Flow cytometric analysis of CD55 and CD59 expression on blood cells in paroxysmal nocturnal haemoglobinuria

PNH is a rare clonal disorder of hematopoietic stem cells, therefore all blood cells lineages are involved. The main feature is an increased sensitivity of erythrocytes to complement-mediated cell lysis due to deficiency of membrane-bound GPI (glycosylphosphatidylinositol)-anchored proteins which normally function as inhibitors of reactive hemolysis. In the present study, we performed flow cytometric analysis using monoclonal antibodies against CD55 and CD59 for the detection of PNH-type clone in the blood of 50 patients (28 females and 22 males, age range 7-67 yrs). In one patient only we found a large population (95%) of granulocytes with decreased expression of both CD55 and CD59 molecules (type I PNH) and in two others with partial loss of CD55 expression (type II PNH). The expression was determined chiefly on granulocytes which in the control group showed reliable and high expression of CD55 and CD59

Rak pęcherzykowy tarczycy z przerzutami do wątroby — diagnostyka, leczenie i prognoza

  Follicular thyroid carcinoma (FTC) is the second most common type of thyroid cancer (TC) and accounts for approximately 10% of all TC cases. Liver metastases are a rare presentation in 0.5–1% of follicular thyroid cancers, usually occurring in the setting of widely disseminated FTC disease, and their presence is associated with poor prognosis. Until now, there have been only 30 cases of FTC liver metastases described in the literature. Herein, we review publications and describe diagnostic tools that may be used in the diagnosis and follow-up of FTC metastases to the liver, including biopsy and imaging techniques like US, CT, MRI, SPECT, PET, and radioiodine scintigraphy. We also present and discuss current methods of treatment, e.g. TSH suppressive therapy with levothyroxine, surgery, radiofrequency ablation (RFA), transarterial embolisation (TAE), liver transarterial chemoembolisation (TACE), chemotherapy with cisplatin and doxorubicin, treatment with Indium- 111-octreotide (or its analogues), and tyrosine kinase inhibitors (sorafenib, sunitinib). At the end we describe the course, results of diagnostics, and treatment in a patient with large multiple FTC metastases to the liver. (Endokrynol Pol 2016; 67 (3): 332–347)    Rak pęcherzykowy tarczycy (FTC) jest drugim najczęstszym typem raka tarczycy (TC) i stanowi około 10% wszystkich TC. Przerzuty do wątroby występują w 0,5–1% przypadków FTC, zwykle w przypadku znacznie zaawansowanej choroby nowotworowej i wiążą się ze złą prognozą. Do tej pory, tylko 30 przypadków FTC z przerzutami do wątroby zostało opisanych w literaturze. W niniejszej pracy dokonano przeglądu literatury i opisu metod diagnostycznych jakie mogą być użyte w badaniu i kontroli przerzutów FTC do wątroby, w tym biopsji, technik obrazowych, takich jak: USG, KT, MRI, SPECT, PET i scyntygrafii jodowej. Zaprezentowano i omówiono aktualne metody leczenia: terapię L-tyroksyną w dawce supresyjnej, leczenie operacyjne, ablację prądem o częstotliwości fal radiowych (RFA), embolizację przeztętniczą (TAE), przeztętniczą chemoembolizację, chemioterapię z użyciem cisplatyny i doksyrubicyny, leczenie z użyciem analogów somatostatyny w tym octreotydu znakowanego izotopem indu 111In, czy terapię z użyciem inhibitorów kinazy tyrozynowej (sorafenib, sunitynib). Na końcu opisano przebieg choroby, wyniki badań diagnostycznych i podjęte leczenie u chorej z ogromnymi mnogimi przerzutami FTC do wątroby. (Endokrynol Pol 2016; 67 (3): 332–347)

Extraneural relapse of medulloblastoma mimicking acute leukemia: A diagnostic challenge in adult patient

Medulloblastoma is the most frequent malignant tumor of the central nervous system (CNS) in children, but it can rarely occur in adults. Extraneural relapse of medulloblastoma occurs very rarely and it is usually associated with dismal prognosis. We present a case of young adult with relapsed medulloblastoma with extraneural metastases in the bone marrow and expression of terminal deoxynucleotidyl transferase (TdT) on the malignant cells mimicking acute leukemia. To the best of our knowledge, this is the first report of medulloblastoma exhibiting expression of the TdT in adult. We would like to emphasize that in cases like this, differential diagnosis of anemia and thrombocytopenia in adults should include a consideration of primary or secondary bone marrow involvement by medulloblastoma or other rare malignancy

Chorzy trudni nietypowi Żylna choroba zakrzepowo-zatorowa u pacjenta z nieinwazyjnym grasiczakiem i wieloletnią pęcherzycą

A case of a 69-year-old man, admitted due to an acute episode of venous thromboembolism (VTE) is described. He had a 3-year history of ‘asymptomatic’ (revealed on routine chest X-ray, but undiagnosed) tumor of anterior mediastinum, and a 8-year history of pemphigus vulgaris treated mainly with steroids. Three months following VTE episode he underwent tumor resection and histopathologic evaluation showed noninvasive, type AB thymoma. Gradual pemphigus remission started some weeks later. We analyse the relationship between thymoma, pemphigus and VTE, and emphasize the usefulness of echocardiographic thymoma imaging as a method complementary to computed tomography/magnetic resonance

Arginase-1 in Plasma-Derived Exosomes as Marker of Metastasis in Patients with Head and Neck Squamous Cell Carcinoma

Immunoregulatory Arginase-1 (Arg-1) is present in the tumor microenvironment of solid tumors. Its association to clinicopathology and its prognostic impact are inconsistent among different tumor types and biological fluids. This study evaluated Arg-1 protein levels in tumors and the circulation of patients with head and neck squamous cell carcinoma (HNSCC) in relation to clinical stage and prognosis. Tumor Arg-1 expression was monitored via immunohistochemistry while plasma Arg-1 levels via ELISA in 37 HNSCC patients. Arg-1 presence in plasma-derived exosomes was assessed using Western blots in 20 HNSCC patients. High tumor Arg-1 expression correlated with favorable clinicopathology and longer recurrence-free survival (RFS), while high plasma Arg-1 levels were associated with unfavorable clinicopathology. All patients with low tumor and high plasma Arg-1 had nodal metastases and developed recurrence. This discrepancy was attributed to the presence of Arg-1-carrying exosomes. Arg-1 was found in plasma-derived exosomes from all HNSCC patients. High exosomal Arg-1 levels were associated with positive lymph nodes and short RFS. Circulating Arg-1+ exosomes represent a mechanism of active Arg-1 export from the tumor to the periphery. Exosomes reflected biologically relevant Arg-1 levels in metastatic HNSCC and emerged as potentially more accurate biomarkers of metastatic disease and RFS than tissue or plasma Arg-1 levels

Correction: The sorafenib anti-relapse effect after alloHSCT is associated with heightened alloreactivity and accumulation of CD8+PD-1+ (CD279+) lymphocytes in marrow.

[This corrects the article DOI: 10.1371/journal.pone.0190525.]

Effects of Low-Dose Atorvastatin on the Peripheral Blood Mononuclear Cell Secretion of Angiogenic Factors in Type 2 Diabetes

The aim of this study was to investigate the influence of statins on the secretion of angiogenesis mediators by the peripheral blood mononuclear cells (PBMCs) derived from patients suffering from type 2 diabetes. The study group comprised 30 participants and included: 10 statin-treated patients with diabetes, 10 statin-free diabetic subjects, and 10 statin-free non-diabetic individuals. PBMCs isolated from the blood were cultured in vitro in standard conditions and in an environment mimicking hyperglycemia. Culture supernatants were evaluated for VEGF, MCP-1, Il-10, and Il-12 by flow cytometry using commercial BDTM. Cytometric Bead Array tests. The secretion of VEGF, MCP-1 and Il-12 by PBMCs, cultured both in standard and hyperglycemic conditions, was significantly lower in the statin-treated patients with type 2 diabetes in comparison with the statin-free diabetic patients. Conversely, the secretion of Il-10 was higher in the statin-treated than in the statin-free diabetic patients. VEGF, MCP-1 and Il-12 levels in PBMCs supernatants from the glucose-containing medium were higher than those from the standard medium in each of the diabetic groups. The results of the study suggest that statins in low doses exhibit an antiangiogenic activity, reducing the secretion of potent proangiogenic factors, such as VEGF and MCP-1, and increasing the secretion of antiangiogenic Il-10 by PBMCs, also under hyperglycemic conditions characteristic for type 2 diabetes

Temporal changes in regulatory T cell subsets defined by the transcription factor Helios in stroke and their potential role in stroke-associated infection: a prospective case–control study

Abstract Background Regulatory T cells (Tregs) are involved in the systemic immune response after ischemic stroke. However, their role remains unclear, and the effect appears to be both neuroprotective and detrimental. Treg suppressor function may result in immunodepression and promote stroke-associated infection (SAI). Thus we assume that the bidirectional effects of Tregs may be in part attributed to the intracellular transcription factor Helios. Tregs with Helios expression (H+ Tregs) constitute 70–90% of all Treg cells and more frequently than Helios-negative Tregs (H− Tregs) express molecules recognized as markers of Tregs with suppressor abilities. Methods and results We prospectively assessed the circulating Treg population with flow cytometry in 52 subjects on days 1, 3, 10 and 90 after ischemic stroke and we compared the results with those obtained in concurrent age-, sex- and vascular risk factor-matched controls. At all studied time points the percentage of H+ Tregs decreased in stroke subjects—D1: 69.1% p < 0.0001; D3: 62.5% (49.6–76.6), p < 0.0001; D10: 60.9% (56.5–72.9), p < 0.0001; D90: 79.2% (50.2–91.7), p = 0.014 vs. controls: 92.7% (81.9–97.0) and the percentage of H− Tregs increased accordingly. In patients with SAI the percentage of pro-suppressor H+ Tregs on post-stroke day 3 was higher than in those without infection (p = 0.03). After adjustment for confounders, the percentage of H+ Tregs on day 3 independently correlated with SAI [OR 1.29; CI 95%: 1.08–1.27); p = 0.02]. Although the percentage of H+ Tregs on day 3 correlated positively with NIHSS score on day 90 (rS = 0.62; p < 0.01) and the infarct volume at day 90 (rS = 0.58; p < 0.05), in regression analysis it was not an independent risk factor. Conclusions On the first day after stroke the proportion of H+ vs. H− Tregs changes in favor of pro-inflammatory H− Tregs, and this shift continues toward normalization when assessed on day 90. A higher percentage of pro-suppressive H+ Tregs on day 3 independently correlates with SAI and is associated positively with NIHSS score, but it does not independently affect the outcome and stroke area in the convalescent phase of stroke

TLR2 Expression on Select Lymphocyte Subsets as a New Marker in Glomerulonephritis

Toll-like receptor (TLR) signaling may be involved in autoimmune kidney disorders and has been implicated in proliferative and non-proliferative glomerulonephritis (PGN and NPGN). In this study, we investigated the expression of TLR2 on T and B lymphocytes in relation to selected clinical parameters in patients with PGN and NPGN. We collected peripheral blood from the ulnar vein of patients with PGN (n = 15) or NPGN (n = 22) and healthy volunteers (n = 20). The percentage of peripheral blood mononuclear cells expressing TLR2 was determined with flow cytometry. TLR2 expression on T and B lymphocytes was increased in PGN patients compared with NPGN patients and controls (p &le; 0.001). In patients with PGN, TLR2 expression correlated negatively with the serum concentrations of IgG and albumin and positively with urine protein excretion. Receiver operating characteristic (ROC) analysis indicated that TLR2 expression is a highly specific marker to distinguish PGN patients from NPGN patients and controls, especially on CD4+ T lymphocytes. Its use as a non-invasive marker of disease should be further investigated