Celiac Disease in the Pediatric Population

Celiac disease is an autoimmune disorder in which the lining of the gastrointestinal tract is damaged by an immune-mediated response to gluten proteins (Allen, 2015). It is a polygenetic disease that only appears in genetically susceptible individuals (Newton & Singer, 2012). It is a worldwide concern, with North America having a high prevalence rate (Liu et al., 2017). Celiac disease can present in a spectrum of manifestations, making it difficult to identify and diagnosis (Reilly & Green, 2012). High-risk populations include those with a positive family history as well as individuals with other autoimmune disorders (Newton & Singer, 2012). Screening and diagnosis are completed with a blood test followed by a biopsy of the small intestinal lining (Zevit & Shamir, 2014). Currently, the only treatment for celiac disease is a strict, gluten-free diet. Further research is warranted in areas of environmental risk factors and treatments (Allen, 2015, Newton, Singer, 2012).     

Pseudotumor cerebri syndrome in a patient with narcolepsy type 1

Type 1 narcolepsy (NT1) is a chronic primary disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disrupted nocturnal sleep.NT1 is linked to hypothalamic hypocretin deficiency, strongly associated with Human Leukocyte Antigen (HLA) marker DQB1*06:02 and of probable autoimmune origin. NT1 is usually associated with increased rates of overweight and obesity, and sometimes with increases in overnight blood pressure and increased rates of hypoventilation with raised CO₂ levels overnight. Many of these are predisposing factors for pseudotumor cerebri syndrome (PTCS).We present a case of a young girl with both NT1 and PTCS that responded well to treatment with acetazolamide after early identification, with improvement of headache and resolution of hypoventilation.     

Genetics of type 1 diabetes

Type 1 diabetes (T1D) results from immune‐mediated loss of pancreatic beta cells leading to insulin deficiency. It is the most common form of diabetes in children, and its incidence is on the rise. This article reviews the current knowledge on the genetics of T1D. In particular, we discuss the influence of HLA and non‐HLA genes on T1D risk and disease progression through the preclinical stages of the disease, and the development of genetic scores that can be applied to disease prediction. Racial/ethnic differences, challenges and future directions in the genetics of T1D are also discussed.     

Changes in immunological markers and influx of macrophages following trans‐scleral thermotherapy of uveal melanoma

Purpose: In trans‐scleral thermotherapy (TSTT), heat is applied through the sclera in order to target an intraocular uveal melanoma. Previously, it had been shown that in uveal melanoma, hyperthermia and transpupillary thermotherapy influenced expression of immunologically relevant proteins, such as S100, HLA and heat‐shock proteins (HSPs). We investigated whether TSTT induced similar changes. Methods: Experimental TSTT was applied on eleven uveal melanomas prior to enucleation. Each tumour sample was processed for histopathological examination; immunohistochemical analysis was performed to determine expression of S100, HLA, HSPs and macrophage markers. Results: In TSTT‐treated areas, expression of S100 and different HSPs was lost, while an upregulated expression of HSP GP96 was observed at the border of these areas. Expression levels of HLA‐A and HLA‐B varied between tumours and were not influenced by TSTT. The borders of the TSTT‐treated areas showed high numbers of infiltrating macrophages, which were predominantly of the M2 phenotype. Conclusion: TSTT has an effect on immunological parameters with local loss of expression of HSPs and S100. The influx of M2 macrophages around the TSTT‐treated areas indicates the presence of an innate immune reaction against the induced necrosis, suggesting that TSTT‐treated tumour cells are removed by a macrophage‐mediated tissue repair mechanism.     

Differentiation of amniotic epithelial cells into various liver cell types and potential therapeutic applications

The aim of Regenerative Medicine is to replace or regenerate human cells, tissues or organs in order to restore normal function. Among all organs, the liver is endowed with remarkable regenerative capacity. Nonetheless, there are conditions in which this ability is impaired, and the use of isolated cells, including stem cells, is being considered as a possible therapeutic tool for the management of chronic hepatic disease.Placenta holds great promise for the field of regenerative medicine. It has long been used for the treatment of skin lesions and in ophthalmology, due to its ability to modulate inflammation and promote healing. More recently, cells isolated from the amniotic membrane are being considered as a possible resource for tissue regeneration, including in the context liver disease. Two cell types can be easily isolated from human amnion: epithelial cells (hAEC) and mesenchymal stromal cells (hAMSC). However only the first cell population has been demonstrated to be a possible source of proficient hepatic cells. This review will summarize current knowledge on the differentiation of hAEC into liver cells and their potential therapeutic application.     

Characteristics of Ankylosing Spondylitis patients living in Qatar

Aim of the work

To study the clinical, laboratory and radiographic characteristics of ankylosing spondylitis (AS) patients living in Qatar.

Post‐transplantation cyclophosphamide versus conventional graft‐versus‐host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation

Post‐transplantation cyclophosphamide (PTCy) is an effective strategy to prevent graft‐versus‐host disease (GVHD) after haploidentical haematopoietic cell transplantation (HCT). We determined the efficacy of PTCy‐based GVHD prophylaxis in human leucocyte antigen (HLA)‐mismatched unrelated donor (MMUD) HCT. We analysed 113 adult patients with high‐risk haematological malignancies who underwent one‐antigen MMUD transplantation between 2009 and 2013. Of these, 41 patients received PTCy, tacrolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis; 72 patients received conventional prophylaxis with anti‐thymocyte globulin, tacrolimus and methotrexate. Graft source was primarily bone marrow (83% PTCy vs. 63% conventional group). Incidence of grade II–IV (37% vs. 36%, P = 0·8) and grade III–IV (17% vs. 12%, P = 0·5) acute GVHD was similar at day 100. However, the incidence of grade II‐IV acute GVHD by day 30 was significantly lower in the PTCy group (0% vs. 15%, P = 0·01). Median time to neutrophil (18 days vs. 12 days, P < 0·001) and platelet (25·5 days vs. 18 days, P = 0·05) engraftment was prolonged in PTCy group. Rates of graft failure, chronic GVHD, 2‐year non‐relapse mortality, relapse, progression‐free survival or overall survival were similar. Our results demonstrate that PTCy, tacrolimus and MMF for GVHD prophylaxis is safe and produced similar results as conventional prophylaxis in patients with one antigen HLA‐MMUD HCT.     

Stable Down-Regulation of HLA Class-I by Serum Starvation in Human PBMCs

Background: The human leukocyte antigen (HLA) matching between organ donor and recipient is an acceptable strategy in clinical transplantation since 1964. However, in bone marrow transplantation, finding matched donors is often problematic. Thus new method for down regulation of HLA can be an alternative strategy to solve this problem. Objective: To examine the effect of serum starvation on HLA class I expression in human peripheral blood mononuclear cells (PBMCs). Methods: PBMCs were cultured in RPMI-1640 supplemented with 10% FBS (non-starved cells) as well as in medium only (starved cells) for 16, 24, 48, 72, 96h under standard cell culture conditions. The pattern of cell death and HLA class I expression was determined by flowcytometry. Antigenicity of the starved PBMCs was evaluated in a one-way mixed lymphocyte culture by MTT assay. Results: Mean fluorescence intensity (MFI) of different indicated starved PBMCs gradually decreased and this reduction was stable after 96h of re-feeding with medium containing FBS. Under serum starvation condition, PBMCs showed apoptotic cell death pattern. There was a linear correlation between percentages of cells, which exhibited the late apoptosis death pattern and serum starvation period (r=0.88, p<0.01). Surprisingly, the starved PBMCs lost their stimulatory property in mixed culture with allo-reactive lymphocyte. Conclusions: Membrane HLA class I expression could be stably reduced in 96h starved human PBMCs culture condition, decreasing their allo-reactivity while their viability rate is enough for possible clinical application.     

Donor‐specific antibodies: Can they predict C4d deposition in pediatric heart recipients?

There is limited evidence regarding the utility of circulating DSA in surveillance for AMR of pediatric heart recipients. Our hypothesis is that quantitation of DSA improves their power for predicting a C4d+, an integral component in the current diagnostic criteria of AMR. All pediatric recipients transplanted between 10/2005 and 1/2011 were retrospectively reviewed for DSA determined within 48 h of EMB. C4d+ was defined as >25% endothelial cell staining by immunohistochemical methods. A total of 183 paired DSA–EMB determinations were identified in 60 patients, a median of three paired studies per patient (range: 1–9). DSA were detected in 60 of these determinations. A receiver‐operating characteristic plot identified a threshold single‐antibody MFI of >6000 that strongly correlated with C4d+ (p < 0.0001) with a high negative predictive value (0.97) and specificity (0.95). The sensitivity and positive predictive values were 0.71 and 0.60, respectively. The predictive power of single‐antigen DSA for C4d deposition was improved in pediatric heart recipients using an institution‐specific MFI threshold value. In post‐transplant care, quantitative DSA should be an essential component in the surveillance for AMR.