Vvax001, a Therapeutic Vaccine for Patients with HPV16-positive High-grade Cervical Intraepithelial Neoplasia: a Phase II Trial.

Purpose: Human papillomavirus (HPV) infection is the major cause of (pre)malignant cervical lesions. We previously demonstrated that Vvax001, a replication-incompetent Semliki Forest virus (SFV) vaccine encoding HPV type 16 (HPV16) E6 and E7, induced potent anti-E6 and -E7 cytotoxic T-cell responses. Here, we investigated the clinical efficacy of Vvax001 in patients with HPV16-positive cervical intraepithelial neoplasia grade 3 (CIN3).

ELISA-4-amyloid: diagnostic accuracy of an ELISA panel for typing the four main types of systemic amyloidosis in subcutaneous abdominal fat tissue samples.

Background: Reliable typing of amyloid is essential. Amyloid extraction from tissue enables immunochemical typing of the precursor protein using an enzyme-linked immunosorbent assay (ELISA).

Objective: To assess the diagnostic accuracy of a panel of ELISAs for typing the four main types (AA, ATTR, AL-kappa and AL-lambda amyloid).

Baseline Blood CD8 T Cell Activation Potency Discriminates Responders from Non-Responders to Immune Checkpoint Inhibition Combined with Stereotactic Radiotherapy in Non-Small-Cell Lung Cancer.

Background: Tumor-infiltrating immune cells have been correlated with prognosis for patients treated with immune checkpoint inhibitor (ICI) treatment of various cancers. However, no robust biomarker has been described to predict treatment response yet. We hypothesized that the activation potency of circulating T cells may predict response to ICI treatment.

HLA-B*51:197: A composite product of interlocus recombination of B*51:01:01:01 and C*01:02:01:01.

The HLA-B*51:197 allele is generated from the interlocus recombination of both HLA-B*51:01:01:01 and HLA-C*01:02:01:01 alleles.

Longitudinal analysis of serum neurofilament light chain levels as marker for neuronal damage in hereditary transthyretin amyloidosis.

Objective: To evaluate serum neurofilament light chain (sNfL) as biomarker of disease onset, progression and treatment effect in hereditary transthyretin (ATTRv) amyloidosis patients and variant (v) carriers.

Methods: sNfL levels were assessed longitudinally in persistently asymptomatic v carriers ( = 12), persistently asymptomatic ATTRv amyloidosis patients (defined as asymptomatic patients but with amyloid detectable in subcutaneous abdominal fat tissue) ( = 8), in v carriers who developed polyneuropathy ( = 7) and in ATTRv amyloidosis patients with polyneuropathy on treatment (TTR-stabiliser ( = 20) or TTR-silencer ( = 18)). Polyneuropathy was confirmed by nerve conduction studies or quantitative sensory testing.

High-Sensitivity Cardiac Troponin T to Exclude Cardiac Involvement in TTR Variant Carriers and ATTRv Amyloidosis Patients.

(1) Background: Individuals carrying a pathogenic transthyretin gene variant () are at high risk for developing hereditary transthyretin (ATTRv) amyloidosis and are routinely screened for the development of cardiomyopathy (ATTRv-CM). This study aims to evaluate whether the cardiac biomarkers N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) can be used to rule out ATTRv-CM. (2) Methods: In this retrospective case-control study, data from 46 ATTRv-CM patients and 101 carriers and ATTRv amyloidosis patients without cardiomyopathy were included.

High serum C-X-C motif chemokine ligand 10 (CXCL10) levels may be associated with new onset interstitial lung disease in patients with systemic sclerosis: evidence from observational, clinical, transcriptomic and in vitro studies.

Background: Systemic sclerosis-interstitial lung disease (SSc-ILD) is the leading cause of death in patients with SSc. There is an unmet need for predictive biomarkers to identify patients with SSc at risk of ILD. Previous studies have shown that interferon (IFN) pathways may play a role in SSc.

Comparison of different immunoassays for the detection of antibodies against Intrinsic Factor and Parietal Cells.

Objectives: In the diagnostic work up of autoimmune gastritis several immunological methods are available for the detection of antibodies against Intrinsic Factor (IF) and Parietal Cells (PC). However, there are no recent reports directly comparing all the available assays and methods. The objective of this study was to compare the performance of several commercially available anti-IF and anti-PC antibody assays from different manufacturers in a multi-center multi-cohort setting.

Increased miR-142-3p Expression Might Explain Reduced Regulatory T Cell Function in Granulomatosis With Polyangiitis.

Regulatory T cells (Tregs) are frequently functionally impaired in patients with granulomatosis with polyangiitis (GPA). However, the mechanism underlying their impaired function is unknown. Here, we hypothesized that Treg dysfunction in GPA is due to altered microRNA (miRNA) expression.

Azathioprine Hypersensitivity Syndrome in a Cohort of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Patients.

Background: Azathioprine hypersensitivity syndrome is a rare complication of azathioprine therapy. Its symptoms resemble infection or relapse of inflammatory disease, hindering correct diagnosis. Current literature is limited to sporadic case reports and reviews.

Involvement of MicroRNAs in the Aging-Related Decline of CD28 Expression by Human T Cells.

Loss of CD28 is a characteristic feature of T cell aging, but the underlying mechanisms of this loss are elusive. As differential expression of microRNAs (miRNAs) has been described between CD28+ and CD28- T cells, we hypothesized that altered miRNA expression contributes to the age-associated downregulation of CD28. To avoid the confounding effects of age-associated changes in the proportions of T cells at various differentiation stages , an experimental model system was used to study changes over time in the expression of miRNA associated with the loss of CD28 expression in monoclonal T cell populations at a lower or higher number of population doublings (PDs).

Impact of Aging on the Frequency, Phenotype, and Function of CD161-Expressing T Cells.

Immune-aging is associated with perturbed immune responses in the elderly. CD161-expressing T cells, i.e.

Argonaute 2 immunoprecipitation revealed large tumor suppressor kinase 1 as a novel proapoptotic target of miR-21 in T cells.

MicroRNA (miR)-21 is an important suppressor of T-cell apoptosis that is also overexpressed in many types of cancers. The exact mechanisms underlying the antiapoptotic effects of miR-21 are not well understood. In this study, we used the Jurkat T-cell line as a model to identify apoptosis-associated miR-21 target genes.

Analysis of serum immune markers in seropositive and seronegative rheumatoid arthritis and in high-risk seropositive arthralgia patients.

Presence of autoantibodies precedes development of seropositive rheumatoid arthritis (SP RA) and seropositive arthralgia patients (SAP) are at risk of developing RA. The aims of the study are to identify additional serum immune markers discriminating between SP and seronegative (SN) RA, and markers identifying high-risk SAP. Sera from SAP (n = 27), SP RA (n = 22), SN RA (n = 11) and healthy controls (n = 20) were analyzed using the Human Cytokine 25-Plex Panel.

Altered Natural Killer Cell Subsets in Seropositive Arthralgia and Early Rheumatoid Arthritis Are Associated with Autoantibody Status.

Objective: The role of natural killer (NK) cells in the immunopathogenesis of rheumatoid arthritis (RA) is unclear. Therefore, numerical and functional alterations of CD56(dim) and CD56(bright) NK cells in the early stages of RA development were studied.

Methods: Whole blood samples from newly diagnosed, treatment-naive, seropositive (SP) and seronegative (SN) patients with RA (SP RA, n = 45 and SN RA, n = 12), patients with SP arthralgia (n = 30), and healthy controls (HC, n = 41) were assessed for numbers and frequencies of T cells, B cells, and NK cells.

Aging-dependent decline of IL-10 producing B cells coincides with production of antinuclear antibodies but not rheumatoid factors.

Aging is associated with development of autoimmunity. Loss of B cell tolerance in the elderly is suggested by an increased prevalence of anti-nuclear antibodies (ANAs) and rheumatoid factors (RFs). Accumulating evidence indicates that B cells also impact autoimmunity via secretion of cytokines.

Inhibition of the miR-155 target NIAM phenocopies the growth promoting effect of miR-155 in B-cell lymphoma.

Several studies have indicated an important role for miR-155 in the pathogenesis of B-cell lymphoma. Highly elevated levels of miR-155 were indeed observed in most B-cell lymphomas with the exception of Burkitt lymphoma (BL). However, the molecular mechanisms that underlie the oncogenic role of miR-155 in B-cell lymphoma are not well understood.

Age-Associated Differences in MiRNA Signatures Are Restricted to CD45RO Negative T Cells and Are Associated with Changes in the Cellular Composition, Activation and Cellular Ageing.

MicroRNAs (miRNAs) have emerged as important players in the regulation of T-cell functionality. However, comprehensive insight into the extent of age-related miRNA changes in T cells is lacking. We established miRNA expression patterns of CD45RO- naïve and CD45RO+ memory T-cell subsets isolated from peripheral blood cells from young and elderly individuals.

T-cell Activation Induces Dynamic Changes in miRNA Expression Patterns in CD4 and CD8 T-cell Subsets.

T-cell activation affects microRNA (miRNA) expression in T-cell subsets. However, little is known about the kinetics of miRNA regulation and possible differences between CD4 and CD8 T cells. In this study we set out to analyze the kinetics of activation-induced expression regulation of twelve pre-selected miRNAs.

Rheumatoid Arthritis, Immunosenescence and the Hallmarks of Aging.

Age is the most important risk factor for the development of infectious diseases, cancer and chronic inflammatory diseases including rheumatoid arthritis (RA). The very act of living causes damage to cells. A network of molecular, cellular and physiological maintenance and repair systems creates a buffering capacity against these damages.

Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis.

Objectives: Precursor Th17 lineage cells expressing CD161 are implicated in Rheumatoid Arthritis (RA) pathogenesis. CD4+CD161+ T-cells accumulate in RA joints and may acquire a non classical Th1 phenotype. The endogenous ligand for CD161 is lectin-like transcript 1 (LLT1).