Distinct Merkel Cell Polyomavirus Molecular Features in Tumour and Non Tumour Specimens from Patients with Merkel Cell Carcinoma

Merkel Cell Polyomavirus (MCPyV) is associated with Merkel Cell carcinoma (MCC), a rare, aggressive skin cancer with neuroendocrine features. The causal role of MCPyV is highly suggested by monoclonal integration of its genome and expression of the viral large T (LT) antigen in MCC cells. We investigated and characterized MCPyV molecular features in MCC, respiratory, urine and blood samples from 33 patients by quantitative PCR, sequencing and detection of integrated viral DNA. We examined associations between either MCPyV viral load in primary MCC or MCPyV DNAemia and survival. Results were interpreted with respect to the viral molecular signature in each compartment. Patients with MCC containing more than 1 viral genome copy per cell had a longer period in complete remission than patients with less than 1 copy per cell (34 vs 10 months, P = 0.037). Peripheral blood mononuclear cells (PBMC) contained MCPyV more frequently in patients sampled with disease than in patients in complete remission (60% vs 11%, P = 0.00083). Moreover, the detection of MCPyV in at least one PBMC sample during follow-up was associated with a shorter overall survival (P = 0.003). Sequencing of viral DNA from MCC and non MCC samples characterized common single nucleotide polymorphisms defining 8 patient specific strains. However, specific molecular signatures truncating MCPyV LT were observed in 8/12 MCC cases but not in respiratory and urinary samples from 15 patients. New integration sites were identified in 4 MCC cases. Finally, mutated-integrated forms of MCPyV were detected in PBMC of two patients with disseminated MCC disease, indicating circulation of metastatic cells. We conclude that MCPyV molecular features in primary MCC tumour and PBMC may help to predict the course of the disease

MIPAS database: New HNO3 line parameters at 7.6 μm validated with MIPAS satellite measurements

Improved line positions and intensities have been generated for the 7.6 m spectral region of nitric acid. They were obtained relying on a recent reinvestigation of the nitric acid band system at 7.6 m and comparisons of HNO3 volume mixing ratio profiles retrieved from the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) limb emission radiances in the 11 and 7.6 m domains. This has led to an improved database called MIPAS-2015. Comparisons with available laboratory information (individual line intensities, integrated absorption cross sections, and absorption cross sections) show that MIPAS-2015 provides an improved description of the 7.6 m region of nitric acid. This study should help to improve HNO3 satellite retrievals by allowing measurements to be performed simultaneously in the 11 and 7.6 m micro-windows. In particular, it should be useful to analyze existing MIPAS and IASI spectra as well as spectra to be recorded by the forthcoming Infrared Atmospheric Sounding Interferometer-New Generation (IASI-NG) instrument.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Lipschütz Genital Ulceration Associated with Mumps

Lipschütz ulcers are characterised by a first flare of non-sexually related acute genital ulcers (AGU) occurring in adolescent girls. Epstein-Barr primary infection is the most frequently reported aetiology but other infectious agents are probably implicated. We report the first case of mumps associated with an AGU in a 21-year-old girl. She presented a bilateral parotitis with genital ulcers, and serology confirmed she had mumps. As in our case, most Lipschütz ulcers heal spontaneously within a couple of weeks and the diagnosis should be reconsidered in case of recurrence.</jats:p

Subacute Cutaneous Lupus Erythematosus Induced and Exacerbated by Proton Pump Inhibitors

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Subacute cutaneous lupus erythematosus (SCLE) can be induced by numerous drugs. We report 3 cases of SCLE induced by proton pump inhibitors (PPIs). &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To highlight a rare cutaneous side effect induced by a frequently prescribed drug such as a PPI. &lt;b&gt;&lt;i&gt;Case Reports:&lt;/i&gt;&lt;/b&gt; Case 1 was a 30-year-old man who developed multiple annular plaques over the trunk and lower limbs 1 month after the initiation of pantoprazole. Antinuclear antibodies (ANA) were positive with anti-Ro/SSA and anti-La/SSB antibodies, and histology confirmed the diagnosis. Clinical improvement was achieved 8 weeks after the discontinuation of pantoprazole and the introduction of a treatment combining topical steroids and hydroxychloroquine. Lesions relapsed when pantoprazole was accidentally rechallenged. The second case was a 31-year-old woman, 28 weeks pregnant, who presented erythematous annular plaques over the trunk 7 weeks after starting esomeprazole. ANA and anti-Ro/SSA antibodies were positive, and the histology was compatible with SCLE. Fetal ultrasound was normal. She was treated with topical and oral steroids and hydroxychloroquine. Clinical improvement was achieved 4 weeks after the discontinuation of esomeprazole. The third case was a 57-year-old woman with systemic erythematosus lupus presenting annular and psoriasiform lesions on the trunk for 15 months. She was treated successively with hydroxychloroquine, azathioprine, mycophenolate mofetil and methotrexate with prednisone. A review of her drug history revealed the introduction of omeprazole a few weeks before the first appearance of skin lesions and omeprazole was contraindicated. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; SCLE should systematically be suspected in case of eruption after the introduction of PPI. The risk of fetal cardiac complications is important in pregnant women.</jats:p

Sarcoidosis in Patients Treated with Vemurafenib for Metastatic Melanoma: A Paradoxical Autoimmune Activation

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Vemurafenib, a BRAF inhibitor, is a first-line treatment for inoperable melanoma. Sarcoidosis has never been reported in patients on vemurafenib. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; We describe 5 cases of sarcoidosis in patients treated with vemurafenib. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Seventy patients receiving vemurafenib for a &lt;i&gt;BRAF&lt;/i&gt;-mutated inoperable stage III or IV melanoma were treated in our centre. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Five patients (7.1%) developed sarcoidosis or a sarcoid-like reaction on vemurafenib; 4 patients had cutaneous signs and 3 had extracutaneous disorders (bilateral hilar lymph nodes, uveitis). Histological analysis of skin lesions revealed epithelioid granulomas without necrosis, consistent with sarcoidosis. Angiotensin-converting enzyme levels were high in 2 patients. Cutaneous and ophthalmological lesions rapidly disappeared on topical corticosteroid treatment without the cessation of vemurafenib treatment. Complete remission of melanoma was observed in 3 patients and partial remission was observed in another. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; BRAF inhibitors probably have immune system-enhancing effects and should therefore be recognized as potential inducers of sarcoidosis.</jats:p

The guanine exchange factor SWAP70 mediates vGPCR-induced endothelial plasticity

International audienceAbstractBackgroundThe viral G protein-coupled receptor (vGPCR) is proposed to act as one of the predominant mediators of Kaposi’s sarcoma (KS), a human herpes virus 8 (HHV8)-elicited disease. The actions of vGPCR manifest pathogenesis, in part, through increased permeability of endothelial cells. Endothelial cell-cell junctions have indeed emerged as an instrumental target involved in the vasculature defects observed within the tumor microenvironment. The pathway leading to adherens junction destabilization has been shown to involve the activation of the small GTPase Rac, in the context of either latent infection or the sole expression of vGPCR. However, the precise molecular mechanisms governed by vGPCR in vascular leakage require further elucidation.FindingsGuanine exchange factors (GEFs) function as critical molecular switches that control the activation of small GTPases. We therefore screened the effects of 80 siRNAs targeting GEFs on vGPCR-driven endothelial permeability and identified switch-associated protein 70 (SWAP70) as necessary for its elevating effects. Pull-down experiments further showed that Rac activation by vGPCR was dependent on SWAP70. Examination of tissues and cells from HHV8-positive patients revealed that SWAP70 was ubiquitously expressed. Furthermore, SWAP70 was found to be crucial for vGPCR-driven endothelial tube formation and endothelial sprouting in vitro.ConclusionsSWAP70 appears to act as a molecular intermediate between vGPCR and endothelial activation. Because of the important role of vGPCR-mediated endothelial plasticity in KS pathogenesis, inhibition of SWAP70 function could be of interest for blocking vGPCR-driven activities in HHV8-defined diseases