Monday, January 13, 2020

Study reveals lower levels of lymphocyte blood cells may indicate increased death risk

Lower levels of lymphocyte blood cells in a condition called lymphopenia, could be an early warning fir future illness according to a recent study. The reduced count of the immune cells was associated with a 60% increase in death from any cause.

The study showed that participants with lymphopenia were at high risk of dying from any cause, regardless of any other risk factor for all-cause mortality including age, says one of the author.


Lymphopenia is often detected during routine blood tests, and patients are nit usually referred for further investigation because the value of lymphopenia as a predictor of future health was not known.


Researchers included 108,135 people of Danish descent aged 20-100 years who were enrolled in the study between 2003 and 2015. An incidental finding of a low lymphocyte count was associated with a 1.6 fold increase in the risk of death from any cause and 1.6 tp 2.8 fold increased risk of death from cancer, cardiovascular disease, respiratory disease, infections and other causes. During the study period, a total of 10,372 people died.


Older age was associated with decreasing lymphocyte counts.


The link between lymphopenia and death may be because of reduced immune capacity to survive potentially lethal diseases. Lymphopenia could also indicate frailty which could lead to illness and death.


The researchers hope their findings may help doctors identify at-risk people. Using the absolute 2-year risks of all-cause mortality, physicians can identify high-risk individuals with lymphopenia ( e.g., smokers older than 8- years) who might benefit from additional surveillance, they write, although the benefits of such surveillance are not known.


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Thursday, February 01, 2018

Study reveals how gene mutations cause immune disease

According to a recent research, a group of scientists have found how a gene mutation affects T cell function to promote immune disorders.

The team then tested a treatment based on the discovery -- successfully fixing donated immune cells from a 16-year-old boy with an abnormally low level of white blood cells called lymphopenia.

The discovery centers on mutation of the gene Gimap5, which is important to the healthy formation and function of CD4+ T cells, one of the immune system's super soldiers against infection and disease.

Scientists noted that the protein associated with the Gimap5 gene (also Gimap5), is important because it regulates a protein that inactivates an enzyme called GSK3.

If GSK3 isn't inactivated it causes DNA damage in T cells that are expanding, causing the cells to not survive or function correctly.

In mice and human blood cells, the researchers tested drugs that inhibit GSK3, improving immune system function in mice and restoring normal T cell function in the human cells.

Study's lead author  said, "Our data suggest GSK3 inhibitors will improve T cell survival and function and may prevent or correct immune-related disorders in people with Gimap5 loss-of-function mutations. Therapeutically targeting this pathway may be relevant for treating people with Gimap5mutations linked to autoimmunity in Type 1 diabetes, systemic lupus erythematosus or asthma." 

The scientists associated with the current study said additional research is needed before the data have clinical relevance for patients.

Meanwhile, new experiments are underway to translate the findings into the clinic, the researcher said. The scientists are investigating if and how genetic variants in Gimap5 affect GSK3 regulation causing malfunctioning T cells in patients with immune disorders.

They also are exploring the therapeutic potential of GSK3 inhibitors in pre-clinical mouse models of allergic lung disease and lupus to see if they can improve patient outcomes.

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Saturday, April 15, 2017

Combination therapy may increase survival rates in brain cancer patients

Researchers found that a combination of vaccine and chemotherapy sessions may help boost both progression-free survival and overall survival rates for patients suffering from glioblastoma, a malignant tumour affecting the brain or spine.

In a clinical trial, 11 patients received a vaccine targeting cytomegalovirus (CMV) antigen pp65, combined with high-dose chemotherapy (temozolomide).

The results demonstrated a median progression-free survival of 25.3 months and a median overall survival of 41.1 months in eight patients.

The researchers said, in the remaining three patients, the disease was progression-free for more than seven years after diagnosis.

Lead author Kristen Batich from the Duke University in North Carolina, US said, "The clinical outcomes in glioblastoma patients who received this combination were very striking".

The typical median survival for glioblastoma patients is less than 15 months.

To overcome these poor numbers, the researchers took advantage of CMV's affinity for glioblastoma, with the viral proteins being expressed in roughly 90 per cent of these tumours.

They used the CMV as a proxy for glioblastoma, while targeting the virus with pp65-specific dendritic cells to spotlight the tumour for the immune system.

Previous work had shown that TMZ generates profound lymphopenia or the loss of immune cells, which offers a unique opportunity to retrain the immune system, Batich explained.

The researchers administered dose-intensified temozolomide (TMZ) as a strategy to further enhance the immune response.

Batich said, "The dose-intensified temozolomide induces a strong state of lymphopenia. With that comes an opportune moment to introduce an antigen-specific vaccine, which redirects the immune system to put all hands on deck and fight that target".

The finding was published in the journal Clinical Cancer Research.


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