Shielding islets with human amniotic epithelial cells enhances islet engraftment and revascularization in a murine diabetes model

Hypoxia is a major cause of considerable islet loss during the early posttransplant period. Here, we investigate whether shielding islets with human amniotic epithelial cells (hAECs), which possess anti‐inflammatory and regenerative properties, improves islet engraftment and survival. Shielded islets were generated on agarose microwells by mixing rat islets (RIs) or human islets (HI) and hAECs (100 hAECs/IEQ). Islet secretory function and viability were assessed after culture in hypoxia (1% O₂) or normoxia (21% O₂) in vitro. In vivo function was evaluated after transplant under the kidney capsule of diabetic immunodeficient mice. Graft morphology and vascularization were evaluated by immunohistochemistry. Both shielded RIs and HIs show higher viability and increased glucose‐stimulated insulin secretion after exposure to hypoxia in vitro compared with control islets. Transplant of shielded islets results in considerably earlier normoglycemia and vascularization, an enhanced glucose tolerance, and a higher β cell mass. Our results show that hAECs have a clear cytoprotective effect against hypoxic damages in vitro. This strategy improves β cell mass engraftment and islet revascularization, leading to an improved capacity of islets to reverse hyperglycemia, and could be rapidly applicable in the clinical situation seeing that the modification to HIs are minor.     

Islet autotransplantation improves glycemic control in patients undergoing elective distal pancreatectomy for benign inflammatory disease

Islet autotransplantation (IAT) is increasingly being performed to mitigate against the diabetic complications of pancreatic resection in patients with benign inflammatory pancreatic disorders; however, the glycemic benefit of IAT in patients undergoing partial pancreatic resection is not known. We aimed to determine whether IAT improved glycemic outcomes in patients undergoing distal pancreatectomy for benign inflammatory disease. We performed a multicenter, retrospective case-control study of patients who underwent distal pancreatic resection with IAT at two U S tertiary care centers. The primary outcome was the mean change in pre- vs post-operative HgA1c following transplant as well as the development of new post-operative diabetes. Nine patients requiring distal pancreatectomy for benign disease underwent IAT and were compared to 13 historical controls without IAT. Baseline characteristics were similar between groups. With a median follow-up of 22 months, those who received an IAT had a smaller increase in their pre- vs post-operative HgA1c (0.42 vs 2.83, P = .004), and one case patient (14.3%) vs three control patients (23.1%) developed new post-operative diabetes (P = .581). We conclude that patients undergoing distal pancreatic resection for benign inflammatory disease should be considered for IAT, as long-term glycemic outcomes appear to be improved in those undergoing transplant.     

Long-term follow-up of children with risk organ-negative Langerhans cell histiocytosis after 2-chlorodeoxyadenosine treatment

The nucleoside analogue, 2-chlorodeoxyadenosine (2CDA), was reported to be an active treatment for childhood Langerhans cell histiocytosis (LCH) without risk organ (RO−) involvement. However, we lack data on long-term effects of 2CDA treatment, including the disease reactivation rate, permanent sequelae and long-term tolerance. This study included 44 children from the French LCH registry, treated for a RO− LCH with 2CDA monotherapy (median number of six courses). The median age at the beginning of 2CDA was 3·6 years (range, 0·3–19·7 years) and the median follow-up after was 5·4 years (range, 0·6–15·1 years). Objective response to 2CDA was observed in 25 patients (56·8%), while six patients (13·6%) had stable disease and 13 patients (29·5%) exhibited progressive disease. Among patients without progression, only two experienced disease reactivation after 2CDA discontinuation. The five-year cumulative incidence of disease progression or reactivation after 2CDA therapy initiation was 34·3%. The lymphopenia reported in all cases [72% below absolute lymphocyte count (ALC) of 0·5 G/l], was addressed with appropriate prophylactic measures. Other toxicities above grade 2 were uncommon, and no second malignant neoplasm or neuropathy was reported. The five-year overall survival was 97·7%. In conclusion, we could confirm that 2CDA monotherapy was a beneficial long-term therapy for treating patients with RO− LCH. Appropriate management of induced immune deficiency is mandatory.     

Effect of smoking on immunity in human chronic periodontitis

Aim

Evaluate the effects of smoking on dendritic cells (DCs), cytokines, clinical periodontal parameters, and number of teeth in samples of human chronic periodontitis (CP).

Material and methods

Gingival samples were obtained from 24 smokers and 21 non-smokers with CP. Periodontal examination was carried out. Immunohistochemical staining was performed to identify Factor XIIIa+ immature, CD1a+ immature, and CD83+ mature DCs. The inflammatory infiltrate was counted, and IL-2, IL-10, IL-4, IL-6, IFN-γ, TNF-α, and IL-17A were measured using the cytometric bead array (CBA). Inflammatory infiltrate, DCs, cytokines, classification of CP, clinical periodontal parameters, number of teeth, smoking habit in years (SH/years), and number of cigarettes smoked per day (C/day) were correlated and compared.

Results

CD83+ mature DCs decreased in the smokers group. Negative correlations could be observed between the number of C/day with levels of IL-17A and number of teeth. Correlations between smoking, periodontal disease status, and other cytokines were not observed.

Conclusions

Smoking decreases mature DCs in chronic periodontitis. Moreover, a dose-dependent relation can be observed between C/day and number of teeth and levels of IL17A observed. Smokers show a different modulation of the CP immune response.     

多系统累及朗格汉斯细胞组织细胞增生症治疗进展

朗格汉斯细胞组织细胞增生症(Langerhans cell histiocytosis,LCH)是一种罕见的树突细胞和网状细胞系统增生性疾病,目前分为单系统LCH(SS-LCH)和多系统LCH(MS–LCH)。MS-LCH的预后较差,及时有效地干预是患者存活的关键。目前有化学治疗、免疫治疗、造血干细胞移植治疗等多种治疗方案。文章就MS-LCH相关治疗方案的进展进行综述。     

Eosinophilic granuloma of the sternum in a child treated with closed biopsy

Langerhans cell histiocytosis is a rare neoplastic proliferative disorder of the Langerhans cells. The clinical course is variable, ranging from a low symptomatic single bone lesion to fatal multiple organ involvement. Rarely, the sternum can be the first and single location of the disease. We report on a 12‐year‐old boy who presented with an aggressive lytic lesion of the proximal sternum associated with local pain and afternoon fever. Histopathological analysis of the closed biopsy specimen indicated eosinophilic granuloma of bone/Langerhans cell histiocytosis. Soon after the biopsy procedure the pain and fever subsided. Computed tomography at 2 months showed healing of the lytic lesion. The patient received no other type of treatment. At 2 year follow up he was symptom and disease free.     

Ultrasonographic features of Langerhans cell histiocytosis of the thyroid

Langerhans cell histiocytosis (LCH) is a rare disease, especially when it involves the thyroid gland. Awareness of ultrasonic features will be helpful for a clinician who should consider this disease in the differential diagnosis from other more common thyroid disorders, especially prior to surgery. Here, we report two patients who have histologically confirmed LCH of the thyroid and summarize the reported cases with ultrasonographic scans from the last 10 years (n=10). Ultrasonograms showed isolated or multiple hypoechoic nodules in unilateral or bilateral thyroid gland. Internal acoustic features of most nodules was heterogeneous (n=5) or hypoechoic (n=2).     

Pediatric liver failure with massive sinusoidal infiltration of histiocytes

Histiocytic neoplasms, such as Langerhans cell histiocytosis (LCH) and disseminated juvenile xanthogranuloma (JXG), can involve the liver and sometimes cause liver failure. We aimed to classify non-LCH histiocytic proliferating disorders that do not exhibit typical disseminated JXG histology. We examined four pediatric patients who presented with liver failure and splenomegaly. Two patients with liver cirrhosis without cholestasis underwent liver transplantation (LT). The other two patients presented with giant cell hepatitis causing neonatal/infantile acute liver failure (ALF). The infantile ALF patient also underwent LT. Liver dysfunction developed after LT in all three transplant cases and the grafts exhibited massive sinusoidal infiltration of histiocytes with hemophagocytosis, similar to the native liver. The neonatal ALF patient was treated with an LCH-type chemotherapy regimen, and is alive and well at 18 months. Infiltrating histiocytes were positive for CD68 and CD163, and negative for CD1a, CD207, and S-100 protein. The BRAF V600E mutation was not present. Liver histological findings were not consistent with conventional disseminated JXG or LCH, although the histological findings in other organs overlapped those of well-known histiocytic neoplasms. The histological and immunohistochemical findings of infiltrating histiocytes suggest that these four cases constituted a disseminated JXG-like systemic disease.