HLA-G Polymorphisms of The 3'-UTR Region Are Involved in Susceptibility to Non-Infectious Uveitis.

Purpose: HLA-G is a non-classical HLA class I gene encoding a molecule endowed with immunomodulatory properties, playing important immunosuppressive and tolerogenic roles in immuno-privileged organs. Fluctuations in its expression levels have been correlated with the predisposition to autoinflammatory disorders, notably uveitis, characterized by inflammation of the uvea. In the present work, DNA was obtained from saliva samples of 147 Spanish patients with uveitis, with subsequent analysis focusing on the distribution of polymorphisms within the 3'UTR region of the gene (a region known to modulate the expression of the HLA-G molecule).

Lack of Specific Immune Response after Five Doses of mRNA SARS-CoV-2 Vaccine in a Patient with CD4 T-Cell Lymphopenia but Preserved Responses to CMV.

Immunogenicity of SARS-CoV-2 mRNA vaccines is highly heterogeneous in patients with inborn errors of immunity (IEIs). This case report analyzes the immune response to mRNA COVID-19 two-dose primary vaccination followed by three boosters in an IEI patient with marked CD4 T-cell cytopenia and diminished thymic output, in comparison with that raised against latent, chronic cytomegalovirus (CMV) infection. Serum IgG antibodies anti-spike (S) protein of SARS-CoV-2 and anti-CMV were both determined by chemiluminescent microparticle immunoassays (CMIAs).

Semi-supervised mixture multi-source exchangeability model for leveraging real-world data in clinical trials.

The traditional trial paradigm is often criticized as being slow, inefficient, and costly. Statistical approaches that leverage external trial data have emerged to make trials more efficient by augmenting the sample size. However, these approaches assume that external data are from previously conducted trials, leaving a rich source of untapped real-world data (RWD) that cannot yet be effectively leveraged.

Evolution and molecular interactions of major histocompatibility complex (MHC)-G, -E and -F genes.

Classical HLA (Human Leukocyte Antigen) is the Major Histocompatibility Complex (MHC) in man. HLA genes and disease association has been studied at least since 1967 and no firm pathogenic mechanisms have been established yet. HLA-G immune modulation gene (and also -E and -F) are starting the same arduous way: statistics and allele association are the trending subjects with the same few results obtained by HLA classical genes, i.

HLA-G: Too Much or Too Little? Role in Cancer and Autoimmune Disease.

HLA-G is a non-classical HLA class I molecule with immunomodulatory properties. It was initially described at the maternal-fetal interface, and it was later found that this molecule was constitutively expressed on certain immuneprivileged tissues, such as cornea, endothelial and erythroid precursors, and thymus. The immunosuppressive effect of HLA-G is exerted through the interaction with its cognate receptors, expressed on immunocompetent cells, like ILT2, expressed on NK, B, T cells and APCs; ILT4, on APCs; KIR, found on the surface of NK cells; and finally, the co-receptor CD8.

HLA-G 3'UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients.

HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune system. The gene shows several polymorphisms involved in mRNA and protein levels.

Anti-influenza hyperimmune intravenous immunoglobulin for adults with influenza A or B infection (FLU-IVIG): a double-blind, randomised, placebo-controlled trial.

Background: Since the 1918 influenza pandemic, non-randomised studies and small clinical trials have suggested that convalescent plasma or anti-influenza hyperimmune intravenous immunoglobulin (hIVIG) might have clinical benefit for patients with influenza infection, but definitive data do not exist. We aimed to evaluate the safety and efficacy of hIVIG in a randomised controlled trial.

Methods: This randomised, double-blind, placebo-controlled trial was planned for 45 hospitals in Argentina, Australia, Denmark, Greece, Mexico, Spain, Thailand, UK, and the USA over five influenza seasons from 2013-14 to 2017-18.

Impact of the Polymorphism near the Gene on HIV-1 DNA Reservoirs in Asymptomatic Chronically Infected Patients Initiating Antiviral Therapy.

Several genome-wide association studies have identified a polymorphism located 35 kb upstream of the coding region of gene (; termed -35 C/T) as a host factor significantly associated with the control of HIV-1 viremia in untreated patients. The potential association of this host genetic polymorphism with the viral reservoirs has never been investigated, nor the association with the viral control in response to the treatment. In this study, we assess the influence of the polymorphism -35 C/T on the outcome of virus burden in 183 antiretroviral-naïve HIV-1-infected individuals who initiated antiviral treatment (study STIR-2102), analyzing HIV-1 RNA viremia and HIV-1 DNA reservoirs.

Analysis of an ordinal endpoint for use in evaluating treatments for severe influenza requiring hospitalization.

Background/Aims A single best endpoint for evaluating treatments of severe influenza requiring hospitalization has not been identified. A novel six-category ordinal endpoint of patient status is being used in a randomized controlled trial (FLU-Intravenous Immunoglobulin - FLU-IVIG) of intravenous immunoglobulin. We systematically examine four factors regarding the use of this ordinal endpoint that may affect power from fitting a proportional odds model: (1) deviations from the proportional odds assumption which result in the same overall treatment effect as specified in the FLU-IVIG protocol and which result in a diminished overall treatment effect, (2) deviations from the distribution of the placebo group assumed in the FLU-IVIG design, (3) the effect of patient misclassification among the six categories, and (4) the number of categories of the ordinal endpoint.

Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: A multicenter prospective study.

Background: New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections.

Methods: We prospectively analyzed 170 adult heart recipients at 8 centers in Spain.

Early intravenous immunoglobulin replacement in hypogammaglobulinemic heart transplant recipients: results of a clinical trial.

Background: Immunoglobulin G (IgG) hypogammaglobulinemia (HGG) is a risk factor for development of severe infections after heart transplantation. We performed a clinical trial to preliminarily evaluate the efficacy and safety of early administration of intravenous immunoglobulin (IVIG) for prevention of severe infection in heart recipients with post-transplant IgG HGG.

Methods: Twelve heart recipients with IgG HGG detected in a screening phase of the clinical trial (IgG <500 mg/dL) were recruited.

Peripheral blood T- and B-cell immunophenotypic abnormalities in selected women with unexplained recurrent miscarriage.

We aimed to investigate if women with recurrent miscarriage disclosed abnormalities in the maturation and activation status of peripheral blood lymphocyte subsets. In a case control study, 24 women with recurrent miscarriage, 37 women with children but no history of miscarriage and 39 women without previous pregnancies were evaluated. Lymphocyte subsets were evaluated using three-colour flow-cytometry.

Experience in IVIg therapy for selected women with recurrent reproductive failure and NK cell expansion.

Problem: Recurrent reproductive failure (RRF) has been associated with expansion of circulating NK cells, key cells for maternal tolerance, decidual vasculogenesis and embryo growth. This study reports our experience in intravenous immunoglobulin (IVIg) therapy of a large cohort of women with RRF with expanded circulating NK and/or NKT-like cells (blood NKT cells are a heterogeneous subset of T cells that share properties of both T cells and NK cells).

Method Of Study: Observational study of RRF women with NK or NKT-like expansion (>12% or 10% cutoff levels of total lymphocytes, respectively), treated with IVIg for the next gestation.

Alterations of naïve and memory B-cell subsets are associated with risk of rejection and infection in heart recipients.

Rejection and infection are relevant causes of mortality in heart recipients. We evaluated the kinetics of the maturation status of B lymphocytes and its relationship with acute cellular rejection and severe infection in heart recipients. We analyzed B-cell subsets using 4-color flow cytometry in a prospective follow-up study of 46 heart recipients.

New decision-tree model for defining the risk of reproductive failure.

Problem: Natural killer (NK) cells play a key role in embryo implantation and pregnancy success, whereas blood and uterine NK expansions have been involved in the pathophysiology of reproductive failure (RF). Our main goal was to design in a large observational study a tree-model decision for interpretation of risk factors for RF.

Methods Of Study: A hierarchical multivariate decision model based on a classification and regression tree was developed.

Intravenous immunoglobulin treatment increased live birth rate in a Spanish cohort of women with recurrent reproductive failure and expanded CD56(+) cells.

Problem: Natural killer (NK, CD3(-)CD56(+)/CD16(+)) and NKT-like cells (CD3(+)CD56(+)/CD16(+)) activity is considered among the key factors for reproductive success. In the absence of immunological screening, beneficial effects of intravenous immunoglobulin (IVIG) in preventing recurrent reproductive failure (RRF) have not been reported. Here, we analyse the IVIG influence on pregnancy success in women with RRF and circulating NK or/and NKT-like cells expansion.

Long-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis.

Myeloid and plasmacytoid dendritic cells (mDCs, pDCs) are central to the initiation and the regulation of immune processes in multiple sclerosis (MS). Natalizumab (NTZ) is a humanized monoclonal antibody approved for the treatment of MS that acts by blocking expression of VLA-4 integrins on the surface of leukocytes. We determined the proportions of circulating DC subsets and analyzed expression of VLA-4 expression in 6 relapsing-remitting MS patients treated with NTZ for 1 year.

Simultaneous monitoring of cytomegalovirus-specific antibody and T-cell levels in seropositive heart transplant recipients.

Purpose: Human cytomegalovirus (CMV) active infection (CMV infection) poses serious risks to CMV-seropositive heart transplant recipients. We evaluated the usefulness of simultaneous assessment of CMV-specific values for parameters of the humoral (antibodies) and cellular (CD4+ and CD8+ T-cells) immune responses in the identification of heart recipients at risk of developing CMV infection after transplantation.

Methods: We prospectively studied 38 CMV-seropositive heart recipients.

Efficacy and safety of subcutaneous vivaglobin® replacement therapy in previously untreated patients with primary immunodeficiency: a prospective, multicenter study.

Treatment of primary immunodeficiency (PI) is typically initiated with intravenous immunoglobulin (IVIG) loading and then continued with IVIG or subcutaneous IgG (SCIG). This prospective, open-label, multicenter, 6-month study evaluated a new regimen of initiating IgG therapy with SCIG in 18 previously untreated patients. In the loading phase, SCIG 100 mg/kg was administered for five consecutive days (total loading dose 500 mg/kg).

A leaky mutation in CD3D differentially affects αβ and γδ T cells and leads to a Tαβ-Tγδ+B+NK+ human SCID.

T cells recognize antigens via their cell surface TCR and are classified as either αβ or γδ depending on the variable chains in their TCR, α and β or γ and δ, respectively. Both αβ and γδ TCRs also contain several invariant chains, including CD3δ, which support surface TCR expression and transduce the TCR signal. Mutations in variable chains would be expected to affect a single T cell lineage, while mutations in the invariant chains would affect all T cells.

Estradiol-dependent perforin expression by human regulatory T-cells.

Background: CD4+CD25+FoxP3+ regulatory T-cells (nT(Reg)) have been shown to suppress immune responses to autoantigens and to other diverse antigens, this suppression is mainly mediated by a cell contact-dependent mechanism not yet fully defined. It has been reported that both human natural and induced T(Reg) exert cytotoxic activity against autologous target cells, which suggests that the perforin/granzyme pathway may be a relevant candidate mechanism for the suppressive function of T(Reg). Previous reports have shown that oestradiol (E2) modulates T(Reg) percentages and function.

Prognostic value of peripheral blood mononuclear cell-associated HIV-1 DNA for virological outcome in asymptomatic HIV-1 chronic infection.

Background: Studies in primary HIV-1 infection and advanced HIV-1 disease have demonstrated that HIV-1 DNA associated with peripheral blood mononuclear cells (PBMC HIV-1 DNA) has predictive value for disease progression.

Objectives: To analyse in asymptomatic HIV-1 chronic infection the predictive value of PBMC HIV-1 DNA for virological failure.

Study Design: In 115 individuals who had previously participated in study STIR-2102, we retrospectively analysed the PBMC HIV-1 DNA by quantitative real-time PCR.