Expression of HDACs 1, 3 and 8 Is Upregulated in the Presence of Infiltrating Lymphocytes in Uveal Melanoma

In Uveal Melanoma (UM), an inflammatory phenotype is strongly associated with the development of metastases and with chromosome 3/BAP1 expression loss. As an increased expression of several Histone Deacetylases (HDACs) was associated with loss of chromosome 3, this suggested that HDAC expression might also be related to inflammation. We analyzed HDAC expression and the presence of leukocytes by mRNA expression in two sets of UM (Leiden and TCGA) and determined the T lymphocyte fraction through ddPCR. Four UM cell lines were treated with IFNγ (50IU, 200IU). Quantitative PCR (qPCR) was used for mRNA measurement of HDACs in cultured cells. In both cohorts (Leiden and TCGA), a positive correlation occurred between expression of HDACs 1, 3 and 8 and the presence of a T-cell infiltrate, while expression of HDACs 2 and 11 was negatively correlated with the presence of tumor-infiltrating macrophages. Stimulation of UM cell lines with IFNγ induced an increase in HDACs 1, 4, 5, 7 and 8 in two out of four UM cell lines. We conclude that the observed positive correlations between HDAC expression and chromosome 3/BAP1 loss may be related to the presence of infiltrating T cells.

Quantitative parameters of lymphocyte nuclear morphology in bronchoalveolar lavage fluid as novel biomarkers for sarcoidosis

Background Bronchoalveolar lavage (BAL) is one of the fundamental examinations for the differential diagnosis of interstitial lung diseases (ILDs), and lymphocytosis strongly indicates alternative diagnoses rather than idiopathic pulmonary fibrosis. However, the BALF lymphocytosis is observed in several ILDs. We considered that quantitative evaluation of the BALF lymphocyte nuclear morphology would be useful in the differential diagnosis of ILDs with increased BALF lymphocyte fraction. Results One hundred and twenty-one patients with ILDs having increased BALF lymphocyte fraction were recruited (68 in the development cohort and 53 in the validation cohort). In the development cohort, BALF lymphocyte nuclei in sarcoidosis patients showed significantly smaller areas, shorter perimeters, lower radius ratios, and increased roundness than those of other ILD patients (p < 0.001 for each). Next, the fractions of lymphocytes with small areas, short perimeters, low radius ratios, and increased roundness, which were determined based on receiver operating characteristic (ROC) analyses-based thresholds, were demonstrated to be higher in sarcoidosis patients than in the other ILD patients (p < 0.001 for each). Furthermore, when we combined size-representing parameters with shape-representing parameters, the fraction of lymphocytes with small and round nuclei showed approximately 0.90 of area under the ROC curve in discriminating sarcoidosis both in the development cohort and the validation cohort. Conclusion This study is the first to demonstrate the usefulness of quantitative parameters of BALF lymphocyte nuclear morphology as novel biomarkers for sarcoidosis.

COVID-19-related pneumonia with a predominant lymphocyte fraction in bronchoalveolar lavage fluid

A 48-year-old woman, considered as a close contact of her husband who was diagnosed with COVID-19. She was clinically diagnosed with COVID-19-related pneumonia because of a positive antibody test. Her BALF contained an elevated lymphocyte fraction, which might explain why steroids are effective against COVID-19-related pneumonia.

Computed Tomography Findings as Determinants of Local and Systemic Inflammation Biomarkers in Interstitial Lung Diseases: A Retrospective Registry-Based Descriptive Study

Purpose To evaluate the association of peripheral blood (PBL) and broncho-alveolar lavage (BAL) biomarkers with inflammatory versus fibrotic high-resolution computed tomography (HRCT) findings in interstitial lung disease (ILD) patients. Methods HRCT findings of 127 consecutive ILD-board patients were semi-quantitatively evaluated: reticulation/honeycombing (RET), traction bronchiectasis (TBR) and emphysema (EMP) were classified as non-inflammatory/fibrotic; consolidations (CON), ground glass opacities (GGO), parenchymal nodules (NDL) and mosaic attenuation (MOS) as active inflammatory. Each HRCT finding was assessed in six distinct lung regions, resulting scores were graded as minimal (0–1 regions involved), medium (2–4) or extensive (5–6). Associations of routinely assessed PBL/BAL biomarkers with these HRCT scores were evaluated using Spearman correlation coefficients and graphical presentation; significance was tested by applying Kruskal–Wallis tests. Results Blood neutrophil, lymphocyte and eosinophil fraction, neutrophil to lymphocyte ratio (NLR) and BAL lymphocyte fraction consistently showed opposite correlations with inflammatory versus non-inflammatory/fibrotic HRCT finding scores. Blood lymphocyte fraction significantly differed by graded GGO (p = 0.032) and CON (p = 0.027) extent, eosinophil fraction by TBR (p = 0.006) and NLR by CON (p = 0.009). C-reactive protein was significantly related to GGO (p = 0.023) and CON (p = 0.004), BAL lymphocyte fraction to GGO (p = 0.017) extent. Conclusion Blood lymphocyte and eosinophil fraction, NLR, CRP and BAL lymphocyte fraction may aid to differentiate inflammatory from non-inflammatory/fibrotic ILD patterns. Trial registration This evaluation was based on data from the ILD registry of Kepler University Hospital Linz, as approved by the ethics committee of the Federal State of Upper-Austria (EK Number. I-26-17).

Computed Tomography Findings as Determinants of Local and Systemic Inflammation Biomarkers in Interstitial Lung Diseases: A Retrospective Registry-based Descriptive Study

Purpose: To evaluate the association of peripheral blood (PBL) and broncho-alveolar lavage (BAL) biomarkers with inflammatory versus fibrotic high-resolution computed tomography (HRCT) findings in interstitial lung diseases (ILD). Methods: HRCT of 127 subsequent ILD-board patients were semi-quantitatively evaluated in a standardized way: Reticulation/honeycombing (RET), traction bronchiectasis (TBR) and emphysema (EMP) were classified as non-inflammatory/fibrotic; consolidations (CON), ground glass opacities (GGO), noduli (NDL) and mosaic attenuation (MOS) as active inflammatory findings. Presence or absence of each HRCT finding was counted in 6 distinct lung regions, resulting scores were graded as minimal (0–1 regions involved), medium (2–4) or extensive (5–6). Associations of routinely assessed PBL/BAL biomarkers with these radiological scores were evaluated using Spearman correlation coefficients and graphical presentation; significance of the graded HRCT scores was tested by applying Kruskal-Wallis tests. Results: Blood neutrophil, lymphocyte and eosinophil fraction, neutrophil-lymphocyte ratio (NLR) and BAL lymphocyte fraction consistently showed opposite correlations for inflammatory versus non-inflammatory/fibrotic HRCT finding scores. Blood lymphocyte fraction significantly differed by graded GGO (p = 0.032) and CON (p = 0.027) extent, eosinophil fraction by TBR (p = 0.006) and NLR by CON (p = 0.009). C-reactive protein was significantly related to GGO (p = 0.023) and CON (p = 0.004), BAL lymphocyte fraction to GGO (p = 0.017). Conclusion: Blood lymphocyte and eosinophil fraction, NLR, CRP and BAL lymphocyte fraction may aid to differentiate inflammatory from non-inflammatory/fibrotic ILD patterns. Trial registration: This evaluation was based on data from the ILD registry of Kepler University Hospital Linz, as approved by the ethics committee of the federal state of Upper-Austria (EK Nr. I-26-17).

Computed Tomography Findings as Determinants of Local and Systemic Inflammation Biomarkers in Interstitial Lung Diseases: A Retrospective Cohort Study

Background: Additional to high-resolution computed tomography (HRCT), peripheral blood (PBL) and broncho-alveolar lavage (BAL) could provide biomarkers to distinguish predominantly inflammatory from non-inflammatory/fibrotic interstitial lung disease (ILD) phenotypes. Methods:HRCT of 127 subsequent ILD-board patients were semi-quantitatively evaluated in a standardized way: Reticulation/honeycombing (RET), traction bronchiectasis (TBR) and emphysema (EMP) were classified as non-inflammatory/fibrotic; consolidations (CON), ground glass opacities (GGO), noduli (NDL) and mosaic attenuation (MOS) as active inflammatory findings. These HRCT findings were counted as present or absent in 6 distinct lung regions, resulting scores were graded as minimal (0-1 regions involved), medium (2-4) or extensive (5-6). Associations between routinely assessed PBL/BAL biomarkers with these radiological scores were evaluated using Spearman correlation coefficients; significance of the graded HRCT scores by applying Kruskal-Wallis tests.Results: Blood neutrophil, lymphocyte and eosinophil fraction, neutrophil-lymphocyte ratio (NLR) and BAL lymphocyte fraction consistently showed opposite correlations for inflammatory versus non-inflammatory/fibrotic HRCT finding scores. Blood lymphocyte fraction significantly differed by graded GGO (p=0.032) and CON (p=0.027) extent, eosinophil fraction by TBR (p=0.006) and NLR by CON (p=0.009). C-reactive protein was significantly related to GGO (p=0.023) and CON (p=0.004), BAL lymphocyte fraction to GGO (p=0.017). Conclusions:Blood lymphocyte and eosinophil fraction, NLR, CRP and BAL lymphocyte fraction may aid to differentiate inflammatory from non-inflammatory/fibrotic ILD patterns. Trial registration:This evaluation was based on data from the ILD registry of Kepler University Hospital Linz, as approved by the ethics committee of the federal state of Upper-Austria (EK Nr. I-26-17).

Parkinson's disease (PD) is the most common neurodegenerative disease

Metabolic impairment of alpha-synuclein protein is considered to be the central event in PDpathogenesis. Recent studies explored usage of alpha-synuclein in peripheral fluids as a biomarker of PD, however alpha-synuclein level in the CSF and plasma is considered to be affected by hemolysis. In order to avoid contamination of a lymphocyte fraction by erythrocytes, we have proposed an algorithm based on measurements of alpha-synuclein levels in the homogeneous CD45+ cell blood fraction. For this study we formed a group of PD patients (N=14) and a control group without the neurological disorders (N=17). We found an increase in the level of the total alpha-synuclein in CD45+ cells of PD patients compared to controls (p = 0,04), and revealed a direct correlation between the level of dopamine in plasma and level of total alpha-synuclein in CD45+ cells in the control group (r=0,71, p = 0,007).The level of alpha-synuclein in CD45+ cells could be suggested as possible PD biomarker.

Changes in selected subpopulations of lymphocytes in dogs infected with Babesia canis treated with imidocarb

SummaryObjective: The purpose of this study was to track changes in selected subpopulations of lymphocytes in the blood of dogs infected with Babesia (B.) canis and treated with imidocarb. Material and methods: The study included 16 dogs divided into two groups. The first group (n = 6) consisted of healthy control animals. Dogs of the second group (n = 10) were infected with B. canis and after establishment of the diagnosis each animal received a single dose of imidocarb (5 mg/kg). Flow cytometry was used to enumerate several immune cell phenotypes. Results: It was concluded that the invasion of B. canis contributes to the decreased percentage of CD3+, CD4+, CD8+, CD21+ lymphocytes in the blood of infected animals. The decreased level of tested subpopulations of lymphocytes in group 2 persisted for the entire 12-day period of the test. After the administration of imidocarb, each tested lymphocyte fraction in the blood of the dogs with babesiosis increased, but did not reach physiological values. Conclusion: The presented results indicate that the resolution of clinical signs associated with babesiosis may be related to the stimulation and intensity of cellular immunity, dependent on the CD4+ T cells profile. After administration of imidocarb, the parasitemia is cleared which allows the recovery of the lymphocyte populations.