During the past years, there has been a global outbreak of allergic diseases, presenting a considerable medical and socioeconomical burden. A large fraction of allergic diseases is characterized by a type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, eosinophils, mast cells, and M2 macrophages. Biomarkers are valuable parameters for precision medicine as they provide information on the disease endotypes, clusters, precision diagnoses, identification of therapeutic targets, and monitoring of treatment efficacies. The availability of powerful omics technologies, How to cite this article: Ogulur I, Pat Y, Ardicli O, et al. Advances and highlights in biomarkers of allergic diseases.

The "epithelial barrier hypothesis" proposes that the exposure to various epithelial barrier-damaging agents linked to industrialization and urbanization underlies the increase in allergic diseases. The epithelial barrier constitutes the first line of physical, chemical, and immunological defense against environmental factors. Recent reports have shown that industrial products disrupt the epithelial barriers. Innate and adaptive immune responses play an important role in epithelial barrier damage. In addition, recent studies suggest that epithelial barrier dysfunction plays an essential role in the pathogenesis of the atopic march by allergen sensitization through the transcutaneous route. It is evident that external factors interact with the immune system, triggering a cascade of complex reactions that damage the epithelial barrier. Epigenetic and microbiome changes modulate the integrity of the epithelial barrier. Robust and simple measurements of the skin barrier dysfunction at the point-of-care are of significant value as a biomarker, as recently reported using electrical impedance spectroscopy to directly measure barrier defects. Understanding epithelial barrier dysfunction and its mechanism is key to developing novel strategies for the

Allergic diseases include asthma, atopic-dermatitis, allergic-rhinitis, drug hypersensitivity and food-allergy. During the past years, there has been a global outbreak of allergic diseases, presenting a considerable medical and socioeconomical-burden. A large fraction of allergic diseases is characterized by a type-2 immune response involving Th2 cells, type-2 innate lymphoid cells, eosinophils, mast cells, and M2 macrophages. Biomarkers are valuable parameters for precision medicine as they provide information on the disease endotypes, clusters, precision diagnoses, identification of therapeutic targets, and monitoring of treatment efficacies. The availability of powerful omics technologies, together with integrated data analysis and network-based approaches can help the identification of clinically useful biomarkers. These biomarkers need to be accurately quantified using robust and reproducible methods, such as reliable and point-of-care systems. Ideally, samples should be collected using quick, cost-efficient and non-invasive methods. In recent years, a plethora of research has been directed towards finding novel biomarkers of allergic diseases. Promising biomarkers of type-2 allergic diseases include sputum eosinophils, serum periostin and exhaled nitric-oxide. Several other biomarkers, such as pro-inflammatory mediators, miRNAs, eicosanoid molecules, epithelial barrier integrity, and microbiota changes are useful for diagnosis and monitoring of allergic diseases and can be quantified in serum, body-fluids and exhaled-air. Herein, we review recent studies on biomarkers for the diagnosis and treatment of asthma, chronic-urticaria, atopic-dermatitis, allergic-rhinitis, chronic-rhinosinusitis, food-allergies, anaphylaxis, drug hypersensitivity and allergen-immunotherapy. In addition, we discuss COVID-19 and allergic diseases within the perspective of biomarkers and recommendations on the management of allergic and asthmatic patients during the COVID-19 pandemic.

This study aimed to compare method-based and newly developed sample-based methods for Mycoplasma gallisepticum (MG) detection in different samples of breeder flocks suffering from respiratory disease problems by using culture, real-time PCR (rPCR) and ELISA from chicks and embryonated eggs. Overall, 450 samples of 19-day-old chicken embryo's trachea, 450 samples of 8-day-old chicken tracheal swabs and 900 blood samples of 20-, 27-, 34-, 40-and 46-week-old breeder chickens from 5 flocks were sampled for 26 weeks, and were all tested for MG by culture, MG-rPCR and MG-ELISA. Culturing assays and rPCR were applied to 450 mixture samples from 19-day-old chicken embryo's trachea and 450 tracheal swab samples (each pooled into groups of 3) from 8-day-old chicks from the same flocks. Also, 900 blood samples from the same 5 breeder flocks suffering from respiratory disease problems were tested by MG-ELISA. In individual sample-based analyses, 55 (18.3%) of the 300 pooled swab samples were positive for MG using culture methods, and 106 (35.3%) of the same samples were found positive by rPCR (sensitivity, specificity). The ELISAs indicated that 252 (28%) of the 900 breeding blood samples were MG seropositive. Using age-based analyses, the most positive period was 46 weeks, followed by 40 weeks, 34 weeks, 27 weeks and at least 20 weeks, in order of decreasing seropositivity. When comparing the culture and rPCR results of the two different sampling methods, chicken embryo's trachea yielded more positive results than did tracheal swabs from the same flocks. In conclusion, rPCR is a highly specific, sensitive and reliable method for MG identification.

Ardicli and Carli contributed equally to the study.

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 to 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 to 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 have implications for future vaccination strategies and possibly cross-reactive T cell immunity.

This study aimed to isolate aerobic and microaerophilic bacteria from mastitis milk samples, as well as to determine their antibiotic resistance. A total of 196 bovine mastitis milk samples were tested by standard bacteriological methods and with API identification test kits. Antimicrobial susceptibility testing was performed by the Kirby-Bauer disk diffusion method. The results revealed that the predominant isolate was S. aureus, with an isolation rate of 28%, followed by Streptococcus spp. (27%) and E. coli (19%). Isolation rates for Corynebacterium spp., Mycoplasma spp., and Pseudomonas aeruginosa were 11%, 6%, and 4%, respectively. Compared to the bacteria mentioned above, lower percentages were observed for Trueperella pyogenes (2%), Pasteurella multocida (2%), and Klebsiella pneumoniae (1%). A broad evaluation of antimicrobial resistance showed that the pathogens were resistant to tetracycline (68.63%), oxytetracycline (41.57%), ampicillin (39.08%), ceftiofur (38.1%), cephalexin (32.26%), penicillin (31.25%), amoxicillin/clavulanic acid (24.53%), enrofloxacin (24.44%), gentamycin (23.68%), and trimethoprim/sulfamethoxazole (22.09%). This study demonstrated that the sources of bacteria isolated from mastitis bovine milk samples were both contagious and environmental. More importantly, the present results demonstrate a critically high antimicrobial resistance in dairy cattle. For instance, E. coli isolates showed a crucial resistance to commonly used and recommended antimicrobials, including ceftiofur (100%), cephalexin (83.33%), and tetracycline (94.44%). The results of this study may provide valuable information about clinical aspects of bovine mastitis infections and current antimicrobial resistance levels in dairy cattle.

Background: The importance of zoonotic fungal infections is increasing today and continues to increase due to changing living conditions. Methods: Between 2012 and 2019 evaluated of fungi species isolated from 51 (20.07%) of 254 samples from 10 different animal species (dog, cat, horse, cow, goat, sheep, camel, penguin, bird, rabbit) with 10 different sample types Thus, the risk of those with zoonotic characteristics was assessed. Despite fungal hyphae and/or spores were seen in 63 (24.8%) of 254 samples in the direct microscopic examination, the isolation of fungi on Sabouraud dextrose agar occurred in only 51 of these samples (20.07%). Conclusion: Of all the 51 samples, 9 (17.64%) samples had more than one fungal agent. The predominant isolate was Aspergillus spp. with an isolation rate of 24 (47.05%), followed by Malassezia spp. 11 (21.56%), Alternaria spp. 6 (11.76%), Penicillium spp. and various yeasts 4 (7.84%), Microsporum spp. 3 (5.88%), Candida spp., Mucor spp., Geotrichum spp. 2 (3.92%) and Trichophyton spp. and Rhizopus spp. 1 (1.96%). Besides, samples were examined for the presence of bacteria and one or more of the bacteria were also isolated from 14 (27.4%) of 51 samples. This assessment in the veterinary microbiology laboratory has shown that the isolated fungi agents pose a significant risk of infection for people who take care of these animals or consume animal products and pet owners.