[Tumor predisposition in endocrinology - from MEN to FIPA]. / Tumorprädisposition in der Endokrinologie ­ von MEN bis FIPA.

Understanding genetic predisposition has a significant impact on the management of patients with endocrine tumours, including therapy, early detection and prevention. These tumours, which develop as part of a familial predisposition, often manifest early in life and frequently affect several endocrine organs. In the following article, both common syndromes, such as multiple endocrine neoplasia (MEN) syndromes, and rare syndromes, such as familial isolated pituitary adenoma (FIPA), are presented based on their indicator diseases.

The G protein-coupled receptor 15 (GPR15) regulates cutaneous immunology by maintaining dendritic epidermal T cells and regulating the skin microbiome.

The G protein-coupled receptor 15 (GPR15) regulates homing of different T-cell populations into the gut, thus, preserving tissue homeostasis. Its potential role in the preservation of homeostasis on other body interfaces, including the skin, is less well understood. We addressed the impact of GPR15 on cutaneous T-cell populations and the skin microbiome under steady-state conditions. Genetic deficiency in GPR15 substantially altered the composition of skin-resident T-cell populations. Precisely, dendritic epidermal T cells were almost absent in the epidermis of Gpr15-/- mice. The niche of dendritic epidermal T cells in the epidermis was, instead, populated by αß TCR+ T cells. These changes were associated with shifts in the skin microbiota in Gpr15-/- mice. Collectively, our results uncover a role of GPR15 in the regulation of the cutaneous immune system and, thus, highlight the receptor as important general regulator of tissue homeostasis of exterior body interfaces.

The G Protein-Coupled Receptor (GPR) 15 Counteracts Antibody-Mediated Skin Inflammation.

The G protein-coupled receptor 15 (GPR15) has recently been highlighted as an important regulator of T cell trafficking into the gut under physiological and pathophysiological conditions. Additionally, circumstantial evidence has accumulated that GPR15 may also play a role in the regulation of chronic inflammation. However, the (patho)physiological significance of GPR15 has, in general, remained rather enigmatic. In the present study, we have addressed the role of GPR15 in the effector phase of autoantibody-mediated skin inflammation, specifically in the antibody transfer mouse model of bullous pemphigoid-like epidermolysis bullosa acquisita (BP-like EBA). Subjecting Gpr15-/- mice to this model, we have uncovered that GPR15 counteracts skin inflammation. Thus, disease was markedly aggravated in Gpr15-/- mice, which was associated with an increased accumulation of γδ T cells in the dermis. Furthermore, GPR15L, the recently discovered cognate ligand of GPR15, was markedly upregulated in inflamed skin. Collectively, our results highlight GPR15 as counter-regulator of neutrophilic, antibody-mediated cutaneous inflammation. Enhancing the activity of GPR15 may therefore constitute a novel therapeutic principle in the treatment of pemphigoid diseases, such as BP-like EBA.

Incidence of subclinical atrial fibrillation in a South Asian population.

BACKGROUND: South Asians have a lower prevalence of atrial fibrillation (AF) compared with Caucasians despite higher rates of conventional risk factors and a higher incidence of stroke. It is not clear whether South Asians truly experience less AF or whether this is due to underdetection of the arrhythmia. Therefore, we aimed to determine whether South Asian patients with pacemakers have a lower incidence of device-detected subclinical episodes of AF compared with Caucasian controls. METHODS: We performed a retrospective cohort study of South Asian and Caucasian patients who underwent pacemaker implantation between 2006 and 2016. Subclinical AF episodes, detected during subsequent device clinic follow-up visits, were identified and the occurrence of clinical AF, cerebrovascular events, and all-cause mortality was recorded. RESULTS: A total of 5 648 patients underwent pacemaker implantation at the Yorkshire Heart Centre, UK, during the study period. Of these, 169 were South Asian and 72 met the eligibility criteria. The cumulative incidence of subclinical AF was significantly lower in South Asians compared with Caucasians (logrank P  =  0.002) with an annual event rate of 6.9% versus 13.9%, and South Asian ethnicity was an independent predictor of a lower incidence of subclinical AF (odds ratio =  0.43; 95% confidence interval  =  1.01-5.38). CONCLUSIONS: South Asians with an implanted pacemaker have a lower rate of subclinical AF compared with Caucasians.