Confined placental mosaicism: Distribution of chromosomally abnormal cells over the term placenta.

OBJECTIVE: Non-invasive prenatal testing (NIPT) investigates placental DNA and may detect confined placental mosaicism (CPM). The aim of this study was to confirm CPM in the term placenta in cases with abnormal NIPT but normal follow-up cytogenetic studies of fetus and mother. Additionally we examined the distribution of abnormal cells over the placenta. METHODS: Four chorionic villus (CV) biopsies from four placental quadrants were requested in cases where CPM was assumed. Both cell lineages of the CV, cytotrophoblast (CTB) and mesenchymal core (MC), were analyzed separately with SNP array. RESULTS: The chromosome aberration was confirmed in 67 % of the placentas. Three quarters of the CTB and MC biopsies from these mosaic placentas were uniformly normal (57 %) or abnormal (20 %), and a minority showed mosaicism. Among 16 cases of CPM where first trimester CV were examined as well, 11 had chromosomally normal results during pregnancy. DISCUSSION: Cytogenetic investigations of term placental biopsies suspected to be affected with CPM did not reveal the chromosome aberration in one third of the placentas. This is caused by the patchy pattern in which chromosomally abnormal cells are distributed over the placenta with the majority of the biopsies being uniformly normal. Further CPM research, including its clinical impact, requires the analysis of more than four biopsies to get insight into the extent of the affected part. Moreover, a subset of CPM type 1 and 3 seems to be only detectable with NIPT and not with first trimester CVS.

Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa.

BACKGROUND: There is a dearth of information on the precise pathogenesis of hidradenitis suppurativa (HS), but immune dysregulation is implicated. OBJECTIVES: To determine the nature of the immune response in HS. METHODS: Skin biopsies - lesional, perilesional (2 cm away) and uninvolved (10 cm away) - were obtained from patients with HS and healthy controls. The expression of various cytokines was determined by enzyme-linked immunosorbent assay, flow cytometry and real-time polymerase chain reaction. RESULTS: The expression of the inflammatory cytokines interleukin (IL)-17, IL-1ß and tumour necrosis factor-α was enhanced in lesional skin of patients with HS. In addition, IL17A and IL1B mRNA were enhanced in clinically normal perilesional skin. CD4(+) T cells produced IL-17 in HS, while CD11c(+) CD1a(-) CD14(+) cells were sources of IL-1ß. Activated caspase-1 was detected in HS skin and was associated with enhanced expression of NLRP3 and IL18. Inhibition of caspase-1 decreased IL-1ß and IL-18 production, suggesting that the caspase-1 pathway participates in IL-1ß and IL-18 expression in HS. Abnormal cytokine expression was detected in perilesional and uninvolved skin, which may suggest that subclinical inflammation is present in HS skin prior to the formation of an active lesion. CONCLUSIONS: This study demonstrates that CD4(+) T cells produce IL-17 in HS and that the IL-17 pathway may be important in HS pathogenesis. CD11c(+) CD1a(-) CD14(+) cells are a source of IL-1ß in HS, the production of which was shown to be mediated, in part, via a caspase-1-dependent pathway. These results suggest that IL-17 and the caspase-1-associated cytokines IL-1ß and IL-18 may play a role in the pathogenesis of HS.

Idiopathic noncirrhotic portal hypertension is associated with poor survival: results of a long-term cohort study.

BACKGROUND: Idiopathic noncirrhotic portal hypertension (INCPH) is a rare disease in the Western world. As a result, little is known about the clinical characteristics and outcome of these patients. Survival in these patients is considered to be similar to that of the general population. AIM: To investigate the clinical manifestations, pathophysiology, outcome and determinants of survival in Western INCPH patients. METHODS: Multicentre cohort study of INCPH patients. RESULTS: A total of 62 patients were followed for a median time of 90 months (range 24-310). Initial manifestations leading to the diagnosis of INCPH were related to portal hypertension in 82% of the patients. Histological signs of portal blood supply disturbances were present in nearly all patients. During follow-up, 12 of 62 patients developed liver decompensation, of which four were considered for liver transplantation. One patient died in the context of variceal bleeding. Hepatocellular carcinoma was not observed during follow-up. A total of 23 patients died during follow-up, only four of them due to liver related mortality. The Kaplan-Meier estimates for overall survival were 100% (95% CI 95-100%), 78% (95% CI 67-89%) and 56% (95% CI 40-72%) at 1, 5 and 10 years respectively. Survival for INCPH was significantly decreased (P < 0.001) compared to survival of the general population. Ascites was an independent predictor of poor outcome. CONCLUSIONS: In comparison to the general population, survival in INCPH patients is poor. Mortality is related to associated disorders and medical conditions occurring at older age. Patients rarely die due to liver related complications. Patients with ascites have a poor prognosis.