lewis-x-antigen and Tuberculosis--Pulmonary

Protective host responses in those exposed to or infected with tuberculosis (TB) is thought to require a delicate balance between pro-inflammatory and regulatory immune responses. Myeloid-derived suppressor cells (MDSCs), regulatory cells that dampen T-cell function, have been described in cancer and other infectious diseases but there are limited data on their role in TB.. Peripheral blood was obtained from patients with active pulmonary TB and participants with presumed latent TB infection (LTBI) from Cape Town, South Africa. MDSC frequency was ascertained by flow cytometry. Purified MDSCs were used to assess (i) their suppressive effect on T-cell proliferation using a Ki67 flow cytometric assay and (ii) their effect on mycobacterial containment by co-culturing with H37. Collectively, these data suggest that circulating MDSCs are induced during active TB disease and can functionally suppress T-cell proliferation and subvert mycobacterial containment. These data may inform the design of vaccines and immunotherapeutic interventions against TB but further studies are required to understand the mechanisms underpinning the effects of MDSCs.

Topics: Adult; Cell Proliferation; Coculture Techniques; Female; Granulocytes; HLA-DR Antigens; Humans; Hydrolases; Latent Tuberculosis; Lewis X Antigen; Macrophages; Male; Microbial Viability; Middle Aged; Mycobacterium tuberculosis; Myeloid-Derived Suppressor Cells; Preliminary Data; Sialic Acid Binding Ig-like Lectin 3; South Africa; T-Lymphocytes; Tuberculosis, Pulmonary

Tuberculosis remains a global health problem caused by infection with Mycobacterium tuberculosis. Numerous studies have established a close correlation between the development of tuberculosis and the roles of neutrophils. Recently, a distinct population of CD15+ granulocytes was found to be present in the peripheral blood mononuclear cell (PBMC) fraction in humans. This population of granulocytes, termed low-density granulocytes (LDGs), was reported to be elevated and associated with disease activity or severity in a number of different conditions including SLE, asthma and HIV infection. However, both the frequency and clinical significance of LDGs associated with tuberculosis are unclear. Here we determined LDG levels and made comparisons between subjects with active pulmonary tuberculosis (PTB) and healthy controls, between PTB patients with mild-to-moderate disease and patients with advanced disease, and among PTB patients following anti-tuberculous therapy of varying durations. The direct correlation between M. tuberculosis infection and LDG levels was confirmed by in vitro infection of whole peripheral blood and isolated granulocytes with mycobacteria. Our results demonstrated that PBMCs in PTB patients contained significantly elevated percentages of LDGs compared with control subjects. LDGs in tuberculosis expressed higher levels of activation markers compared to normal-density granulocytes (NDGs). M. tuberculosis induced the generation of LDGs in both whole blood and isolated NDGs from control subjects, which suggests that LDGs associated with M. tuberculosis infection are likely to originate from in situ activation. Furthermore, our results revealed that the frequency of LDGs is associated with the severity of tuberculosis.

Topics: Adult; Female; Granulocytes; Humans; Leukocyte Count; Lewis X Antigen; Male; Middle Aged; Mycobacterium tuberculosis; Reactive Oxygen Species; Severity of Illness Index; Tuberculosis, Pulmonary

A 43-year-old female was admitted to our hospital with mild cough, sputum and right chest pain. The chest X-ray revealed an inhomogeneous shadow in the right upper lung field and mediastinal lymphadenopathy. At first we considered the patient had bronchogenic carcinoma, as her serum CA19-9 and SLX levels were high and the right upper bronchus was obstructed by necrotic tissues. However bronchoscopic specimen showed necrotizing epithelioid cell granulomas and Mycobacterium tuberculosis was detected, and her disease was diagnosed as endobronchial tuberculosis. The case responded well to anti-tuberculosis chemotherapy. The differential diagnosis between bronchogenic carcinoma and endobronchial tuberculosis was very difficult in this case because of high serum level tumor marker and endoscopic findings, which turned to normal after treatment. We discussed the cause of high serum level of CA19-9 and SLX in nonmalignant lung disease.

Topics: Adult; Bronchial Diseases; CA-19-9 Antigen; Female; Humans; Lewis X Antigen; Tuberculosis, Pulmonary

Serum tumor markers (CEA, SLX, CA125) were evaluated in 123 patients with active pulmonary tuberculosis. The results were as follows: Elevated serum CEA, SLX and CA125 levels were found in 16.9%, 39.5% and 44.4%, respectively, of patients with active pulmonary tuberculosis. Markedly elevated serum CA125 levels were found in some cases. On chest X-ray films, the factors associated with elevation of serum tumor marker levels were examined. Serum CEA and SLX levels were correlated with the extent of disease. Pleural effusion had no influence on serum tumor marker levels. Serum SLX levels were higher in patients without a tuberculous cavity than in those with a tuberculous cavity. After therapy with antituberculous drugs, the mean values of serum SLX and CA125 levels significantly decreased. The decrease in mean value of serum CEA levels was not significant, but in 4 of 8 cases, elevated serum CEA levels were normalized after therapy. On the other hand, two cases with increased serum CEA or SLX level died of respiratory failure. These results suggest that to follow up patients with elevated serum tumor markers is useful for the evaluation of disease activity of pulmonary tuberculosis. Further elevation of serum tumor marker levels after antituberculous therapy may indicate the presence of cancer or deterioration of the disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Lewis X Antigen; Male; Middle Aged; Tuberculosis, Pulmonary