RMHP_A_354377 611..627

Background Tuberculosis (TB) is an infectious disease that poses a significant health threat and is one of the leading causes of death worldwide. Diabetes mellitus (DM) has high morbidity and mortality rates. Previous studies have reported that comorbidities can influence one another and aggravate immune disorders. A systematic and comprehensive evaluation of the immune status of patients with TB and DM (TB-DM) is helpful for early clinical immune intervention and for promoting the recovery of patients with TB-DM. Methods This study included 159 patients with TB without DM (TB-NDM) and 168 patients with TB-DM. Interferon-γ (IFN-γ) release assays (IGRAs) and TB-specific antibodies against 38kD+16kD proteins were used to detect humoral and cellular immune responses. Flow cytometry was used to analyze the absolute counts of the lymphocyte subsets. Results There was no significant difference in the positive rate of enzyme-linked immunospot (ELISPOT) assays, enzyme linked immunosorbent assay (ELISA), and 38kD+16kD antibodies between the TB-DM and TB-NDM groups. Pulmonary lobe lesion and cavity formation rates were significantly higher in patients with TB-DM with poor glycemic control than patients with TB-NDM and TB-DM with normal glycemic control. The absolute counts of T lymphocytes, CD8+ T lymphocytes, and B lymphocytes in patients with TB-DM were markedly lower than those in patients with TB-NDM. The absolute counts of T lymphocytes and CD8+ T lymphocytes in patients with TB-DM and hyperglycemia were lower than those in patients with euglycemia. Linear regression analysis revealed that the absolute counts of total T lymphocytes, CD8+ T lymphocytes, and NK cells in patients with TB-DM significantly decreased with increasing fasting blood glucose (FBG) levels. Conclusion Hyperglycemia is a risk factor for pulmonary cavity formation and lobe lesions in patients with TB-DM and suppresses the absolute counts of total T lymphocytes, CD8+ T lymphocytes, and NK cells in patients with TB-DM. The potential mechanism may involve the downregulation of innate and adaptive immune responses.

[1]  T. Petnak,et al.  Prevalence of Diabetes Mellitus in Patients with Tuberculosis: A Prospective Cohort Study. , 2022, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[2]  Yan Liang,et al.  A peptide-based vaccine ACP derived from antigens of Mycobacterium tuberculosis induced Th1 response but failed to enhance the protective efficacy of BCG in mice. , 2021, The Indian journal of tuberculosis.

[3]  Yoon Mi Shin,et al.  Clinical Factors Associated with Cavitary Tuberculosis and Its Treatment Outcomes , 2021, Journal of Personalized Medicine.

[4]  Xueqiong Wu,et al.  Differential Diagnosis of Latent Tuberculosis Infection and Active Tuberculosis: A Key to a Successful Tuberculosis Control Strategy , 2021, Frontiers in Microbiology.

[5]  Xueqiong Wu,et al.  Tuberculosis vaccine BCG: the magical effect of the old vaccine in the fight against the COVID-19 pandemic , 2021, International reviews of immunology.

[6]  Yan Liang,et al.  Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model , 2021, Frontiers in Immunology.

[7]  Xiaomei Wang,et al.  Chinese Traditional Medicine NiuBeiXiaoHe (NBXH) Extracts Have the Function of Antituberculosis and Immune Recovery in BALB/c Mice , 2021, Journal of immunology research.

[8]  J. Critchley,et al.  The Interaction of Diabetes and Tuberculosis: Translating Research to Policy and Practice , 2021, Tropical medicine and infectious disease.

[9]  Subhakar Kandi,et al.  Clinico-radiological profile and treatment outcome of pulmonary tuberculosis with and without type 2 diabetes mellitus. , 2020, The Indian journal of tuberculosis.

[10]  Xueqiong Wu,et al.  Is the tuberculosis vaccine BCG an alternative weapon for developing countries to defeat COVID-19? , 2020, Indian Journal of Tuberculosis.

[11]  M. Murray,et al.  Metformin enhances protection in guinea pigs chronically infected with Mycobacterium tuberculosis , 2020, Scientific Reports.

[12]  M. Ponnana,et al.  Enumeration of Lymphocyte subsets during follow-up in the pulmonary tuberculosis patients with co morbid diabetes mellitus. , 2020, Clinica chimica acta; international journal of clinical chemistry.

[13]  C. Wijmenga,et al.  Impact of Intermediate Hyperglycemia and Diabetes on Immune Dysfunction in Tuberculosis , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  N. Gandhi,et al.  Adults with Mycobacterium tuberculosis infection and pre-diabetes have increased levels of QuantiFERON interferon-gamma responses. , 2020, Tuberculosis.

[15]  R. Raqib,et al.  Slow radiological improvement and persistent low-grade inflammation after chemotherapy in tuberculosis patients with type 2 diabetes , 2020, BMC Infectious Diseases.

[16]  Z. Avaliani,et al.  THE RELATIONSHIP BETWEEN TYPE-2 DIABETES AND TUBERCULOSIS. , 2020, Georgian medical news.

[17]  Tewodros Shibabaw,et al.  Immunological Impacts of Diabetes on the Susceptibility of Mycobacterium tuberculosis , 2019, Journal of immunology research.

[18]  B. Restrepo,et al.  The re-emerging association between tuberculosis and diabetes: Lessons from past centuries. , 2019, Tuberculosis.

[19]  Laura R. Sadofsky,et al.  Effect of High Glucose on Human Alveolar Macrophage Phenotype and Phagocytosis of Mycobacteria , 2018, Lung.

[20]  Rusdiana,et al.  CD4 and Its Relevance to Advanced Glycation End Products in Tuberculosis Patients with Co-morbidity Diabetes , 2018, Open access Macedonian journal of medical sciences.

[21]  D. Lim,et al.  Functional status of immune cells in patients with long‐lasting type 2 diabetes mellitus , 2018, Clinical and experimental immunology.

[22]  D. Chandramohan,et al.  Risk of active tuberculosis among people with diabetes mellitus: systematic review and meta‐analysis , 2018, Tropical medicine & international health : TM & IH.

[23]  Xueqiong Wu,et al.  The current status, challenges, and future developments of new tuberculosis vaccines , 2018, Human vaccines & immunotherapeutics.

[24]  N. Probst-Hensch,et al.  Hyperglycaemia is inversely correlated with live M. bovis BCG‐specific CD4+ T cell responses in Tanzanian adults with latent or active tuberculosis , 2018, Immunity, inflammation and disease.

[25]  R. Hernández-Pando,et al.  Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis , 2018, Memorias do Instituto Oswaldo Cruz.

[26]  Frank B. Hu,et al.  Global aetiology and epidemiology of type 2 diabetes mellitus and its complications , 2018, Nature Reviews Endocrinology.

[27]  Hui Liang,et al.  T Cell Profile was Altered in Pulmonary Tuberculosis Patients with Type 2 Diabetes , 2018, Medical science monitor : international medical journal of experimental and clinical research.

[28]  S. Babu,et al.  Influence of diabetes mellitus on immunity to human tuberculosis , 2017, Immunology.

[29]  V. Viswanathan,et al.  Modulation of dendritic cell and monocyte subsets in tuberculosis-diabetes co-morbidity upon standard tuberculosis treatment. , 2016, Tuberculosis.

[30]  A. Tvinnereim,et al.  NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during Mycobacterium tuberculosis Infection , 2016, PLoS pathogens.

[31]  V. Viswanathan,et al.  Effect of standard tuberculosis treatment on naive, memory and regulatory T‐cell homeostasis in tuberculosis–diabetes co‐morbidity , 2016, Immunology.

[32]  S. Babu,et al.  Profiling leucocyte subsets in tuberculosis–diabetes co‐morbidity , 2015, Immunology.

[33]  T. Nutman,et al.  Type 2 diabetes mellitus is associated with altered CD 8 + T and NK cell function in pulmonary tuberculosis , 2014 .

[34]  H. Dockrell,et al.  Acquired immunodeficiencies and tuberculosis: focus on HIV/AIDS and diabetes mellitus , 2015, Immunological reviews.

[35]  L. Schlesinger,et al.  Impact of diabetes on the natural history of tuberculosis. , 2014, Diabetes research and clinical practice.

[36]  T. Nutman,et al.  Expansion of pathogen-specific T-helper 1 and T-helper 17 cells in pulmonary tuberculosis with coincident type 2 diabetes mellitus. , 2013, The Journal of infectious diseases.

[37]  J. Priatel,et al.  NKT Cells Are Required for Complete Freund’s Adjuvant-Mediated Protection from Autoimmune Diabetes , 2011, The Journal of Immunology.

[38]  I. Sugawara,et al.  Significant Increase in Natural-Killer T Cells in Patients with Tuberculosis Complicated by Type 2 Diabetes Mellitus , 2011, The Journal of international medical research.

[39]  M. Netea,et al.  The role of interferon-gamma in the increased tuberculosis risk in type 2 diabetes mellitus , 2008, European Journal of Clinical Microbiology & Infectious Diseases.

[40]  A. Sanduzzi,et al.  T lymphocyte phenotypic profile in lung segments affected by cavitary and non‐cavitary tuberculosis , 2003, Clinical and experimental immunology.

[41]  P. Bacchetti,et al.  Sample size calculations in clinical research. , 2002, Anesthesiology.

[42]  J. Locutura El inglés en Enfermedades Infecciosas y Microbiología Clínica , 2002 .

[43]  J. Locutura [English in Enfermedades Infecciosas y Microbiología Clínica]. , 2002, Enfermedades infecciosas y microbiologia clinica.

[44]  J. Flynn,et al.  Immunology of tuberculosis. , 2003, Annual review of immunology.

[45]  T. Yoshikawa,et al.  Infections in diabetes. , 2001, Infectious disease clinics of North America.

[46]  G. Puavilai,et al.  Diagnostic criteria for diabetes mellitus and other categories of glucose intolerance: 1997 criteria by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (ADA), 1998 WHO consultation criteria, and 1985 WHO criteria. World Health Organization. , 1999, Diabetes research and clinical practice.