Search

Background: Antibodies have been proven effective as diagnostic agents for detecting zoonotic diseases. The variable domain of camel heavy chain antibody (VHH), as an antibody derivative, may be used as an alternative for traditional antibodies in existing immunodiagnostic reagents for detecting rapidly spreading infectious diseases. Objectives: To expedite the isolation of specific antibodies for diagnostic purposes, we constructed a semi‐synthetic camel single domain antibody library based on the phage display technique platform (PDT) and verified the validity of this study. Methods: The semi‐synthetic single domain antibody sequences consist of two parts: one is the FR1‐FR3 region amplified by RT‐PCR from healthy camel peripheral blood lymphocytes (PBLs), and the other part is the CDR3‐FR4 region synthesised as an oligonucleotide containing CDR3 randomised region. The two parts were fused by overlapping PCR, resulting in the rearranged variable domain of heavy‐chain antibodies (VHHs). Y. pestis low‐calcium response V protein (LcrV) is an optional biomarker to detect the Y. pestis infection. The semi‐synthetic library herein was screened using recombinant (LcrV) as a target antigen. Results: After four cycles of panning the library, four VHH binders targeting 1–270 aa residues of LcrV were isolated. The four VHH genes with unique sequences were recloned into an expression vector and expressed as VHH‐hFc chimeric antibodies. The purified antibodies were identified and used to develop a lateral flow immunoassay (LFA) test strip using latex microspheres (LM) for the rapid and visual detection of Y. pestis infection. Conclusions: These data demonstrate the great potential of the semi‐synthetic library for use in isolation of antigen‐specific nanobodies and the isolated specific VHHs can be used in antigen‐capture immunoassays. [ABSTRACT FROM AUTHOR]

Neoantigen delivery using extracellular vesicles (EVs) has gained extensive interest in recent years. EVs derived from tumour cells or immune cells have been used to deliver tumour antigens or antitumor stimulation signals. However, potential DNA contamination from the host cell and the cost of large‐scale EV production hinder their therapeutic applications in clinical settings. Here, we develop an antigen delivery platform for cancer vaccines from red blood cell‐derived EVs (RBCEVs) targeting splenic DEC‐205+ dendritic cells (DCs) to boost the antitumor effect. By loading ovalbumin (OVA) protein onto RBCEVs and delivering the protein to DCs, we were able to stimulate and present antigenic OVA peptide onto major histocompatibility complex (MHC) class I, subsequently priming activated antigen‐reactive T cells. Importantly, targeted delivery of OVA using RBCEVs engineered with anti‐DEC‐205 antibody robustly enhanced antigen presentation of DCs and T cell activation. This platform is potentially useful for producing personalised cancer vaccines in clinical settings. [ABSTRACT FROM AUTHOR]

Anthrax infection is associated with severe illness and high mortality. Protective antigen (PA) is the central component of the anthrax toxin, which is one of two major virulence factors of Bacillus anthracis, the causative agent of anthrax disease. Upon endocytosis, PA opens a pore in the membranes of endosomes, through which the cytotoxic enzymes of the toxin are extruded. The PA pore is formed by a cooperative conformational change in which the membrane‐penetrating loops of PA associate, forming a hydrophobic rim that pierces the membrane. Due to its crucial role in anthrax progression, PA is an important target for monoclonal antibody‐based therapy. cAb29 is a highly effective neutralizing antibody against PA. Here, the cryo‐EM structure of PA in complex with the Fab portion of cAb29 was determined. It was found that cAb29 neutralizes the toxin by clamping the membrane‐penetrating loop of PA to the static surface‐exposed loop of the D3 domain of the same subunit, thereby preventing pore formation. These results provide the structural basis for the antibody‐based neutralization of PA and bring into focus the membrane‐penetrating loop of PA as a target for the development of better anti‐anthrax vaccines. [ABSTRACT FROM AUTHOR]

Nanoparticle‐based electrochemical immunosensors are fascinating and promising screening systems that rely on the affinity binding between antibodies and antigens, allowing the specific detection of diverse types of targets (e. g., proteins, hormones, antibodies). The employment of nanoparticles in the realization of such devices dramatically improves the selectivity, sensitivity, and the transducer surface area for effectively immobilizing the bioreceptor or target molecules. During the last years, the nanoparticles design and fabrication was mainly focused on taking advantage from synergistic effects due to the coupling of different materials. In this review, we summarize the very recent advancements in this regard, with specific emphasis to nanoparticle syntheses procedures, antibody oriented immobilization strategies and transduction techniques. Moreover, the last trends and applications have been extensively discussed along with the remaining challenges and future perspectives. [ABSTRACT FROM AUTHOR]

Cancer immunotherapies have improved human health, and one among the important technologies for cancer immunotherapy is cancer vaccine. Antigens are the most important components in cancer vaccines. Generally, antigens in cancer vaccines can be divided into two categories: pre‐defined antigens and unidentified antigens. Although, cancer vaccines loaded with predefined antigens are commonly used, cancer vaccine loaded with mixed unidentified antigens, especially whole cancer cells or cancer cell lysates, is a very promising approach, and such vaccine can obviate some limitations in cancer vaccines. Their advantages include, but are not limited to, the inclusion of pan‐spectra (all or most kinds of) antigens, inducing pan‐clones specific T cells, and overcoming the heterogeneity of cancer cells. In this review, the recent advances in cancer vaccines based on whole‐tumor antigens, either based on whole cancer cells or whole cancer cell lysates, are summarized. In terms of whole cancer cell lysates, the focus is on applying whole water‐soluble cell lysates as antigens. Recently, utilizing the whole cancer cell lysates as antigens in cancer vaccines has become feasible. Considering that pre‐determined antigen‐based cancer vaccines (mainly peptide‐based or mRNA‐based) have various limitations, developing cancer vaccines based on whole‐tumor antigens is a promising alternative. [ABSTRACT FROM AUTHOR]

Several technical limitations of Luminex single antigen (LSA) assays have been described so far. This study focused on a reactivity pattern observed in many sera that cannot be explained by eplets described in the Epitope Registry database and sometimes appearing against a self‐HLA allele or antigen. In most cases, this pattern is revealed by a discrepant result when compared with other assays (Luminex PRA, cell‐binding assays such as flow cytometry cross match, LSA from another manufacturer...). We focus here on the Cw1/12/15 pattern appearing on the LABScreen class I LSA provided by One Lambda. We documented its behavior using this LSA after acid denaturation of the beads, using Lifecodes LSA from Immucor, and adsorption of sera either on spleen mononuclear cells from deceased donors or on single HLA transfected cell clones. We studied 33 sera from different patients positive for the three Cw beads, selected from our routine patients' LSA database. Nine patients had transplants from a Cw12 or Cw15 donor without any pejorative evolution of the graft, nor post‐transplant MFI (mean fluorescence intensity) increase of the Cw1/12/15 beads. A significant increase of MFI was observed after acid denaturation of the LABScreen beads. All sera tested by Lifecodes LSA were negative for these Cw beads. Finally, we found no significant difference of MFI after adsorption on cells from either origin. Therefore, the Cw1/12/15 pattern appears to be a false positive reactivity of the LABScreen single antigen assay. [ABSTRACT FROM AUTHOR]

Objective: Simultaneous antibody testing during screening for autoimmune conditions is discouraged. The incidence of positive extractable nuclear antigen (ENA) in the setting of a negative antinuclear antibody (ANA) has been reported as low. Our objective was to characterize the frequency of diagnosis of new ANA‐associated rheumatic disease (AARD) in the setting of a negative ANA with a positive ENA. Methods: This was a 7‐year retrospective study from a multicenter tertiary health network in Australia. Clinical information was sought on patients over 18 years old who had a negative ANA but positive ENA test result. Results were extracted from hospital computer systems. Results: From March 19, 2011, to July 23, 2018, ENA testing was ordered simultaneously with an ANA test on 4,248 occasions in 3,484 patients. ANA was positive in 2,520 patients (59.3%) and ENA was positive in 1,980 patients (46.6%). Among positive ANA patients, ENA was positive in 1,563 patients (62.0%). Among 1,728 negative ANA tests, ENA was positive in 417 (24.1%) (P < 0.001). A total of 328 patients with discordant ANA/ENA results had data available for further analysis, of whom 279 had no pre‐established rheumatologic condition. A new AARD was diagnosed in 17 of 279 patients, yielding a positive predictive value of 6.09% (95% confidence interval 3.59–9.58). Conclusion: Despite the higher‐than‐expected incidence of positive ENA in the setting of a negative ANA, the yield of newly diagnosed rheumatic diseases was low. Our findings support the stepwise addition of ENA requests when an ANA test result is positive and clinical suspicion of an AARD is high. [ABSTRACT FROM AUTHOR]

People are expected to have been previously vaccinated with a Vaccinia‐based vaccine, as until 1980 smallpox vaccination was a standard protocol in China. It is unclear whether people with smallpox vaccine still have antibody against vaccinia virus (VACV) and cross‐antibody against monkeypox virus (MPXV). Herein, we assessed the binding antibodies with antigen of VACV‐A33 and MPXV‐A35 in the general population and HIV‐1 infected patients. Firstly, we detected VACV antibody with A33 protein to evaluate the efficiency of smallpox vaccination. The result show that 29% (23 of 79) of hospital staff (age ≥ 42 years) and 63% (60 of 95) of HIV‐positive patients (age ≥ 42 years) from Guangzhou Eighth People's Hospital were able to bind A33. However, among the subjects below 42 years of age, 1.5% (3/198) of the hospital volunteer samples and 1% (1/104) of the samples from HIV patients were positive for antibodies against A33 antigen. Then, we assessed the specific cross‐reactive antibodies against MPXV A35 protein. 24% (19 of 79) hospital staff (age〉 = 42 years) and 44% (42 of 95) of HIV‐positive patients (age〉 = 42 years) were positive. 98% (194/198) of the hospital staff and 99% (103/104) of the HIV patients had no A35‐binding antibodies. Further, we found significant sex differences for the reactivity to A35 antigen were observed in HIV population, but no significant sex differences in hospital staff. Further, we analyzed the positivity rate of anti‐A35 antibody of men who have sex with men (MSM) and non‐MSM in HIV patients (age〉 = 42years). We found that 47% of no‐MSM population and 40% of MSM population were positive for A35 antigen, with no significant difference. Lastly, we found only 59 samples were positive for anti‐A33 IgG and anti‐A35 IgG in all participants. Together, we demonstrated A33 and A35 antigens binding antibodies were detected in HIV patients and general population who were older than 42 years, and cohort studies only provided data of serological detection to support early response to monkeypox outbreak. [ABSTRACT FROM AUTHOR]

Objective: Proteinase 3 (PR3) is the major antigen for antineutrophil cytoplasmic antibodies (ANCAs) in the systemic autoimmune vasculitis, granulomatosis with polyangiitis (GPA). PR3‐targeting ANCAs (PR3‐ANCAs) recognize different epitopes on PR3. This study was undertaken to study the effect of mutations on PR3 antigenicity. Methods: The recombinant PR3 variants, iPR3 (clinically used to detect PR3‐ANCAs) and iHm5 (containing 3 point mutations in epitopes 1 and 5 generated for epitope mapping studies) immunoassays and serum samples from patients enrolled in ANCA‐associated vasculitis (AAV) trials were used to screen for differential PR3‐ANCA binding. A patient‐derived monoclonal ANCA 518 (moANCA518) that selectively binds to iHm5 within the mutation‐free epitope 3 and is distant from the point mutations of iHm5 was used as a gauge for remote epitope activation. Selective binding was determined using inhibition experiments. Results: Rather than reduced binding of PR3‐ANCAs to iHm5, we found substantially increased binding of the majority of PR3‐ANCAs to iHm5 compared to iPR3. This differential binding of PR3‐ANCA to iHm5 is similar to the selective moANCA518 binding to iHm5. Binding of iPR3 to monoclonal antibody MCPR3‐2 also induced recognition by moANCA518. Conclusion: The preferential binding of PR3‐ANCAs from patients, such as the selective binding of moANCA518 to iHm5, is conferred by increased antigenicity of epitope 3 on iHm5. This can also be induced on iPR3 when captured by monoclonal antibody MCPR2. This previously unrecognized characteristic of PR3‐ANCA interactions with its target antigen has implications for studying antibody‐mediated autoimmune diseases, understanding variable performance characteristics of immunoassays, and design of potential novel treatment approaches. [ABSTRACT FROM AUTHOR]

High‐frequency mutation of the TP53 tumor suppressor gene is observed in multiple human cancers, which promotes cancer progression. However, the mutated gene‐encoded protein may serve as a tumor antigen to elicit tumor‐specific immune responses. In this study, we detected widespread expression of shared TP53‐Y220C neoantigen in hepatocellular carcinoma with low affinity and low stability of binding to HLA‐A0201 molecules. We substituted the amino acid sequences VVPCEPPEV with VLPCEPPEV in the TP53‐Y220C neoantigen to yield a TP53‐Y220C (L2) neoantigen. This altered neoantigen was found to increase affinity and stability and induce more cytotoxic T lymphocytes (CTLs), indicating improvements in immunogenicity. In vitro assays showed the cytotoxicity of CTLs stimulated by both TP53‐Y220C and TP53‐Y220C (L2) neoantigens against multiple HLA‐A0201‐positive cancer cells expressing TP53‐Y220C neoantigens; however, the TP53‐Y220C (L2) neoantigen showed higher cytotoxicity than the TP53‐Y220C neoantigen against cancer cells. More importantly, in vivo assays demonstrated greater inhibition of hepatocellular carcinoma cell proliferation by TP53‐Y220C (L2) neoantigen‐specific CTLs relative to TP53‐Y220C neoantigen in zebrafish and nonobese diabetic/severe combined immune deficiency mouse models. The results of this study demonstrate enhanced immunogenicity of the shared TP53‐Y220C (L2) neoantigen, which has the potential as dendritic cells or peptide vaccines for multiple cancers. [ABSTRACT FROM AUTHOR]

Lung transplant (LTX) patients are at high risk of cytomegalovirus (CMV) infection, which is often associated with high mortality and morbidity. Reactivation of CMV causes cell injury due to the cytopathic effect of viral replication and triggering of T cell immunity. The aim of this study was to compare expression of immune checkpoints (ICs) (PD‐1, CTLA‐4, LAG‐3 and TIGIT) in CD4, CD8 and CD56 and activation markers CD137, CD154 and CD69 of end‐stage patients awaiting lung transplant. Eighteen pre‐LTX positive for anti‐CMV IgG titres and 18 healthy subjects were enrolled. IC and activation markers have been evaluated through flow cytometric analysis in HC and pre‐LTX patients. Reactive (QF+) and unreactive (QF−) patients were stratified according to QuantiFERON‐CMV assays. ICs' and activation markers' expression were determined before and after in vitro stimulation with pp‐65 and IE‐1 antigens. Lower expression of PD‐1 was observed in CD4 and CD8 cells of pre‐LTX patients than controls, whereas CTLA4 appeared upregulated in CD56 and CD8 cells. TIGIT is increased on the surface of CD4, CD8 and NK cells after peptide stimulation in QF‐negative patients and PD‐1 is only downregulated after stimulation in the QF‐positive patients. This study provides new evidence of immune dysregulation in patients with end‐stage lung disorders, particularly in relation to immune checkpoint cell biology. The change in QF+ mostly happens on cytotoxic cells NK and CD8, while the changes in QF− were observed in adaptive immune cells, including CD4 and CD8. [ABSTRACT FROM AUTHOR]

Materials‐based antigen delivery systems can augment the immune response by improving antigen uptake in antigen‐presenting cells, targeting lymph nodes, prolonging antigen exposure, enhancing cross‐presentation, etc. Recent research revealed that some antigen carriers activate the innate immune pathways without additional adjuvant. Here, a vaccine delivery platform (antigen nanocapsules) constructed by a one‐step in situ polymerization is reported, weaving a biodegradable polymer network around the antigen surface. This simple technology allowed us to study the immunomodulatory effect of various antigen carriers. An antigen nanocapsule (NC7) capable of inducing dendritic cell activation and cross‐presentation is identified. Further mechanistic studies revealed that NC7 activated the cGAS‐STING pathway in a cGAS‐dependent manner. Moreover, the subcutaneously injected NC7 accumulated in the lymph nodes and elicited strong cytotoxic T cell immunity and T cell memory against established cancer. Collectively, the often‐neglected immunomodulatory effect of various cationic antigen carriers, enabling potential application in cancer vaccines, is uncovered. [ABSTRACT FROM AUTHOR]

Background and Objectives: Current manual and automated phenotyping methods are based on visual detection of the antigen–antibody interaction. This approach has several limitations including the use of large volumes of patient and reagent red blood cells (RBCs) and antisera to produce a visually detectable reaction. We sought to determine whether the flow cytometry could be developed and validated to perform RBC phenotyping to enable a high‐throughput method of phenotyping using comparatively miniscule reagent volumes via fluorescence‐based detection of antibody binding. Materials and Methods: RBC phenotyping by flow cytometry was performed using monoclonal direct typing antisera (human IgM): anti‐C, ‐E, ‐c, ‐e, ‐K, ‐Jka, ‐Jkb and indirect typing antisera (human IgG): anti‐k, ‐Fya, ‐Fyb, ‐S, ‐s that are commercially available and currently utilized in our blood transfusion services (BTS) for agglutination‐based phenotyping assays. Results: Seventy samples were tested using both flow‐cytometry‐based‐phenotyping and a manual tube standard agglutination assay. For all the antigens tested, 100% concordance was achieved. The flow‐cytometry‐based method used minimal reagent volume (0.5–1 μl per antigen) compared with the volumes required for manual tube standard agglutination (50 μl per antigen) Conclusion: This study demonstrates the successful validation of flow‐cytometry‐based RBC phenotyping. Flow cytometry offers many benefits compared to common conventional RBC phenotyping methods including high degrees of automation, quantitative assessment with automated interpretation of results and extremely low volumes of reagents. This method could be used for high‐throughput, low‐cost phenotyping for both blood suppliers and hospital BTS. [ABSTRACT FROM AUTHOR]

Background and Objectives: A group AB D‐positive child presented 1 year after haematopoietic stem cell transplant (HSCT) from a group O D‐negative donor as group A D‐negative. Engraftment remained at 100% in white cell lineages. The reason for the unusual result was explored, and the scarcely reported phenomenon of adsorption of secreted antigen was considered. This study also investigated the prevalence of secreted antigen adsorbed onto donor‐derived group O red blood cells (RBCs) in children after HSCT and defined a process for laboratory management. Materials and Methods: Retrospective data analysis of HSCTs carried out over 19 months at Great Ormond Street Hospital was conducted to identify cases of adsorbed A antigen after HSCT. Investigation of RBC reactions with different clones of anti‐A and in vitro experiments was performed to recreate adsorption. Results: Nineteen A to O HSCTs were conducted over 19 months, of which six (31%) displayed weak A antigen on RBCs despite full myeloid engraftment. Negative reactions with anti‐A were obtained when run on an alternative clone. Laboratory protocols for the future management of these cases have been developed. Conclusion: Passive adsorption of secreted antigen is responsible for these results and is more widespread than previously reported, as a third of A to O HSCTs at our centre demonstrated this phenomenon. A process has been implemented into the laboratory to manage this cohort, ensuring component groups compatible with both donor and recipient are given, and the shared care centres are aware of these requirements. [ABSTRACT FROM AUTHOR]

The human cytomegalovirus (HCMV) is an asymptomatic common virus that is typically harmless, but in some cases, it can be life threatening. Thus, there is an urgent need to develop novel diagnostic methods and strengthen the efforts to combat this virus. A microcantilever‐based biosensor functionalised with the UL83‐antibody of HCMV (UL83‐HCMV antibody) has been developed to detect the UL83‐antigen of HCMV (UL83‐HCMV antigen) at different concentrations ranging from 0.3 to 300 ng/ml. The response of the biosensor to the presence of UL83‐HCMV antigen was measured through the shift in resonance frequency before and after antigen–antibody binding. The system shows a low detection limit of 84 pg/ml, which is comparable to traditional sensors, and a detection time of less than 15 min was achieved. The selectivity of the sensor was demonstrated using three different proteins with and without the UL83‐HCMV antigen. The biosensor shows high selectivity for the UL83‐HCMV antigen. Mass loading by the UL83‐HCMV antigen was roughly estimated with a sensitivity of ∼30 fg/Hz. This technique is crucial for the fabrication of portable and low‐cost biosensors that can be used in real‐time monitoring and enables early medical diagnosis. [ABSTRACT FROM AUTHOR]

Recent clinical studies show activating multiple innate immune pathways drives robust responses in infection and cancer. Biomaterials offer useful features to deliver multiple cargos, but add translational complexity and intrinsic immune signatures that complicate rational design. Here a modular adjuvant platform is created using self‐assembly to build nanostructured capsules comprised entirely of antigens and multiple classes of toll‐like receptor agonists (TLRas). These assemblies sequester TLR to endolysosomes, allowing programmable control over the relative signaling levels transduced through these receptors. Strikingly, this combinatorial control of innate signaling can generate divergent antigen‐specific responses against a particular antigen. These assemblies drive reorganization of lymph node stroma to a pro‐immune microenvironment, expanding antigen‐specific T cells. Excitingly, assemblies built from antigen and multiple TLRas enhance T cell function and antitumor efficacy compared to ad‐mixed formulations or capsules with a single TLRa. Finally, capsules built from a clinically relevant human melanoma antigen and up to three TLRa classes enable simultaneous control of signal transduction across each pathway. This creates a facile adjuvant design platform to tailor signaling for vaccines and immunotherapies without using carrier components. The modular nature supports precision juxtaposition of antigen with agonists relevant for several innate receptor families, such as toll, STING, NOD, and RIG. [ABSTRACT FROM AUTHOR]

The hallmark of DCs is their potent and outstanding capacity to activate naive resting T cells. As such, DCs are the sentinels of the immune system and instrumental for the induction of immune responses. This is one of the reasons, why DCs became the focus of immunotherapeutical strategies to fight infections, cancer, and autoimmunity. Besides the exploration of adoptive DC‐therapy for which DCs are generated from monocytes or purified in large numbers from the blood, alternative approaches were developed such as antigen targeting of DCs. The idea behind this strategy is that DCs resident in patients' lymphoid organs or peripheral tissues can be directly loaded with antigens in situ. The proof of principle came from mouse models; subsequent translational studies confirmed the potential of this therapy. The first clinical trials demonstrated feasibility and the induction of T‐cell immunity in patients. This review will cover: (i) the historical aspects of antigen targeting, (ii) briefly summarize the biology of DCs and the immunological functions upon which this concept rests, (iii) give an overview on attempts to target DC receptors with antibodies or (glycosylated) ligands, and finally, (iv) discuss the translation of antigen targeting into clinical therapy. [ABSTRACT FROM AUTHOR]

Expressing heterologous antigens by plasmids may cause antibiotic resistance. Additionally, antigen expression via plasmids is unstable due to the loss of the plasmid. Here, we developed a balanced‐lethal system. The Listeria monocytogenes (LM) balanced‐lethal system has been previously used as an antigen carrier to induce cellular immune response. However, thus far, there has been no reports on Listeria ivanovii (LI) balanced‐lethal systems. The dal and dat genes from the LI‐attenuated LIΔatcAplcB (LIΔ) were deleted consecutively, resulting in a nutrient‐deficient LIΔdd strain. Subsequently, an antibiotic resistance‐free plasmid carrying the LM dal gene was transformed into the nutrient‐deficient strain to generate the LI balanced‐lethal system LIΔdd:dal. The resultant bacterial strain retains the ability to proliferate in phagocytic cells, as well as the ability to adhere and invade hepatocytes. Its genetic composition was stable, and compared to the parent strain, the balanced‐lethal system was substantially attenuated. In addition, LIΔdd:dal induced specific CD4+/CD8+ T‐cell responses and protected mice against LIΔ challenge. Similarly, we constructed an LM balanced‐lethal system LMΔdd:dal. Sequential immunization with different recombinant Listeria strains will significantly enhance the immunotherapeutic effect. Thus, LIΔdd:dal combined with LMΔdd:dal, or with other balanced‐lethal systems will be more promising alternative for vaccine development. [ABSTRACT FROM AUTHOR]

Summary: Background: Treatment of hepatitis C virus (HCV) infection with direct‐acting antivirals (DAAs) is monitored by assessing plasma HCV‐RNA load. However, detection of HCV core antigen (HCVcAg) may be an alternative. Aim: To evaluate the diagnostic performance of the HCVcAg assay to monitor the efficacy of DAAs in HCV‐infected patients Methods: We performed searches in multiple electronic databases until 6 July 2022, of studies evaluating the HCVcAg detection in plasma or serum compared with the HCV‐RNA test (gold standard). We calculated pooled measurement at 2 and 4 weeks of treatment, and at end‐of‐treatment (EOT), as well as sustained virological response (SVR; 12 weeks after EOT). Results: We selected 16 studies from 2016 to 2022, with 3237 patients and 8958 samples. Overall, the diagnostic performance and clinical utility of the HCVcAg assay were poor at week 2 (sensitivity = 0.40, specificity = 0.96, positive likelihood ratio (PLR) = 9.16, negative likelihood ratio (NLR) = 0.63, and area under the summary receiver operating curve (SROC) = 0.57), fair at week 4 (sensitivity = 0.30, specificity = 0.90, PLR = 3.18, NLR = 0.77, and AUC = 0.79), acceptable at EOT (sensitivity = 0.40, specificity =0.98, PLR = 16.54, NLR = 0.62, and AUC = 0.97) and excellent for SVR (sensitivity = 0.94, specificity = 0.99, PLR = 107.54, NLR = 0.06, and AUC = 0.99). Conclusions: The HCVcAg assay may be helpful for monitoring the efficacy of HCV treatment with DAAs in HCV‐infected patients at EOT and for documenting SVR, but not at weeks 2 and 4 of treatment due to poor diagnostic performance. [ABSTRACT FROM AUTHOR]

Mtb8.4, a secretory T‐cell antigen of Mycobacterium tuberculosis, is important for providing an antigen‐specific immune response. In this study, we showed Mtb8.4 to have both heme‐binding and fibril‐forming properties, using experimental and in silico methods. High absorbance at 410 nm and interaction with hemin‐agarose demonstrated its heme‐binding nature. Titration of Mtb8.4 with heme resulted in 1 : 1 stoichiometry. The heme‐binding pocket in Mtb8.4 was identified by molecular modeling, and binding residues were predicted using molecular docking. The molecular dynamics simulations of apo‐ and heme‐bound Mtb8.4 confirmed that the heme group forms a stable complex. Transmission electron microscopy analyses and dye‐binding assays showed that Mtb8.4 forms fibers. Computational studies predicted that the C‐terminal sequence (93AAQYIGLVESV103) is important for forming fibers. In silico analyses further anticipated the probable epitope (82AMAAQLQAV90) of Mtb8.4. The fiber‐forming properties of Mtb8.4 could be advantageous from a vaccine perspective for aggregate/fibril‐based vaccine delivery or it might influence the epitope presentation of Mtb8.4. [ABSTRACT FROM AUTHOR]

Background: Although the prevalence and mortality of hepatitis is high in the Asia‐Pacific region, few studies are available on the diagnosis, treatment, and cure rates for viral hepatitis among people living with HIV in this area. This study aims to report the cascade of care (CoC) for hepatitis B (HBV) and C (HCV) among people living with HIV receiving combined antiretroviral therapy (ART). Methods: Patients enrolled in the TREAT Asia HIV Observational Database Low Intensity Transfer (TAHOD‐LITE) cohort, on ART, and with follow‐up data from 2010 to 2019 were included. Patients were determined as positive for HCV or HBV co‐infection if they ever tested positive for HCV antibody (anti‐HCV) or HBV surface antigen (HBsAg), respectively. Results: In total, 39% (8612/22 340) of the adult HIV cohort had undergone HBsAg testing, with 8% (672/8612) testing positive. HBV CoC demonstrated that 71% (474/672) of those with HBsAg positive results initiated treatment, 67% (318/474) of those on treatment had HBV DNA testing to evaluate treatment progression, and 18% (58/318) of those tested reached viral suppression. Of the cohort, 37% (8231/22 340) had anti‐HCV testing, of whom 10% (779/8231) tested positive. The HCV CoC showed that 68% (526/779) of those with positive anti‐HCV tests had HCV RNA tests, of whom 51% (267/526) had detectable HCV RNA. Among those with detectable HCV RNA, 65% (174/267) initiated HCV treatment. Of the 40% (69/174) who initiated HCV treatment, 90% (62/69) reached sustained virological response. Conclusion: Our findings identified less frequent testing in the healthcare system and limited access to treatment as gaps in the CoC for viral hepatitis. More routine HCV RNA and HBV DNA testing is required for patients with positive screening tests to identify those in need of treatment. [ABSTRACT FROM AUTHOR]

Noroviruses are major causative agents of nonbacterial acute gastroenteritis in humans. Ten genogroups of noroviruses have been identified to date, among which genogroup I (GI) and genogroup II (GII) noroviruses are major pathogens for humans. GI and GII noroviruses are further classified into nine and 27 genotypes, respectively. Noroviruses are well known to bind to histo‐blood group antigens (HBGAs). Many studies have revealed that virus‐like particles (VLPs) from different genotypes exhibit distinct patterns of HBGA binding, but the assay conditions used in these studies were not identical. To enable comparison of the binding to HBGA of nine GI genotypes, I purified VLPs from insect cells and analysed their HBGA‐binding profiles. Although each genotype exhibited a distinct pattern of HBGA binding, Lewis b antigen was commonly recognized by all of the genogroup I strains, suggesting that this antigen plays a critical role in the pathogenesis of noroviruses. [ABSTRACT FROM AUTHOR]

The ongoing global COVID‐19 pandemic, caused by the SARS‐CoV‐2 virus, has resulted in significant loss of life since December 2019. Timely and precise virus detection has been proven as an effective solution to reduce the spread of the virus and to track the epidemic. Rapid antigen diagnostics has played a significant role in the frontline of COVID‐19 testing because of its convenience, low cost, and high accuracy. Herein, different types of recently innovated in‐lab and commercial antigen diagnostic technologies with emphasis on the strengths and limitations of these technologies including the limit of detection, sensitivity, specificity, affordability, and usability are systematically reviewed. The perspectives of assay development are looked into. [ABSTRACT FROM AUTHOR]

CD4+FOXP3+ Tregs are currently explored to develop cell therapies against immune‐mediated disorders, with an increasing focus on antigen receptor‐engineered Tregs. Deciphering their mode of action is necessary to identify the strengths and limits of this approach. Here, we addressed this issue in an autoimmune disease of the CNS, EAE. Following disease induction, autoreactive Tregs upregulated LAG‐3 and CTLA‐4 in LNs, while IL‐10 and amphiregulin (AREG) were increased in CNS Tregs. Using genetic approaches, we demonstrated that IL‐10, CTLA‐4, and LAG‐3 were nonredundantly required for the protective function of antigen receptor‐engineered Tregs against EAE in cell therapy whereas AREG was dispensable. Treg‐derived IL‐10 and CTLA‐4 were both required to suppress acute autoreactive CD4+ T‐cell activation, which correlated with disease control. These molecules also affected the accumulation in the recipients of engineered Tregs themselves, underlying complex roles for these molecules. Noteworthy, despite the persistence of the transferred Tregs and their protective effect, autoreactive T cells eventually accumulated in the spleen of treated mice. In conclusion, this study highlights the remarkable power of antigen receptor‐engineered Tregs to appropriately provide multiple suppressive factors nonredundantly necessary to prevent autoimmune attacks. [ABSTRACT FROM AUTHOR]

Background and Objectives: D‐negative patients undergoing orthotopic liver transplantation (OLT) might require a large number of red blood cell (RBC) units, which can impact the inventory of D‐negative blood. The blood bank might need to supply these patients with D‐positive RBCs because of inventory constraints. This study evaluates the prevalence of anti‐D formation in D‐negative OLT patients who received D‐positive RBCs perioperatively, as this will assist in successful patient blood management. Materials and Methods: This was a retrospective study performed at a single academic medical centre. Electronic medical records for all 1052 consecutive patients who underwent OLT from January 2007 through December 2017 were reviewed. D‐negative patients who were transfused perioperatively with D‐positive RBCs and had antibody screening at least 30 days after transfusion were included. Results: Of a total of 155 D‐negative patients, 23 (14.8%) received D‐positive RBCs perioperatively. Seventeen patients were included in the study. The median age was 54 years (range 36–67 years); 13 (76.5%) were male. The median number of D‐positive RBC units transfused perioperatively was 7 (range 1–66 units). There was no evidence of D alloimmunization in any patient after a median serologic follow‐up of 49.5 months (range 31 days to 127.7 months). The average number of antibody screening post OLT was 7.29. Conclusion: Our study showed that transfusion of D‐positive RBCs in D‐negative OLT recipients is a safe and acceptable practice in the setting of immunosuppression. This practice allows the conservation of D‐negative RBC inventory. [ABSTRACT FROM AUTHOR]

Complement‐mediated interference is a well described phenomenon in single antigen bead (SAB) Luminex assay that leads to falsely low or negative results for anti‐HLA antibody (Ab). In a context of high amount of Ab, the enrichment of the Ab around the bead can lead to complement cascade activation and deposition, thereafter impairing Ab detection. EDTA is now routinely used to circumvent this interference. In this report, we attempted to decipher the role of the phycoerythrin (PE) label conjugated to the secondary Ab in this interference. Indeed, PE is a huge molecule (240 kDa) that could participate to limiting access of the conjugate to its Ab target on the bead. To this purpose, 22 sera displaying complement interference without pre‐treatment with EDTA were compared on SAB assay with three detection strategies: the recommended PE‐conjugated secondary Ab (IgGPE), an Alexa Fluor 532‐conjugated Ab (IgGAF) bearing a tiny 724 Da fluorochrome, and a biotinylated Ab followed by PE‐conjugated streptavidin (IgGBiot). Complement interference occurred with the three detection methods, but its depth, defined by the percentage of MFI loss with neat serum, was the highest for IgGPE. Our study highlighted the partial role of the PE fluorochrome in complement interference in SAB assays. [ABSTRACT FROM AUTHOR]

Familial clustering of the skin disease primary hyperhidrosis suggests a genetic component to the disease. The human leucocyte antigen (HLA) is implicated in a range of diseases, including many comorbidities to hyperhidrosis. No study has investigated whether the HLA genes are involved in the pathogenesis of hyperhidrosis. We, therefore, compared HLA alleles in individuals with and without hyperhidrosis in this study of 65 000 blood donors. In this retrospective cohort study, we retrieved information on individuals with and without hyperhidrosis using self‐reported questionnaires, the Danish National Patient Registry and the Danish National Prescription Registry on participants recruited to the Danish Blood Donor Study between 2010 and 2019. Association tests using logistic regression were conducted for each HLA allele corrected for sex, age, body mass index, smoking and principal components. Overall, 145 of 65 795 (0.2%) participants had hospital diagnosed hyperhidrosis. Similarly, 1379 of 15 530 (8.9%) participants had moderate‐severe self‐reported hyperhidrosis, of whom 447 (2.9%) had severe self‐reported hyperhidrosis. Altogether, 28 participants had both hospital diagnosed and moderate‐severe self‐reported hyperhidrosis. Severe self‐reported hyperhidrosis was associated with HLA‐A*80:01 (adjusted odds ratio 26.97; 95% confidence interval 5.32‐136.70; n = 7; P <.001). Moderate‐severe self‐reported hyperhidrosis and hospital diagnosed hyperhidrosis were not associated with any HLA. The association between hyperhidrosis and HLA‐A*80:01 was based on a very small number of cases and not replicated in other patient subsets, and therefore likely a chance finding. Thus, this study suggests that genes other than the HLA are involved in the pathogenesis of hyperhidrosis. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies with nuclear antigen (nAg) specificity. Using (SWRxNZB)F1 (SNF1) mice, we showed higher levels of Immunoglobulin A (IgA) production in the intestine and the nAg reactivity of faecal IgA under lupus susceptibility. Here, we determined whether the faecal IgA abundance and nAg reactivity are higher in, different among, various lupus‐prone preclinical models (MRL/lpr, NZBxNZW‐F1, SNF1, NZM2410 and NZM2328). We also determined whether the faecal IgA nAg reactivity at preseropositive ages correlates with the eventual serum autoantibody levels in males and females of these mouse models. We show that age‐dependent increase in the abundance and nAg reactivity of faecal IgA can vary among different lupus‐prone mouse models. Importantly, faecal IgA in these mice show significant levels of nAg reactivity, starting as early as at juvenile age. Furthermore, the pre‐seropositive stage nAg reactivity of faecal IgA in most lupus‐prone strains correlates well with that of eventual, seropositive stage systemic autoantibody levels. Gender differences in serum autoantibody levels were preceded by similar differences in the faecal IgA abundance and nAg reactivity. These observations suggest that faecal IgA features, nAg reactivity particularly, could serve as a biomarker for early prediction of the eventual systemic autoimmunity in lupus‐prone subjects. [ABSTRACT FROM AUTHOR]

Acral melanocytic neoplasms often pose diagnostic difficulty. Preferentially expressed antigen in melanoma (PRAME) expression and loss of p16 expression have diagnostic utility in melanocytic tumors. We examined PRAME and p16 expression in 30 acral melanocytic neoplasms (n = 11 nevi; n = 2 dysplastic nevi; n = 7 Spitz nevi; n = 10 acral melanomas). PRAME was scored as % positive nuclei: negative = 0%; 1% to 25% = 1+; 25% to 50% = 2+; 50% to 75% = 3+, or positive: 75% to 100% = 4+. p16 expression was defined as retained (homogeneous or checkerboard) or lost (complete or partial/regionally). PRAME expression was negative in all benign, dysplastic, and Spitz nevi. Conversely, all acral melanomas were diffusely (4+) positive for PRAME expression. p16 expression was retained in all benign acral nevi (8/11 homogeneous, 3/11 checkerboard), completely lost in one dysplastic nevus, and retained in all acral Spitz nevi (3/7 homogeneous, 4/7 checkerboard). p16 was retained in five of 10 acral melanomas (3/10 homogeneous; 2/10 checkerboard), and negative in five of 10 acral melanomas (absent in 3/10, partially lost in 2/10). Our data suggest that 4+ PRAME expression is highly sensitive and specific in the setting of acral melanomas and is a more predictive diagnostic tool compared with p16 immunohistochemistry. [ABSTRACT FROM AUTHOR]

Ferrocene‐derivatives have a well‐defined electrochemical behaviour, which can be changed upon binding to other molecules (including nonelectroactive species), as the conjugate presents a slower diffusion to the electrode surface. Therefore, the binding event can be easily detected by monitoring the decrease in the current intensity of the ferrocene‐derivative oxidation peak. An electrochemical probe composed of ferrocenecarboxylic acid conjugated with Sambucus nigra agglutinin was prepared and used to selectively detect the STn antigen, a pan‐carcinoma glycobiomarker. The probe showed high selectivity towards the STn antigen present in glycoproteins and demonstrated effectiveness in the analysis of serum samples from carcinoma patients. [ABSTRACT FROM AUTHOR]

Background: Cutaneous warts represent a challenging condition to treat. Objective: To evaluate the safety and efficacy of intralesional injection of MMR (mumps, measles, and rubella) antigen, BCG (bacillus Calmette‐Guerin) vaccine, and candida antigen for the treatment of multiple warts. Methods: A total of ninety (90) clinically confirmed adult patients complaining of recalcitrant extragenital warts of various sizes and durations were recruited in this randomized clinical trial. They were divided into three groups (A, B, and C). Each group consisted of (30) patients. Group (A) subjects received intralesional MMR injections. Group (B) subjects received intralesional BCG injection and Group (C) received intralesional candida antigen injection. Results: Full clearance of warts was observed in (73.33%, 70%, and 43.33%) in groups A, B, and C, respectively. Infrequent side effects including pain, erythema, and minimal induration were reported in all groups but did not necessitate termination of treatment. Conclusion: All the three modalities used demonstrated a simple, safe modality with low adverse events, and with no recurrence. To achieve an optimal response with an ideal immunotherapeutic agent and ideal dose, further comparative studies are warranted and on different populations and larger sample sizes. [ABSTRACT FROM AUTHOR]

Background and Objectives: Isoantibodies to human neutrophil antigen 2 (CD177) have been associated with several clinical conditions but to date the molecular basis for altered or non‐expression has not been determined. Reliance on phenotyping and crossmatch to investigate these neutropenic clinical cases are inconvenient for the patients and demanding of resources within the laboratory. Therefore, a molecular approach has been introduced to address both issues. Materials and Methods: A DNA panel of 100 randomly selected blood donors were collected and supplemented with 18 DNA samples from blood donors previously shown to be CD177 null. All DNA samples were sequence‐based typed for all exons and observed polymorphisms recorded. The DNA from two families previously investigated for neonatal alloimmune neutropenia due to CD177 isoantibodies were also analysed. Results: The incidence of CD177 null could be associated with a known exon 7 single‐nucleotide polymorphism in 16/21 known CD177 null samples, which is consistent with previously published findings. Two additional mutations that may lead to null expression were also identified, of which one may be novel. In both family investigations, this same mutation could also be observed in the maternal DNA sample. Conclusion: Based on these observations, introduction of CD177 genotyping into routine use would identify null expression in over 75% (16/21) of associated cases. In turn, this could significantly reduce the need for supplementary testing and associated inconvenience to patients while permitting increased efficiency of laboratory testing. An added benefit would potentially elucidate other clinically relevant mutations and associated antigenic targets. [ABSTRACT FROM AUTHOR]

Background and Objectives: Antigens of the MNS blood group system are expressed on the red blood cell (RBC) membrane on glycophorin A (GPA) and glycophorin B (GPB) or on hybrid molecules of GPA and GPB. This study investigated the distribution of glycophorin variants and alloantibodies against Hil and MINY among Japanese individuals. Methods: Mi(a+) or Hil+ RBCs were screened using an automated blood grouping machine (PK7300) with monoclonal anti‐Mia or polyclonal anti‐Hil. Glycophorin variants were defined by serology with monoclonal antibodies against Mia, Vw, MUT and Mur, and polyclonal antibodies against Hil, MINY and Hop + Nob (KIPP). The glycophorin variants were further confirmed by immunoblotting and Sanger sequencing. Alloanti‐Hil and alloanti‐MINY in the plasma were screened using GP.Hil RBCs in an antiglobulin test. The specificity of anti‐Hil or anti‐MINY was assessed using GP.Hil (Hil+MINY+) and GP.JL (Hil‒MINY+) RBCs. Results: The GP.HF, GP.Mur, GP.Hut, GP.Vw, GP.Kip and GP.Bun frequencies in 1 005 594 individuals were 0·0357%, 0·0256%, 0·0181%, 0·0017%, 0·0009% and 0·0007%, respectively. GP.Hil was found in as four of the 13 546 individuals (0·0295%). Of 137 370 donors, 10 had anti‐Hil (0·0073%) and three had anti‐MINY (0·0022%). Conclusions: Glycophorin variants were relatively rare in Japanese individuals, with the major variants being GP.HF (0·0357%), GP.Hil (0·0295%) and GP.Mur (0·0256%). Only one example of anti‐MINY was previously reported, but we found three more in this study. [ABSTRACT FROM AUTHOR]

Antigen and antigen-specific IgE can activate IgE receptors and induce IL-4 production by mast cells or basophils. In allergic inflammation, the cells existing in the mucosa take up antigens and present them to produce specific immunoglobulin E (IgE). Mast cells or basophil express the IgE receptor binding to antigen-specific IgE and antigens. [Extracted from the article]

Aims: We are studying the dialogue between β‐cells and the immune system in type 1 diabetes and have identified a cell surface receptor, signal regulatory protein‐alpha (SIRPα) as an important component in the regulation of β‐cell survival. SIRPα interacts with another protein, CD47, to mediate signalling. In the present work, we have studied the expression and role of CD47 in human islet cells in type 1 diabetes. Methods: Clonal EndoC‐βH1 cells were employed for functional studies. Cells were exposed to pro‐inflammatory cytokines and their viability monitored by flow cytometry after staining with propidium iodide. Targeted knockdown of CD47 or SIRPα was achieved with small interference RNA molecules and the expression of relevant proteins studied by Western blotting or immunocytochemistry. Human pancreas sections were selected from the Exeter Archival Diabetes Biobank and used to examine the expression of CD47 by immunofluorescence labelling. Image analysis was employed to quantify expression. Results: CD47 is abundantly expressed in both α and β cells in human pancreas. In type 1 diabetes, the levels of CD47 are increased in α cells across all age groups, whereas the expression in β‐cells varies according to disease endotype. Knockdown of either CD47 or SIRPα in EndoC‐βH1 cells resulted in a loss of viability. Conclusions: We conclude that the CD47 plays a previously unrecognised role in the regulation of β‐cell viability. This system is dysregulated in type 1 diabetes suggesting that it may be targeted therapeutically to slow disease progression. [ABSTRACT FROM AUTHOR]

The outer surfaces of mycobacteria, including the organism that causes tuberculosis, are decorated with an array of immunomodulatory glycans. Among these are lipooligosaccharides (LOSs), a class of molecules for which the function remains poorly understood. We describe the chemical synthesis of the glycan portion of a tridecasaccharide LOS from the opportunistic pathogen Mycobacterium kansasii. The target contains a number of unusual structural motifs that complicate its assembly and is the most complex mycobacterial LOS glycan to be synthesized to date when considering size and number of unique monosaccharides and glycosidic linkages. These studies not only provide a roadmap for the preparation of additional members of this family of glycans, but also provides a valuable probe for use in structure–activity relationship investigations. [ABSTRACT FROM AUTHOR]

The outer surfaces of mycobacteria, including the organism that causes tuberculosis, are decorated with an array of immunomodulatory glycans. Among these are lipooligosaccharides (LOSs), a class of molecules for which the function remains poorly understood. We describe the chemical synthesis of the glycan portion of a tridecasaccharide LOS from the opportunistic pathogen Mycobacterium kansasii. The target contains a number of unusual structural motifs that complicate its assembly and is the most complex mycobacterial LOS glycan to be synthesized to date when considering size and number of unique monosaccharides and glycosidic linkages. These studies not only provide a roadmap for the preparation of additional members of this family of glycans, but also provides a valuable probe for use in structure–activity relationship investigations. [ABSTRACT FROM AUTHOR]

Background and Objectives: There is limited evidence regarding the advantage of transfusing extended phenotype‐matched (EPM) packed red blood cells (PRBCs) to prevent alloimmunization in haemato‐oncology patients. This randomized control trial aimed to determine the alloimmunization in haemato‐oncology patients transfused with PRBCs which are EPM for Rh (C, E, c, e) and Kell (K) antigens (group I) versus those receiving standard compatible PRBCs (group II). Materials and Methods: Patients having a negative antibody screen (ABS), direct antiglobulin test (DAT) and autologous control (AC) were randomly allocated to either group I or II (n = 50 each). A follow‐up (FU) testing post‐transfusion was conducted for haemoglobin (Hb), ABS and DAT at 1 week, 1 month and 3 months. ABS was conducted using fully automated immunohaematology analyser, while DAT, compatibility testing and extended phenotyping were conducted manually using column agglutination technique. Results: There was no significant difference between the two groups with respect to mean (±SD) Hb at initial enrolment (group I, 5·06 ± 1·29 g/dl and group II, 5·41 ± 1·37 g/dl; P = 0·179), age (40 ± 17·3 years v/s 42·2 ± 17·2 years; P = 0·523), gender (P = 0·835) and diagnosis (P = 0·06). All patients in group I and II had negative ABS, DAT and AC at all three FUs. Group II patients were transfused more PRBCs (372 v/s 187, P = 0·000), while the mean Hb increment between successive FU was significant in both the groups (P = 0·003). Conclusion: It appears that there is no added benefit of providing EPM PRBCs in haemato‐oncology patients, as none developed RBC alloantibodies. [ABSTRACT FROM AUTHOR]

Aim: The clinical significance of carcinoembryonic antigen (CEA) combined with carbohydrate antigen 19‐9 (CA19‐9) in patients with rectal cancer is not well established. The aim of this study was to determine the prognostic value of these combined tumour markers in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT). Method: A total of 687 consecutive patients with LARC who underwent nCRT and radical surgery were analysed. Tumour characteristics, recurrence‐free survival (RFS) and overall survival (OS) were compared according to the number of elevated tumour markers measured before and after nCRT. In addition, the prognostic significance of perioperative changes in the combined tumour markers was further evaluated. Result: The RFS and OS rates decreased in a stepwise manner in association with the number of elevated pre‐ and post‐nCRT tumour markers (all p < 0.05). Multivariate analysis showed that only the number of elevated post‐nCRT tumour markers was an independent prognostic factor (both p < 0.05). For 311 patients with elevated pre‐nCRT tumour markers, normalization of the tumour markers after nCRT was an independent prognostic protective factor (both p < 0.05), and patients with both markers elevated post‐nCRT had a 2.5‐ and 3.7‐fold increased risk of recurrence and death, respectively (p < 0.05). Furthermore, normalization of post‐nCRT tumour markers after surgery was also closely related to an improved prognosis. Conclusion: This combination of post‐nCRT tumour markers can accurately predict the long‐term survival of patients with LARC treated with nCRT and curative resection, and normalization of the combined tumour markers after either nCRT or surgery was associated with better survival. [ABSTRACT FROM AUTHOR]

In this study, a novel biosensor based on molecular imprinting polymer (MIP) methodology was fabricated toward recognition of carcinoembryonic antigen (CEA). For this purpose, poly (toluidine blue) (PTB) was electropolymerized on the surface of gold electrode in the absence and presence of CEA. So, the target molecules were entrapped into the imprinted specific cavities of MIP. Obtained results show that, the binding affinity of the MIP system was significantly higher than that of revealed for the nonimprinted polymer (NIP) system, MIP‐based biosensor revealed linear response from (0.005 to 75 μg/L) and low limit of quantification of (0.005 μg/L) by using chronoamperometry technique, leading to CEA monitoring in real and clinical samples. Thus, a novel technique for rapid, simple, sensitive and affordable monitoring of CEA (LLOQ = 0.005 μg/L) has provided through developed biosensor. From a future perspective, moreover, this method can be considered as an applicable candidate in biomedical and clinical analysis for point‐of‐care usages. [ABSTRACT FROM AUTHOR]

As a good alternative, direct probe-based RT-LAMP assay or other nucleic acid amplification (NAA)-based POCT strategies should be recommended to use alone or together with rapid antigen test in mass screening or community-based testing of SARS-CoV-2. Currently, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still the biggest public health crisis faced by the world. Rapid antigen detection alone may not be sufficient for early diagnosis and/or mass screening of COVID-19. [Extracted from the article]

CD20 SP + sp T cells constitute about 5% of all circulating T cells. Success of anti-CD20 therapy has placed B cells center stage, to an extent that T cells are becoming perceived as minor players in the pathogenesis of multiple sclerosis (MS). [Extracted from the article]

Agreement, antigen capture enzyme-linked immunosorbent assay (AC-ELISA), Avian influenza virus, Cohen's kappa, H7N9, virus detection REFERENCES 1 Yang F, Xiao Y, Liu F, Yao H, Wu N, Wu H. Development of a monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay for detection of H7N9 subtype avian influenza virus. Comment on Yang et al., Development of a monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay for detection of H7N9 subtype avian influenza virus. [Extracted from the article]