Specific Immunoglobulin Research Articles

Assessing risks of secondary immunodeficiency in children with aluminum contamination in biological media and polymorphism of the cell death gene FAS rs1159120 and the antigen-recognizing gene of the toll-like receptor TLR4 rs1927911

Secondary immunodeficiency remains an incompletely understood medical problem, and despite a significant number of international and scientific studies, there is no complete picture of the causes and consequences of this pathology. Metal cations have been proven to participate in the formation of acquired immunodeficiency. In particular, aluminum properties as an immune suppressor have been established and its targets in the body have been identified in case aluminum was present in biological media. However, no evaluations have been accomplished so far as regards the role of specific point genetic changes, that is, polymorphisms in the genes of immune system compartments that determine the risk of negative effects caused by contamination with metal cations, including aluminum. It is quite relevant to search and substantiate immunogenetic markers to create an indicator system for diagnostics and prevention of secondary immunodeficiency states in children associated with aluminum contamination in biological media. We examined 97 preschool children exposed to elevated levels of airborne aluminum (in an area influenced by a metallurgic production). The study groups were divided depending on either presence or absence of secondary immunodeficiency as immune system pathology (common variable immunodeficiency D83). Several markers of the immune system were evaluated: aluminum-specific IgG, CD3+, CD4+, CD8+, CD127-, CD95+, CD284+, and phagocytic activity; we also evaluated polymorphism of TLR4 A8595G (rs1927911) and FAS C14405T (rs1159120) genes of innate and acquired immunity. According to the results obtained by examining biological media composition, children with secondary immunodeficiency had 1.8 times higher aluminum levels in urine (0.0095 ± 0.0014 vs. 0.0054 ± 0.0009 mg/dm3, reference range < 0.0075 mg/dm3) as opposed to their conditionally healthy peers. We established an authentic inverse dependence between the expression level of the main CD clusters (CD3+: r = -0.38; CD4+: r = -0.39; CD8+: r = -0.26) as well as indicators of phagocytic activity (r = -0.22–0.23) and the level of aluminum contamination in biological media (urine). Expression of T-mature lymphocyte clusters was found to be inhibited by 1.3–3.1 times (including T-helper, effector T-lymphocytes, NK-killers, regulatory lymphocytes) and we also detected some changes in expression of specific immunoglobulin of IgG class to aluminum. All this results in an unacceptable level of relative risk (RR = 1.23–1.63) of developing secondary immunodeficiency against increased frequency of allele C and genotype CC of FAS gene (rs1159120) by 1.2 and 1.5 times respectively, as well as minor allele G of TLR4 gene (rs1927911) by 1.8 times relative to the comparison group (OR = 4.05; CI: 1.41–11.59; p = 0.006; RR = 1.23; CI: 1.02–1.48) and (OR = 2.01; CI: 1.04–3.91; p = 0.037; RR = 1.64; CI:1.46–1.94). Toll-dependent and FAS-dependent mechanism of this risk is associated with aluminum contamination. It is recommended to use a combination of immune and genetic markers as indicator ones when evaluating the immune system state, in order to prevent the risk (RR = 1.23–1.63) of secondary immunodeficiency associated with aluminum contamination in biological media.

Spleen aminopeptides (FUKETUO) elevate the therapeutic effect of house dust mite desensitization on allergic asthma by inducing interleukin-10 positive regulatory T cells (IL-10+ Tregs) expression.

As a novel immunomodulator, spleen aminopeptides (FUKETUO) can correct the imbalance of immune cells and elevate their functions. Spleen aminopeptides have been used in the treatment of respiratory diseases. However, the regulatory mechanism of it on allergic asthma and desensitization has not been reported, further study is critically needed. This study aimed to investigate the effect and mechanism of spleen aminopeptides on allergic asthma and desensitization. We established an allergic asthma model by house dust mite (HDM) with/without desensitization treatment. The allergic asthma mouse model was established with HDM and treated with desensitization and increasing dose of spleen aminopeptides according to different immune phases. Pathological markers such as airway hyper-responsiveness, and cell composition were monitored to determine the effectiveness of treatment. Spleen aminopeptides can promote the proportion of interleukin-10 positive (IL10+) allergen-specific regulatory T cells (Tregs), and further promote interleukin-10 (IL-10) expression in desensitization. They alleviated the allergic symptoms and elevated desensitization, decreased airway hyper-reaction and lung tissue injury, reduced specific immunoglobulin E (IgE) in serum, eosinophil number and interleukin-4 (IL-4) expression in bronchoalveolar lavage fluid (BALF), therefore, being able to control allergic asthma. Our results suggested that spleen aminopeptides (FUKETUO) could elevate the expression of (CD4+CD25+IL10+) Tregs, especially when it co-immunized with desensitization. Thereby, FUKETUO improved the efficacy of desensitization, and inhibited the development of allergic asthma.

Malondialdehyde-specific natural IgM inhibit NETosis triggered by culprit site-derived extracellular vesicles from myocardial infarction patients.

Abstract Background and Aims Neutrophil extracellular traps (NETs) trigger atherothrombosis during acute myocardial infarction (AMI), but mechanisms of induction remain unclear. Levels of extracellular vesicles (EV) carrying oxidation-specific epitopes (OSE), which are targeted by specific natural immunoglobulin M (IgM), are increased at the culprit site in AMI. This study investigated EV as inducers of NETosis and assessed the inhibitory effect of natural anti-OSE–IgM in this process. Methods Blood from the culprit and peripheral site of ST-segment elevation myocardial infarction (STEMI) patients (n = 28) was collected, and myocardial function assessed by cardiac magnetic resonance imaging (cMRI) 4 ± 2 days and 195 ± 15 days post-AMI. Extracellular vesicles were isolated from patient plasma and cell culture supernatants for neutrophil stimulation in vitro and in vivo, in the presence of a malondialdehyde (MDA)-specific IgM or an isotype control. NETosis and neutrophil functions were assessed via enzyme-linked immunosorbent assay and fluorescence microscopy. Pharmacological inhibitors were used to map signalling pathways. Neutrophil extracellular trap markers and anti-OSE–IgM were measured by ELISA. Results CD45+ MDA+ EV and NET markers were elevated at the culprit site. Extracellular vesicles induced neutrophil activation and NET formation via TLR4 and PAD4, and mice injected with EV showed increased NETosis. Malondialdehyde-specific IgM levels were inversely associated with citH3 in STEMI patient blood. An MDA-specific IgM inhibited EV-induced NET release in vitro and in vivo. CD45+ MDA+ EV concentrations inversely correlated with left ventricular ejection fraction post-AMI. Conclusions Culprit site–derived EV induce NETosis, while MDA-specific natural IgM inhibit this effect, potentially impacting outcome after AMI.

Experimental immunotherapy of association infections of the gastrointestinal tract of newborn calves using yolk melange enriched with specific Y class immunoglobulins

Mass gastrointestinal diseases of newborn calves manifested by symptoms of diarrhea are caused by various etiological factors and most often occur in the form of mixed infections. Mixed infections have a more severe diarrhea than mono-infections. The economic consequences of such infections due to the high prevalence, frequent mortality and loss of productivity during further exploitation of the animal can be significant. The most common causative agents of gastrointestinal diseases of newborn calves of viral etiology is rotavirus and coronavirus infections. Mixed (viral-bacterial) infection can lead to 100% mortality of the diseased calves. Specific vaccination of springer cows against gastrointestinal pathogens in calves, which is performed to increase the number of pathogen-specific immunoglobulins in the colostrum at calf birth, and ingestion of colostrum by the calves during the first 4 hours of life are the most important strategies to prevent severe diarrhea. But as practice shows, this is not always enough. The purpose of this work was to study the effectiveness of immunoprophylaxis of associative infections of the gastrointestinal tract of newborn calves with the use of melange prepared from chicken eggs previously immunized with the vaccine "Rotagal" (Pharmagal-BIO s.r.o., Slovakia), used for the prevention of colibacillosis, rotavirus and coronavirus infections of cattle. As a result of the study, it was established that the addition of yolk melange rich in specific immunoglobulins of Y class to the colostrum in the first hours of life of the calves has a pronounced prophylactic effect, facilitates the course of the infectious process in case of the disease, saves costs for the treatment of sick animals, increases survival rate, contributes to the acceleration of live weight gain. The use of an immunobiological preparation based on transovarial immunoglobulins has a positive effect on the indicators of nonspecific resistance of newborn calves compared to the calves with early postnatal disease and antibiotic treatment.

Relation of ICAM-1 and VCAM-1 markers in COVID-19 patients in Kirkuk province.

The advent of the Coronavirus Disease 2019 (COVID-19) has presented a substantial and urgent global public health issue. Biomarkers have the potential to be utilized for the identification of endothelium and/or alveolar epithelial damage in instances of COVID-19 infection. to evaluate the levels of Intercellular adhesion molecule-1 (ICAM-1) and Vascular cell adhesion molecule (VCAM-1) biomarkers in hospitalized patients who tested positive for COVID-19 infection using Polymerase Chain Reaction (PCR) with the virus specific Immunoglobulins; IgM, and IgG testing. This can help with improved clinical management and treatment programs. A case-control study that involved 90 hospitalized patients who tested positive for COVID-19 and 40 apparently healthy control patients, subjects in both groups underwent nasopharyngeal swabs for PCR and blood sample collection for evaluation of serum; IgM, IgG, ICAM-1 and VCAM-1 levels. Males made up the vast majority of the patients (78.9%), with only a minor percentage of females (21.1%) P value 0.1641. Furthermore, every patient in this study had a minimum of one risk factor for COVID-19. The investigator's results show that COVID-19 patients had higher amounts of endothelial cell adhesion indicators (ICAM-1 and VCAM-1) with mean values of 126.27 ± 89.51 ng/mL and 109.74 ± 96.57 ng/mL respectively. While, ICAM-1 and VCAM-1, were present at normal levels in the control group with difference P value 0.0028 and 0.0032 in comparison to the patient's group respectively. The adhesive markers ICAM and VCAM play a crucial role in the development of COVID-19 and the strong endothelial activation and dysfunction linked to both acute and persistent immunological responses is shown by the substantial correlation found in COVID-19 patients between the presence of IgM and IgG antibodies and higher levels of ICAM-1 and VCAM-1.

Infantile colic is associated with development of later constipation and atopic disorders.

Infantile colic is a common condition with limited knowledge about later clinical manifestations. We evaluated the role of the early life gut microbiome in infantile colic and later development of atopic and gastrointestinal disorders. Copenhagen Prospective Studies on Asthma in Childhood2010 cohort was followed with 6 years of extensive clinical phenotyping. The 1-month gut microbiome was analyzed by 16S rRNA sequencing. Infantile colic was evaluated at age 3 months by interviews. Clinical endpoints included constipation to age 3 years and prospectively diagnosed asthma and atopic dermatitis in the first 6 years of life, and allergic sensitization from skin prick tests, specific Immunoglobulin E, and component analyses. Of 695 children, 55 children (7.9%) had infantile colic. Several factors were associated with colic including race, breastfeeding, and pets. The 1-month gut microbiome composition and taxa abundances were not associated with colic, however a sparse Partial Least Squares model including combined abundances of nine species was moderately predictive of colic: median, cross-validated AUC = 0.627, p = .003. Children with infantile colic had an increased risk of developing constipation (aOR, 2.88 [1.51-5.35], p = .001) later in life, but also asthma (aHR, 1.69 [1.02-2.79], p = .040), atopic dermatitis (aHR, 1.84 [1.20-2.81], p = .005) and had a higher number of positive allergic components (adjusted difference, 116% [14%-280%], p = .012) in the first 6 years. These associations were not mediated by gut microbiome differences. We link infantile colic with risk of developing constipation and atopic disorders in the first 6 years of life, which was not mediated through an altered gut microbiome at age 1-month. These results suggest infantile colic to involve gastrointestinal and/or atopic mechanisms.

Basophil FceRI expression-A management tool in anti-IgE treatment of allergic asthma.

Immune-based therapy targeting immunoglobulin E (IgE), anti-IgE treatment, has emerged as an adjunct treatment for children with severe allergic asthma. After start of anti-IgE treatment, an effect of the treatment cannot be monitored by Total-IgE, because current methods measure both bound and free IgE molecules. Basophil activation test may be very useful for monitoring anti-IgE treatment efficacy. The objective of this paper is to evaluate if basophil activation test is applicable in regulating the anti-IgE treatment. A case series of 20 children with IgE-mediated severe allergic asthma were treated according to guidelines with anti-IgE (Omalizumab). Blood samples were drawn for total IgE, specific IgE, number of IgE receptors (FcεRI) and basophil sensitivity were measured at baseline before anti-IgE treatment and 4 months after initiation of anti-IgE treatment. A total of 19 out of 20 children had statistically significant and clinically relevant effects of anti-IgE treatment on symptom score, lung function and medication. All 20 children had a significant reduction in basophil allergen sensitivity and the number of IgE receptors (FcεRI) on blood basophils. Anti-IgE treatment was found to be well controlled by measuring basophil allergen sensitivity and FceRI density on blood basophils. This cohort study demonstrates a promising method, measuring basophil allergen sensitivity and in particular blood basophil FceRI density, concerning the monitoring of anti-IgE treatment in different clinical situations. There are no randomized controlled trials evaluating this method in clinical settings.

Experimentally investigated “CoronaDerm-PS”-driven SARS-CoV-2-specific cellular immunity and safety

Novel coronavirus disease 2019, caused by the SARS-CoV-2, initiate humoral and cellular immune responses against diverse virus antigens. The assessment of SARS-CoV-2-specific is mainly carried out in routine practice by determining specific immunoglobulins. However, high variability in S-protein structure in new genovariants of SARS-CoV-2 virus and the lack of correlation between specific antibodies and CD8+ T-lymphocytes underlie false negative responses, and mass assessment of cellular immunity is complicated due to the complexity of applying ELISPOT and cytofluorometry techniques. To solve this issue, a diagnostic method was developed for assessing SARS-CoV-2-specific cellular immune response, which is based on a skin test followed by evaluating a delayed-type hypersensitivity reaction involving antigen-specific memory T-lymphocytes. A diagnostic preparation CoronaDerm-PS is based on Cord_PS, which is a hybrid recombinant protein consisting of parts of the SARS-CoV-2 structural proteins S, M, N, E. The specific activity of this chimeric antigen was analyzed in cultured T-lymphocyte activation test by assessing interferon-γ production using cytofluorometry. To investigate the chimeric antigen specific activity, a preclinical safety study with CoronaDerm-PS preparation in experimental animals was conducted. A dose-dependent developing skin reaction was observed in 90–100% of guinea pigs vaccinated by EpiVacCorona, CoviVac, Gam-COVID-Vac, which confirms a potential for assessing post-vaccination cellular immunity using CoronaDerm-PS preparation. Upon this, the presence of functionally active T-cell-antigenic epitopes in the recombinant polypeptide allows to evaluate SARS-CoV-2-specific response illustrated by detected response after Gam-COVID-Vac (S-protein) and EpiVacCorona (N-protein) vaccination. Thus, a skin test based on CoronaDerm-PS preparation may be a promising diagnostic tool for rapid mass screening requiring no specialized laboratory equipment for assessing populational SARS-CoV-2-specific immunity. Such a test is distinguished by advantages such as ease of analysis, high specificity and sensitivity. The final decision-making on using this test in a real-world practice may achieved after conducting further clinical safety and effectiveness trials.

Challenges in the Diagnosis of SARS-CoV-2 Infection in the Nervous System.

Neurological involvement has been widely reported in SARS-CoV-2 infection. However, viral identification in the cerebrospinal fluid (CSF) is rarely found. The aim of this study is to evaluate the accuracy of virological and immunological biomarkers in CSF for the diagnosis of neuroCOVID-19. We analyzed 69 CSF samples from patients with neurological manifestations: 14 with suspected/confirmed COVID-19, with 5 additional serial CSF samples (group A), and as a control, 50 non-COVID-19 cases (group B-26 with other neuroinflammatory diseases; group C-24 with non-inflammatory diseases). Real-time reverse-transcription polymerase chain reaction (real-time RT-PCR) was used to determine SARS-CoV-2, and specific IgG, IgM, neopterin, and protein 10 induced by gamma interferon (CXCL-10) were evaluated in the CSF samples. No samples were amplified for SARS-CoV-2 by real-time RT-PCR. The sensitivity levels of anti-SARS-CoV-2 IgG and IgM were 50% and 14.28%, respectively, with 100% specificity for both tests. CXCL-10 showed high sensitivity (95.83%) and specificity (95.83%) for detection of neuroinflammation. Serial CSF analysis showed an association between the neuroinflammatory biomarkers and outcome (death and hospital discharge) in two cases (meningoencephalitis and rhombencephalitis). The detection of SARS-CoV-2 RNA and specific immunoglobulins in the CSF can be used for neuroCOVID-19 confirmation. Additionally, CXCL-10 in the CSF may contribute to the diagnosis and monitoring of neuroCOVID-19.

Genetic Polymorphisms of GP1BA, PEAR1, and PAI-1 may be Associated with Serum sIgE and Blood Eosinophil Levels in Chinese Patients with Allergic Diseases.

It has been suggested that genetic factors may be substantially linked to allergy disorders. This study aims to investigate the relationship between the serum specific Immunoglobulin E (sIgE), blood eosinophil, and the polymorphisms of glycoprotein Ib alpha gene (GP1BA) rs6065, platelet endothelial aggregation receptor 1 gene (PEAR1) rs12041331, and plasminogen activator inhibitor 1 gene (PAI-1) rs1799762. From the Peking Union Medical College Hospital, this study enrolled 60 healthy participants and 283 participants with allergic diseases. TaqMan-minor groove binder (MGB) quantitative polymerase chain reaction (qPCR) was used to examine the gene polymorphisms in each group. The TaqMan-MGB qPCR results were completely consistent with the DNA sequencing results, according to other studies in this medical center (Kappa =1, p <0.001). The GP1BA rs6065, PEAR1 rs12041331, and PAI-1 rs1799762 polymorphisms did not show different distribution between allergy patients and healthy individuals. Concerning allergy patients, the CT (n=33) genotype of GP1BA rs6065 had higher blood eosinophil level than the CC (n=250) genotype (0.59, IQR 0.32-0.72 vs 0.31, IQR 0.15-0.61, *109/L, p =0.005). The serum sIgE of AA (n=46) genotype of PEAR1 rs12041331 was lower (median 3.7, interquartile quartiles (IQR) 0.2-16.8, kU/L) than the GA (n=136) and GG (n=101) genotypes (GA median 16.3, IQR 3.1-46.3, kU/L, p = 0.002; GG median 12.9, IQR 3.0-46.9, kU/L, p =0.003). The GA genotypes of PEAR1 rs12041331were with higher blood eosinophil levels (median 0.42, IQR 0.17-0.74 *109/L) than the AA genotype (median 0.25, IQR 0.15-0.41*109/L, p =0.012). The sIgE of the 5G5G (n=44) genotype of PAI-1 rs1799762 was lower (median 5.0, IQR 0.1-22.8, kU/L) than the 4G5G (n=144) (median 17.3, IQR 3.7-46.0, kU/L, p = 0.012). The GP1BA rs6065, PEAR1 rs12041331, and PAI-1 rs1799762 polymorphisms may be associated with the genetic susceptibility of serum sIgE or blood eosinophil in Chinese allergic disease patients.

B cells expressing mutated IGHV1-69-encoded antigen receptors related to virus neutralization show lymphoma-like transcriptomes in patients with chronic HCV infection.

Chronic HCV infection leads to a complex interplay with adaptive immune cells that may result in B cell dyscrasias like cryoglobulinemia or lymphoma. While direct-acting antiviral therapy has decreased the incidence of severe liver damage, its effect on extrahepatic HCV manifestations such as B cell dyscrasias is still unclear. We sequenced B cell receptor (BCR) repertoires in patients with chronic HCV mono-infection and patients with HCV with a sustained virological response (SVR) after direct-acting antiviral therapy. This data set was mined for highly neutralizing HCV antibodies and compared to a diffuse large B cell lymphoma data set. The TKO model was used to test the signaling strength of selected B-BCRs in vitro. Single-cell RNA sequencing of chronic HCV and HCV SVR samples was performed to analyze the transcriptome of B cells with HCV-neutralizing antigen receptors. We identified a B cell fingerprint with high richness and somatic hypermutation in patients with chronic HCV and SVR. Convergence to specific immunoglobulin genes produced high-connectivity complementarity-determining region 3 networks. In addition, we observed that IGHV1-69 CDR1 and FR3 mutations characterizing highly neutralizing HCV antibodies corresponded to recurrent point mutations found in clonotypic BCRs of high-grade lymphomas. These BCRs did not show autonomous signaling but a lower activation threshold in an in vitro cell model for the assessment of BCR signaling strength. Single-cell RNA sequencing revealed that B cells carrying these point mutations showed a persisting oncogenic transcriptome signature with dysregulation in signaling nodes such as CARD11, MALT1, RelB, MAPK, and NFAT. We provide evidence that lymphoma-like cells derive from the anti-HCV immune response. In many patients, these cells persist for years after SVR and can be interpreted as a mechanistic basis for HCV-related B cell dyscrasias and increased lymphoma risk even beyond viral elimination.

Time-resolved fluorescence (TRF) for total IgG and HPV16-specific antibody detection in first-void urine and serum: A comparative study

Recent studies demonstrated that human papillomavirus (HPV) specific immunoglobulins (IgG) are present and detectable in non-invasively collected first-void urine (FVU) samples. As IgG levels in urine are low, we evaluated the potential of a highly sensitive HPV16-specific assay based on time-resolved fluorescence, DELFIA, and compared it with three immunoassays, GST-L1-MIA, M4ELISA, and M9ELISA. A total of 225 paired serum and FVU samples from two cohorts of healthy female volunteers were analyzed. Strong Spearman rank correlations between HPV16-specific IgG results measured with DELFIA, M4ELISA, GST-L1-MIA, and M9ELISA were found for both sample types (rs > 0.80). Additionally, total human IgG results, determined in all samples using HTRF human IgG kit and BioPlex Pro™ Human Isotyping Assay, were compared. Moderate correlations between total human IgG concentrations in FVU samples were found for the two total IgG assays (rs ≥ 0.42, p < 0.0001), while correlations for serum were non-significant. In conclusion, the HPV16-DELFIA assay is usable for detecting HPV16-specific antibodies in FVU and serum samples. As total human IgG remains an interesting parameter for the normalization of HPV-specific IgG in FVU, the accuracy of both assays needs to be validated further.

The search for still unknown pathomechanisms of allergy

In recent decades, atopic diseases, such as atopic dermatitis (AD), allergic asthma (AA), allergic rhinitis (AR), and food allergy (FA) have been estimated rapidly increasing in prevalence. These diseases are characterized by the presence of specific immunoglobulin E (sIgE) and often relate to each other and develop in sequence (the so-called “atopic march”). AD may be the first early manifestation in infants followed by FA often within the first year of life. Moreover, AD is a risk factor for developing sensitization to airborne allergens later in life that can cause clinical manifestations of AA and AR. According to the dual-allergen exposure hypothesis, allergic sensitization to food allergens is promoted through cutaneous exposure, rather than the oral route. Moreover, there is evidence that exposure to food allergens, in particular peanuts, in the airway would also lead to food sensitization. The most frequent route of sensitization for inhalant allergens is still debated. Of note, a recent case report supports the development of sensitization to cat dander through a cat bite. Our review aims to provide an overview of current knowledge and unmet needs in the pathophysiology of respiratory and FAs.

Evaluation of the suitability of β-lactoglobulin and whey protein in a BALB/c mouse model of cow's milk allergy

Cow's milk allergy (CMA) is common in infants and young children, which can adversely affect their growth and quality of life. Currently, research on CMA is mainly carried out in mouse models due to ethical constraints in population studies, but the determination of the optimal modelling protocol remains controversial. Here, we aim to evaluate the applicability of β-lactoglobulin (BLG) and whey protein from multiple perspectives in the construction of CMA models in BALB/c mice. To this end, the mice were sensitized by oral gavage of allergens, and then challenged by BLG or whey protein orally administered as well as whey intradermally in the ear, respectively. The allergic reactions were determined by the evaluation of anaphylactic symptoms, levels of specific immunoglobulins and Th2 cytokines, and intestinal tissue histopathology. Overall, mice in the BLG group showed more severe allergic symptoms and decreased body temperature than the other groups. The stronger allergic reactions to BLG in mice were also proved in higher levels of mouse mast cell protease-1 (mMCP-1), allergen specific antibodies, and Th2 cytokines as well as more serious intestinal damage than whey protein. These results suggest that BALB/c mice vary in the susceptibility to different cow's milk allergens, and the single component represented by BLG instead of whey protein, may be a more appropriate and effective allergen for the construction of BALB/c mouse model of CMA.

Physician’s perspectives on skin prick testing and allergy diagnostics in Germany

Summary Purpose Novel technologies standardising the testing process of immediate hypersensitivities have been developed and validated in recent years. Meanwhile, challenges with regard to availability of testing agents and shortage of trained personnel have increased. Novel technologies could fight these challenges, but their distribution is at present not known. The current survey, conducted by the German Society for Allergology (AeDA), aimed to assess current practices of allergy diagnostics in Germany. Methods Members of AeDA were invited to complete an online questionnaire to obtain information on their perspectives on allergy testing and diagnostics. Results A total of 150 allergologists from different disciplines treating patients with allergy completed the questionnaire. This survey revealed that twice as many skin prick tests (SPT; 21.2 tests/week) compared to serum specific immunoglobulin E tests (IgE; 10.4 tests/week) are being performed. Nasal allergen provocation tests are being performed in 56.0% of hospitals and physicians’ offices. An individual standard allergen panel for SPT is applied in 78.0% of testing cases. Methods used to perform a read out of SPT are variable with measurement of the longest wheal diameter being used most frequently (68.0%), followed by a qualitative evaluation (46.6%) or the longest wheal diameter including pseudopods (34.4%). In all, 66% of allergologists indicated that a device that automating the SPT process would be valuable for clinical practice. Conclusion Skin prick tests and serum IgE tests are still the cornerstones in the diagnostic work-up of immediate-type allergies. Variability in the execution of skin prick tests exists between different hospitals and physicians’ offices in Germany. Inconsistent availability of testing reagents was considered most problematic for maintaining allergy diagnostics in Germany. A majority of allergologists are open to evaluating tools that may contribute to standardize skin prick tests.

Routinely Used and Emerging Diagnostic and Immunotherapeutic Approaches for Wheat Allergy.

Wheat, a component of the staple diet globally, is a common food allergen in children. The symptoms of wheat allergy (WA) range from skin rash to shortness of breath, significantly impairing quality of life. Following initial clinical suspicion, individuals may undergo routinely used allergy tests such as a wheat allergen-specific skin prick test (SPT), a blood test for specific immunoglobulin E (sIgE) levels, or oral food challenge. Conventional management of WA lies in wheat avoidance, yet accidental consumption may be inevitable owing to the ubiquity of wheat in various food products. This article aims to provide an overview of the immunologic pathway of WA, followed by its emerging diagnostic methods, namely alcohol-soluble SPT extracts, component-resolved diagnosis, and the basophil activation test (BAT). The mechanisms underlying wheat allergen-specific oral immunotherapy (OIT) as well as a summary of the efficacy, tolerability, and safety of related clinical trials will then be discussed.

Periostin as a marker of eosinophilic inflammation in patients with asthma and chronic obstructive pulmonary disease

BACKGROUND: Asthma and chronic obstructive pulmonary disease are common chronic respiratory diseases. Given their heterogeneity, the study of periostin is a relevant area for establishing the endotypes of airway inflammation and determining further therapy tactics. AIM: To evaluate periostin levels and determine its significance as a marker of eosinophilic inflammation in patients with asthma and chronic obstructive pulmonary disease. MATERIALS AND METHODS: The study included 59 patients with asthma and 33 patients with chronic obstructive pulmonary disease. The control group consisted of 37 apparently healthy people, comparable in age and sex, without allergic and bronchial obstructive diseases in anamnesis. The anamnesis data, the number of peripheral blood eosinophils and induced sputum, indices of external respiratory function were evaluated. Levels of specific immunoglobulin E to allergens, periostin level were determined in blood serum by immunoenzyme method. The obtained data were processed using STATISTICA 13 and SPSS Statistic 27 software systems. RESULTS: The maximum serum periostin concentration 22.5 (17–38) ng/ml was recorded in the patients with asthma, which was significantly higher than in the chronic obstructive pulmonary disease group [16 (12–21) ng/ml; p = 0.006] and control group [20.1 (14.6–24.8) ng/ml; p = 0.044]. The level of periostin in induced sputum in the patients with asthma was significantly higher than in the chronic obstructive pulmonary disease group — 0.05 (0.03–0.6) ng/ml vs 0.03 (0.02–0.04) ng/ml (p = 0.008). The study revealed the correlation between serum periostin level and eosinophil level (r = 0.406; p 0.05) and with forced expiratory volume in the first second after bronchodilator test (r = 0.366; p 0.05) as well as with forced expiratory volume in the first second divided by forced vital capacity after bronchodilator test (r = 0.572; p 0.05). CONCLUSIONS: Periostin is a promising marker of eosinophilic inflammation in patients with asthma, which can be considered as an indicator of fixed bronchial obstruction and a molecule linking T2-inflammation and airway remodelling. In a group of chronic obstructive pulmonary disease patients, the use of periostin for diagnostic and prognostic purposes requires further investigation and larger studies.

A real-life ImmunoCAT study: impact of molecular diagnosis through ImmunoCAPTM ISAC 112 on immunotherapy prescription in pollen-polysensitized patients in Catalonia, Spain.

Molecular diagnosis in allergology helps to identify multiple allergenic molecules simultaneously. The use of purified and/or recombinant allergens increases the accuracy of individual sensitization profiles in allergic patients. To assess the impact of molecular diagnosis through the ImmunoCAPTM ISAC 112 microarray on etiological diagnosis and specific immunotherapy (SIT) prescription. This was compared to the use of conventional diagnoses in pediatric, adolescent, and young adult patients with rhinitis or rhinoconjunctivitis and/or allergic asthma, sensitized to three or more pollen allergens of different botanical species. A multicenter, prospective, observational study was conducted in patients aged 3-25 years who received care at the Allergology service of 14 hospitals in Catalonia from 2017 to 2020. Allergology diagnosis was established based on the patient's clinical assessment and the results of the skin prick test and specific immunoglobulin E assays. Subsequently, molecular diagnosis was conducted using ImmunoCAPTM ISAC® 112 to recombinant and/or purified allergen components. A total of 109 patients were included; 35 (32.1%) were pediatric patients and 74 (67.9%) were adolescents or young adults (mean age: 18 years), with 58.0% being females. A change of 51.0% was observed in SIT prescription following molecular etiological diagnosis by means of a multi-parameter microarray. Molecular diagnosis by means of multi-parameter tests increases the accuracy of etiological diagnosis and helps to define an accurate composition of SIT.

A diagnostic approach to IgE-mediated food allergy: A practical algorithm.

A food reaction history is the basis of food allergy diagnoses. Several levels of food allergy diagnostic testing can confirm or refute the presence of food allergy. The choice of food allergy testing modality should be informed by the reaction history and determined by the testing goals. Testing modalities include skin-prick testing, in vitro specific immunoglobulin E testing, component-resolved testing, epitope threshold testing, and basophil activation testing. The goal of food allergy testing may be merely to confirm the diagnosis of food allergy or may be used to guide passive (avoidance) or active (allergen immunotherapy) management. The most appropriate diagnostic path should consider testing predictive value, the goal of the evaluation, patient and family food allergy anxiety, and cost. Peanut allergy testing provides an algorithm for testing pathways.

Dupilumab induces a significant decrease of food specific immunoglobulin E levels in pediatric atopic dermatitis patients.

Dupilumab induces a significant decrease of food specific immunoglobulin E levels in pediatric atopic dermatitis patients.