Mutant huntingtin impairs immune cell migration in Huntington disease

In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed.     

Intrathoracic papillary thyroid carcinoma from occult primary disease

A 42-year-old woman undertook a chest radiograph for a routine evaluation prior to surgery for pelvic endometrioma, which revealed a right paratracheal mass slightly displacing the trachea to the left. CT of the thorax disclosed a well demarcated, heterogeneous, lobular, right paratracheal mass, bearing punctate, coarse, and curvilinear calcifications. MRI further revealed two components within the lesion: a larger, cystic, exhibiting thin septations, and a solid component at the lower part exhibiting strong enhancement. No continuity of the mass with the thyroid gland was demonstrated, which had normal size and no focal lesion. Histological examination of the resected mass disclosed lymph node tissue infiltrated by papillary thyroid carcinoma; subsequent total thyroidectomy revealed small foci of papillary carcinoma within both lobes of the thyroid gland. Ablative dose I-131 was administered and the patient was put on daily thyroid supplements.     

Esophageal intramural pseudodiverticulosis,an unusual cause of dysphagia: report of a case

Esophageal intramural pseudodiverticulosis (EIP) is a rare disorder of unknown etiology. On histopathology, it is characterized by dilation of the submucosal esophageal glands. The main presenting symptom is dysphagia to solid foods. Most patients diagnosed with EIP also have a history of diabetes mellitus, gastroesophageal reflux disease, esophageal candidiasis, or chronic alcohol and nicotine abuse. Yet, the exact pathophysiologic mechanism still remains unclear. The most frequent complication, occurring in 80 % of the patients, is esophageal stricture. The mainstay of therapy is directed towards symptom relief with administration of proton pump inhibitors (PPIs) combined with antifungals and/or endoscopic dilations, if necessary. We report a case of a 69-year-old man who presented with a 9-month history of progressive dysphagia and a 25 kg-weight loss, with typical endoscopic findings of EIP and successful response to medical therapy with oral antifungals alone.     

Long-Term Changes of Macular Thickness after Pars Plana Vitrectomy in Optic Disc Pit Maculopathy: A Spectral-Domain Optical Coherence Tomography Study

Purpose: To evaluate macular thickness (MT) changes, using spectral domain optical coherence tomography (SD-OCT) in patients with optic disc pit (ODP) maculopathy after pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peeling. Procedures: Our retrospective study included nine patients with ODP maculopathy, treated with either PPV (n?=?5) or PPV with ILM peeling (n?=?4). All participants, who had a mean long-term follow-up of 33.4?±?7.0 months, underwent a complete ophthalmological examination and SD-OCT. Due to the preoperative macular elevation, the postoperative MT in the operated patients was compared with that of fellow eyes and with normative data. Results: A significant reduction in MT was noticed in all macular sectors of the operated cases at the last examination. The reduction was more evident in the group of PPV with ILM peeling. At the last examination of the follow-up, there was a statistically significant improvement regarding BCVA in both groups in comparison with baseline, while the two groups did not differ significantly in between (p?=?0.245). Conclusions: In the long-term follow-up period, our study demonstrated a significant reduction in MT in patients with ODP maculopathy treated with PPV, which was more profound in those cases where PPV included ILM peeling.     

Infectome: A platform to trace infectious triggers of autoimmunity

The “exposome” is a term recently used to describe all environmental factors, both exogenous and endogenous, which we are exposed to in a lifetime. It represents an important tool in the study of autoimmunity, complementing classical immunological research tools and cutting-edge genome wide association studies (GWAS). Recently, environmental wide association studies (EWAS) investigated the effect of environment in the development of diseases. Environmental triggers are largely subdivided into infectious and non-infectious agents. In this review, we introduce the concept of the “infectome”, which is the part of the exposome referring to the collection of an individual's exposures to infectious agents. The infectome directly relates to geoepidemiological, serological and molecular evidence of the co-occurrence of several infectious agents associated with autoimmune diseases that may provide hints for the triggering factors responsible for the pathogenesis of autoimmunity. We discuss the implications that the investigation of the infectome may have for the understanding of microbial/host interactions in autoimmune diseases with long, pre-clinical phases. It may also contribute to the concept of the human body as a superorganism where the microbiome is part of the whole organism, as can be seen with mitochondria which existed as microbes prior to becoming organelles in eukaryotic cells of multicellular organisms over time. A similar argument can now be made in regard to normal intestinal flora, living in symbiosis within the host. We also provide practical examples as to how we can characterise and measure the totality of a disease-specific infectome, based on the experimental approaches employed from the “immunome” and “microbiome” projects.     

Colonic anastomotic healing in the context of altered macrophage function and endotoxemia

Purpose  

Prevention of perioperative activation of intestinal muscularis macrophages is a promising intervention to avoid post-traumatic gastrointestinal tract dysfunction. However, impaired macrophage function could have deleterious consequences on anastomotic healing, especially in complications aggravating the healing process itself, such as infectious problems either as preexisting local inflammation or infection (e.g., complicated diverticulitis) or endotoxemia due to early postoperative infections (e.g., pneumonia). Aim of this study was to investigate colonic anastomotic healing in macrophage-depleted mice in the presence of endotoxemia.     

Rituximab in the treatment of systemic sclerosis-associated interstitial lung disease: Comment on the article by Yoo

Several lines of evidence from basic research indicate that B cells may contribute to the pathogenesis of systemic sclerosis. Clinical studies as well have provided preliminary data pointing to the direction that B-cell depletion with rituximab might be a therapeutic option for patients with this debilitating disease.