Human immune system is closely associated with disease occurrence and progression, and accurate monitoring and evaluation of the immunologic status is highly useful for disease diagnosis and treatment. While peripheral blood lymphocyte phenotyping by flow cytometry remains one of the most sophisticated techniques for immune function analysis, it has predominantly been used as a laboratory tool for basic research and seldom applied in clinical settings (except for AIDS studies).
Early in 1990s, the Department of Infectious Diseases of Peking Union Medical College Hospital (PUMCH) extended the application of T lymphocyte and its subset analyses to clinical laboratory. Over 20 years later, the immune function testing platform has become an important monitoring and research platform for some infectious and non-infectious diseases, offering essential theoretical and data supports for more comprehensive and rational diagnosis and treatment of immune disorders.
Behind the scenes: starting from serving AIDS patients
The immune system of patients with acquired immunodeficiency syndrome (AIDS) is damaged after being attacked by the human immunodeficiency virus (HIV). “Early in 1996, Prof. Wang Aixia at the Department of Infectious Diseases of Peking Union Medical College Hospital for the first in China applied this technique to analyze T lymphocyte and its subsets.” introduced Prof. Li Taisheng, chief of the Department of Infectious Diseases of PUMCH, “CD4 and CD8 in T cells of AIDS patients were detected every three months to assess and monitor the immunologic status.”
Since he finished his training in France in 1999, Li has long been committed to exploring AIDS treatment protocols in Chinese populations. It was with the help of the immune function testing platform Li and his team deeply investigated the changes of T cell subsets in AIDS patients, the timing of immune restoration after antiretroviral therapy, the mechanism of impaired immune reconstitution and its solution, and the coping strategies of abnormal immune activation, which paved the way for developing multidisciplinary HIV/AIDS management strategies. "If the Chinese AIDS treatment protocol is a leading role under the spotlight, the immune function testing platform can be regarded as one of the heroes behind the scenes." commented Li.
Fight against SARS
In 2001, the Department of Infectious Disease officially opened its immune function tests (IFTs) for the whole hospital. The tests not only covered the counting of CD4+ T cells, CD8+ T cells, B cells, and NK cells but also included the testing for the expression of CD28, a second signal receptor, in CD4+T and CD8+ T cells, the activated CD8+ T cells, and the pure and memory CD4+ T cells. Thus, PUMCH took lead in the assessment of T cell subsets in China.
Two years later, the Department of Infectious Disease and the immune function testing team faced a severe challenge when the severe acute respiratory syndrome (SARS) crisis occurred in 2003. Li was keenly aware of the abnormality of the infected patients. He began to collect specimens to evaluate the T cell subsets in these patients. Soon he found the characteristics T cell subsets were quite different from those in patients with common viral infections: the amounts of CD4 and CD8 T cells rapidly dropped to about 200 after one week of fever, which was even earlier than the notable changes on chest radiograph.
Thus the PUMCH team for the first proposed that the early diagnosis of SARS could be achieved based on the changes in T cell subsets. The team further investigated the early changes of lymphocyte subsets in SARS patients and recommended the individualized treatment of SARS with hormones, which proved to be a successful strategy in fighting against SARS outbreak. In 2007, Li and his team won the National Science and Technology Progress Award (second class) due to their outstanding basic and clinical research on SARS.
Mapping the trends in aging among healthy populations after ten years of tracking
The success in the Battle of SARS greatly inspired the team. They decided to apply the IFTs in larger scenes.
By using IFTs and other technical platforms, Li's team had completed a large-scale immune function study in 1,068 healthy individuals aged 18 to 80 years since 2006 and for the first revealed the normal thresholds of immune function indicators in different age groups and their changes with age. Their findings were published in Aging, the journal with the highest impact factor in its field, in 2016, offering more accurate indicators for the clinical evaluation and monitoring of immune functions for healthy people.
Providing dual support for the management of infectious and non-infectious diseases
In addition to HIV/AIDS and SARS, many other infectious diseases including chronic hepatitis B, hand, foot and mouth disease, EB virus infection, and epidemic hemorrhagic fever have been assessed by IFTs, which provide a reliable basis for the diagnosis, treatment, and monitoring of these diseases.
Human immune function also plays a key role in the occurrence and development of non-infectious diseases. As useful technical tools, IFTs can inform and guide disease diagnosis, treatment, and prevention. Therefore, the platform has gradually become a powerful aid to the management of autoimmune diseases, tumors, organ transplants, and blood system diseases and has been applied in disciplines including intensive care and geriatrics. It even helps to optimize disease treatment strategies in some cases.
According to Li, a study jointly performed by the Department of Infectious Diseases and the Department of Rheumatology and Immunology has found that the immune function (number of T cells) in patients with lupus erythematosus is associated with cytomegalovirus infection. This finding will shed new light on the diagnosis and treatment of such diseases. A relevant article will be published in Medicine soon.
As the roles of IFTs have increasingly been recognized by other clinical departments in PUMCH, more tests have been performed by the platform. Up to 13,843 patients received IFTs in 2018. The platform is among the leading centers in China and globally in terms of capacity and expertise and it is a model from basic research to clinical application. So far, Li and his team have published 118 scientific articles, among which 49 were published in SCI journals.
“In future, our team will focus more on quality-based assessments - rather than quantity-based tests, with an attempt to improve the clinical diagnosis and treatment of diseases by using more sophisticated immune function testing and evaluation systems.” concluded Li.