Abstract
Background
Tuberculosis (TBC) in solid organ transplant recipients represents a severe complication. The incidence among transplant recipients is higher than in the general population, and ...the diagnosis and treatment remain challenging. We present a case of active disseminated tuberculosis in a kidney transplant recipient treated with an anti-CD40 monoclonal antibody, who had been previously exposed to an active form of the disease, but latent tuberculosis (LTBI) was repeatedly ruled out prior to transplantation. To the best of our knowledge, no other case has been reported in a patient treated with the anti-CD40 monoclonal antibody.
Case presentation
A 49-year-old patient, 1.5 years after primary kidney transplantation, presented with vocal cord problems, a dry irritating cough, and a sore throat. A detailed investigation, including a high-resolution chest CT scan, revealed the diagnosis of disseminated tuberculosis. The antituberculosis treatment consisting of rifampicin, isoniazid, pyrazinamide, and ethambutol was started immediately. The patient's condition became complicated by relapsing diarrhoea. The colonoscopy revealed a circular stenosis above Bauhin’s valve. Microscopical findings showed active colitis and vaguely formed collections of epithelioid macrophages without fully developed caseous granulomas and were consistent with the clinical diagnosis of tuberculosis. The antituberculosis treatment was subsequently enhanced by moxifloxacin and led to a great improvement in the patient’s condition.
Conclusion
In this case, false negativity of interferon-γ release assays and possibly higher risk for intracellular infections in patients on costimulatory signal blockers are discussed.
Rifapentine, a synthetic derivate of rifampicin which was developed in 1965, has interesting pharmacological properties, including a long terminal half-life (13 h, compared to 2-3 h for rifampicin) ...and promising bactericidal activity against Mycobacterium tuberculosis. Despite being approved in 1998 by the US Food and Drug Administration (FDA) for the treatment of pulmonary tuberculosis, its global use has been limited by unavailability. In the past decade, new evidence has emerged to define rifapentine as a key component for treatment of active disease and latent infection with M. tuberculosis (LTBI).
p140Cap is an adaptor protein involved in assembling multi-protein complexes regulating several cellular processes. p140Cap acts as a tumor suppressor in breast cancer (BC) and neuroblastoma ...patients, where its expression correlates with a better prognosis. The role of p140Cap in tumor metabolism remains largely unknown. Here we study the role of p140Cap in the modulation of the mevalonate (MVA) pathway in BC cells. The MVA pathway is responsible for the biosynthesis of cholesterol and non-sterol isoprenoids and is often deregulated in cancer. We found that both in vitro and in vivo, p140Cap cells and tumors show an increased flux through the MVA pathway by positively regulating the pace-maker enzyme of the MVA pathway, the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), via transcriptional and post-translational mechanisms. The higher cholesterol synthesis is paralleled with enhanced cholesterol efflux. Moreover, p140Cap promotes increased cholesterol localization in the plasma membrane and reduces lipid rafts-associated Rac1 signalling, impairing cell membrane fluidity and cell migration in a cholesterol-dependent manner. Finally, p140Cap BC cells exhibit decreased cell viability upon treatments with statins, alone or in combination with chemotherapeutic at low concentrations in a synergistic manner. Overall, our data highlight a new perspective point on tumor suppression in BC by establishing a previously uncharacterized role of the MVA pathway in p140Cap expressing tumors, thus paving the way to the use of p140Cap as a potent biomarker to stratify patients for better tuning therapeutic options.
