No abstract

Gadoxetic acid-enhanced MR imaging facilitates the differentiation of FNH from HCA.

We investigated the molecular and cellular basis of severe combined immunodeficiency (SCID) in six patients with otofaciocervical syndrome type 2 who failed to attain T cell reconstitution after allogeneic hematopoietic stem cell transplantation, despite successful engraftment in three of them. We identified rare biallelic PAX1 rare variants in all patients. We demonstrated that these mutant PAX1 proteins have an altered conformation and flexibility of the paired box domain and reduced transcriptional activity. We generated patient-derived induced pluripotent stem cells and differentiated them into thymic epithelial progenitor cells and found that they have an altered transcriptional profile, including for genes involved in the development of the thymus and other tissues derived from pharyngeal pouches. These results identify biallelic, loss-of-function PAX1 mutations as the cause of a syndromic form of SCID due to altered thymus development.

Primary immune deficiencies (PID) comprise a heterogeneous group of genetically determined disorders that affect development and/or function of innate or adaptive immunity. Consequently, patients with PID suffer from recurrent and/or severe infections that frequently involve the lung. While the nature of the immune defect often dictates the type of pathogens that may cause lung infection, there is substantial overlap of radiological findings, so that appropriate laboratory tests are mandatory to define the nature of the immune defect and to prompt appropriate treatment. At the same time, the recent identification of a large number of PID-causing genes now allows early, even presymptomatic diagnosis, thus representing an essential tool for prevention of lung damage. This review article describes the most common forms of PID, their cellular and molecular bases, and the associated lung abnormalities, and reports on available treatment.

Hepatocellular adenomas (HCAs) are currently categorized into distinct genetic and pathologic subtypes as follows: inflammatory hepatocellular adenoma, hepatocyte-nuclear-factor-1-alpha (HNF-1α-mutated) hepatocellular adenoma, and β-catenin-mutated hepatocellular adenomas; the fourth, defined as unclassified subtype, encompasses HCAs without any genetic abnormalities. This classification has accepted management implications due to different risks of haemorrhage and malignant transformation of the four subtypes. Imaging guided biopsy and/or surgical resection very important in obtaining definitive characterization; nevertheless, MRI with intra-extravascular and hepatobiliary (dual phase) agents, is an important tool not only in differential subtypes definition but even in surveillance with early identification of complications and discovery of some signs of HCA malignant degeneration. Inflammation, abnormal rich vascularisation, peliotic areas, and abundant fatty infiltration are pathologic findings differently present in the HCA subtypes and they may be detected by multiparametric MRI approach. Lesion enlargement and heterogeneity of signal intensity and of contrast enhancement are signs to be considered in malignant transformation. The purpose of this paper is to present the state of the art of MRI in the diagnosis of HCA and subtype characterization, with particular regard to morphologic and functional information available with dual phase contrast agents, and to discuss differential diagnosis with the most common benign and malignant lesions mimicking HCAs.

On computed tomography, the type and severity of lung lesions do not correlate either with the type of immunodeficiency or with the severity of the sinusal involvement.

Purpose:To compare the efficacy of two different MR contrast agents for the detection and diagnosis of focal nodular hyperplasia (FNH). Materials and Methods:Fifty patients with 83 FNH lesions detected on spiral CT were studied in two different MRI sessions with Gd-BOPTA (MultiHance) and ferumoxides (Endorem®). MRI with Gd-BOPTA was performed precontrast (T1wGRE and T2wTSE sequences) and during the dynamic and late (1-3 hours) phases after injection (T1wGRE sequences only). MRI with ferumoxides (T1wGRE and T2wTSE sequences) was performed before and at least 30 minutes after injection. Hyper-or isointensity of FNH in the late phase was considered typical for Gd-BOPTA, while isointensity or lesion hypointensity was considered typical for ferumoxides.Results: With Gd-BOPTA, 83 FNH lesions (100%) appeared hyperintense during the arterial phase of dynamic MRI. All but one lesion was iso-or slightly hyperintense in the portal-venous and equilibrium phases. In the late phase, 81 FNH lesions were hyper-or isointense to the surrounding parenchyma, with two lesions appearing slightly hypointense. With ferumoxides, a significant (P Ͻ 0.001) number (21/83, 25.3%) of FNH lesions (mean diameter ϭ 16.8 Ϯ 6.6 mm) were not visible. Of the visible FNH lesions, 38/62 were slightly hyperintense, and 24/62 were isointense to the surrounding parenchyma on the T2wTSE images. On the T1wGRE images, 42/62 lesions were isointense, 19/62 were slightly hyperintense, and one lesion was slightly hypointense. Seventeen lesions in 12 patients with previous neoplasia were all detected after Gd-BOPTA administration, whereas only nine of these 17 lesions (52.9%) were detected after ferumoxide administration. Two of these nine lesions showed atypical enhancement features. Conclusion:Gd-BOPTA-enhanced MRI is significantly better than ferumoxide-enhanced MRI for the identification and characterization of FNH.

Background: Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) is a severe non-infectious complication of Common Variable Immunodeficiency (CVID), often associated with extrapulmonary involvement. Due to a poorly understood pathogenesis, GLILD diagnosis and management criteria still lack consensus. Accordingly, it is a relevant cause of long-term loss of respiratory function and is closely associated with a markedly reduced survival. The aim of this study was to describe clinical, immunological, laboratory and functional features of GLILD, whose combination in a predictive model might allow a timely diagnosis.Methods: In a multicenter retrospective cross-sectional study we enrolled 73 CVID patients with radiologic features of interstitial lung disease (ILD) associated to CVID (CVID-ILD) and 125 CVID patients without ILD (controls). Of the 73 CVID-ILD patients, 47 received a definite GLILD diagnosis while 26 received a clinical-radiologic diagnosis of CVID related ILD defined as uILD.Results: In GLILD group we found a higher prevalence of splenomegaly (84.8 vs. 39.2%), autoimmune cytopenia (59.6 vs. 6.4%) and bronchiectasis (72.3 vs. 28%), and lower IgA and IgG serum levels at CVID diagnosis. GLILD patients presented lower percentage of switched-memory B cells and marginal zone B cells, and a marked increase in the percentage of circulating CD21lo B cells (14.2 vs. 2.9%). GLILD patients also showed lower total lung capacity (TLC 87.5 vs. 5.0%) and gas transfer (DLCO 61.5 vs. 5.0%) percent of predicted. By univariate logistic regression analysis, we found IgG and IgA levels at CVID diagnosis, presence of splenomegaly and autoimmune cytopenia, CD21lo B cells percentage, TLC and DCLO percent of predicted to be associated to GLILD. The joint analysis of four variables (CD21lo B cells percentage, autoimmune cytopenia, splenomegaly and DLCO percent of predicted), together in a multiple logistic regression model, yielded an area under the ROC curve (AUC) of 0.98 (95% CI: 0.95-1.0). The AUC was only slightly modified when pooling together GLILD and uILD patients (0.92, 95% CI: 0.87-0.97).Conclusions: we propose the combination of two clinical parameters (splenomegaly and autoimmune cytopenia), one lung function index (DLCO%) and one immunologic variable (CD21lo%) as a promising tool for early identification of CVID patients with interstitial lung disease, limiting the use of aggressive diagnostic procedures.