Rapamycin, known as the "miracle drug", has made another contribution, and researchers have discovered new uses for the treatment of lupus erythematosus.
Recently, Bao Chunde, chief physician of the Department of Rheumatology at Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, and Zhang Xiaoming, a researcher at the Shanghai Pasteur Institute of the Chinese Academy of Sciences, jointly published a research paper entitled "Highly Activated and Dysfunctional MTORC1 Pathway in Atypical Memory B Cells of Lupus-associated Atypical Memory B" in Annals of the Rheumatic Diseases, a journal ranked first in the field of international rheumatology. Their study found that a high proportion of atypical memory B cells (AtMs) are present in patients with systemic lupus erythematosus (SLE), which is closely associated with disease activity in lupus, suggesting that rapamycin may be a new potentially effective treatment for SLE.
Bao Chunde and Zhang Xiaoming are the co-corresponding authors of the paper, and the co-first authors are Wu Chunmei, ph.D. in the Department of Rheumatology, Renji Hospital, Fu Qiong, deputy chief physician, and Guo Qiang, chief physician.
The body's immune system is responsible for immune defense, immune surveillance and immune regulation, and correctly identifying the "self" and "non-self" is a key feature of the immune system to play a normal function. If immunomodulatory function is disrupted, the body produces an abnormal immune response and inflammation against the components of the "self", and it will suffer from autoimmune diseases.
Bao Chunde introduced that in the 1980s, Professor Chen Shunle of Renji Hospital found that the incidence of systemic lupus erythematosus was about 70/100,000. Systemic lupus erythematosus (SLE) often occurs in women of childbearing age, and there are a variety of autoantibodies in the patient's body, which is clinically manifested as multi-system multi-organ involvement, and the treatment is not timely, and the failure of various organs throughout the body such as the kidney, nervous system, heart and lung, and blood system can occur, and even cause patient death.
However, the etiology of SLE is complex, and the specific pathogenesis is not yet clear, resulting in limited clinical treatment methods.
B lymphocytes derived from the bone marrow of mammals are an important class of immune cells that can produce autoantibodies under disease conditions and play a very important role in the development of SLE. Targeted drugs targeting B cells can be used to treat SLE, however, indiscriminate and complete clearance of B cells can also have serious side effects.
Therefore, it is extremely important to look for specific subpopulations of B cells associated with disease and to study their function and pathogenic effects.
Bao Chunde's team and Zhang Xiaoming's research group found that the proportion of atypical memory B cells (i.e., AtMs) in the peripheral blood of newly untreated SLE patients increased. This group of cells has unique cellular phenotype, molecular, and functional characteristics, is highly positively correlated with SLE disease activity, and is highly infiltrated in the renal tissue of patients with lupus nephritis, suggesting that AtMs are a group of lupus-specific B cells with pathogenic characteristics.
After in-depth research using high-throughput sequencing technology, researchers found that the presence of rapamycin target protein complex 1 (mTORC1) signaling pathway in AtMs is highly activated.
Rapamycin, a metabolite secreted by soil Streptomyces found in the soil of Easter Island in Chile, is a mTORC1-specific inhibitor and is currently mainly used clinically for anti-rejection after organ transplantation.
It is worth mentioning that in recent years, rapamycin has been found to be a new use in anti-aging, inhibition of pancreatic cancer development, treatment of blood diseases, cerebral malaria and other fields, and has attracted the attention of scientists, and the industry has called it a "miracle drug".
This study found that rapamycin can effectively block The production of AtMs, and can effectively inhibit the differentiation of AtMs to form plasma cells and secrete autoantibodies, indicating that blocking the mTORC1 pathway is an important and feasible strategy for effectively removing pathogenic B cell AtMs in vivo, further suggesting that rapamycin may be a new potential effective therapeutic drug for SLE.
As a national clinical key specialty, the Rheumatology Department of Renji Hospital covers all diseases of rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid antibody syndrome, inflammatory myopathy, Behcet's disease, adult Steele's disease, etc. After more than 30 years of continuous exploration, many pioneering work has been completed, and the clinical and scientific research level has reached the international level.
The research was supported by Professor Shen Nan, and was also funded by the 973 Project of the Ministry of Science and Technology, the National Natural Science Foundation of China, the Pilot Program of the Chinese Academy of Sciences and the "Innovation Cross Team".
Author: Tang Wenjia, Ye Jiaqi, Yuan Huiyun
Editor: Yingjie Zhu
Editor-in-charge: Xu Qimin
*Wenhui exclusive manuscript, please indicate the source when reprinting.