Central retinal vein occlusion revealing celiac disease

Introduction: Thrombosis has been widely reported in coeliac disease (CD) but central retinal vein occlusion (CRVO) is rarely described. Case presentation: A 27-year-old woman presented with acute visual loss and was diagnosed with CRVO. Her protein S and protein C levels were low and CD was diagnosed on the basis of endoscopic, immunological and histological results. A gluten-free diet resulted in favourable evolution. Conclusion: CD should be considered in young patients with thrombosis, especially if in an unusual location. Treatment is based on a gluten-free diet

Primary Sjögren’s syndrome complicated by anti-neutrophil cytoplasmic antibody-mediated crescentic glomerulonephritis

Ocular and oral dryness are the hallmark of Sjögren’s syndrome (SS). However, SS can be associated with a variety of complications, affecting organs such as the liver, kidneys, lungs, muscle, and nervous system. Renal involvement has been usually in the form of tubulointerstitial nephritis. However, glomerulonephritis is rare in primary SS. We report three clinical cases of SS with anti-neutrophil cytoplasmic antibody-mediated crescentic glomerulo-nephritis treated with prednisone and cyclophosphamide, with favorable outcome

The pharmalogical reactivation of p53 function improves breast tumor cell lysis by granzyme B and NK cells through induction of autophagy

« The pharmalogical reactivation of p53 function improves breast tumor cell lysis by granzyme B and NK cells through induction of autophagy » Cell Death Dis, 2019 Sep 20;10(10):695 doi: 10.1038/s41419-019-1950-1International audienceAbstract Cytotoxic T lymphocytes (CTL) and natural killer cells (NK)-mediated elimination of tumor cells is mostly dependent on Granzyme B apoptotic pathway, which is regulated by the wild type (wt) p53 protein. Because TP53 inactivating mutations, frequently found in human tumors, could interfere with Granzyme B-mediated cell death, the use of small molecules developed to reactivate wtp53 function in p53-mutated tumor cells could optimize their lysis by CTL or NK cells. Here, we show that the pharmalogical reactivation of a wt-like p53 function in p53-mutated breast cancer cells using the small molecule CP-31398 increases their sensitivity to NK-mediated lysis. This potentiation is dependent on p53-mediated induction of autophagy via the sestrin-AMPK-mTOR pathway and the ULK axis. This CP31398-induced autophagy sequestrates in autophagosomes several anti-apoptotic proteins, including Bcl-X L and XIAP, facilitating Granzyme B-mediated mitochondrial outer membrane permeabilization, caspase-3 activation and Granzyme B- or NK cell-induced apoptosis. Together, our results define a new way to increase cytotoxic lymphocyte-mediated lysis of p53-mutated breast cancer cell, through a p53-dependent autophagy induction, with potential applications in combined immunotherapeutic approaches

Comparison of Clinical Features of Behcet Disease According to Age in a Tunisian Cohort

Behcet's disease (BD) is a multisystemic inflammatory disease that occurs most often between the second and fourth decade of life. Patients have been reported during the first months of life and after 70 years. Our objective was to determine the clinical, paraclinical and genetic characteristics of BD in patients aged 40 years. We conducted a comparative retrospective study including patients with BD (Criteria of International Study Group on BD). Patients were divided into two groups: those 40 years (Group two). The clinical, paraclinical and genetic (HLA) characteristics were determined and compared in the two groups. The data were compiled and analyzed using SPSS 11.0. Thirty totals of 430 patients were included. Group one included 81 patients (55 men and 26 women). Group two included 68 patients (45 men and 23 women). Cutaneous involvement (88.9 versus 76.5%; P=0.043), pseudofolliculitis (84 versus 64.5%; P=0.004) and vena cava thrombosis (11.11 vs 0%; P=0.004) were significantly more frequent in group one while joint involvements were more common in group two (57.4 versus 40.7%; P= 0.043). The frequency of erythema nodosum as well as ocular, vascular and neurological disorders was comparable between the two groups. Few studies in the literature have compared the clinical, paraclinical and genetic characteristics of BD, who had first symptom onset after 40 years of age. Late-onset BD, usually, affects both genders equally. According to present results, the frequency of severe organ involvement is equal regardless of age, except for vena cava thrombosis

Granzyme B-activated p53 interacts with Bcl-2 to promote cytotoxic lymphocyte-mediated apoptosis

Abstract Granzyme B (GzmB) plays a major role in CTLs and NK cell–mediated elimination of virus-infected cells and tumors. Human GzmB preferentially induces target cell apoptosis by cleaving the proapoptotic Bcl-2 family member Bid, which, together with Bax, induces mitochondrial outer membrane permeabilization. We previously showed that GzmB also induces a rapid accumulation of the tumor-suppressor protein p53 within target cells, which seems to be involved in GzmB-induced apoptosis. In this article, we show that GzmB-activated p53 accumulates on target cell mitochondria and interacts with Bcl-2. This interaction prevents Bcl-2 inhibitory effect on both Bax and GzmB-truncated Bid, and promotes GzmB-induced mitochondrial outer membrane permeabilization. Consequently, blocking p53–Bcl-2 interaction decreases GzmB-induced Bax activation, cytochrome c release from mitochondria, and subsequent effector caspases activation leading to a decreased sensitivity of target cells to both GzmB and CTL/NK-mediated cell death. Together, our results define p53 as a new important player in the GzmB apoptotic signaling pathway and in CTL/NK-induced apoptosis.</jats:p