Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
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Question: The nationwide prevalence of latent tuberculosis infection (LTBI) in Italian patients with psoriasis has never been investigated. To estimate the nationwide prevalence of LTBI in Italian patients with psoriasis who are candidates for systemic treatment. Data were obtained from the Psocare Registry on those patients (n=4946) with age >18years, systemic treatment at entry specified and tuberculin skin test (TST) performed according to the Mantoux method. LTBI diagnosis was based on a positive TST result in the absence of any clinical, radiological or microbiological evidence of active tuberculosis. Latent tuberculosis infection was diagnosed in 83% of patients with psoriasis (409 of 4946). The prevalence of LTBI was lower in patients on biologics than in those on conventional systemic treatments, ranging from 43% (19 of 444) of patients on adalimumab to 31% (eight of 26) of those on psoralen-ultraviolet A (P<005). Independent factors associated with LTBI were male sex [odds ratio (OR) 130, 95% confidence interval (CI) 104-162; P=002], age over 55years (OR 293, 95% CI 218-393; P<0001) and being entered into a conventional treatment (OR 383, 95% CI 310-474; P<0001). Positive history of tuberculosis was seen in 1% of patients (n=49). The nationwide prevalence of LTBI in Italian patients with psoriasis candidate to systemic treatment is high, and screening is recommended prior to biological treatment.

Answer: The Mantoux test detects what latent infection/disease?


Question: The TNF family member receptor activator for NF-B ligand (RANKL) and its receptors RANK and osteoprotegerin are key regulators of bone remodeling but also influence cellular functions of tumor and immune effector cells. In this work, we studied the involvement of RANK-RANKL interaction in NK cell-mediated immunosurveillance of acute myeloid leukemia (AML). Substantial levels of RANKL were found to be expressed on leukemia cells in 53 of 78 (68%) investigated patients. Signaling via RANKL into the leukemia cells stimulated their metabolic activity and induced the release of cytokines involved in AML pathophysiology. In addition, the immunomodulatory factors released by AML cells upon RANKL signaling impaired the anti-leukemia reactivity of NK cells and induced RANK expression, and NK cells of AML patients displayed significantly upregulated RANK expression compared with healthy controls. Treatment of AML cells with the clinically available RANKL Ab Denosumab resulted in enhanced NK cell anti-leukemia reactivity. This was due to both blockade of the release of NK-inhibitory factors by AML cells and prevention of RANK signaling into NK cells. The latter was found to directly impair NK anti-leukemia reactivity with a more pronounced effect on IFN- production compared with cytotoxicity. Together, our data unravel a previously unknown function of the RANK-RANKL molecule system in AML pathophysiology as well as NK cell function and suggest that neutralization of RANKL with therapeutic Abs may serve to reinforce NK cell reactivity in leukemia patients.

Answer: To the ligand of which receptors does Denosumab (Prolia) bind?


Question: In melanoma, transition to the vertical growth phase is the critical step in conversion to a deadly malignant disease. Here, we offer the first evidence that an antioxidant enzyme has a key role in this transition. We found that the antioxidant enzyme peroxiredoxin-2 (Prx2) inversely correlated with the metastatic capacity of human melanoma cells. Silencing Prx2 expression stimulated proliferation and migration, whereas ectopic expression of Prx2 produced the opposite effect. Mechanistic investigations indicated that Prx2 negatively regulated Src/ERK activation status, which in turn fortified adherens junctions function by increasing E-cadherin expression and phospho-Y654-dependent retention of -catenin in the plasma membrane. In murine melanoma cells, Prx2 silencing enhanced lung metastasis in vivo. Interestingly, the natural compound gliotoxin, which is known to exert a Prx-like activity, inhibited proliferation and migration as well as lung metastasis of Prx2-deficient melanoma cells. Overall, our findings reveal that Prx2 is a key regulator of invasion and metastasis in melanoma, and also suggest a pharmacologic strategy to effectively decrease deadly malignant forms of this disease.

Answer:
What type of enzyme is peroxiredoxin 2 (PRDX2)?