Virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, despite successful treatment, hepatitis C virus (HCV) may progress to HCC from initiated liver cirrhosis. Cytotoxic T cells (Tcs) are known to be involved in HCV-related cirrhotic complications and HCC pathogenesis. The inhibitory checkpoint leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on Tcs. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression and to evaluate LAIR-1 expression as a noninvasive biomarker for HCC progression in the context of liver cirrhosis related to HCV genotype 4 (G4) in Egyptian patients' peripheral venous blood liquid biopsy. A total of 64 patients with HCC and 37 patients with liver cirrhosis were enrolled in this case-controlled study, and their LAIR-1 expression on Tc related to the progression of liver cirrhosis was examined and compared to that of the apparently healthy control group (n = 20). LAIR-1 expression was analyzed using flow cytometry. Results: The HCC group had significantly higher LAIR-1 expression on Tc and percentage of Tc positive for LAIR-1 (LAIR-1+Tc%) than the HCV G4-related liver cirrhosis group. LAIR-1+Tc% was correlated with the HCC surrogate tumor marker AFP (r = 0.367, p = 0.001) and insulin resistance and inflammation prognostic ratios/indices. A receiver operating characteristic (ROC) curve revealed that adding LAIR-1+Tc% to AFP can distinguish HCC transformation in the Egyptian patients' cohort. Upregulated LAIR-1 expression on Tc could be a potential screening noninvasive molecular marker for chronic inflammatory HCV G4 related liver cirrhosis. Moreover, LAIR-1 expression on Tc may be one of the players involved in the progression of liver cirrhosis to HCC.

Memory B cells (MBCs) can persist for a lifetime, but the mechanisms that allow their long-term survival remain poorly understood. Here, we isolated and analyzed human splenic smallpox/vaccinia protein B5-specific MBCs in individuals who were vaccinated more than 40 years ago. Only a handful of clones persisted over such an extended period, and they displayed limited intra-clonal diversity with signs of extensive affinity-based selection. These long-lived MBCs appeared enriched in a CD21hiCD20hi IgG+ splenic B cell subset displaying a marginal-zone-like NOTCH/MYC-driven signature, but they did not harbor a unique longevity-associated transcriptional or metabolic profile. Finally, the telomeres of B5-specific, long-lived MBCs were longer than those in patient-paired naive B cells in all the samples analyzed. Overall, these results imply that separate mechanisms such as early telomere elongation, affinity selection during the contraction phase, and access to a specific niche contribute to ensuring the functional longevity of MBCs.
Copyright © 2022 Elsevier Inc. All rights reserved.

Psoriasis vulgaris (PsV) is an immune-mediated inflammatory disorder with devastating psychosocial consequences. Expression of immunoregulator molecules on leukocytes in PsV remains unclear. Leukocyte-associated Ig-like receptor-1 (LAIR-1) and complement receptor-1 (CR-1) are immunoregulator receptors reported to bind complement component 1q involved in phagocytosis. We aimed to explore if altered leukocyte expression of LAIR-1 and CR-1 is associated with PsV. This case-control study included 36 PsV patients and 36 healthy controls. Neutrophils, monocytes and B and T cells were examined by flow cytometry for LAIR-1 and CR-1 mean fluorescence intensity (MFI) and positive cell percentage. Comparison between both groups revealed a significant decrease in LAIR-1 MFI on neutrophils and T cells (P < 0.001 and P = 0.003, respectively). CR-1 MFI on neutrophils, monocytes and T cells also showed a significant decrease in patients (P = 0.033, P = 0.001 and P = 0.040, respectively). There was a significant positive correlation of LAIR-1 MFI on neutrophils with CR-1 MFI on neutrophils (r = 0.503; P = 0.002) and LAIR-1 MFI on monocytes with CR-1 MFI on monocytes (r = 0.371; P = 0.026). Receiver operating characteristic curves revealed that CR-1 MFI on monocytes had the highest discrimination power to differentiate patients from controls, with 86.1% specificity and 75% sensitivity (P = 0.001). In conclusion, altered leukocytes expression of LAIR-1 and CR-1 is associated with PsV. Down-regulated CR-1 MFI on monocytes is a promising diagnostic biomarker for PsV.

We demonstrate that prostate cancer can be identified by flow cytometric profiling of blood immune cell subsets. Herein, we profiled natural killer (NK) cell subsets in the blood of 72 asymptomatic men with Prostate-Specific Antigen (PSA) levels < 20 ng ml-1, of whom 31 had benign disease (no cancer) and 41 had prostate cancer. Statistical and computational methods identified a panel of eight phenotypic features ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]) that, when incorporated into an Ensemble machine learning prediction model, distinguished between the presence of benign prostate disease and prostate cancer. The machine learning model was then adapted to predict the D'Amico Risk Classification using data from 54 patients with prostate cancer and was shown to accurately differentiate between the presence of low-/intermediate-risk disease and high-risk disease without the need for additional clinical data. This simple blood test has the potential to transform prostate cancer diagnostics.
© 2020, Hood et al.

Neonatal sepsis (NS) is an important cause of morbidity and mortality among newborns. Its diagnosis depends mainly on blood culture that takes at least 48 hours to give results. Therefore, searching for biomarkers for early diagnosis is of value. We aimed to assess presepsin, soluble triggering receptor expressed on myeloid cells (sTREM-1), and neutrophil CD64 (nCD64) as early diagnostic biomarkers in NS, and to compare them individually and in combination.
This hospital-based case-control study has been conducted on 60 full-term neonates recruited from the neonatal intensive care unit, Al-Zahraa Hospital, Al-Azhar University, Cairo, Egypt. Thirty infants with sepsis were compared to 30 postnatal age- and sex-matched healthy controls. Studied neonates were evaluated using clinical and laboratory indicators for sepsis. nCD64 was measured by flow cytometry and, serum presepsin and sTREM-1 were measured by ELISA.
Presepsin, sTREM-1, and nCD64 levels were significantly elevated in septic neonates vs control group (P<0.05). The sensitivities of presepsin, sTREM, and nCD64 were 100%, 96.7%, and 86.7%, respectively. Presepsin had the best diagnostic performance in early diagnosis of NS followed by sTREM-1 and nCD64.
Presepsin and sTREM-1 are promising biomarkers in screening for NS in comparison with nCD64. However, nCD64 is better used in combination with other biomarkers as CRP.