Discussion 1.1 Role of TNFα in host immunity against TB TNFα is a cytokine that plays a key role in the 3 steps of host immune response against TB. In intrinsic immunity, Mycobacterium tuberculosis can be phagocytosed by macrophages, which can stimulate the release of TNFα and recruit inflammatory cells such as neutrophils to kill Mycobacterium bovis. In acquired immunity, TNFα can cooperate with gamma interferon (IFNγ) to activate macrophages to kill Mycobacterium bovis. In granuloma formation, TNF α recruits naïve macrophages to the nascent granuloma and maintains the integrity of the nodule granuloma by inhibiting the over-activation of the Th1 immune response. nodules are easily induced by the absence or impaired binding of TNFα in the host. 1.2 TNFα deficiency increases the risk of tuberculosis TNFα deficiency has been shown to predispose to tuberculosis in animal studies and clinical studies. The literature reports that TNFα knockout mice infected with Mycobacterium tuberculosis have a significantly higher bacterial load and mortality rate than control mice. Clinical studies suggest that the incidence of TB in patients with rheumatoid arthritis treated with TNF inhibitors is four times higher than that in patients not treated with TNF inhibitors. A Meta-analysis showed that the risk of TB reignition was 4.68 times higher in patients using TNFα inhibitors in various clinical situations than in non-users [1]. The incidence of TB induction varies between the different types of TNFα antagonists, with monoclonal biologics having a higher probability of TB induction than receptor inhibitors, with probabilities of 136/100,000 patient-years and 144/100,000 patient-years with infliximab and adalimumab, respectively, compared with only 39/100,000 patient-years with the receptor inhibitor etanercept. The reason is that in the mechanism of inhibition of transmembrane TNF-binding cells by TNF inhibitors, etanercept has no complement-dependent cytotoxic effect and counter-signaling effect, and antibody-dependent cell-mediated cytotoxicity is weak, which is less likely to cause cell lysis , and the inhibition is weak, so the incidence of nodules is low [2]. In addition, TNFα inhibitors can also induce nontuberculous mycobacteriosis, and Shimizu et al [3] reported a case of pleurisy induced by TNFa inhibitors with Mycobacterium avium as the pathogen. In the present case, the patient had infliximab (trade name class gram) induced tuberculosis. The characteristics of this case of tuberculosis included: extensive tuberculosis lesions accumulating in the lungs, thoracic spine and lymph nodes; poor treatment efficacy; and co-infection with bacteria. All were considered to be related to the patient’s reduced immunity after the use of biological agents. Heiko et al [4] explored in depth the immunological mechanism of TB development in this patient and found that TNFα inhibitors caused a decrease in antigen-specific effector CD8+ T lymphocytes and a decrease in antimicrobial viability, which may be a key mechanism of impaired host immunity. key mechanism. 1.3 Problems to be noted in the use of biological agents Biological agents are now widely used in the treatment of rheumatic diseases such as rheumatoid arthritis and ankylosing spondylitis, psoriasis, and inflammatory bowel disease [5-7]. However, TNFα inhibitors are exactly like a double-edged sword that may induce infectious diseases while treating autoimmune diseases. Adverse reactions to TNFα inhibitors inducing tuberculosis should be taken into account in their use. In such patients, the risk benefit needs to be carefully assessed before the use of biological agents, and screening procedures need to be completed [8]. The IGRA is more specific than the PPD skin test because it uses the antigens ESAT-6 and CF-10, which are present in M. tuberculosis but not in BCG, to stimulate monocytes and detect the production of IFNγ released from them. The presence of active or latent tuberculosis infection requires anti-tuberculosis treatment before the use of biological agents, as this reduces the risk of active tuberculosis in those who use them [9]; when using biological agents, the type of agent is carefully selected, and the use of receptor inhibitors is preferable from the perspective of reducing adverse effects and preventing tuberculosis; if tuberculosis occurs after the use of biological agents, the biological agents need to be discontinued immediately and a rational plan developed as soon as possible. Strong anti-tuberculosis treatment. According to the guidelines for the use of biologics [10], patients with tuberculosis induced by the use of TNFα antagonists can restart the treatment with biologics after the end of the anti-tuberculosis course. However, another literature [11] states that active tuberculosis occurring during TNFα antagonist therapy may not be a contraindication to restarting biologic therapy before the end of TB treatment, especially in patients who have had good results on anti-TB therapy for at least 2 months but have a relapse of the underlying autoimmune disease. 1.4 Research outlook There are still many basic and clinical issues related to TNFα-induced TB that need to be investigated. For example, the introduction of more sensitive and specific immunological tests to diagnose latent TB infection in such patients, the optimization of the regimen and course of prophylactic chemotherapy in patients with underlying TB infection, the best time to reintroduce biologics after anti-TB treatment in patients receiving biologics, and the changes in cellular immunity in patients receiving biologics all deserve further investigation. 1.5 Humanistic insights of this case Such cases can also bring us some humanistic insights. In recent years, the doctor-patient relationship in China has been tense, with disputes and even criminal cases occurring. The cases of killing doctors in China have even attracted the attention of the international famous magazine Lancet. One of the defendants in the 2012 case at Harbin Medical University was an ankylosing spondylitis patient who developed tuberculosis after using analogs. Patients with TNFα antagonist-induced tuberculosis are often complex, financially costly, and often under-treated. Tuberculosis in China is managed under a centralized system, and treatment of tuberculosis and compulsory spondylitis is often not in the same medical unit, so patients need to travel to and from their treatment. Without adequate medical coverage, poor communication between doctors and patients can easily lead to doctor-patient disputes and even criminal tragedies. While calling for an improved medical environment, it would be helpful to strengthen the informed consent process, improve the service concept, learn from accidents, and purchase accident insurance for doctors to prevent doctor-patient disputes. Some authors [12] have particularly emphasized the importance of focusing on every detail of consultation and treatment activities to avoid doctor-patient disputes. In this case, the medical and nursing staff of the ward paid great attention to communication with the patient and family members, took great pains to provide informed consent for the use of anti-tuberculosis drugs, surgery, and other diagnostic measures, as well as patient prognosis, focused on the health economics of drug use, and made every effort to be careful and meticulous in consultation and treatment. The Department of Tuberculosis, the Department of Orthopedics and the Department of Rheumatology cooperate with each other to provide consultation and referral facilities for patients as much as possible. After all these efforts, the diagnosis and treatment measures were approved by the patient and his family, and the patient was finally cured of tuberculosis. From this case, we can see that strengthening doctor-patient communication and medical multidisciplinary cooperation is the key to avoiding doctor-patient disputes.