Antiphospholipid antibodies detected by line immunoassay differentiate among patients with antiphospholipid syndrome, with infections and asymptomatic carriers

Background: Antiphospholipid antibodies (aPL) can be detected in asymptomatic carriers and infectious patients. The aim was to investigate whether a novel line immunoassay (LIA) differentiates between antiphospholipid syndrome (APS) and asymptomatic aPL+ carriers or patients with infectious diseases (infectious diseases controls (IDC)). Methods: Sixty-one patients with APS (56 primary, 22/56 with obstetric events only, and 5 secondary), 146 controls including 24 aPL+ asymptomatic carriers and 73 IDC were tested on a novel hydrophobic solid phase coated with cardiolipin (CL), phosphatic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, beta2-glycoprotein I (\u3b22GPI), prothrombin, and annexin V. Samples were also tested by anti-CL and anti-\u3b22GPI ELISAs and for lupus anticoagulant activity. Human monoclonal antibodies (humoAbs) against human \u3b22GPI or PL alone were tested on the same LIA substrates in the absence or presence of human serum, purified human \u3b22GPI or after CL-micelle absorption. Results: Comparison of LIA with the aPL-classification assays revealed good agreement for IgG/IgM a f2GPI and aCL. Anti-CL and anti- f2GPI IgG/IgM reactivity assessed by LIA was significantly higher in patients with APS versus healthy controls and IDCs, as detected by ELISA. IgG binding to CL and f2GPI in the LIA was significantly lower in aPL+ carriers and Venereal Disease Research Laboratory test (VDRL)+samples than in patients with APS. HumoAb against domain 1 recognized \u3b22GPI bound to the LIA-matrix and in anionic phospholipid (PL) complexes. Absorption with CL micelles abolished the reactivity of a PL-specific humoAb but did not affect the binding of anti-\u3b22GPI humoAbs. Conclusions: The LIA and ELISA have good agreement in detecting aPL in APS, but the LIA differentiates patients with APS from infectious patients and asymptomatic carriers, likely through the exposure of domain 1

A Comparative Study of Human TLR 7/8 Stimulatory Trimer Compositions in Influenza A Viral Genomes

Background: Variation in the genomes of single-stranded RNA viruses affects their infectivity and pathogenicity in two ways. First, viral genome sequence variations lead to changes in viral protein sequences and activities. Second, viral genome sequence variation produces diversity at the level of nucleotide composition and diversity in the interactions between viral RNAs and host toll-like receptors (TLRs). A viral genome-typing method based on this type of diversity has not yet been established. Methodology/Principal Findings: In this study, we propose a novel genomic trait called the ‘‘TLR stimulatory trimer composition’ ’ (TSTC) and two quantitative indicators, Score S and Score N, named ‘‘TLR stimulatory scores’ ’ (TSS). Using the complete genome sequences of 10,994 influenza A viruses (IAV) and 251 influenza B viruses, we show that TSTC analysis reveals the diversity of Score S and Score N among the IAVs isolated from various hosts. In addition, we show that low values of Score S are correlated with high pathogenicity and pandemic potential in IAVs. Finally, we use Score S and Score N to construct a logistic regression model to recognize IAV strains that are highly pathogenic or have high pandemic potential. Conclusions/Significance: Results from the TSTC analysis indicate that there are large differences between human and avian IAV genomes (except for segment 3), as illustrated by Score S. Moreover, segments 1, 2, 3 and 4 may be majo

Parvovirus B19 DNA CpG Dinucleotide Methylation and Epigenetic Regulation of Viral Expression

CpG DNA methylation is one of the main epigenetic modifications playing a role in the control of gene expression. For DNA viruses whose genome has the ability to integrate in the host genome or to maintain as a latent episome, a correlation has been found between the extent of DNA methylation and viral quiescence. No information is available for Parvovirus B19, a human pathogenic virus, which is capable of both lytic and persistent infections. Within Parvovirus B19 genome, the inverted terminal regions display all the characteristic signatures of a genomic CpG island; therefore we hypothesised a role of CpG dinucleotide methylation in the regulation of viral genome expression

Toll-like receptor gene polymorphisms are associated with susceptibility to graves' ophthalmopathy in Taiwan males

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs) are a family of pattern-recognition receptors, which plays a role in eliciting innate/adaptive immune responses and developing chronic inflammation. The polymorphisms of TLRs have been associated with the risk of various autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis and rheumatorid arthritis. The aim of this study was to evaluate whether TLR genes could be used as genetic markers for the development of Graves' ophthalmopathy (GO).</p> <p>Methods</p> <p>6 TLR-4 and 2 TLR-9 gene polymorphisms in 471 GD patients (200 patients with GO and 271 patients without GO) from a Taiwan Chinese population were evaluated.</p> <p>Results</p> <p>No statistically significant difference was observed in the genotypic and allelic frequencies of TLR-4 and TLR-9 gene polymorphisms between the GD patients with and without GO. However, sex-stratified analyses showed that the association between TLR-9 gene polymorphism and GO phenotype was more pronounced in the male patients. The odds ratios (ORs) was 2.11 (95% confidence interval [CI] = 1.14-3.91) for rs187084 AàG polymorphism and 1.97 (95% CI = 1.07-3.62) for rs352140 AàG polymorphism among the male patients. Increasing one G allele of rs287084 and one A allele of rs352140 increased the risk of GO (<it>p </it>values for trend tests were 0.0195 and 0.0345, respectively). Further, in haplotype analyses, the male patients carrying the GA haplotype had a higher risk of GO (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.09-3.73) than those not carrying the GA haplotype.</p> <p>Conclusion</p> <p>The present data suggest that TLR-9 gene polymorphisms were significantly associated with increased susceptibility of ophthalmopathy in male GD patients.</p

Síndrome antifosfolípide e trombocitopenia na infância

OBJETIVO: Relatar o caso de uma criança com diagnóstico de síndrome do anticorpo antifosfolípide associada à trombocitopenia grave e realizar uma revisão de literatura sobre o assunto. DESCRIÇÃO DO CASO: Criança de nove anos e oito meses de idade com trombocitopenia grave associada a anticorpo anticardiolipina positivo. Os dados foram coletados por meio de anamnese, exame físico e exames complementares da paciente. O diagnóstico foi determinado de acordo com os critérios estabelecidos para a síndrome antifosfolípide, associados às manifestações mais comuns na faixa etária pediátrica: livedo reticular e trombocitopenia. COMENTÁRIOS: A síndrome do anticorpo antifosfolípide é uma doença incomum na população pediátrica e suas manifestações clínicas, com a redução do número de plaquetas, devem ser consideradas.OBJETIVO: Relatar el caso de un niño con diagnóstico de síndrome del anticuerpo antifosfolípido asociado a trombocitopenia grave y realizar una revisión de literatura sobre el tema. DESCRIPCIÓN DEL CASO: Niño de nueve años y ocho meses de edad, con trombocitopenia grave asociada a anticuerpo anticardiolipina positivo. Los datos fueron recogidos por medio de historia, examen físico y exámenes complementarios de la paciente internada en un hospital de Curitiba, en Paraná (Brasil). El diagnóstico fue determinado conforme a los criterios establecidos para el síndrome antifosfolípido, asociados a las manifestaciones más comunes en la franja de edad pediátrica: livedo recticular y trombocitopenia. COMENTARIOS: El síndrome del anticuerpo antifosfolípido es una enfermedad poco común en la población pediátrica, y su manifestación con reducción del número de plaquetas debe ser considerada.OBJECTIVE: To report the case of a child diagnosed with antiphospholipid syndrome associated with severe thrombocytopenia, and to review the literature on the subject. CASE DESCRIPTION: Child aged nine years and eight months old with severe thrombocytopenia associated with a positive anticardiolipin antibody. Data were collected by clinical history, physical examination, and laboratorial exams. Diagnosis was confirmed according to criteria established for the antiophospholipid syndrome, associated with the presence of the most common manifestations of the syndrome in children: livedo reticularis and thrombocytopenia. COMMENTS: The antiphospholipid syndrome is an uncommon pediatric disease, and clinical manifestations such as decreased platelet number should be considered

Interleukin 6 Accelerates Mortality by Promoting the Progression of the Systemic Lupus Erythematosus-Like Disease of BXSB. Yaa Mice

IL6 is a multifunctional cytokine that drives terminal B cell differentiation and secretion of immunoglobulins. IL6 also cooperates with IL21 to promote differentiation of CD4(+) T follicular helper cells (TFH). Elevated serum levels of IL6 correlate with disease flares in patients with systemic lupus erythematosus (SLE). We previously reported that IL21 produced by T-FH plays a critical role in the development of the SLE-like disease of BXSB. Yaa mice. To examine the possible contributions of IL6 to disease, we compared disease parameters in IL6-deficient and IL6-competent BXSB. Yaa mice. We report that survival of IL6-deficient BXSB. Yaa mice was significantly prolonged in association with significant reductions in a variety of autoimmune manifestations. Moreover, B cells stimulated by co-engagement of TLR7 and B cell receptor (BCR) produced high levels of IL6 that was further augmented by stimulation with Type I interferon (IFN1). Importantly, the frequencies of T-FH and serum levels of IL21 were significantly reduced in IL6-deficient mice. These findings suggest that high-level production of IL6 by B cells induced by integrated signaling from the IFN1 receptor, TLR7 and BCR promotes the differentiation of IL21-secreting T-FH in a signaling sequence that drives the lethal autoimmune disease of BXSB. Yaa mice.Peer reviewe

Long-term trajectories of SARS-CoV-2 neutralizing antibodies and predictive value of first dose vaccination-induced IgG-antibodies in hemodialysis patients

Abstract Purpose The predictive value of antibody titers after the first SARS-CoV-2 vaccination and long-term trajectories of antibody titers in hemodialysis patients are unknown. Methods SARS-CoV-2 IgG antibodies and their neutralizing effect six weeks after the first and second vaccination were analysed in 30 hemodialysis patients. IgG titers served to classify participants as responders or non-responders and to calculate sensitivity, specificity, and accuracy. Associations between potential risk factors and post-vaccine non-response were analysed by Mann–Whitney-U test and Chi-Squared test. Long-term follow-up analysis (ANOVA) on the evolution of neutralizing IgG-titers was performed in 24 participants 94 and 135 days after the second immunization. Results IgG antibodies ≥ 1 AU/L (mean 9 ± 20 AU/L) after the first dose were found in 20 patients (66.7%). After the second dose only two participants (6.7%) remained sero-negative and 16.6% showed neutralizing levels below 30%, whereas 25 patients showed IgG antibodies with the high neutralizing activity of 86 ± 18%. Positive IgG antibodies 6 weeks after the first vaccination predicted vaccination effectiveness after two cycles with a specificity of 100%, sensitivity of 76%, and accuracy of 87%. Even low-dose immunosuppressive therapy increased the relative risk for non-response after the first and second dose 1.9 (95% CI 0.8–4.6) and 4.9 (95% CI 1.0–23.8) times, respectively. Over a period of about 4.5 months IgG titers slowly declined by 51% from baseline or by 0.45 AU/mL per day, respectively. Conclusion Two cycles of SARS-CoV-2 vaccination-induced high seroconversion rates comparable to the general population. Immunosuppressive medication is a major risk factor for vaccination non-response. Mounted IgG antibodies showed a high neutralizing capacity as evidence of protective effectiveness. IgG antibodies after the first dose may serve to predict later vaccination outcome. Patients on dialysis display a more rapid decline in antibody titers on long-term follow-up compared to healthy controls. </jats:sec