Toll-like receptor-2 Arg753Gln and Arg677Trp polymorphisms and susceptibility to pulmonary and peritoneal tuberculosis.

Recent evidence suggests that toll-like receptor-2 (TLR2) is important for host defense against Mycobacterium tuberculosis (MTB). TLR2 polymorphisms have shown significant impact on susceptibility or resistance to tuberculosis (TB). This case-control study aims to determine the influence of TLR2 (Arg753Gln and Arg677Trp) polymorphisms on the susceptibility to develop pulmonary or peritoneal TB. Genotyping of TLR2 (Arg753Gln and Arg677Trp) polymorphisms was carried out on 52 patients with pulmonary TB, 44 patients with peritoneal TB, and 50 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). There was a significant association between the GA genotype (heterozygous mutant) of TLR2 Arg753Gln polymorphism and the risk of infection with pulmonary TB (p = 0.003, OR = 4.83) and TB peritonitis (p = 0.003, OR = 6.2). Differences in the genotype frequencies of TLR2 Arg677Trp polymorphisms between patients with pulmonary or peritoneal TB and healthy controls were not detected. GA753 TLR2 polymorphism may play a role in the susceptibility to pulmonary and peritoneal TB infection. Further studies on a large number of ethnically diverse patient cohorts may help to confirm the possible effect of these polymorphisms on the susceptibility to pulmonary and peritoneal TB.

Disseminated tuberculosis after pregnancy progressed to paradoxical response to the treatment: report of two cases.

BACKGROUND: Early postpartum women are more likely to develop tuberculosis than nonpregnant women mainly due to immune reconstitution after delivery. Paradoxical response (PR) during antituberculosis treatment also arises via recovery from immunosuppression. However, no study focused on PR during antituberculosis treatment in a postpartum patient has been reported. CASE PRESENTATION: We present two sequential cases (Patient 1: 26-year-old; Patient 2: 29-year-old) of postpartum tuberculosis with pulmonary and extrapulmonary lesions (Patient 1: peritonitis; Patient 2: psoas abscess secondary to spondylitis). Both cases progressed to PR (worsening of pre-existing lung infiltrations (Patients 1, 2) and new contralateral effusion (Patient 2)) in a relatively short time after initiation of treatment (Patient 1: 1 week; Patient 2: 3 weeks), suggesting that immune modulations during pregnancy and delivery may contribute to the pathogenesis of both disseminated tuberculosis and its PR. The pulmonary lesions and effusion of both cases gradually improved without change of chemotherapy regimen. CONCLUSION: Physicians should recognize PR in tuberculosis patients with postpartum and then evaluate treatment efficacy.

Mucosal-associated invariant T-cell function is modulated by programmed death-1 signaling in patients with active tuberculosis.

RATIONALE: Mucosal-associated invariant T (MAIT) cells have been proven to play an important role in host defense against mycobacterial infection in animal infection models; however, the functional role of MAIT cells in patients with active tuberculosis (TB) is still largely unknown. OBJECTIVES: To understand the clinical features and functions of MAIT cells in patients with active TB. METHODS: MAIT cells were analyzed in patients with pulmonary TB, tuberculous pleurisy, and tuberculous peritonitis by flow cytometry. The functions of MAIT cells were compared between patients with active TB and healthy control subjects. MEASUREMENTS AND MAIN RESULTS: The frequency of MAIT cells was significantly reduced both in peripheral blood from patients with active pulmonary TB (P < 0.0001) and in tuberculous pleural effusions compared with healthy control subjects but not in ascitic fluids from patients with tuberculous peritonitis. A comparison of bacillus Calmette-Guérin (BCG)-stimulated cytokine production showed that patients with active TB had significantly higher production of IFN-γ (P = 0.0034) and tumor necrosis factor (TNF)-α (P = 0.0399) compared with healthy control subjects. In contrast, when MAIT cells were stimulated with Escherichia coli, patients with active TB had significantly lower production of IFN-γ (P = 0.0007) and TNF-α (P = 0.0032). MAIT cells in patients with active TB exhibited elevated expression of programmed death-1 (PD-1) (P = 0.0015), and blockade of PD-1 signaling resulted in a significantly higher frequency of BCG-stimulated IFN-γ production in MAIT cells (P = 0.0178). CONCLUSIONS: MAIT-cell immune response to antigen stimulation in patients with active TB is regulated by PD-1, which could be a potential target for TB immunotherapy.

[Changes parameters of humoral immunity in abdominal tuberculosis].

We measured the levels of IL-1beta, IL-8, and TNF-alpha, as well as humoral immunity in blood serum of patients with abdominal tuberculosis before and after Koch's test. The content of TNF-alpha increased 2.5 times, the content of IL-8 decreased almost twice, and concentration of IL-1beta decreased three times compared to the controls. We found that Koch's test exacerbates pathogenic manifestations of chronic inflammation which shows changes in cytokine spectrum of blood and allows us to refine diagnosis of abdominal tuberculosis.

Assessment by meta-analysis of interferon-gamma for the diagnosis of tuberculous peritonitis.

AIM: To investigate the performance and diagnostic accuracy of interferon-gamma (IFN-γ) for tuberculous peritonitis (TBP) by meta-analysis. METHODS: A systematic search of English language studies was performed. We searched the following electronic databases: MEDLINE, EMBASE, Web of Science, BIOSIS, LILACS and the Cochrane Library. The Standards for Reporting Diagnostic Accuracy initiative and Quality Assessment for Studies of Diagnostic Accuracy tool were used to assess the methodological quality of the studies. Sensitivity, specificity, and other measures of the accuracy of IFN-γ concentration in the diagnosis of peritoneal effusion were pooled using random-effects models. Receiver operating characteristic (ROC) curves were applied to summarize overall test performance. Two reviewers independently judged study eligibility while screening the citations. RESULTS: Six studies met the inclusion criteria. The average inter-rater agreement between the two reviewers for items in the quality checklist was 0.92. Analysis of IFN-γ level for TBP diagnosis yielded a summary estimate: sensitivity, 0.93 (95%CI, 0.87-0.97); specificity, 0.99 (95%CI, 0.97-1.00); positive likelihood ratio (PLR), 41.49 (95%CI, 18.80-91.55); negative likelihood ratio (NLR), 0.11 (95%CI, 0.06-0.19); and diagnostic odds ratio (DOR), 678.02 (95%CI, 209.91-2190.09). χ(2) values of the sensitivity, specificity, PLR, NLR and DOR were 5.66 (P = 0.3407), 6.37 (P = 0.2715), 1.38 (P = 0.9265), 5.46 (P = 0.3621) and 1.42 (P = 0.9220), respectively. The summary receiver ROC curve was positioned near the desirable upper left corner and the maximum joint sensitivity and specificity was 0.97. The area under the curve was 0.99. The evaluation of publication bias was not significant (P = 0.922). CONCLUSION: IFN-γ may be a sensitive and specific marker for the accurate diagnosis of TBP. The level of IFN-γ may contribute to the accurate differentiation of tuberculosis (TB) ascites from non-TB ascites.

[The symptoms and surgical tactics for complicated forms of the abdominal cavity tuberculosis].

The results of treatment of 12 patients, suffering complicated forms of abdominal tuberculosis and external intestinal fistulas, were presented. Late diagnosis of abdominal tuberculosis in the patients, suffering the complications phase of the disease, is caused by unclear symptoms presence in early stages of the disease. Clinical and laboratory indices in peritonitis of a phthisis origin are nonspeciphic. In 91% of patients, admitted to the hospital for complicated forms of abdominal tuberculosis and external intestinal fistulas, the operative treatment was indicated. Surgical intervention (more frequently right-sided hemicolectomy, enterostomy, the abscesses opening, the caseously-changed lymph nodes excision, formation of anastomosis) was performed in 11 patients for peritonitis and external intestinal fistulas. The method of a secure invagination anastomoses formation was elaborated, permitting to perform primary restoration operations. An early diagnosis, early effective therapy and radical surgical intervention conduction for complicated abdominal tuberculosis promote the patients to survive.

Primary tuberculous peritonitis during infliximab therapy for Crohn's disease.

A 64 year old male patient suffering from Crohn's disease received infliximab therapy for a period of 5 months prior to presentation to our hospital. Due to the symptoms fever, ascites, and diffuse abdominal tenderness on palpation of unknown origin, a CT scan of the abdomen was performed and led to the suspected diagnosis of a peritoneal carcinomatosis. QuantiFERON™ test revealed a tuberculosis infection and molecular analyses of a peritoneal specimen obtained by laparoscopy clearly identified Mycobacterium tuberculosis DNA. Quadruple tuberculostatic therapy was initiated and the patient's condition continuously improved thereafter.

Multiple organ tuberculosis of lung, pleura, and peritoneum in ankylosing spondylitis during adalimumab therapy.

A case of multiple organ tuberculosis (TBc) involving lung, pleura, and peritoneum in a 39-year-old man with long-standing ankylosing spondylitis (AS) treated with adalimumab was presented. The relationship between antitumor necrosis factor-α (anti-TNF-α) therapy and TBc was also reviewed. This case illustrates that TBc can develop in multiple organs during adalimumab therapy, and thus, the awareness of serious complications of multiple organs and atypical extrapulmonary pattern of TBc during anti-TNF-α therapy needs to be increased.

Primary small intestinal natural killer/T cell lymphoma mimicking tuberculous peritonitis: report of a case and review of the literature.

Extranodal natural killer/T cell lymphoma is very rarely encountered in clinical practice. It has a high mortality rate and very short median survival. Early diagnosis of these rare tumors, especially those originating from the small intestine, is usually difficult because of its nonspecific symptoms. Herein, we describe a case of a primary small intestinal natural killer/T cell lymphoma in a 52-year-old man who presented with abdominal fullness and weight loss. The clinical symptoms, elevation of serum levels of cancer antigen-125, and presence of ascites initially led to the suspicion of tuberculous peritonitis. Abdominal computed tomography scan demonstrated a hypodense tumor in the jejunum. Finally, the tumor was surgically confirmed to be a natural killer/T-cell lymphoma. Although aggressive chemotherapy was prescribed, the patient subsequently died of disease progression. In addition, we also review the English literature on this rare disease.

[Tuberculous peritonitis during etanercept therapy for rheumatoid arthritis].

In August 2010, a 73-year-old woman with rheumatoid arthritis receiving etanercept (ETN) therapy for two years, developed high-fever and abdominal fullness. Though she had not been exposed to tuberculosis, isoniazid prophylaxis was administrated. Antibiotics were not effective. CT images revealed the massive ascites and peritonitis, and Ga scintigraphy demonstrated notable uptake in the peritoneum. Ascites analysis showed an elevated adenosine deaminase activity value (104.9 IU/l) without malignant cells. Moreover, PCR and culture for Mycobacterium tuberculosis were positive. Finally, a diagnosis of tuberculous peritonitis was established. After initiating a standard anti-tuberculosis regimen with four drugs, her clinical condition ameliorated and ascites promptly regressed. Although the tuberculous peritonitis during ETN therapy is rare, this report emphasized the importance of initial suspicion of tuberculosis in these patients with tumor necrosis factor inhibitors such as ETN.

Unmasking tuberculosis-associated immune reconstitution inflammatory syndrome in HIV-1 infection after antiretroviral therapy.

The exaggerated immune response to the subclinical opportunistic microorganisms or their antigens can be found in HIV-1 infected patients after receiving antiretroviral (ARV) therapy. We report a case of unmasking tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in the HIV-1 infected patient who had no previous history of mycobacterial infection. She had tuberculosis of intestines, peritoneum and mesenteric glands within 2 months of ARV. However, her sputum acid-fast bacilli stain, sputum, blood and cervical lymph node aspiration cultures for mycobacterium were negative. Her CD4 cell count increased of from 46 cells/microL at baseline before receiving ARV to 155 cells/microL at month 6 of ARV. In addition, her plasma pro-inflammatory (IFN-gamma and TNF-alpha) and anti-inflammatory (IL-10) cytokine measurement was supported the occurrence of immune restoration reaction. Therefore, the changing in these cytokine profiles may be an important marker of developing unmasking TB-IRIS.

Ascites and highly elevated CA-125 levels in a case of peritoneal tuberculosis.

Peritoneal tuberculosis (PT) is uncommon in industrialized countries. We report the case of a 35-y-old female with a 1-y history of abdominal discomfort, ascites, systemic symptoms, and highly elevated CA-125 suggesting malignancy, in whom the diagnosis of PT was considered. Both clinical symptoms and CA-125 levels regressed under tuberculostatic treatment.

Complement and immunoglobulin levels in serum and ascitic fluid of patients with spontaneous bacterial peritonitis, malignant ascites, and tuberculous peritonitis.

BACKGROUND: We determined complement and immunoglobulin levels in ascitic fluid and serum of 47 patients with spontaneous bacterial peritonitis, malignant ascites, or tuberculous ascites. METHODS: Paracentesis was done to confirm the underlying cause of ascites. Biochemical, hematologic, and microbiologic investigations were also done. RESULTS: The highest serum and ascitic fluid C3 and C4 levels and ascitic fluid IgM, IgA, and IgG levels were found in patients with tuberculosis. Ascitic fluid C3 level was found to be higher in the tuberculous group than in the patients with spontaneous bacterial peritonitis or malignant ascites. Ascitic fluid C4 levels were higher in patients with tuberculosis than in those with spontaneous bacterial peritonitis. CONCLUSION: We believe that further studies of the in vivo kinetics of immunoglobulins and complement in ascitic fluid of various causes are necessary for a better understanding of the host defense mechanisms of these fluids.

Increased Bcl-2 and reduced Bax expression in infected macrophages in slowly progressive primary murine Mycobacterium tuberculosis infection.

Mycobacterium tuberculosis (MTB) persists in host macrophages (Mphis) because it has developed mechanisms to escape Mphi killing. In vitro studies have shown that MTB can induce and inhibit apoptosis by causing the expression of Bax and Bcl-2, respectively, suggesting that the infected cells' fate depends on pro- and antiapoptotic signals. In the present study, we investigated the role of Bcl-2 in MTB infection in situ. The aim was to study the pattern and distribution of Bcl-2 and Bax in cellular infiltrates of MTB-infected B6D2F1 hybrid mice and correlate the expression with the presence of MTB antigens (MAgs). Using formalin-fixed lung tissues (n = 45), our results showed a significant difference in the percentage of Mphis stained for Bcl-2 or MAgs and Bax (P < 0.0001). Bcl-2 expression was increased in a population of Mphis and corresponded in intensity, colocalization and percentage with that of MAgs on the same cells, while Bax expression was reduced. In lymphocyte aggregates, Bcl-2 and Bax did not show any differences. We conclude that overexpression of Bcl-2 in Mphis containing MTB may be associated with intracellular survival of the bacilli, thus demonstrating one way by which MTB can escape the host's cellular response and killing.

Genetic aspects and microenvironment affect expression of CD18 and VLA-4 in experimental tuberculosis.

Control of infection by Mycobacterium tuberculosis is dependent on macrophage activation and efficient migration of effector T-cell populations. Lymphocyte differentiation is associated with changes in cell surface phenotype and alterations in the migratory pattern of these cells. In this study, we investigated the expression of adhesion receptors involved in activation and migration process in experimental tuberculosis. We observed that susceptible BALB/c mice infected with virulent M. tuberculosis by intraperitoneal route presented downmodulation of very late antigen 4 (VLA-4) and unchanged levels of CD18 and CD44hi on peritoneal lymphocytes. On the other hand, lymphocytes from resistant C57BL/6 mice infected by the same route showed unchanged levels of VLA-4 and upregulation of CD18 and CD44hi. However, when BALB/c mice were infected by intratracheal route, lung lymphocytes presented a different pattern of CD18, CD44hi and VLA-4 expression from that observed on peritoneal cells, characterized by unchanged levels of VLA-4 and upregulation of CD18 and CD44hi- coincidentally the same phenotype found on peritoneal cells from C57BL/6. These results suggest that susceptibility and resistance to M. tuberculosis infection, depending on the experimental model, are related to the expression of CD18, CD44hi and VLA-4. Moreover, the microenvironment at the site of infection seems to differentially regulate the expression of these receptors. Thus, the up- or downmodulation of these adhesion receptors is probably associated with differential recruitment of T cells at the site of infection, which may or may not mediate protection in experimental tuberculosis.