Mycobacterium tuberculosis is a very old germ on the earth. Humans have been fighting for many years, but they have not been able to completely overcome it. The number of people with global latent tuberculosis infection (LTBI) is as high as 1.7 billion, and about 10 million new cases of tuberculosis are added each year; there are 300 million people with latent tuberculosis in China, 5 million people with tuberculosis, and about 900,000 new tuberculosis patients every year. For those with latent tuberculosis, when their immune system works normally, it is no different from ordinary people, but once the body’s immune system is suppressed, the risk of tuberculosis outbreaks will increase.
Recessive tuberculosis is different from active tuberculosis. Patients with active tuberculosis will have obvious cough, fever, weight loss and other diseases. It is difficult for people with recessive tuberculosis to detect tubercle bacilli in the body and there is no manifestation of any symptoms. The common method of detecting hidden tuberculosis in China is the tuberculin skin test (TST, skin test), in which the tuberculosis protein derivative (PPD) is injected intradermally into the patient, and the skin test reaction of the body is used to determine whether the patient contains Mycobacterium tuberculosis. infection. When a skin test positive result occurs, it means that there is an infection of Mycobacterium tuberculosis in the patient, and a delayed type hypersensitivity reaction is produced in the body.
However, the PPD antigen used in TST is complex and susceptible to BCG, non-tuberculous mycobacterial infection (NTM) and some skin test agents. Most of the population in China have received BCG vaccination in infants and young children, resulting in skin The test positive rate is too high. In addition, the sensitivity of TST decreases with age and impaired cellular immune function, and lacks sufficient sensitivity for patients with impaired immune function.
The IGRA method, which uses the principle of detecting TB-specific antigen-stimulated T cells to produce γ-interferon, overcomes the shortcomings of TST. The IGRA method has higher sensitivity and specificity and does not cross-react with the BCG vaccine. IGRA is the most widely used method for detecting tuberculosis infection in developed countries.
Unlike TST, IGRA requires fresh blood samples to obtain the right cellular material, as well as sophisticated laboratory equipment and highly trained technicians. This makes it difficult for China, a country with a large population of hidden TB, to be widely used. IGRA is not only complicated in testing procedures, but also expensive (about 800 yuan/time). It is difficult to conduct large-scale tuberculosis screening, which is difficult for domestic primary medical institutions. Conduct IGRA testing.
Dr. Jianrong Jian, who has been deeply involved in the in vitro diagnostic (IVD) industry in the United States for 20 years, knows the gap between China and the United States in the field of IVD. He is a Ph.D. in Microbiology at the University of Kentucky, and a postdoctoral fellow in molecular biology at Hopkins University. He has worked in several international first-class in vitro diagnostic companies.
Regarding the difference in in vitro diagnosis between China and the United States, he concluded: “In China, the average per capita consumption of IVD is about 4 US dollars, while in the United States and other developed countries, the per capita IVD consumption is above 40 US dollars; China’s hidden tuberculosis infections account for In the United States, the proportion of people with invisible tuberculosis can be reduced to 0.01%. Behind the 2000-fold gap is the lack of early intervention in tuberculosis in China, and the in vitro diagnosis of tuberculosis in China is still at an early stage of development.”
Developed countries use IGRA technology to detect tuberculosis infection, while China’s IGRA test is difficult to popularize the public. How many drawbacks does TST have, which represents how big IGRA is in China. Solving the pain points of the existing IGRA technology and creating the “mobile universal IGRA tuberculosis infection detection technology” is the direction that Lou Jianrong started to see.
In 2013, Lou Jianrong returned to China, which is in the midst of rapid development of the entire Chinese medical industry. Especially in the research field of the immune system, more and more pharmaceutical companies are involved. The rapidly evolving field of immunotherapy brings more opportunities and challenges to the development of IVD. When the patient is treated with immunotherapy, the immune system will be interfered. The immune system will accelerate the outbreak of occult tuberculosis. These immune drugs will increase the rate of tuberculosis by more than ten times. Therefore, screening for tuberculosis before immunotherapy will be necessary. Indispensable, this also brings a huge market for the in vitro diagnosis of tuberculosis.
Independent research and development to create a high-performance, easy-to-operate, mobile IGRA-type tuberculosis infection detection system
In order to popularize the popularization of IGRA in China, Lou Jianrong summed up the following points: First, all core materials of IGRA must be independently developed; second, IGRA testing costs must be reduced to large-scale screening. Under the cost; third, IGRA testing equipment must be mobile, portable belt; Fourth, the performance of IGRA testing products must reach international standards.
These four points are easy to understand, but they are not easy to do. Leidebio team graduated more than half of the graduates and above, in the core raw material production, each step of the design, research and development ideas can not be biased, in order to ensure that the final product can be popular. In the development process, it is necessary to consider how to ensure that the reagents are sensitive, efficient, and can cover a wide range of HLA populations, easy to operate, long-term stable, and how to implement the application without laboratory conditions. The research and development difficulties to truly popularize IGRA detection are numerous. After six years of efforts by the Leidebio team, the AIMTB M. tuberculosis-specific cellular immune response test kit (ELISA) was developed.
AIMTB is a tuberculosis test kit based on the principle of IGRA technology. It can realize immediate detection or concentrated storage after stimulation with a blood collection of only 1.8ml. The specificity is 93.6%, the sensitivity is 85.3%, and the sensitivity exceeds the international similar products. . AIMTB is independently developed by Leidebio and is currently CE certified in Europe.
LeidebioAIMTB Tuberculosis Infection Detection System
What’s more commendable is that AIMTB is very simple to operate, and medical staff can learn to use it after a few minutes of training. The results are fast and accurate, and users can get results directly within 24 hours. The device can be used not only for clinical TB diagnosis, but also for screening applications, and can be applied to grassroots scenes such as schools and health institutions.
At present, Leidebio’s AIMTB tuberculosis infection detection system has been promoted in overseas markets, laying a solid sales base in Southeast Asian countries and African countries. China is expected to go on sale before the end of this year.
Focus on IVD diagnosis, find new biological targets, and improve the diagnostic rate of rheumatoid arthritis by 15%
AIMTB is the core product of Leidebio, but as a company focused on IVD diagnostics, Leidebio’s IVD products are not limited to this. Most of the traditional IVD diagnosis uses the static analysis of biomarkers as the core of diagnosis. Lou Jianrong attempts to achieve higher precision in vitro diagnosis through the “dynamic + static” innovative full immune diagnosis. The static diagnosis is the traditional biomarker analysis, the dynamic diagnosis is the functional analysis of the immune cells, and the dynamic and static combination provides more diagnostic information for the clinic.
In the diagnosis of rheumatoid arthritis (RA), most of the international use of CCP (cyclic citrullinated peptide) or RF (rheumatoid factor) as biomarkers, but found in the clinical practice of CCP and RF does not effectively screen out all RA patients. Although the CCP recommended by the international guidelines has good specificity, because some patients have no anti-CCP antibody in the serum, 30-40% of RA patients can not be detected, which leads to clinical missed diagnosis and delay of the disease.
Leidebio used a large number of comparative studies on CCP to screen a library of peptides containing specific citrulline sites, and then compared the citrulline-containing peptide library with the serum of patients with rheumatoid arthritis, and finally screened the most relevant protein. The marker, named RA_CP (rheumatoid-like protein). The detection of this protein can effectively improve the sensitivity of RA diagnosis. In CCP-negative RA serum, RA_CP can still detect about 50% of clinical RA confirmed cases, which makes up for the deficiency of CCP negative test results in RA patients. More valuable is that the citrullinated protein antigen often precedes the appearance of antibodies. In principle, RA_CP can be used for the diagnosis of early rheumatoid arthritis.
It is worth mentioning that RA_CP has been approved by CFDA in China and has obtained CE certification. RA_CP is the first high-sensitivity innovative product in the world to detect rheumatoid arthritis by antigen. It has a great lead in early diagnosis and treatment of difficult cases. It has significantly improved the detection sensitivity of current gold standards through the use of CCP. Authorized by experts.
Regarding the future, Leidebio will create an IVD brand in the field of influential immune systems worldwide. Recently, the company continued to focus on the quality of its products and broaden its domestic and international markets while ensuring large-scale production of its products. Currently, Leidebio has completed the Angel Wheel, Round A and Round B financing, and a new round of financing is expected to start next year.