A novel telomere biology disease-associated gastritis identified through a whole exome sequencing-driven approach

A whole exome sequencing (WES)-driven approach to uncover the etiology of unexplained inflammatory gastritides has been underutilized by surgical pathologists. Here, we discovered the pathobiology of an unusual chronic atrophic gastritis in two unrelated patients using this approach. The gastric biopsies were notable for an unusual pattern of gastritis with persistent dense inflammation, loss of both parietal and neuroendocrine cells in the oxyntic mucosa, and sparing of the antral mucosa. The patients were found to harbor pathogenic variants in telomeropathic genes (POT1 and DCLRE1B). Clonality testing for one of the patients showed evidence of evolving clonality of TCR-gene rearrangement. Both patients showed significantly decreased numbers of stem/progenitor cells by immunohistochemistry, which appears to be responsible for the development of mucosal atrophy. No such cases of unusual chronic atrophic gastritis in the setting of telomeropathy have been previously reported. The loss of stem/progenitor cells suggests that stem/progenitor cell exhaustion in the setting of telomere dysfunction is the likely mechanism for development of this unusual chronic atrophic gastritis. The results underscore the need for close monitoring of these gastric lesions, with special regard to their neoplastic potential. This combined WES-driven approach has promise to identify the cause and mechanism of other uncharacterized gastrointestinal inflammatory disorders

The therapeutic effect of anti-CD52 treatment in murine experimental autoimmune encephalomyelitis is associated with altered IL-33 and ST2 expression levels

Experimental autoimmune encephalomyelitis (EAE) mice were administered with murine anti-CD52 antibody to investigate its therapeutic effect and whether the treatment modulates IL-33 and ST2 expression. EAE severity and central nervous system (CNS) inflammation were reduced following the treatment, which was accompanied by peripheral T and B lymphocyte depletion and reduced production of various cytokines including IL-33, while sST2 was increased. In spinal cords of EAE mice, while the number of IL-33+ cells remained unchanged, the extracellular level of IL-33 protein was significantly reduced in anti-CD52 antibody treated mice compared with controls. Furthermore the number of ST2+ cells in the spinal cord of treated EAE mice was downregulated due to decreased inflammation and immune cell infiltration in the CNS. These results suggest that treatment with anti-CD52 antibody differentially alters expression of IL-33 and ST2, both systemically and within the CNS, which may indicateIL-33/ST2 axis is involved in the action of the antibody in inhibiting EAE

C-Type Lectin Receptors in Asthma

This review is submitted as part of PhD thesis by SH. SH incepted, wrote the manuscript. G.D.B and F.B. edited the manuscript. SH PhD studentship was funded by CIDRI (Wellcome Trust initiative, South Africa) and the University of Aberdeen College studentship. GDB is funded by the Wellcome Trust and Medical Research Council Centre for Medical Mycology at the University of Aberdeen.Peer reviewedPublisher PD

The Contribution of Allergen-Specific IgG to the Development of Th2-Mediated Airway Inflammation

In both human asthmatics and animal models of allergy, allergen-specific IgG can contribute to Th2-mediated allergic inflammation. Mouse models have elucidated an important role for IgG and Fc-gamma receptor (FcγR) signaling on antigen presenting cells (APC) for the induction of airway inflammation. These studies suggest a positive feedback loop between IgG produced by the adaptive B cell response and FcγR signaling on innate immune cells. Studies of IgG and FcγRs in humans with asthma or allergic lung disease have been more controversial. Some reports have identified associations between allergen-specific IgG and severity of allergic responses, while other studies have found associations of IgG subclass IgG4 with allergic tolerance. In this paper, we review the literature to help define the nature of IgG and FcγR signaling on innate immune cells and how it contributes to the development of allergic immune responses

A case of dual-mechanism immune-related anaemia in a patient with metastatic melanoma treated with nivolumab and ipilimumab

BackgroundThe combination of the immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab is a mainstay of treatment for selected patients with metastatic melanoma. This combination also results in more frequent immune-related adverse events (irAEs) than either ICI alone. These irAEs can be severe and their pathogenesis is poorly understood.Case presentationWe report a case of a woman with metastatic melanoma, treated with combined ipilimumab and nivolumab, who developed severe anaemia. While initial workup revealed autoimmune haemolytic anaemia, the anaemia persisted despite corticosteroids and paradoxical reticulocytopenia was observed. Bone marrow biopsy demonstrated a CD8+ T cell-mediated destruction of the red cell precursors implying concurrent pure red cell aplasia. Both processes resolved after the addition of cyclosporine A.ConclusionsThis report describes a rare case of two concurrent mechanisms of haematological irAE in a patient treated with combined ICI therapy. Successful treatment resulted only after the second underlying mechanism of toxicity was uncovered. Prompt recognition of these unusual presentations of rare irAEs is now key to effective irAE management

Evaluasi Sanitasi Pangan pada Produksi Brownies Skala Industri (Studi Kasus di UMKM Libby Brownies)

Saat ini, industri rumah tangga banyak berkembang di Indonesia. UMKM (Usaha Mikro Kecil Menengah) Libby brownies merupakan salah satu usaha rumah tangga di Kota Tangerang Selatan yang bergerak dalam bidang tata boga khususnya dalam usaha pembuatan brownies. Penelitian bertujuan untuk mengevaluasi proses produksi brownies dan sistem sanitasi pangan yang diterapkan oleh UMKM Libby Brownies. Penelitian dilakukan dengan observasi tempat produksi dan wawancara langsung dengan pemilik UMKM dan pekerja. Hasil penelitian menunjukkan bahwa UMKM Libby Brownies telah menerapkan konsep CPPOB (Cara Produksi Pangan Olahan yang Baik). Dalam penerapan CPPOB, UMKM Libby Brownies telah melakukan upaya dalam menjaga sanitasi produk. Namun, masih banyak ditemukan masalah, seperti kondisi keramik lantai yang pecah serta cat dinding yang sudah mengelupas dan bernoda kecoklatan. Masalah-masalah ini perlu ditangani karena dapat berdampak buruk pada produk yang dihasilkan dan juga kepada konsumen. Oleh karena itu, UMKM Libby Brownies masih harus menjalani banyak perbaikan berkaitan dengan kebersihan dan kelayakan lokasi produksi. Sosialiasi dan pengawasan perlu dilakukan oleh pemerintah pusat melalui dinas terkait untuk meningkatkan tanggung jawab dan kepedulian UMKM terhadap keamanan dan sanitasi pangan yang diterapkan