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BACKGROUND: Snail allergy is rare but can be fatal. Pila polita, a freshwater snail, was considered as a popular exotic food, particularly in tropical countries, and consumed in processed forms. Thus, the purpose of this study was to identify the major and cross‐reactive allergens of P. polita and to determine the impact of food processing on the allergen stability. RESULTS: Sodium dodecyl sulfate–polyacrylamide gel electrophoresis fractionated raw snail extract to approximately 24 protein bands, between 9 and 245 kDa. The prominent band at 33 kDa was detected in all raw and processed snail extracts. Immunoblotting tests of the raw extract demonstrated 19 immunoglobulin E (IgE)‐binding proteins, and four of them, at 30, 35, 42 and 49 kDa, were revealed as the major IgE‐binding proteins of P. polita. Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry identified the 49 and 42 kDa major allergens as actin, whereas the 30 and 35 kDa major allergens were identified as tropomyosin. Immunoblotting revealed that the raw snail had more allergenic proteins than the processed snail. The degree of allergenicity in decreasing order was raw > brine pickled> boiled > roasted > fried > vinegar pickled. The presence of cross‐reactivity between P. polita and the shellfish tested was exhibited with either no, complete, or partial inhibitions. CONCLUSION: Actin and tropomyosin were identified as the major and cross‐reactive allergens of P. polita among local patients with snail allergy. Those major allergens are highly stable to high temperatures, acidic pH, and high salt, which might played a crucial role in snail allergy in Malaysia. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin β1, only some integrin β7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients. During an infection, plasmablasts circulating in blood represent ongoing formation of antibody-producing cells from activated B cells. Here we study the early plasmablasts in previously naïve COVID-19 patients arriving at hospital. We find extensive cross-reactivity to circulating and non-circulating beta-coronaviruses, that IgA1 responses dominate, and that the cells express markers suggesting mucosal homing. [ABSTRACT FROM AUTHOR]

Introduction: In allergy diagnostics, component-resolved diagnostics (CRD) allows the clinician to assess the presence of specific IgE (sIgE) to allergenic proteins. Molecular diagnostics has improved our ability to identify not only species-specific, but also panallergen components. Aim: To characterize the Georgian allergic population according to the most frequently recognized plant panallergen components (profilins, PR-10 and nonspecific lipid transfer proteins) using sensitization data from multiplex CRD and investigate their association with particular allergic diseases. Material and methods: Patients, IgE positive to at least one studied panallergen component, were selected out of total 435 allergic individuals and stratified in two age groups: children and adults. Descriptive statistics, Chi square test (X2) and Pearson Correlation test (r) were used for analysing the data. Results: 38% (164/435) of investigated allergic patients showed IgE reactivity to at least one molecule belonging to Profilin, PR-10 and nsLTP families. Generally, PR-10 reactive individuals represented the largest group of patients (56.0%), followed by Profilins (43.0%) and nsLTP (32.0%). For the PR-10 allergen group, IgE sensitization was dominated by Bet v 1, for Profilin - by Hev b 8 and for nsLTP - by Pru p 3. It was shown that sensitization with nsLTPs revealed statistically important associations with allergic rhinitis (p = 0.005) and dermatitis (p = 0.02). PR-10 allergen sensitization was associated with allergic rhinitis (p = 0.04) and asthma (p = 0.04). Conclusions: According to our results, sensitization to plant panallergens in the Georgian population creates characteristic features overlapping serotypes of Central Europe and Mediterranean region. [ABSTRACT FROM AUTHOR]

p-phenylenediamine derivatives are widely used in industry and in cosmetics, and several of them are well-known sensitizers. One group of allergenic p-phenylenediamine derivatives are used as colour film developers. Cross-reactivity between the colour film developers has been reported. In this paper, an occupational facial dermatitis due to colour film developers is described. The patient reacted to colour film developers (CD-1, CD-2, CD-3. and CD-4), but not to other p-phenylenediamine derivatives tested. He also showed allergic reactions to Disperse Blue 106 and Disperse Blue 124 and to Disperse Red 17, but not to Disperse Orange 3. The activation of the colour him developers by oxidation at physiological pH was analysed with chemical methods, and the mechanism responsible tar the concomitant reactivities to the colour film developers and the disperse dyes at a molecular level is discussed. [ABSTRACT FROM AUTHOR]

Background: Allergy to celery is often associated with sensitization to birch and;or mugwort pollen. Objective and Methods: In a multi-centre study. sera from 23 patients suffering from type I allergy to celery and 1 5 patients with positive celery RAST hut no clinical sensitization were compared. To examine whether cross-reactivity between celery and mugwort pollen includes cross-sensitization to birch pollen allergens, we determined cross-reacting structure in birch pollen. mugwort pollen and celery by means of immunoblotting. Inhibition studies were performed by preincubation of sent with extracts of birch pollen. mugwort pollen, and celery. Results: We identified three groups of proteins homologues of Bet v 1 and birch profilin (Bet v2) as well as a group of proteins with a molecular range of 46 to 60KD displaying IgE-cross-reactivity. which were shared by birch pollen and celery. Two of these groups of allergens (profilin and the 46 to 60 U) proteins) were also present in mugwort pollen. In this paper we demonstrate that most cross-reacting allergens present in mugwort pollen and celery can also be detected in birch pollen extract. Conclusion therefore we propose. Iron a serological point of view, to extend the mugwort-celery syndrome to the birch-mugwort-celery syndrome. [ABSTRACT FROM AUTHOR]

Shellfish, including various species of mollusks (e.g., mussels, clams, and oysters) and crustaceans (e.g., shrimp, prawn, lobster, and crab), have been a keystone of healthy dietary recommendations due to their valuable protein content. In parallel with their consumption, allergic reactions related to shellfish may be increasing. Adverse reactions to shellfish are classified into different groups: (1) Immunological reactions, including IgE and non-IgE allergic reactions; (2) non-immunological reactions, including toxic reactions and food intolerance. The IgE-mediated reactions occur within about two hours after ingestion of the shellfish and range from urticaria, angioedema, nausea, and vomiting to respiratory signs and symptoms such as bronchospasm, laryngeal oedema, and anaphylaxis. The most common allergenic proteins involved in IgE-mediated allergic reactions to shellfish include tropomyosin, arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, troponin c, and triosephosphate isomerase. Over the past decades, the knowledge gained on the identification of the molecular features of different shellfish allergens improved the diagnosis and the potential design of allergen immunotherapy for shellfish allergy. Unfortunately, immunotherapeutic studies and some diagnostic tools are still restricted in a research context and need to be validated before being implemented into clinical practice. However, they seem promising for improving management strategies for shellfish allergy. In this review, epidemiology, pathogenesis, clinical features, diagnosis, and management of shellfish allergies in children are presented. The cross-reactivity among different forms of shellfish and immunotherapeutic approaches, including unmodified allergens, hypoallergens, peptide-based, and DNA-based vaccines, are also addressed. [ABSTRACT FROM AUTHOR]

Dengue is the most common viral infection spread by mosquitoes, prevalent in tropical countries. The acute dengue virus (DENV) infection is a benign and primarily febrile illness. However, secondary infection with alternative serotypes can worsen the condition, leading to severe and potentially fatal dengue. The antibody raised by the vaccine or the primary infections are frequently cross-reactive; however, weakly neutralizing, and during subsequent infection, they may increase the odds of antibody-dependent enhancement (ADE). Despite that, many neutralizing antibodies have been identified against the DENV, which are thought to be useful in reducing dengue severity. Indeed, an antibody must be free from ADE for therapeutic application, as it is pretty common in dengue infection and escalates disease severity. Therefore, this review has described the critical characteristics of DENV and the potential immune targets in general. The primary emphasis is given to the envelope protein of DENV, where potential epitopes targeted for generating serotype-specific and cross-reactive antibodies have critically been described. In addition, a novel class of highly neutralizing antibodies targeted to the quaternary structure, similar to viral particles, has also been described. Lastly, we have discussed different aspects of the pathogenesis and ADE, which would provide significant insights into developing safe and effective antibody therapeutics and equivalent protein subunit vaccines. [ABSTRACT FROM AUTHOR]

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to cross-reacting material CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Haemophilus influenzae type b (Hib) and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable. [ABSTRACT FROM AUTHOR]

The current study was initiated when our specific-pathogen-free laboratory toms developed unexpectedly high levels of cross-reactive antibodies to human SARS-CoV-2 (SCoV2) receptor binding domain (RBD) upon mating with feline coronavirus (FCoV)-positive queens. Multi-sequence alignment analyses of SCoV2 Wuhan RBD and four strains each from FCoV serotypes 1 and 2 (FCoV1 and FCoV2) demonstrated an amino acid sequence identity of 11.5% and a similarity of 31.8% with FCoV1 RBD (12.2% identity and 36.5% similarity for FCoV2 RBD). The sera from toms and queens cross-reacted with SCoV2 RBD and reacted with FCoV1 RBD and FCoV2 spike-2, nucleocapsid, and membrane proteins, but not with FCoV2 RBD. Thus, the queens and toms were infected with FCoV1. Additionally, the plasma from six FCoV2-inoculated cats reacted with FCoV2 and SCoV2 RBDs, but not with FCoV1 RBD. Hence, the sera from both FCoV1-infected cats and FCoV2-infected cats developed cross-reactive antibodies to SCoV2 RBD. Furthermore, eight group-housed laboratory cats had a range of serum cross-reactivity to SCoV2 RBD even 15 months later. Such cross-reactivity was also observed in FCoV1-positive group-housed pet cats. The SCoV2 RBD at a high non-toxic dose and FCoV2 RBD at a 60–400-fold lower dose blocked the in vitro FCoV2 infection, demonstrating their close structural conformations essential as vaccine immunogens. Remarkably, such cross-reactivity was also detected by the peripheral blood mononuclear cells of FCoV1-infected cats. The broad cross-reactivity between human and feline RBDs provides essential insights into developing a pan-CoV vaccine. [ABSTRACT FROM AUTHOR]

Dengue and Zika are arthropod-borne viral diseases present in more than 100 countries around the world. In the past decade, Zika emerged causing widespread outbreaks in new regions, where dengue has been endemicepidemic for a long period. The wide and extensive dissemination of the mosquito vectors, Aedes aegypti, and Ae. albopictus, favor the co-existence of both infections in the same regions. Together with an important proportion of asymptomatic infections, similar clinical manifestations, and a short time window for acute infection confirmatory tests, it is difficult to differentially estimate both dengue and Zika incidence and prevalence. DENV and ZIKV flavivirus share high structural similarity, inducing a cross-reactive immune response that leads to false positives in serological tests particularly in secondary infections. This results in overestimation of recent Zika outbreaks seroprevalence in dengue endemic regions. In this review, we address the biological basis underlying DENV and ZIKV structural homology; the structural and cellular basis of immunological cross reactivity; and the resulting difficulties in measuring dengue and Zika seroprevalence. Finally, we offer a perspective about the need for more research to improve serological tests performance. [ABSTRACT FROM AUTHOR]

Bacteriophages (phages) are viruses infecting bacteria. They are widely present in the environment, food, and normal microflora. The human microbiome is a mutually interdependent network of bacteria, bacteriophages, and human cells. The stability of these tri-kingdom interactions may be essential for maintaining immunologic and metabolic health. Phages, as with each other's antigens, may evoke an immune response during a human's lifetime and induce specific antibody generation. In this manuscript, we labeled these antibodies as naturally generated. Naturally generated antibodies may be one of the most important factors limiting the efficacy of phage therapy. Herein, we attempted to determine the physiological level of these antibodies specific to a population bacteriophage named I11mO19 in human sera, using an ELISA-based assay. First, we purified the phage particles and assessed the immunoreactivity of phage proteins. Then, affinity chromatography was performed on columns with immobilized phage proteins to obtain a fraction of human polyclonal anti-phage antibodies. These antibodies were used as a reference to elaborate an immunoenzymatic test that was used to determine the level of natural anti-phage antibodies. We estimated the average level of anti-I11mO19 phage antibodies at 190 µg per one milliliter of human serum. However, immunoblotting revealed that cross-reactivity occurs between some proteins of I11mO19 and two other coliphages: T4 and ΦK1E. The antigens probably share common epitopes, suggesting that the determined level of anti-I11mO19 phage might be overestimated and reflects a group of antibodies reactive to a broad range of other E. coli phages. Anti-I11mO19 antibodies did not react with Pseudomonas bacteriophage F8, confirming specificity to the coliphage group. In this work, we wanted to show whether it is possible to determine the presence and level of anti-phage antibodies in nontargeted-immunized sera, using an immunoenzymatic assay. The conclusion is that it is possible, and specific antibodies can be determined. However, the specificity refers to a broader coliphage group of phages, not only the single phage strain. [ABSTRACT FROM AUTHOR]

Ragweed (Ambrosia artemisiifolia) pollen is a major endemic allergen source responsible for severe allergic manifestations in IgE-sensitized allergic patients. It contains the major allergen Amb a 1 and cross-reactive allergen molecules, such as the cytoskeletal protein profilin, Amb a 8 and calcium-binding allergens Amb a 9 and Amb a 10. To assess the importance of Amb a 1, profilin and calcium-binding allergen, the IgE reactivity profiles of clinically well-characterized 150 ragweed pollen-allergic patients were analysed regarding specific IgE levels for Amb a 1 and cross-reactive allergen molecules by quantitative ImmunoCAP measurements, IgE ELISA and by basophil activation experiments. By quantifying allergen-specific IgE levels we found that Amb a 1-specific IgE levels accounted for more than 50% of ragweed pollen-specific IgE in the majority of ragweed pollen-allergic patients. However, approximately 20% of patients were sensitized to profilin and the calcium-binding allergens, Amb a 9 and Amb a 10, respectively. As shown by IgE inhibition experiments, Amb a 8 showed extensive cross-reactivity with profilins from birch (Bet v 2), timothy grass (Phl p 12) and mugwort pollen (Art v 4) and was identified as a highly allergenic molecule by basophil activation testing. Our study indicates that molecular diagnosis performed by the quantification of specific IgE to Amb a 1, Amb a 8, Amb a 9 and Amb a 10 is useful to diagnose genuine sensitization to ragweed pollen and to identify patients who are sensitized to highly cross-reactive allergen molecules present in pollen from unrelated plants, in order to enable precision medicine-based approaches for the treatment and prevention of pollen allergy in areas with complex pollen sensitization. [ABSTRACT FROM AUTHOR]

Cross-reactivity of metal allergies can make metal allergy treatment complicated because the background of immune response in cross-reactions remains unknown. In clinical settings, cross-reactivity among several metals has been suspected. However, the precise mechanism of immune response in cross-reactivity is unclear. Two sensitizations with nickel, palladium, and chromium plus lipopolysaccharide solution into the postauricular skin were followed by a single nickel, palladium, and chromium challenge of the oral mucosa to generate the intraoral metal contact allergy mouse model. Results showed that the infiltrating T cells in nickel-sensitized, palladium- or chromium-challenged mice expressed CD8+ cells, cytotoxic granules, and inflammation-related cytokines. Thus, nickel ear sensitization can cause cross-reactive intraoral metal allergy. [ABSTRACT FROM AUTHOR]

A systematic review and narrative synthesis of publications was undertaken to analyze the role of component-resolved diagnosis technology in identifying polysensitization for the provision of allergen-specific immunotherapy to patients with seasonal allergic rhinitis. A search of publications was carried out in electronic databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search helped to identify 568 publications, 12 of which were included in this review. Overall, 3302 patients were enrolled. The major finding was that component-resolved diagnostics change the choice of relevant allergens for allergen-specific immunotherapy in at least 50% of cases. Sensitization to allergen components differs with age, type of disease, and overall disease duration. Patients who had both bronchial asthma and allergic rhinitis were sensitized to a larger number of allergens than patients who had bronchial asthma alone. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are among the main causes of fixed drug eruption (FDE). Cross‐sensitivity between chemically unrelated NSAIDs has been rarely described in FDE. We report herein two cases of NSAID‐induced FDE confirmed by oral provocation test (OPT) with a literature review. Case 1 is a 49‐year‐old woman who took mefenamic, naproxen and acetaminophen for lumbago. On the second day, she noticed three erythematous plaques, located in the upper lip, chin and the right hand, which faded spontaneously, leaving residual patches. Three months later, she took mefenamic acid with reactivation of the same plaques. She received naproxen. On the same day, she exhibited a reactivation of lesions with the development of a new one. These lesions have disappeared leaving hyperpigmented sequelae. After negative patch test to naproxen, an OPT was performed with positive reaction, observed on the third day. To establish the cross‐reactivity, she underwent OPTs, which gave positive results to indomethacin, ketoprofen and tiaprofenic acid. Case 2 is a 52‐year‐old woman who presented painful dusky‐red macules, located in the right and left wrists, 24 hours after taking mefenamic acid. She described two similar events that occurred in the past with an undefined drug and piroxicam. Patch tests to lysine acetylsalicylate, mefenamic acid, piroxicam, naproxen and celecoxib were negative. OPTs to the same NSAIDs gave positive results to lysine acetylsalicylate, piroxicam and mefenamic acid. Thirteen case reports, seven case series and one retrospective analysis, including cases with confirmed cross‐reactivity between NSAIDs, were reported in literature. Clinicians should be aware of such phenomenon. [ABSTRACT FROM AUTHOR]

Drug reaction with eosinophilia and systemic symptom (DRESS) is a severe adverse drug‐induced reaction. Commonly related to anticonvulsant and allopurinol, DRESS can affect both adults and children. Cefotaxime is rarely associated with DRESS, especially with children. We report a cefotaxime‐induced DRESS in a child and emphasize the role of allergological work‐up to point out the culprit drug in exploring cross‐reactivity and identifying a possible cosensitization. A 2‐year‐old boy was treated with cefotaxime, vancomycin and metronidazole for acute otomastoiditis. Metronidazole was withdrawn and vancomycin was changed by teicoplanin 10 and 15 days later, respectively. Nineteen days after ongoing cefotaxime and 4 days after teicoplanin intake, the patient developed hyperthermia, a widespread exanthema, facial oedema with neither mucosal involvement nor palpable lymphadenopathy. Biological tests revealed eosinophilia, atypical lymphocytes, mild cytolysis and a high lactate dehydrogenase level. Serological tests for viral and bacterial infections were negative. DRESS was suspected and the 2 antibiotics were withdrawn. Intradermal tests (IDT) were carried out 2 months later with cefotaxime and teicoplanin. They revealed a positive result at 48‐hour reading. To assess cross‐reactivity among β‐lactams, IDT to penicillins (benzylpenicillin, amoxicillin and oxacillin) was performed showing negative results at 48‐hour reading. Nevertheless, IDT to cephalosporins (cefazolin, cefuroxime, ceftazidime and ceftriaxone) displayed positive results at 48‐hour reading. As a result, IDT are of great interest and should be performed to confirm the role of cefotaxime and detect a potential cross‐reactivity with chemically similar drugs and drugs taken before and during the episode of DRESS. [ABSTRACT FROM AUTHOR]

CD34 is a cell surface glycoprotein expressed by hematopoietic progenitors and endothelial cells. It is widely used in the clinic for isolation of human hematopoietic stem cells. In recent years large animals are gaining increasing importance in biomedical research for the study and therapy of human diseases. Sheep has proved to be an useful experimental model for preclinical trials in transplantation procedures. Unfortunately, the lack of specie-specific monoclonal antibodies (MABS) recognizing hemopoietic progenitor cells hampers the use of this animal in experimental hematology. The aim of this paper was to determine whether commercial monoclonal antibodies specific for human CD34 molecule could cross-react with hematopoietic progenitor cells (HPC) present in sheep umbilical cord blood (UCB). Six antihuman CD34 MABS, recognizing the three different epitope classes, were tested in flow cytometry on purified mononuclear cells (MNC) isolated from cord blood of both species. None of the MABS used in this trial seemed to be able to identify HPC from sheep UCB. These data suggest that the panel of monoclonal antibodies used for cross reactivity detection has to be expanded with recently produced reagents. Further studies should be directed towards the production of ovine specific anti CD34 MABS. [ABSTRACT FROM AUTHOR]

Electrochemical biosensors based on structure‐switching aptamers offer many advantages because they can operate directly in complex samples and offer the potential to integrate with miniaturized electronics. Unfortunately, these biosensors often suffer from cross‐reactivity problems when measuring a target in samples containing other chemically similar molecules, such as precursors or metabolites. While some progress has been made in selecting highly specific aptamers, the discovery of these reagents remains slow and costly. In this work, a novel strategy is demonstrated to distinguish molecules with miniscule difference in chemical composition (such as a single hydroxyl group)—with cross reactive aptamer probes—by tuning the charge state of the surface on which the aptamer probes are immobilized. As an exemplar, it is shown that the strategy can distinguish between DOX and many structurally similar analytes, including its primary metabolite doxorubicinol (DOXol). Then the ability to accurately quantify mixtures of these two molecules based on their differential response to sensors with different surface‐charge properties is demonstrated. It is believed that this methodology is general and can be extended to a broad range of applications. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 Omicron (B.1.1.529) lineages rapidly became dominant in various countries reflecting its enhanced transmissibility and ability to escape neutralizing antibodies. Although T cells induced by ancestral SARS-CoV-2-based vaccines also recognize Omicron variants, we showed in our previous study that there was a marked loss of T cell cross-reactivity to spike epitopes harboring Omicron BA.1 mutations. The emerging BA.4/BA.5 subvariants carry other spike mutations than the BA.1 variant. The present study aims to investigate the impact of BA.4/BA.5 spike mutations on T cell cross-reactivity at the epitope level. Here, we focused on universal T-helper epitopes predicted to be presented by multiple common HLA class II molecules for broad population coverage. Fifteen universal T-helper epitopes of ancestral spike, which contain mutations in the Omicron BA.4/BA.5 variants, were identified utilizing a bioinformatic tool. T cells isolated from 10 subjects, who were recently vaccinated with mRNA-based BNT162b2, were tested for functional cross-reactivity between epitopes of ancestral SARS-CoV-2 spike and the Omicron BA.4/BA.5 spike counterparts. Reduced T cell cross-reactivity in one or more vaccinees was observed against 87% of the tested 15 non-conserved CD4+ T cell epitopes. These results should be considered for vaccine boosting strategies to protect against Omicron BA.4/BA.5 and future SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Background: Although avian coronavirus infectious bronchitis virus (IBV) and SARS‐CoV‐2 belong to different genera of the Coronaviridae family, exposure to IBV may result in the development of cross‐reactive antibodies to SARS‐CoV‐2 due to homologous epitopes. We aimed to investigate whether antibody responses to IBV cross‐react with SARS‐CoV‐2 in poultry farm personnel who are occupationally exposed to aerosolized IBV vaccines. Methods: We analyzed sera from poultry farm personnel, COVID‐19 patients, and pre‐pandemic controls. IgG levels against the SARS‐CoV‐2 antigens S1, RBD, S2, and N and peptides corresponding to the SARS‐CoV‐2 ORF3a, N, and S proteins as well as whole virus antigens of the four major S1‐genotypes 4/91, IS/1494/06, M41, and D274 of IBV were investigated by in‐house ELISAs. Moreover, live‐virus neutralization test (VNT) was performed. Results: A subgroup of poultry farm personnel showed elevated levels of specific IgG for all tested SARS‐CoV‐2 antigens compared with pre‐pandemic controls. Moreover, poultry farm personnel, COVID‐19 patients, and pre‐pandemic controls showed specific IgG antibodies against IBV strains. These antibody titers were higher in long‐term vaccine implementers. We observed a strong correlation between IBV‐specific IgG and SARS‐CoV‐2 S1‐, RBD‐, S2‐, and N‐specific IgG in poultry farm personnel compared with pre‐pandemic controls and COVID‐19 patients. However, no neutralization was observed for these cross‐reactive antibodies from poultry farm personnel using the VNT. Conclusion: We report here for the first time the detection of cross‐reactive IgG antibodies against SARS‐CoV‐2 antigens in humans exposed to IBV vaccines. These findings may be useful for further studies on the adaptive immunity against COVID‐19. [ABSTRACT FROM AUTHOR]

Background: Both natural immunity and vaccine-induced immunity to COVID-19 may be useful to reduce the mortality/morbidity of this disease, but still a lot of controversy exists. Aims: This narrative review analyzes the literature regarding these two immunitary processes and more specifically: (a) the duration of natural immunity; (b) cellular immunity; (c) cross-reactivity; (d) the duration of post-vaccination immune protection; (e) the probability of reinfection and its clinical manifestations in the recovered patients; (f) the comparisons between vaccinated and unvaccinated as to the possible reinfections; (g) the role of hybrid immunity; (h) the effectiveness of natural and vaccine-induced immunity against Omicron variant; (i) the comparative incidence of adverse effects after vaccination in recovered individuals vs. COVID-19-naïve subjects. Material and Methods: through multiple search engines we investigated COVID-19 literature related to the aims of the review, published since April 2020 through July 2022, including also the previous articles pertinent to the investigated topics. Results: nearly 900 studies were collected, and 246 pertinent articles were included. It was highlighted that the vast majority of the individuals after suffering from COVID-19 develop a natural immunity both of cell-mediated and humoral type, which is effective over time and provides protection against both reinfection and serious illness. Vaccine-induced immunity was shown to decay faster than natural immunity. In general, the severity of the symptoms of reinfection is significantly lower than in the primary infection, with a lower degree of hospitalizations (0.06%) and an extremely low mortality. Conclusions: this extensive narrative review regarding a vast number of articles highlighted the valuable protection induced by the natural immunity after COVID-19, which seems comparable or superior to the one induced by anti-SARS-CoV-2 vaccination. Consequently, vaccination of the unvaccinated COVID-19-recovered subjects may not be indicated. Further research is needed in order to: (a) measure the durability of immunity over time; (b) evaluate both the impacts of Omicron BA.5 on vaccinated and healed subjects and the role of hybrid immunity. [ABSTRACT FROM AUTHOR]

Background: Insights into the IgE cross‐sensitization and possible cross‐reactivity patterns of sera reactive to chlorhexidine (CHX) are still incomplete and are likely to benefit from a functional exploration using a passive mast cell activation test (pMAT). Therefore, we want to study whether the pMAT with CHX‐specific IgE (sIgE) enables to depict effector cell degranulation in response to alexidine (ALX), octenidine (OCT) and/or polyhexamethylene biguanide (PHMB) indicative of cross‐reactivity between these compounds and CHX. Methods: Serum of 10 CHX‐allergic patients, nine individuals with an isolated sIgE CHX and five healthy controls were included. Human cultured mast cells (MCs) were, before and after sensitization, challenged with CHX, ALX, OCT or PHMB. Degranulation was measured via quantification of upregulation of CD63. Results: Mast cell responsiveness to ALX and OCT was demonstrable with 4/10 and 3/10 of the sera of CHX‐allergic patients respectively. Percentage of degranulation varied between 12 and 34% for ALX‐reactive MCs and between 4 and 22% for OCT‐reactive MCs. No reactivity to ALX or OCT was demonstrable when using sera obtained from individuals with an isolated sIgE CHX or from healthy controls. Unlike CHX, ALX and OCT, PHMB turned out to be a direct MC activator via occupation of MRGPRX2. PHMB‐reactive sIgEs were demonstrable in some patients with an isolated sIgE CHX but were unable to trigger PHMB‐induced degranulation in MRGPRX2 knockdown MCs. Conclusion: Mast cells constitute an attractive tool to explore cross‐reactivity between structurally similar compounds. Along with the identification of safe alternatives for the individual patient, the pMAT can advance our insights into sIgE cross‐reactivity patterns including assessment of molecules not yet approved for human use. [ABSTRACT FROM AUTHOR]

Background: Several studies have reported in vitro cross‐reactivity between wheat and barley. However, evidence regarding the clinical cross‐reactivity of wheat and barley is limited. This study examined the clinical cross‐reactivity of barley and wheat among children with immediate‐type wheat allergies. Methods: We examined the threshold dose of a wheat oral food challenge for wheat‐allergic children. We examined the reactivity of barley, and the oral food challenges of barley tea and barley rice were implemented as needed. We measured the specific immunoglobulin E (sIgE) levels in wheat, ω‐5 gliadin, and barley. Results: We evaluated 53 children (39 [74%] boys) with a median age of 6.6 years. Among them, 39 (74%) patients had a history of anaphylaxis to wheat. The median wheat‐, barley‐, and ω‐5 gliadin‐sIgE levels were 57.3, 12.1, and 3.2 kUA/L, respectively. Twelve patients reacted to barley tea (1.8 mg), 14 reacted to barley rice (220–440 mg), and 27 were tolerant to barley tea and barley rice. Barley‐allergic patients had significantly higher wheat‐ and ω‐5 gliadin‐ and barley‐sIgE levels and significantly lower threshold doses of wheat than barley‐tolerant patients. Omega‐5 gliadin‐sIgE was the most useful predictor of barley allergy among wheat‐allergic patients; the ω‐5 gliadin‐sIgE 95% positive predictive value for barley allergy was 4.6 kUA/L. Conclusions: Half of wheat‐allergic children reacted to barley. A lower threshold dose of wheat is related to cross‐reactive barley allergies. Omega‐5 gliadin‐sIgE predicts cross‐reactive barley allergy in children allergic to wheat. Clinical cross‐reactivity to barley should be considered in the management of wheat‐allergic children. [ABSTRACT FROM AUTHOR]

To solve the future food insecurity problem, alternative and sustainable protein sources (e.g. insects, rapeseed, fava bean and algae) are now being explored for the production of food and feed. To approve these novel protein sources for future food a comprehensive risk assessment is needed according to the European food legislation. Allergenicity risk assessment might pose some major difficulties, since detailed guidance on how to assess the allergenic potential of novel foods is not available. At present, the approach relies mostly on the guidance of allergenicity assessment for genetically modified (GM) plant foods. The most recent one was proposed by EFSA (2010 and 2011); “weight-of-evidence approach”. However this guidance is difficult to interpret, not completely applicable or validated for novel foods and therefore needs some adjustments. In this paper we propose a conceptual strategy which is based on the “weight-of-evidence approach” for food derived from GM plants and other strategies that were previously published in the literature. This strategy will give more guidance on how to assess the allergenicity of novel food proteins and protein sources. [ABSTRACT FROM AUTHOR]

The immunologic significance of cross-reactivity of TCR recognition of peptide:MHC complexes is still poorly understood. We have described TCR cross-reactivity in a system involving polyclonal CD8 T cell recognition of the well characterized influenza viral M158-66 epitope. While M158-66 is generally conserved between influenza A isolates, error-prone transcription generates stable variant RNA during infection which could act as novel epitopes. If packaged and viable, variant genomic RNA generates an influenza quasispecies. The stable RNA variants would generate a new transmissible epitope that can select a specific repertoire, which itself should have crossreactive properties. We tested two candidate peptides in which Thr65 is changed to Ala (A65) or Ser (S65) using recall responses to identify responding T cell clonotypes. Both peptides generated large polyclonal T cell repertoires of their own with repertoire characteristics and cross-reactivity patterns like that observed for the M158-66 repertoire. Both substitutions could be present in viral genomes or mRNA at sufficient frequency during an infection to drive immunity. Peptides from the resulting protein would be a target for CD8 cells irrespective of virus viability or transmissibility. These data support the hypothesis that cross-reactivity is important for immunity against RNA virus infections. [ABSTRACT FROM AUTHOR]

Dengue is a major public health concern, affecting almost 400 million people worldwide, with about 70% of the global burden of disease in Asia. Despite revised clinical classifications of dengue infections by the World Health Organization, the wide spectrum of the manifestations of dengue illness continues to pose challenges in diagnosis and patient management for clinicians. When the Zika epidemic spread through the American continent and then later to Africa and Asia in 2015, researchers compared the characteristics of the Zika infection to Dengue, considering both these viruses were transmitted primarily through the same vector, the Aedes aegypti female mosquitoes. An important difference to note, however, was that the Zika epidemic diffused in a shorter time span compared to the persisting feature of Dengue infections, which is endemic in many Asian countries. As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been proposed as biomarkers to predict the risk of the disease progression to a severe form, at a much earlier stage of the illness. However, the findings for most biomarkers are highly discrepant between studies. Meanwhile, the cross-reactivity of CD8+ and CD4+ T cells response to Dengue and Zika viruses provide important clues for further development of potential treatments. This review discusses similarities between Dengue and Zika infections, comparing their disease transmissions and vectors involved, and both the innate and adaptive immune responses in these infections. Consideration of the genetic identity of both the Dengue and Zika flaviviruses as well as the cross-reactivity of relevant T cells along with the actions of CD4+ cytotoxic cells in these infections are also presented. Finally, a summary of the immune biomarkers that have been reported for dengue and Zika viral infections are discussed which may be useful indicators for future anti-viral targets or predictors for disease severity. Together, this information appraises the current understanding of both Zika and Dengue infections, providing insights for future vaccine design approaches against both viruses. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients. [ABSTRACT FROM AUTHOR]

Human toxocariasis is one of the neglected helminthiases and it is caused by the zoonotic roundworm species Toxocara canis and Toxocara cati. Diagnosis of human toxocariasis is based on the combination of clinical, parasitological, and epidemiological criteria, as well as serology tests that detect anti-Toxocara antibodies. Notwithstanding, due to the absence of pathognomonic symptoms and signs of the disease, serology is the key evidence to support a conclusive diagnosis. TES-ELISA is the most widely used serological test for diagnosis. However, cross-reaction of TES antigens with antibodies produced to other helminth antigens is a major drawback for its application in countries with high parasitic prevalence. T. canis recombinant antigens have been described as an alternative to native TES for diagnosis. Nevertheless, the selection of antigenic proteins is a complex process that requires validation. In this paper, we developed an eGFP carrier-based system to express and purify blocks of recombinant polypeptides of T. canis antigenic proteins. Intense cross-reaction polypeptides were detected by Immunoblot and avoided to finally produce a chimeric prototype protein. Additionally, a control chimeric protein that harbors the complete tested proteins was produced. Purified chimeric antigens were tested in ELISA and Immunoblot assays with 310 sera samples of negative and positive control individuals. Our results showed that chimeric rCHITC0 and rCHITC1 antigens (with sensitivities of 62% 58%, 38% and 16% in IB-rCHITC0, ELISA-rCHITC0, ELISA-rCHITC1 and IB-rCHITC1 respectively for OLMS) can perform better in terms of specificity (being 91%, 89%, 87% and 76% for ELISA-rCHITC1, IB-rCHITC1, ELISA-rCHITC0 and IB-rCHITC0 respectively for OLMS) than T. canis TES-ELISA (with 61% specificity), giving a higher signal with serum samples of infected individuals as well the possibility to discriminate false positive cases with other parasitic infections. Our data suggest that T. canis chimeric proteins, represent candidate antigens for phase II studies.

Background: The world has been battling several vector-borne diseases since time immemorial. Socio-economic marginality, precipitation variations and human behavioral attributes play a major role in the proliferation of these diseases. Lockdown and social distancing have affected social behavioral aspects of human life and somehow impact on the spread of vector borne diseases. This article sheds light into the relationship between COVID-19 lockdown and global dengue burden with special focus on India. It also focuses on the interconnection of the COVID-19 pandemic (waves 1 and 2) and the alteration of human behavioral patterns in dengue cases.Methods: We performed a systematic search using various resources from different platforms and websites, such as Medline; Pubmed; PAHO; WHO; CDC; ECDC; Epidemiology Unit Ministry of Health (Sri Lanka Government); NASA; NVBDCP from 2015 until 2021. We have included many factors, such as different geographical conditions (tropical climate, semitropic and arid conditions); GDP rate (developed nations, developing nations, and underdeveloped nations). We also categorized our data in order to conform to COVID-19 duration from 2019 to 2021. Data was extracted for the complete duration of 10 years (2012 to 2021) from various countries with different geographical region (arid region, semitropic/semiarid region and tropical region).Results: There was a noticeable reduction in dengue cases in underdeveloped (70-85%), developing (50-90%), and developed nations (75%) in the years 2019 and 2021. The dengue cases drastically reduced by 55-65% with the advent of COVID-19 s wave in the year 2021 across the globe.Conclusions: At present, we can conclude that COVID-19 and dengue show an inverse relationship. These preliminary, data-based observations should guide clinical practice until more data are made public and basis for further medical research. [ABSTRACT FROM AUTHOR]

Omicron BA.1 variant can readily infect people with vaccine-induced or naturally acquired SARS-CoV-2 immunity facilitated by escape from neutralizing antibodies. In contrast, T-cell reactivity against the Omicron BA.1 variant seems relatively well preserved. Here, we studied the preexisting T cells elicited by either vaccination with the mRNA-based BNT162b2 vaccine or by natural infection with ancestral SARS-CoV-2 for their cross-reactive potential to 20 selected CD4+ T-cell epitopes of spike-protein-harboring Omicron BA.1 mutations. Although the overall memory CD4+ T-cell responses primed by the ancestral spike protein was still preserved generally, we show here that there is also a clear loss of memory CD4+ T-cell cross-reactivity to immunodominant epitopes across the spike protein due to Omicron BA.1 mutations. Complete or partial loss of preexisting T-cell responsiveness was observed against 60% of 20 nonconserved CD4+ T-cell epitopes predicted to be presented by a broad set of common HLA class II alleles. Monitoring such mutations in circulating strains helps predict which virus variants may escape previously induced cellular immunity and could be of concern. [ABSTRACT FROM AUTHOR]

Antibodies to the foot-and-mouth disease virus (FMDV) capsid induced by infection or vaccination can provide serotype-specific protection and be measured using virus neutralization tests and viral structural-protein (SP-)ELISAs. Separate tests are needed for each serotype, but cross-serotype reactions complicate serotyping. In this study, inter-serotypic responses were quantified for five SP-ELISA formats by testing 294 monovalent mainly bovine sera collected following infection, vaccination, or vaccination and infection with one of five serotypes of FMDV. Over half of the samples, representing all three immunization categories, scored positive for at least one heterologous serotype and some scored positive for all serotypes tested. A comparative approach to identifying the strongest reaction amongst serotypes O, A and Asia 1 improved the accuracy of serotyping to 73–100% depending on the serotype and test system, but this method will be undermined where animals have been infected and/or vaccinated with multiple FMDV serotypes. Preliminary studies with stabilized recombinant capsid antigens of serotypes O and A that do not expose internal epitopes showed reduced cross-reactivity, supporting the hypothesis that capsid integrity can affect the serotype-specificity of the SP-ELISAs. The residual cross-reactivity associated with capsid surface epitopes was consistent with the evidence of cross-serotype virus neutralization. [ABSTRACT FROM AUTHOR]

Ephrin-B1,-B2 and -B3 proteins share a high degree of sequence similarity. Investigation of these proteins as putative prognostic markers in human cancers including oral squamous cell carcinoma (OSCC) has been limited by challenges in generating specific antibodies against them. The current study examined the reactivity of a polyclonal anti-human ephrin-B2 antibody (HPA008999) against ephrin-B proteins and investigated the prognostic significance of immunoreactivity of the same antibody at different intra-tumor sites in OSCC specimens. By amino acid sequence comparison, immunocytochemistry and Western blot analysis on cell lysates and precipitates from HEK-293T cells transfected with EFNB1, EFNB2, or EFNB3 expression constructs, we demonstrated that HPA008999 reacted to all ephrin-B proteins. Using immunohistochemistry (IHC) with the HPA008999 antibody in a cohort (n = 131) of OSCC, we showed high immunoreactivity at the tumor center, but not at the tumor invading front, was significantly associated with worse 5-year overall survival probabilities. In conclusion, the HPA008999 antibody reacted to all ephrin-B proteins and the immunoreactivity at the tumor center might be useful as a prognostic marker in OSCC. These data underscore the need for the investigation of antibodies for cross-reactivity to similar protein members for obtaining reliable and meaningful results in IHC based biomarker studies. [ABSTRACT FROM AUTHOR]

Background: Oral immunotherapy (OIT) is a treatment option for patients with milk, egg, and peanut allergy, but data on the efficacy and safety of cashew OIT are limited. Methods: A cohort of 50 cashew‐allergic patients aged ≥4 years, who were consecutively enrolled into cashew OIT (target dose 4000 mg protein) between 4/2016 and 12/2019. Fifteen cashew‐allergic patients who continued cashew elimination served as observational controls. Co‐allergy to pistachio and walnut was determined. Full desensitization rate and associated immunological changes in both groups were compared. Patients fully desensitized to cashew were instructed to consume a dose of 1200 mg cashew protein for 6 months and were then challenged to a full dose. Patients with co‐allergy to pistachio or walnut were challenged to the respective nut. Results: Forty‐four of 50 OIT‐treated patients (88%) compared to 0% in controls tolerated a dose of 4000 mg cashew protein at the end of the study (odds ratio 8.3, 95% CI 3.9–17.7, p < 0.001). An additional three patients were desensitized to 1200 mg cashew protein, and three patients stopped treatment. Three patients (6%) were treated with injectable epinephrine for home reactions. Desensitized patients had decreased SPT, sIgE, basophil reactivity, and increased sIgG4, following treatment. Following cashew desensitization, all pistachio (n = 35) and four of eight walnut co‐allergic patients were cross‐desensitized to the respective nut. All (n = 44) patients consuming a low cashew dose for ≥6 months following desensitization passed a full‐dose cashew OFC. Conclusions: Cashew OIT desensitizes most cashew‐allergic patients and cross‐desensitizes to pistachio. Safety is similar to OIT for other foods. [ABSTRACT FROM AUTHOR]

Beta-lactam antibiotics are the most commonly reported drug allergy in adults and children. More than 95% of those with reported allergy labels to beta lactams are not confirmed when subjected to allergy testing. Beta lactam antibiotics are associated with a wide spectrum of immediate and delayed drug hypersensitivity reactions. The latency period to symptoms and clinical presentation aids in the causality assessment. Risk stratification based on diagnosis and timing then allows for appropriate management and evaluation. Skin prick testing, intradermal testing and oral challenge are well established for evaluation of immediate reactions. Delayed intradermal testing, patch testing and oral challenge can also be considered for evaluation of mild to moderate delayed reactions. Cross-reactivity between beta-lactams appears to be driven most commonly by a shared R1 side-chain. Standardized algorithms, protocols and pathways are needed for widespread implementation of a pragmatic and effective approach to patients reporting beta lactam allergy. [ABSTRACT FROM AUTHOR]

(1) Background: alpha-gal syndrome (AGS) is a serious, potentially life-threatening allergic reaction. This is a type of food allergy to red meat and other mammalian products (e.g., gelatin). In Poland, this problem seems to be rare or, more likely, very underdiagnosed. The diagnosis of AGS is difficult. It seems that the knowledge about this syndrome is insufficient. There are no effective diagnostic tools able to clearly diagnose this cross-reactive allergy. This paper presents the clinical application of a non-standard method in the diagnosis of a cross-reactive allergy using the example of AGS. (2) Methods: standard tests for in vitro allergy diagnostics and the non-standard ImmunoCAP inhibition test(IT) were carried out for serum collected from a patient with a red meat allergy. (3) Results: the serum concentration of anti-α-Gal IgE was very high (302 kUA/L), and IgE antibodies toanti-mammalian-meat allergens were found. The level of IgE antibodies to mammalian meat allergens decreased after blocking on α-GAL-CAP. The concentration of anti-α-Gal IgE decreased after blocking on CAPs coated with various mammalian meat allergens. Blocking with allergens of poultry meat did not affect the concentration of anti-α-Gal IgE. (4) Conclusions: the ImmunoCAP ITseems to be a useful tool in the diagnosis of cross-reactive allergies. Based on their clinical history and test results, the patient was diagnosed with AGS caused by a primary sensitization to α-Gal after a tick bite. This is the second case of AGS described in Poland and the first in Pomerania.

Despite the global interest and the unprecedented number of scientific studies triggered by the COVID-19 pandemic, few data are available from developing and low-income countries. In these regions, communities live under the threat of various transmissible diseases aside from COVID-19, including malaria. This study aims to determine the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroreactivity of antibodies from COVID-19 and pre-COVID-19 samples of individuals in Mali (West Africa). Blood samples from COVID-19 patients (n = 266) at Bamako Dermatology Hospital (HDB) and pre-COVID-19 donors (n = 283) from a previous malaria survey conducted in Dangassa village were tested by ELISA to assess IgG antibodies specific to the full-length spike (S) protein, the receptor-binding domain (RBD), and the receptor-binding motif (RBM436–507). Study participants were categorized by age, gender, treatment duration for COVID-19, and comorbidities. In addition, the cross-seroreactivity of samples from pre-COVID-19, malaria-positive patients against the three antigens was assessed. Recognition of the SARS-CoV-2 proteins by sera from COVID-19 patients was 80.5% for S, 71.1% for RBD, and 31.9% for RBM (p < 0.001). While antibody responses to S and RBD tended to be age-dependent, responses to RBM were not. Responses were not gender-dependent for any of the antigens. Higher antibody levels to S, RBD, and RBM at hospital entry were associated with shorter treatment durations, particularly for RBD (p < 0.01). In contrast, higher body weights negatively influenced the anti-S antibody response, and asthma and diabetes weakened the anti-RBM antibody responses. Although lower, a significant cross-reactive antibody response to S (21.9%), RBD (6.7%), and RBM (8.8%) was detected in the pre-COVID-19 and malaria samples. Cross-reactive antibody responses to RBM were mostly associated (p < 0.01) with the absence of current Plasmodium falciparum infection, warranting further study. [ABSTRACT FROM AUTHOR]

Cryptococcus is an opportunistic pathogenic fungus and is the major cause of fungal meningitis. The cryptococcal antigen (CrAg) lateral flow assay (LFA) is an immunochromatographic test system that has simplified diagnosis as a point-of-care test. In this study, we evaluated the diagnostic performance of Cryptococcal capsular polysaccharide detection FungiXpert (Genobio Pharmaceutical, Tianjin, China) using serum and cerebrospinal fluid (CSF) samples for the diagnosis of cryptococcosis and investigated the cross-reaction of the assays to pathogenic fungi and bacterium by comparing it to the U.S. Food and Drug Administration (US FDA)-approved IMMY CrAg LFA. Eighty CSF and 119 serum/plasma samples from 158 patients were retrospectively collected to test for qualitative or semi-quantitative detection of CrAg. Cross-reaction of the assays was tested using 28 fungi and 1 bacterium. Compared to IMMY CrAg LFA, the FungiXpert LFA demonstrated 99.1% sensitivity and 98.9% specificity in the qualitative test. In the 96 semi-quantitative CrAg assay results, 39 (40.6%) test titers of FungiXpert LFA were 1–2 dilutions higher than those of IMMY CrAg LFA. The Intraclass Correlation Coefficient of the Semi-quantitative results of CrAg titer tests via the two assays was 0.976. Similar to IMMY CrAg LFA, FungiXpert LFA showed cross-reactivity with Trichosporon asahii. Compared with the IMMY CrAg LFA, the FungiXpert LFA showed an equal, yet, excellent performance. However, it is important to note that these two assays have potential cross-reactivity to T. asahii when diagnosing patients. FungiXpert LFA is a rapid screening method for the effective and practical diagnosis and treatment of cryptococcosis. Lay summary The FungiXpert LFA was developed to diagnose fungal meningitis caused by Cryptococcus yeasts, by using serum or cerebrospinal fluid. It was compared to an existing lateral flow assay (LFA). The FungiXpert LFA performed well in qualitative and semi-quantitative tests. [ABSTRACT FROM AUTHOR]

Genetically encoded photosensitizers are able to produce reactive oxygen species upon illumination and are exploited in a wide range of applications, especially in the medical field. In this work, we envisioned to further apply these genetically encoded photosensitizers for the light-dependent control of single enzymes in multi-step biocatalysis. One of the challenges in the application of several enzymes in a cascade is the unwanted crossreactivity of these biocatalysts on reaction intermediates when all enzymes are simultaneously present in the reaction. As one strategy to address this issue, we investigated whether the introduction of genetically encoded photosensitizers as fusion tags would allow the selective inactivation of enzymes after successful transformation by simply turning on light. We tested five different photosensitizers as molecular biological fusion tags to inactivate the pyruvate decarboxylase variant E469G/W543H from Acetobacter pasteurianus. Dimeric photosensitizer tags, like the flavin-binding fluorescent proteins from Bacillus subtilis and Pseudomonas putida showed the tendency to form insoluble protein aggregates in combination with the tetrameric carboligase. Enzyme activity was, to some extent, retained in these aggregates, but the handling of the insoluble aggregates proved to be unfeasible. Monomeric photosensitizer tags appeared to be much more suitable when fused to the tetrameric enzyme. In the dark, the singlet oxygen photosensitizing protein (SOPP3)-tagged carboligase retained 79% of its activity as compared to the unfused enzyme. Upon blue light exposure, the SOPP3 tag showed the best specific inactivation and enabled complete inactivation of the carboligase within 30 min. SOPP3 is thus seen as a promising photosensitizer tag to be applied in future multi-step enzyme cascades to overcome the challenge of cross-reactivity. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease of the central nervous system (CNS) with a high socioeconomic relevance. The pathophysiology of MS, which is both complex and incompletely understood, is believed to be influenced by various environmental determinants, including diet. Since the 1990s, a correlation between the consumption of bovine milk products and MS prevalence has been debated. Here, we show that C57BL/6 mice immunized with bovine casein developed severe spinal cord pathology, in particular, demyelination, which was associated with the deposition of immunoglobulin G. Furthermore, we observed binding of serum from casein-immunized mice to mouse oligodendrocytes in CNS tissue sections and in culture where casein-specific antibodies induced complement-dependent pathology. We subsequently identified myelin-associated glycoprotein (MAG) as a cross-reactive antigenic target. The results obtained from the mouse model were complemented by clinical data showing that serum samples from patients with MS contained significantly higher B cell and antibody reactivity to bovine casein than those from patients with other neurologic diseases. This reactivity correlated with the B cell response to a mixture of CNS antigens and could again be attributed to MAG reactivity. While we acknowledge disease heterogeneity among individuals with MS, we believe that consumption of cow’s milk in a subset of patients with MS who have experienced a previous loss of tolerance to bovine casein may aggravate the disease. Our data suggest that patients with antibodies to bovine casein might benefit from restricting dairy products from their diet. [ABSTRACT FROM AUTHOR]

In the context of HLA-DP-mismatched allogeneic stem cell transplantation, mismatched HLA-DP alleles can provoke profound allo-HLA-DP-specific immune responses from the donor T-cell repertoire leading to graft-versus-leukemia effect and/or graft-versus-host disease in the patient. The magnitude of allo-HLA-DP-specific immune responses has been shown to depend on the specific HLA-DP disparity between donor and patient and the immunogenicity of the mismatched HLA-DP allele(s). HLA-DP peptidome clustering (DPC) was developed to classify the HLA-DP molecules based on similarities and differences in their peptide-binding motifs. To investigate a possible categorization of HLA-DP molecules based on overlap of presented peptides, we identified and compared the peptidomes of the thirteen most frequently expressed HLA-DP molecules. Our categorization based on shared peptides was in line with the DPC classification. We found that the HLA-DP molecules within the previously defined groups DPC-1 or DPC-3 shared the largest numbers of presented peptides. However, the HLA-DP molecules in DPC-2 segregated into two subgroups based on the overlap in presented peptides. Besides overlap in presented peptides within the DPC groups, a substantial number of peptides was also found to be shared between HLA-DP molecules from different DPC groups, especially for groups DPC-1 and -2. The functional relevance of these findings was illustrated by demonstration of cross-reactivity of allo-HLA-DP-reactive T-cell clones not only against HLA-DP molecules within one DPC group, but also across different DPC groups. The promiscuity of peptides presented in various HLA-DP molecules and the cross-reactivity against different HLA-DP molecules demonstrate that these molecules cannot be strictly categorized in immunogenicity groups. [ABSTRACT FROM AUTHOR]

Sensitization to lipid transfer protein (LTP), the most frequent cause of food allergy in southern Europe, still shows several controversial, but also intriguing, aspects. Some of these include the degree of cross‐reactivity between LTPs from botanically distant sources, the definition of risk factors, the role of some cofactors, clinical outcomes, geographical differences and the identification of the primary sensitizer in different areas. This review article tries to analyse and comment on these aspects point by point suggesting some explanatory hypotheses with the final scope to stimulate critical thoughts and elicit the scientific discussion about this issue in the readership. [ABSTRACT FROM AUTHOR]

Background: Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. Methods: A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. Results: The rate of positive reactions for the specific IgE antibodies was 59·40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39·10% (52) and 42·86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7·5%), were significantly fewer than the cross-reacting positive cases (36) to PG ( P < 0·01). In the RAST inhibition studies all drugs exhibited good inhibitory potencies, and in some instances the side-chain of the penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. Conclusion: Radioallergosorbent test is a good complementary test in persons who are skin-test negative with PG, and the sensitivity of RAST increaes with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross-reactivity. [ABSTRACT FROM AUTHOR]

Abstract: Pharmacokinetic characterization of therapeutic antibodies plays an important role during preclinical and clinical development. However, accurate pharmacokinetic evaluation of therapeutic antibodies in serum samples from non-human primates is often complicated by insufficient specificity of the assays to measure drug levels. The present paper describes the use of a murine monoclonal antibody in an immunoassay format to specifically and quantitatively measure human therapeutic antibodies in serum from non-human primates. This murine antibody is directed against a unique epitope on the constant region CH2 domain of all isotypes of human immunoglobulin G (IgG). The antibody, designated anti-human Fcγ-pan: R10Z8E9, does not cross-react with serum from mouse, rat, and the non-human primates marmoset, rhesus macaque, cynomolgus monkey and baboon when using an enzyme-linked immunosorbent assay (ELISA) or surface plasmon resonance technology (Biacore) format for measurement of the therapeutic antibody. Use of the antibody anti-human Fcγ-pan: R10Z8E9 as capturing and detection reagent allowed human-specific quantitation of total therapeutic antibody anti-IGF-1R in spiked cynomolgus monkey serum via a Sandwich ELISA format. In contrast, a commercially available polyclonal antibody (PAB) directed to the Fcγ fragment of human IgG only specifically measured the therapeutic antibody in buffer samples, but not in serum from cynomolgus monkeys. This generic human IgG assay was already applied in several pharmacokinetic studies in cynomolgus monkeys to determine serum levels of different therapeutic antibodies, including the anti-IGF-1R. Validation of the assay for a humanized IgG1 therapeutic antibody against a membrane protein revealed a lower limit of quantitation of 8ng/mL in undiluted serum. Intra-assay and inter-assay precision was characterized by a coefficient of variation of less than 10% and accuracy was within 15%. Dilutional linearity was evidenced by a recovery of 98.7–114% of expected concentrations. In conclusion, the monoclonal antibody anti-human Fcγ-pan: R10Z8E9 provides a standard means for human-specific quantitation of therapeutic antibodies with high sensitivity in serum samples from non-human primates in a generic human IgG assay. [Copyright &y& Elsevier]

In the immunoassays, an antibody used as a reagent, detects an analyte (antigen) of interest. Although the noncovalent bound between analyte and complementary antibody is specific, false-positive and false-negative interferences are possible. Some interferences are similar to those in chemical analyses and some are typical only for immunoassays. One should suspect interferences in following cases: upon receiving an unacceptable result, if there is non-linearity during dilution, if there is no agreement with other test results or clinical data, if different immunoassays in determination of the same analyte provide significantly different results. This paper reviews some of the possible interferences: 1) cross-reactivity with endogenous and exogenous non antibody-structured substances; 2) cross-reactivity with endogenous and exogenous antibody-structure substances; 3) the hook effect; and 4) the matrix effect. By knowing and recognizing interferences in immunoassays, one can avoid possible undesired consequences: diagnostic errors, treatment and monitoring of its efficacy, unnecessary additional laboratory testing, unnecessary therapy. [ABSTRACT FROM AUTHOR]

Abstract: Binding of fructose to the fructose imprinted polymer (MIP(Frc)) and pinacol imprinted polymer (control) were studied both in batch and a flow through mode. The influence of the cross-linkers ethylene glycol dimethacrylate (EDMA) and trimethylolpropane trimethacrylate (TRIM) on the binding characteristics was analysed. TRIM cross-linked MIPs showed a lower (unspecific) binding for the control polymer (pinacol imprinted) and higher binding of fructose as compared with the EDMA-MIPs. Furthermore interactions of a TRIM cross-linked molecularly imprinted polymer against fructose and its corresponding template were studied using a thermistor. Label-free detection of fructose was realised in the range of 0.5–10mM. The difference in enthalpy changes between specific binding of fructose to boronic acid moieties of the MIP and non-specific binding to the matrix leads to an 18-fold higher apparent imprinting factor than batch binding studies. Cross-reactivity studies using MIP sensor indicate that the interaction of fructose to MIP generates higher signal than disaccharides. The studies described in this paper demonstrate the potential of direct characterisation of molecular binding events. [Copyright &y& Elsevier]