often need to receive immunosuppressive treatment to avoid rejection, but this puts them at greater risk of a disease called "post-transplant lymphoproliferative disease" (PTLD). This disease is mainly caused by the uncontrolled proliferation of B cells caused by Epstein-Barr Virus. Its symptoms and manifestations are diverse, seemingly ordinary but extremely threatening.
Symptoms and diagnosis
The symptoms of PTLD can be non-specific and similar to many other conditions, including fever, weight loss, night sweats, and fatigue. These symptoms sometimes resemble infectious mononucleosis caused by the Epstein-Barr virus. Patients' discomfort caused by enlarged lymph nodes or tumors sometimes worsens and affects their quality of life.
Actual diagnosis usually requires a biopsy of the affected tissue to determine whether a lymphoproliferative neoplasm is present.
Imaging tests, such as CT scans, can show enlarged lymph nodes or local masses, and PET scans can help evaluate metabolic activity and guide the location of biopsy. Neurologic symptoms, such as confusion or partial weakness, may further require an MRI of the brain to determine whether EBV infection is present.
Causes of PTLD
The root cause of PTLD is the uncontrolled proliferation of B cells caused by Epstein-Barr virus. Immunosuppressive therapy, especially in patients using calcineurin inhibitors (such as tacrolimus and cyclosporine), cannot effectively control EBV infection due to suppression of T cell function. Therefore, these B cells may further mutate and become malignant lymphoma.
In some cases, these malignant cells become the primary proliferating cells, leading to the formation of lymphoma.
The higher the degree of immunosuppression, the greater the risk of PTLD, especially in the year before transplantation, when about 80% of PTLD cases will occur.
Treatment and Prognosis
For the treatment of PTLD, reducing or discontinuing the use of immunosuppressants may lead to spontaneous regression of the disease. It can also be alleviated by adding antiviral treatment. Some patients may progress to non-Hodgkin's lymphoma, in which case the disease can become fatal.
A phase II study demonstrates that delivery of specific Epstein-Barr virus T cells can combat PTLD with high efficiency and low toxicity.
Epidemiology
PTLD is one of the most common malignant tumors after solid organ transplantation. Lung and heart transplants require relatively high doses of immunosuppressants, so the incidence of PTLD is most significant in these patients. Additionally, studies have shown that HLA-mismatched bone marrow transplantation increases the risk of PTLD. In patients who have not been infected with Epstein-Barr virus and receive an organ transplant from an Epstein-Barr virus-positive donor, the risk of developing PTLD can be increased up to 24-fold.
Overall, the complex interactions between EBV and the immune system reveal its impact on patient health, especially in vulnerable immune states. In the future, scientists will need to delve deeper into the behavior of EBV to better prevent and treat these immune system-related diseases. Can we use ever-growing technology and knowledge to find more effective solutions to combat these problems caused by Epstein-Barr virus?
