Quick Insights:
A woman suffering from HIV and fast-progressing leukemia received a cord blood transplant as a part of treatment. These cells were lacking the receptors required by HIV to survive. 14 months later, no hint of the virus is found in her body.
The case of the patient:
The patient, self-identified as a mixed race person, had fast-progressing leukemia as well as HIV. HIV is a virus (human immunodeficiency virus) that attacks the white blood cells of the human immune system. The white blood cells (or T-cells or T-Lymphocyte) are the key players that protect the body against disease causing viruses, bacteria and other microorganisms. The HIV operates by killing T-cells and reducing their population in the blood. Upon severe loss of T cells, the body becomes unprotected for future infections and the patient’s diseases progresses to Acquired Immuno Deficiency Syndrome (AIDS). So while HIV or AIDS directly is not fatal, they weaken the body severely thereby making it unable to defend from diseases.
Biology behind HIV and T-cell:
The T-cell receptors responsible for cell death are activated. CC chemokine receptor 5 (CCR5) is present on the T-cell surface that are targeted by the HIV. Upon binding to this receptor, the virus is then capable of entering the T-cell and switching on various biochemical processes for protein production and viral multiplication. This eventually leads to pyroptosis of the T-cell through the release of proinflammatory cytokines and capase-1 dependent cell death.
Nature’s defense against HIV:
There is a rare occurrence of a small segment of this CCR5 gene being removed in the body. This happens naturally to certain people and is termed as a polymorphism. It does not cause any problems to the individual but there is significant research about it conferring resistance to HIV. This polymorphism is termed as CCR5 Δ32 (since there is a 32 DNA deletion in this gene). There are many papers that show the CCR5 Δ32 providing significant defense against HIV infections.
The HIV enters the T-cell through communication or association with CCR5 Δ32.
CCR5 Δ32 – a new hope:
This deletion thusly became very popular among those looking for a cure for HIV and scientists began using this polymorphism as HIV management. This specific case was done by a clinical trial research team in Weill Cornell Medicine. They identified a newborn with this deletion and use the baby’s cord blood cells to treat the aforementioned patient. When the patient undergoes radiology and chemotherapy for their cancer, it drastically reduces the population of the white blood cells. This combined with HIV is fatal. In order to increase the uninfected white blood cell population in the blood, the patient is usually supplemented with white blood cells from another person. But this is tricky because there always needs to be compatibility between the donor and the acceptor. If the compatibility is low, it can lead to severe reactions in the patient’s body thereby leading to death. Cells, blood and other biological samples are therefore always tested for suitability before introduction into the patient’s body. Reintroduction of T-cells with a CCR5 Δ32 polymorphism offers a very promising method for longer T-cell survival in HIV patients.
A promising HIV management:
Isolation of compatible cord blood cells is the challenge present in this treatment. Moreover, CCR5 Δ32 polymorphic versions are rather difficult to find. This issue was addressed as a two step procedure. The stems cells from an adult was used to reinstate the white blood cell population in the patient. Further, cord blood stem cell population from the stem cell bank containing the CCR5 Δ32 was transplanted into the same patient.
Cord blood cells come from the umbilical cord of the newborn.
This is the first time cord blood stem cells with CCR5 Δ32 was used as all previous attempts were done with adult stem cells harboring this polymorphism. Three months post this treatment, there were no HIV virus detected by various sensitive HIV test kits. Eventually the patient was advised to stop HIV medication as the disease was no longer prevalent.
Take away point:
CCR5 Δ32 containing cord blood stem cells offers an effective strategy against the HIV and malignant cancers. They must definitely be considered for patients with HIV infections as well as cancers.