A prospective humoral immune monitoring study of kidney transplant recipients receiving three doses of SARS-CoV-2 mRNA vaccine.

Kidney transplant recipients (KTRs), like other solid organ transplant recipients display a suboptimal response to mRNA vaccines, with only about half achieving seroconversion after two doses. However, the effectiveness of a booster dose, particularly in generating neutralizing antibodies (NAbs), remains poorly understood, as most studies have mainly focused on non-neutralizing antibodies. Here, we have longitudinally assessed the humoral response to the SARS-CoV-2 mRNA vaccine in 40 KTRs over a year, examining changes in both anti-spike IgG and NAbs following a booster dose administered about 5 months post-second dose.

Longitudinal monitoring of SARS-CoV-2 viral load in self-collected saliva from health care workers during breakthrough infections to spare working days.

Real-time quantitative PCR (RT-qPCR) on nasopharyngeal swabs (NPS) has been used as the standard method for detecting and monitoring SARS-CoV-2 infection during the pandemic. However, NPS collection often causes discomfort and poses a higher risk of transmission to health care workers (HCW). Furthermore, RT-qPCR only provides relative quantification and does not allow distinguishing those samples with residual, no longer active infection, whereas droplet digital PCR (ddPCR) allows for precise quantification of viral load, offering greater sensitivity and reproducibility.

SARS-CoV-2 Detection by Digital Polymerase Chain Reaction and Immunohistochemistry in Skin Biopsies from 52 Patients with Different COVID-19-Associated Cutaneous Phenotypes.

Background: COronaVIrus Disease 19 (COVID-19) is associated with a wide spectrum of skin manifestations, but SARS-CoV-2 RNA in lesional skin has been demonstrated only in few cases.

Objective: The objective of this study was to demonstrate SARS-CoV-2 presence in skin samples from patients with different COVID-19-related cutaneous phenotypes.

Methods: Demographic and clinical data from 52 patients with COVID-19-associated cutaneous manifestations were collected.

Enhanced Spontaneous Skin Tumorigenesis and Aberrant Inflammatory Response to UVB Exposure in Immunosuppressed Human Papillomavirus Type 8‒Transgenic Mice.

Human papillomaviruses (HPVs) from the beta genus are commensal viruses of the skin usually associated with asymptomatic infection in the general population. However, in individuals with specific genetic backgrounds, such as patients with epidermodysplasia verruciformis, or those with immune defects, such as organ transplant recipients, they are functionally involved in sunlight-induced skin cancer development, mainly keratinocyte carcinoma. Despite their well-established protumorigenic role, the cooperation between β-HPV infection, impaired host immunosurveillance, and UVB exposure has never been formally shown in animal models.

Persistence of Neutralizing Antibodies to SARS-CoV-2 in First Wave Infected Individuals at Ten Months Post-Infection: The UnIRSA Cohort Study.

Longitudinal mapping of antibody-based SARS-CoV-2 immunity is critical for public health control of the pandemic and vaccine development. We performed a longitudinal analysis of the antibody-based immune response in a cohort of 100 COVID-19 individuals who were infected during the first wave of infection in northern Italy. The SARS-CoV-2 humoral response was tested using the COVID-SeroIndex, Kantaro Quantitative SARS-CoV-2 IgG Antibody RUO Kit (R&D Systems, Bio-Techne, Minneapolis, USA) and pseudotype-based neutralizing antibody assay.

Toll-like receptor 4-mediated inflammation triggered by extracellular IFI16 is enhanced by lipopolysaccharide binding.

Damage-associated molecular patterns (DAMPs) are endogenous molecules activating the immune system upon release from injured cells. Here we show that the IFI16 protein, once freely released in the extracellular milieu of chronically inflamed tissues, can function as a DAMP either alone or upon binding to lipopolysaccharide (LPS). Specifically, using pull-down and saturation binding experiments, we show that IFI16 binds with high affinity to the lipid A moiety of LPS.

Serum IFI16 and anti-IFI16 antibodies in psoriatic arthritis.

Nuclear interferon-inducible protein 16 (IFI16) and anti-IFI16 antibodies have been detected in subjects with several rheumatic diseases, often correlating with disease severity, and in this study we investigated their prevalence and clinical associations in psoriatic arthritis (PsA) compared to psoriasis (Pso). We tested sera and synovial fluids of patients with PsA for IFI16 protein levels by capture enzyme-linked immunosorbent assay (ELISA) and for anti-IFI16 immunoglobulin (Ig)G and IgA by ELISA, protein radio-immunoprecipitation and immunoprecipitation-Western blot of IgG. Sera from patients with Pso and healthy subjects were used as controls, and in a subgroup of patients with PsA we also studied sera after treatment with etanercept.

Integrated serum proteins and fatty acids analysis for putative biomarker discovery in inflammatory bowel disease.

The diagnosis and management of Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is still challenging. There is no definitive gold standard diagnostic test, which is made on patient history and with endoscopic and histological findings. This study analyzed serum proteins and fatty acids using mass spectrometry-based techniques.

The Absent in Melanoma 2-Like Receptor IFN-Inducible Protein 16 as an Inflammasome Regulator in Systemic Lupus Erythematosus: The Dark Side of Sensing Microbes.

Absent in melanoma 2 (AIM2)-like receptors (ALRs) are a newly characterized class of pathogen recognition receptors (PRRs) involved in cytosolic and nuclear pathogen DNA recognition. In recent years, two ALR family members, the interferon (IFN)-inducible protein 16 (IFI16) and AIM2, have been linked to the pathogenesis of various autoimmune diseases, among which systemic lupus erythematosus (SLE) has recently gained increasing attention. SLE patients are indeed often characterized by constitutively high serum IFN levels and increased expression of IFN-stimulated genes due to an abnormal response to pathogens and/or incorrect self-DNA recognition process.

Distinct Anti-IFI16 and Anti-GP2 Antibodies in Inflammatory Bowel Disease and Their Variation with Infliximab Therapy.

Background: Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the gut, partly driven by defects in the expression and function of pattern recognition receptors, including the IFI16 protein. Because this protein is a target for autoantibodies and its aberrant expression was reported in colonic mucosa from active patients with ulcerative colitis, we studied its expression and specific seroresponse in patients with IBD before and after infliximab (IFX) therapy.

Methods: Anti-IFI16 antibodies (IgG and IgA subtypes) were measured in the sera of 74 patients with IBD: 48 patients with Crohn's disease (CD) and 26 patients with ulcerative colitis, prospectively harvested before and after IFX therapy.

Interferon gamma-inducible protein 16 (IFI16) and anti-IFI16 antibodies in primary Sjögren's syndrome: findings in serum and minor salivary glands.

The interferon (IFN) signature, namely the overexpression of IFN-inducible genes is a crucial aspect in the pathogenesis of primary Sjögren's syndrome (pSS). The IFN-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders including pSS. This leads to tolerance breaking to this self-protein and development of anti-IFI16 antibodies.

Circulating Interferon-Inducible Protein IFI16 Correlates With Clinical and Serological Features in Rheumatoid Arthritis.

Objective: The interferon-inducible protein 16 (IFI16) has been detected in sera from patients with autoimmune/inflammatory diseases, but not in healthy subjects. This leaking leads to loss of tolerance toward this self-protein and the development of autoantibodies. In this study, clinical significance of both IFI16 protein and anti-IFI16 antibodies in rheumatoid arthritis (RA) was investigated.

Interferon gamma-inducible protein 16 in primary Sjögren's syndrome: a novel player in disease pathogenesis?

Introduction: There is evidence that interferon is involved in the pathogenesis of primary Sjögren's syndrome (pSS). The interferon-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders. This leads to tolerance breaking to this self-protein with consequent development of anti-IFI16 antibodies.

The Extracellular IFI16 Protein Propagates Inflammation in Endothelial Cells Via p38 MAPK and NF-κB p65 Activation.

The nuclear interferon-inducible-16 (IFI16) protein acts as DNA sensor in inflammasome signaling and as viral restriction factor. Following Herpesvirus infection or UV-B treatment, IFI16 delocalizes from the nucleus to the cytoplasm and is eventually released into the extracellular milieu. Recently, our group has demonstrated the occurrence of IFI16 in sera of systemic-autoimmune patients that hampers biological activity of endothelia through high-affinity membrane binding.

Nuclear DNA sensor IFI16 as circulating protein in autoimmune diseases is a signal of damage that impairs endothelial cells through high-affinity membrane binding.

IFI16, a nuclear pathogenic DNA sensor induced by several pro-inflammatory cytokines, is a multifaceted protein with various functions. It is also a target for autoantibodies as specific antibodies have been demonstrated in the sera of patients affected by systemic autoimmune diseases. Following transfection of virus-derived DNA, or treatment with UVB, IFI16 delocalizes from the nucleus to the cytoplasm and is then eventually released into the extracellular milieu.

Human papillomavirus tumor-infiltrating T-regulatory lymphocytes and P53 codon 72 polymorphisms correlate with clinical staging and prognosis of oropharyngeal cancer.

The association between human papillomavirus (HPV) DNA positivity, p53 codon 72 polymorphisms, and the type of leukocyte infiltration in head and neck squamous cell carcinomas (HNSCC) and their combined impact upon patient survival is poorly investigated. For this reason, leukocyte infiltration profile and p53 codon 72 polymorphisms were assessed in freshly removed HNSCC specimens (N=71 patients). HPV detection was performed by nested-PCR followed by DNA sequencing.

Anti-IFI16 antibodies and their relation to disease characteristics in systemic lupus erythematosus.

Objective: Several studies have shown the presence of anti-IFI16 antibodies in systemic lupus erythematosus (SLE), Sjögren Syndrome (SjS), systemic sclerosis (SSc) and other autoimmune diseases. However, the significance of anti-IFI16 antibodies in SLE has not been fully characterized. The aim of this study was to investigate associations between anti-IFI16 antibodies and clinical and serologic parameters of SLE.

Detection of anti-IFI16 antibodies by ELISA: clinical and serological associations in systemic sclerosis.

Objectives: To validate the clinical significance of anti-IFI16 autoantibodies in SSc and assess their associations with serological markers of SSc.

Methods: A semi-quantitative ELISA was used to detect anti-IFI16 autoantibodies in the sera of 344 SSc patients from seven Italian hospitals and 144 healthy controls. SSc-associated autoantibodies [anti-RNA polymerase III (anti-RNAP III) antibodies, anti-centromere, anti-topo I] and IF patterns were evaluated using commercial assays.