The present manuscript represents an updated review on different aspects of immunology involved during hepatitis C virus infection in human beings. This includes a brief mention of HCV structure, presentation of viral components to host immune system, and ensuing immune response and immunopathogenesis occurring during HCV infection. The present article also highlights immunodiagnosis of HCV infection and the current status of immunotherapy available for HCV eradication. Its envelope protein, E2, is the primary mediator of virus attachment and cell entry. CD81 molecule on cell surface acts as a major receptor for viral entry into the host cells. Mature dendritic cells play an important role in presenting viral antigen, activate T-cells, and initiate anti-viral immune response. Relative T-cell populations and release of different cytokines from activated T-cells ultimately determine the clearance or persistence of HCV viremia through cellular and humoral immune responses. Natural killer (NK) cells constitute the first line of host defense against invading viruses by recruiting virus-specific T-cells and inducing antiviral immunity in liver. Diagnosis of acute or chronic hepatitis C virus (HCV) infection is established by serological assays for presence of antibodies against different sets of viral proteins during varied periods post infection. An effective immunotherapy and vaccine against HCV is still awaited.
Objective To explore the survival benefit of tofacitinib in addition to dexamethasone in hospitalized patients treated for COVID-19 pneumonia. Patients and methods Single center retrospective observational study. All patients hospitalized, at Delta Regional Medical Center, regional hospital in the Mississippi Delta, with a COVID-19 diagnosis and discharged between March 1 st and September 30 th , 2020 are included. The primary outcome was in-hospital mortality in relation to receipt of tofacitinib alone or in addition to dexamethasone (designated as the Tofacitinib Group), vs dexamethasone alone (designated as the Dexamethasone Group). Results Of 269 eligible patients, 138 (51.3%) received tofacitinib uniformly and 131 (48.7%) patients received dexamethasone without tofacitinib. A total of 44 patients expired: 14 (31.82%) in the Tofacitinib Group and 30 (68.18%) in the Dexamethasone Group. The proportions of death among the Tofacitinib and Dexamethasone groups were respectively, 10.14% and 22.90%. This represents a 70% reduction in odds of dying among the Tofacitinib group compared to the Dexamethasone group after adjusting for age and clinical parameters captured at hospitalization (adjusted odds ratio=0.30, 95% confidence interval =0.12-0.76; p=0.01). Conclusions The in-patient treatment of COVID-19 pneumonia has rapidly evolved. The addition of dexamethasone has made a relevant improvement on survival. Other immunomodulators are yet to show an impact. Here we present the potential survival benefit of the JAK-STAT inhibitor tofacitinib on COVID-19 pneumonia. We found that adding tofacitinib based anti-inflammatory therapy to a treatment regimen including dexamethasone in COVID-19 pneumonia seems to have potential benefit of improving survival when compared to dexamethasone alone.
This study describes the prevalence and association of Torque teno virus (TTV) infection with blood-transmitted viral hepatitis including hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in patients with chronic renal failure (CRF) on maintenance hemodialysis (HD). TTV infection was diagnosed by detection of TTV-DNA in serum, using the polymerase chain reaction (PCR) technique. TTV-DNA was estimated in a total number of one hundred patients with CRF and in 100 voluntary blood donors as controls. The markers of HBV and HCV were also tested in sera samples of these patients. TTV-DNA was detected in 39 of 100 patients (39%) with CRF and in 27 of 100 (27%) healthy controls. The analysis of the results demonstrated HBsAg, IgM anti-HBc, anti-HCV, and HCV core antigen in 5.0, 3.0, 6.0, and 4.0% of patients, respectively. This study could not show any association of TTV with HBV and HCV infections for the transmission pattern or any impact on severity of diseases caused by these viruses in CRF patients. TTV also could not show any association with demographic characteristics of patients, duration of dialysis, number of blood transfusions and renal/liver function of the patients. As such, this study concludes that TTV appears as a benign pathogen, showing no sign of renal/liver damage or any change in the severity of diseases caused by blood-borne hepatitis viruses.
AIM:To investigate the prevalence and genotype distribution of Torque teno virus (TTV) in patients with different liver diseases and chronic renal failure treated at a referral hospital in North India. METHODS: Whereas prevalence of TTV was based on amplification of conserved region of ORF2 of TTV genome, the genotyping of TTV was carried out using restriction fragment length polymorphism (RFLP) procedure on the N22 region of ORF1. RESULTS: TTV-DNA was detected in 137 of 513 (26.7%) patients with liver diseases and 38 of 65 (58.5%) patients with chronic renal failure. TTV was also detected in 27% of healthy controls. The sequence analysis of the PCR product from 10 randomly selected cases failed to show a significant sequence divergence when compared with that of the TRM1 isolate of TTV genotype 1. The results of genotyping in 55 randomly selected patients showed the presence of genotype 1 (G1) in 53 (96.4%) and genotype 2 (G2) in 2 cases (3.6%), respectively. Other genotypes were not identified in this patient subgroup, suggesting that G1 is predominant in this area. The results of genotyping by RFLP were also supported by phylogenetic tree analysis, where G1 was found to be the major genotype. CONCLUSION: These results indicate that TTV is moderately present in Indian patients, with G1 to be the major genotype in North India. The pathogenicity and etiological role of TTV in different diseases is still a question mark and warrant further studies.
The present study describes the cloning and expression of ORF-2 region of TTV genome and the use of expressed peptide in developing immunoassay for detection of anti-TTV antibodies in serum. Presence of TTV-DNA in serum was detected by PCR amplifying N-22 region of ORF-1 of TTV genome. This was followed by genotyping of TTV by RFLP using N-22 amplicon. Using genotype-1 positive serum as the source of TTV, the ORF-2 region was amplified by PCR and subsequently cloned and expressed in pET-19b vector. The expressed protein, identified as 20 kDa protein on SDS-PAGE gel, was purified by affinity chromatography and then used as antigen to develop western blot assay for detection of anti-TTV antibodies in serum. Analysis of sera for anti-TTV antibodies and their comparison with presence of TTV-DNA, produced encouraging results. There was a good relation between presence of anti-TTV and TTV-DNA in these sera samples. Anti-TTV antibodies could be detected in all TTV-DNA positive sera irrespective of the presence of TTV-genotype. This investigation demonstrates that ORF-2 peptide may be used in developing immunoassay for identification of TTV infection.
Most arch anomalies are asymptomatic and detected incidentally on imaging or on autopsy. Occasionally, such anomalies can manifest clinically when associated with another vascular pathology such as an intracranial aneurysm. In this report, we describe a rare case of agenesis of the left common carotid artery with separate origin of the left internal carotid artery and the external carotid artery from the arch discovered on digital subtraction angiography performed during the evaluation of subarachnoid hemorrhage. Knowledge of such anomalies and radiographic appearance is essential for interventional neuroradiologist in planning treatment of such cases.
Classical homocystinuria is the most common cause of isolated homocystinuria. The variants of the CBS gene remain unidentified in Indian children with this disorder. Based on the hallmark clinical features, family history, and/or biochemical clues for classical homocystinuria, 16 children below the age of 18 years were evaluated by Sanger sequencing of the coding exons of CBS gene with flanking intronic regions. The common C677T variant of the MTHFR gene was also screened by restriction fragment length polymorphism. Fifteen children were clinically suspected of having classical homocystinuria and one asymptomatic child with positive family history. Only seven children had biochemical features of classical homocystinuria. Sanger sequencing of the CBS gene confirmed 15 different pathogenic or likely pathogenic variants in 14 cases. Of these, seven variants were novel (three frameshift deletions, two nonsense, one missense, one splice site variant) and were predicted to be deleterious by Mutation Taster software. Seven cases were homozygous, another six were compound heterozygous, and one case was single heterozygous in the study. None of the three most frequent mutations reported worldwide viz., I278T, G307S, and IVS 11-2A>C were found in our cohort. No variants were detected in the exons 2, 8, 12, and 14 as compared to reported literature. Eleven out of 15 variants were associated with the conserved catalytic domain of the CBS polypeptide. The MTHFR polymorphism C677T was observed in heterozygous state in six cases. Our study reports the detailed genotype and seven novel variants in the CBS gene, causing classical homocystinuria in Indian children. The genetic analysis will help to offer accurate genetic counseling, prenatal diagnosis, and development of mutation-based novel therapeutic strategies.
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