Cross-reactive Reactions Research Articles

Pathomechanism of Adverse Reactions to Biological Treatment of Inflammatory Skin Conditions.

Biological agents are widely used across medicine, including for immune-mediated skin conditions such as psoriasis and atopic dermatitis. When used to treat a relevant pathological process, they demonstrate impressive efficacy and credible safety, helping to achieve remission and improved function and quality of life. However, with their expanded use, awareness and understanding of adverse reactions to biologicals have also increased. Herein, we discuss the pathomechanism of adverse reactions to biological agents used to treat skin conditions and apply these to Pichler's classification system. This classification differentiates five distinct types, namely overstimulation (type α), hypersensitivity or immunogenicity (β), immunodeviation (γ), cross-reactivity (δ) and nonimmunologic adverse reactions (ε). This classification covers most types of adverse reactions associated with use of biological agents and could be used to better understand the reaction pathogenesis and manage the clinical features of biological adverse effects.

Antibody Cross-Reactivity in Auto-Immune Diseases.

Autoimmunity is defined by the presence of antibodies and/or T cells directed against self-components. Although of unknown etiology, autoimmunity commonly is associated with environmental factors such as infections, which have been reported to increase the risk of developing autoimmune diseases. Occasionally, similarities between infectious non-self and self-tissue antigens may contribute to immunological cross-reactivity in autoimmune diseases. These reactions may be interpreted as molecular mimicry, which describes cross-reactivity between foreign pathogens and self-antigens that have been reported to cause tissue damage and to contribute to the development of autoimmunity. By focusing on the nature of antibodies, cross-reactivity in general, and antibody-antigen interactions, this review aims to characterize the nature of potential cross-reactive immune reactions between infectious non-self and self-tissue antigens which may be associated with autoimmunity but may not actually be the cause of disease onset.

Different Patterns of Response in Hypersensitivity Reactions to Arylpropionic Acid Derivatives

Ibuprofen and other arylpropionic acid derivatives (APs) are among the most consumed nonsteroidal anti-inflammatory drugs worldwide at all age ranges; however, little is known about drug hypersensitivity reactions (DHRs) they induce. To characterize in detail patients reporting DHRs to APs. We prospectively evaluated patients with symptoms suggestive of AP-DHRs and analyzed their clinical characteristics, reported reactions, and diagnostic approaches. Six hundred sixty-two patients confirmed as hypersensitive to APs were included: 489 with cross-reactive reactions (CRs) (73.86%) and 173 with selective reactions (SRs) (26.13%). The percentage of subjects reporting reactions to ibuprofen and dexketoprofen was higher in CRs (P= .005 and P= .01, respectively), whereas naproxen and ketoprofen were more frequently involved in SRs (P= .0002 and P= .00001, respectively). The most frequent symptoms induced by ibuprofen, dexketoprofen, and naproxen were isolated angioedema and urticaria, combined or not with angioedema in both CRs and SRs. The result of nasal provocation test with lysine acetylsalicylate was positive in 156 cases (77.14% in patients showing exclusively respiratory symptoms, and in 68.18% of those with both cutaneous and respiratory involvement). To confirm diagnosis, drug provocation test with acetylsalicylic acid was required in 246 CR patients (50.3%), whereas in 28 SR patients (16.18%) drug provocation test with the culprit AP was required. Skin is the organ most commonly involved in AP-DHRs, with ibuprofen and dexketoprofen inducing most frequently CRs, and naproxen and ketoprofen SRs. More studies are necessary to clarify the underlying mechanism in DHRs induced by APs.

Evaluation of fidaxomicin use in patients with a macrolide allergy/intolerance.

Fidaxomicin, a macrolide antibiotic, has been shown to be non-inferior to oral vancomycin for the treatment of Clostridioides difficile infection (CDI) and is associated with lower recurrence rates.1 The 2021 update to the IDSA and Society of Healthcare Epidemiology of America CDI guidelines recommend fidaxomicin 200 mg orally twice daily for 10 days as a first-line treatment option for non-severe and severe CDI.2 However, the use of fidaxomicin in patients with a macrolide allergy may pose a challenge for clinicians given the potential structural similarities and risk for cross-reactivity.3 The product labelling also has a warning to use fidaxomicin with caution in patients with a history of a macrolide allergy because they may be at an increased risk for hypersensitivity reactions.4 While macrolide allergies are relatively rare, with an incidence of 0.4%–3%,3,5 clinicians may encounter this scenario in clinical practice. However, limited published reports are currently available to describe potential cross-reactivity and hypersensitivity reactions between fidaxomicin and other macrolides.3,6,7 Herein, we describe a small cohort of patients with a labelled macrolide allergy/intolerance who received fidaxomicin.

Detection of Serum-Specific IgE by Fluoro-Enzyme Immunoassay for Diagnosing Type I Hypersensitivity Reactions to Penicillins.

Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs). Among in vitro complementary tests, the fluoro-enzyme immunoassay (FEIA) ImmunoCAP® (Thermo-Fisher, Waltham, MA, USA) is the most widely used commercial method for detecting drug-specific IgE (sIgE). In this study, we aimed to analyze the utility of ImmunoCAP® for detecting sIgE to penicillin G (PG) and amoxicillin (AX) in patients with confirmed penicillin allergy. The study includes 139 and 250 patients evaluated in Spain and Italy, respectively. All had experienced type I hypersensitivity reactions to penicillins confirmed by positive STs. Additionally, selective or cross-reactive reactions were confirmed by DPTs in a subgroup of patients for further analysis. Positive ImmunoCAP® results were 39.6% for PG and/or AX in Spanish subjects and 52.4% in Italian subjects. When only PG or AX sIgE where analyzed, the percentages were 15.1% and 30.4%, respectively, in Spanish patients; and 38.9% and 46% in Italian ones. The analysis of positive STs showed a statistically significant higher percentage of positive STs to PG determinants in Italian patients. False-positive results to PG (16%) were detected in selective AX patients with confirmed PG tolerance. Low and variable sensitivity values observed in a well-defined population with confirmed allergy diagnosis, as well as false-positive results to PG, suggest that ImmunoCAP® is a diagnostic tool with relevant limitations in the evaluation of subjects with type I hypersensitivity reactions to penicillins.

MRNA COVID-19 vaccine safety in patients with previous immediate hypersensitivity to pegaspargase

mRNA COVID-19 vaccine safety in patients with previous immediate hypersensitivity to pegaspargase

Ipersensibilità ai FANS: intolleranza o allergia?

Non-steroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity reactions in children. According to the EAACI latest classification NSAIDs hypersensitivity reactions are differentiated into cross-reactive reactions, with non-immunological mechanisms (based on COX-1 inhibition), and selective reactions, with immunological mechanisms. Paediatric clinical manifestations of NSAID hypersensitivity are typically cutaneous, but sometimes, similarly to anaphylaxis, can involve other systems, especially the respiratory one. Differentiating between NSAID intolerance and NSAID allergy through drug provocation tests is crucial for the patient because the two clinical entities require different management.

Structural Characterization of Act c 10.0101 and Pun g 1.0101-Allergens from the Non-Specific Lipid Transfer Protein Family.

(1) Background: Non-specific lipid transfer proteins (nsLTPs), which belong to the prolamin superfamily, are potent allergens. While the biological role of LTPs is still not well understood, it is known that these proteins bind lipids. Allergen nsLTPs are characterized by significant stability and resistance to digestion. (2) Methods: nsLTPs from gold kiwifruit (Act c 10.0101) and pomegranate (Pun g 1.0101) were isolated from their natural sources and structurally characterized using X-ray crystallography (3) Results: Both proteins crystallized and their crystal structures were determined. The proteins have a very similar overall fold with characteristic compact, mainly α-helical structures. The C-terminal sequence of Act c 10.0101 was updated based on our structural and mass spectrometry analysis. Information on proteins’ sequences and structures was used to estimate the risk of cross-reactive reactions between Act c 10.0101 or Pun g 1.0101 and other allergens from this family of proteins. (4) Conclusions: Structural studies indicate a conformational flexibility of allergens from the nsLTP family and suggest that immunoglobulin E binding to some surface regions of these allergens may depend on ligand binding. Both Act c 10.0101 and Pun g 1.0101 are likely to be involved in cross-reactive reactions involving other proteins from the nsLTP family.

Cross-reactive hypersensitivity to NSAIDs: Experience of a Tunisian allergology center

BackgroundThe accurate diagnosis of cross-reactive reactions (CRR) to nonsteroidal anti-inflammatory drugs (NSAIDs) depends on a careful history and oral drug challenge. In this study, we report the result of a new procedure implemented in Tunisian allergology center to explore CRR to NASIDs in patients with immediate hypersensitivity (IHS) to NSAIDs. MethodsOur structured protocol using oral provocation tests (OPTs) was based on the latest advances in the literature. This protocol was tested in patients with a clinical history of IHS reactions to one or more NSAIDs and referred to the pharmacology department of Sfax (Tunisia) between 2012 and 2018. Patients were classified into 5 subgroups: an ASA subgroup, a multiple NSAIDs subgroup, a single non-selective NSAID subgroup, a paracetamol subgroup, and a celecoxib subgroup. ResultsA total of 34 patients were enrolled. Personal history of atopy was found in 26 (76.5%). A diagnosis of CRR to NSAIDs was made in 24 patients (70.6%): 6 patients in the ASA subgroup, 12 patients in the multiple NSAIDs subgroup, 4 patients in the single non-selective NSAID subgroup, 1 patient in the paracetamol subgroup and 1 patient in the celecoxib subgroup. Regarding safe alternatives in patients with CRR to NSAIDs (n=24), prevalence of cross-reactivity to paracetamol or celecoxib was found in 20% and 27.3% of patients with confirmed CRR to NSAIDs, respectively. ConclusionOur structured protocol based on standardized oral provocation tests helps physicians to prescribe a suitable drug in patients with a history of IHS reactions to NSAIDs.

A robust method for the estimation and visualization of IgE cross-reactivity likelihood between allergens belonging to the same protein family

Among the vast number of identified protein families, allergens emanate from relatively few families which translates to only a small fraction of identified protein families. In allergy diagnostics and immunotherapy, interactions between immunoglobulin E and allergens are crucial because the formation of an allergen-antibody complex is necessary for triggering an allergic reaction. In allergic diseases, there is a phenomenon known as cross-reactivity. Cross-reactivity describes a situation where an individual has produced antibodies against a particular allergenic protein, but said antibodies fail to discriminate between the original sensitizer and other similar proteins that usually belong to the same family. To expound the concept of cross-reactivity, this study examines ten protein families that include allergens selected specifically for the analysis of cross-reactivity. The selected allergen families had at least 13 representative proteins, overall folds that differ significantly between families, and include relevant allergens with various potencies. The selected allergens were analyzed using information on sequence similarities and identities between members of the families as well as reports on clinically relevant cross-reactivities. Based on our analysis, we propose to introduce a new A-RISC index (Allergens’–Relative Identity, Similarity and Cross-reactivity) which describes homology between two allergens belonging to the same protein family and is used to predict the likelihood of cross-reactivity between them. Information on sequence similarities and identities, as well as on the values of the proposed A-RISC index is used to introduce four categories describing a risk of a cross-reactive reaction, namely: high, medium-high, medium-low and low. The proposed approach can facilitate analysis in component-resolved allergy diagnostics, generation of avoidance guidelines for allergic individuals, and help with the design of immunotherapy.

A Hypoallergenic Polygalacturonase Isoform from Olive Pollen Is Implicated in Pollen-Pollen Cross-Reactivity

Background: Cross-reactivity reactions between allergenic polygalacturonases (PGs) from different biological sources, especially foods and pollens from the Oleaceae family, have been described using Salsola kali PG (Sal k 6). No PG from olive pollen has been characterized to date, hampering further knowledge about cross-reactions through PGs. Objectives: The aim of this work was to determine the potential allergenicity of the PG from olive pollen and clarify its role in cross-reactivity. Methods: A cDNA-encoding olive pollen PG sequence was subcloned into the pET41b vector and used to transform BL21(DE3) Escherichia coli cells to produce a His-tag fusion recombinant protein. The allergenic properties of olive pollen PG were determined by immunoblotting and ELISA in comparison to Sal k 6. The cross-reactivity potential of the protein with other pollen sources was analyzed by inhibition immunoassays. Results: The existence of other isoforms of Ole e 14 with different allergenicity was confirmed by proteomics and a meta-analysis of the recently reported olive genome. Sal k 6 showed a higher IgE recognition than Ole e 14 regardless of patient sensitization, suggesting the existence of more allergenic Ole e 14 isoforms in olive pollen. IgG and IgE inhibition assays supported the existence of cross-reactions between them and with other PGs from Oleaceae and Poaceae plant families. Conclusions: A new allergen from olive pollen, Ole e 14, has been identified, produced as a recombinant isoform, and structurally and immunologically characterized. Its role in cross-reactivity has been confirmed and, due to its smaller IgE binding capacity, it could have an important role for therapeutic purposes.

Plant Pathogenesis-Related Proteins PR-10 and PR-14 as Components of Innate Immunity System and Ubiquitous Allergens.

Pathogenesis-related (PR) proteins are components of innate immunity system in plants. They play an important role in plant defense against pathogens. Lipid transfer proteins (LTPs) and Bet v 1 homologs comprise of two separate families of PR-proteins. Both LTPs (PR-14) and Bet v 1 homologs (PR-10) are multifunctional small proteins involving in plant response to abiotic and biotic stress conditions. The representatives of these PR-protein families do not show any sequence similarity but have other common biochemical features such as low molecular masses, the presence of hydrophobic cavities, ligand binding properties, and antimicrobial activities. Besides, many members of PR-10 and PR-14 families are ubiquitous plant panallergens which are able to cause sensitization of human immune system and crossreactive allergic reactions to plant food and pollen. This review is aimed at comparative analysis of structure-functional and allergenic properties of the PR-10 and PR-14 families, as well as prospects for their medicinal application.

Papular urticaria: A review of causal agents in Colombia.

Papular urticaria is a chronic allergic reaction induced by insect bites, which is common in the tropics. The objective of this review was to deepen on epidemiological and immunological aspects of this disease, focused on data published in Latin American countries.We conducted a non-systematic review of the literature through electronic search on the epidemiology of papular urticaria, the entomological characteristics of the causative agents and associated immunological mechanisms.Several reports from medical centers suggest that papular urticaria is common in Latin America. Only one epidemiological survey designed to estimate prevalence of papular urticaria has been published, reporting that about a quarter of children under six years of age is affected by this condition in Bogotá. There is evidence on the causal relationship among exposure to indoor fleas, poverty and papular urticaria in Bogotá, a representative city of the Andean altitudes. Information about causal insects in tropical warmer areas is scarce, although from clinical reports Aedes aegypti and Culex quienquefasciatus appear to be the most common. Th2 cellular-mediated mechanisms are involved in its pathogenesis, which explains its delayed hypersensitivity. The role of immunoglobulin E is not clear in this disease. Insect-derived antigens directly involved in papular urticaria etiology are unknown. However, it is possible that common molecules among causal insects mediate cross-reactive reactions, such as Cte f 2 allergen, found in cat fleas, and its counterparts in mosquitoes.Papular urticaria is a frequent disease in Latin America that should be further investigated. Immunological characterization of the molecular components that cause this condition may solve questions about its pathogenesis.

Food allergy in children

Food allergy represents a highly up-to-date and continually increasing problem of modern man. Although being present in all ages, it most often occures in children aged up to three years. Sensitization most often occurs by a direct way, but it is also possible to be caused by mother's milk, and even transplacentally. Predisposition of inadequate immune response to antigen stimulation, reaginic or nonreaginic, is of non-selective character so that food allergy is often multiple and to a high rate associated with inhalation and/or contact hypersensitivity. Also, due to antigen closeness of some kinds of food, cross-reactive allergic reaction is also frequent, as is the case with peanuts, legumes and tree nuts or cow's, sheep's and goat's milk. Most frequent nutritive allergens responsible for over 90% of adverse reactions of this type are proteins of cow's milk, eggs, peanuts, tree nuts, wheat, soy, fish, shellfish, crustaceans, and cephalopods. Allergy intolerance of food antigens is characterized by a very wide spectrum of clinical manifestations. Highly severe systemic reactions, sometimes fatal, are also possible.The diagnosis of food allergy is based on a detailed personal and family medical history, complete clinical examination, and corresponding laboratory and other examinations adapted to the type of hypersensitivity and the character of patient's complaints, and therapy on the elimination diet. A positive effect of elimination diet also significantly contributes to the diagnosis. Although most children "outgrow" their allergies, allergy to peanuts, tree nuts, fish, shellfish, crustaceans, and cephalopods are generally life-long allergies.

Oral Allergy Syndrome Following Soy Milk Ingestion in Patients with Birch Pollen Allergy

Persons allergic to birch pollen often report oral and pharyngeal hypersensitivity to fruit and vegetables, due to immunological cross-reactivity between pollen and foods. This phenomenon is referred to as the oral allergy syndrome (GAS). Such cross-reactive antigen reactions mainly involve Bet v 1, which is the major birch-pollen allergen, and partially involve birch-pollen profilin Bet v 2. Soybean contains Bet v 1-related antigen (Gly m 4), and soy milk often causes the OAS with severe symptoms such as precordial and abdominal burning sensation because soy milk undergoes little denaturation, and this water-soluble liquid is consumed by most people rather quickly. We evaluated the frequency of the oAS after ingestion of soymilk and examined IgE antibodies to various allergens. A total of 167 patients [122 women, 45 men; age range, 4-72 years (mean age, 32 years)], who had experienced GAS episodes and had IgE birch--pollen antibodies, were interviewed. Using the CAP system, we examined IgE antibodies to birch pollen and other allergens. Of 167 patients, 161 were examined for IgE antibodies to Bet v 1, Bet v 2, Gly m 4, and soybean. We evaluated the frequency of the GAS after soy milk ingestion based on reports by GAS patients with birch pollen allergy, and evaluated the positive rates of some of the IgE antibodies. Among the 167 patients with birch-pollen allergy and GAS on ingestion of any of the foods, there were 16 cases (10%) with OAS following soy milk ingestion. In addition, the foods that caused OAS most often were apples (123 cases, 74%), peaches (67%), and cherries (55%), followed by pears (37%) and kiwi (37%). A higher CAP class for birch pollen, Bet v 1, Gly m 4, and soybean was associated with a higher prevalence of OAS to soy milk. Of 15 patients who had GAS on ingestion of soy milk and had birch-pollen allergy, 47% (7cases) were CAP class 1 for soybean and only 7% (case) was CAP class c2, whereas 93% (14cases) were CAP class 1 for Gly m 4, and 87% (3cases) were CAP class ≥ 2 for Gly m 4. Among the birch-pollen allergic OAS patients, 10% had the OAS on ingestion of soy milk, and among these with birch-pollen allergy and the OAS on ingestion of soy milk, the positive rate for soy milk CAP was low, whereas that for Gly m 4 CAP was high.

Çocuklarda Tek Non-steroid Anti-inflamatuar İlaç ile Oluşan Hipersensitivite Reaksiyonları

Non-steroidal anti-inflammatory drug (NSAID) hypersensitivity is one of the most common drug-related reactions in children. According to European Network for Drug Allergy, NSAID hypersensitivity is mainly divided into two groups: single drug induced IgE or T cell-mediated reactions and cross-reactive reactions due to inhibition of cyclooxygenases. These major groups are classified in phenotypes according to the clinical findings and the presence of the underlying diseases. However, it may not sometimes be so easy to classify each patient according to these phenotypes. In this presentation, three children who had single NSAID-induced reactions but different clinical presentations have been described. Also, two of these children had some manifestations common to cross-reactive types of NSAID hypersensitivity which further complicated phenotyping.

Multiple drug hypersensitivity syndrome

The multiple drug hypersensitivity syndrome (MDH) is a distinct clinical entity, different from cross-reactivity and flare-up reactions. Following its initial description in 1989 by Sullivan et al., several authors have addressed the issues surrounding this peculiar form of drug hypersensitivity. Whether this syndrome is single or can be further classified in several entities is still a matter of debate. Case reports, case series or studies involving large populations on MDH are few. The use of this term in the literature is heterogeneous, and the definitions variable. Given the major advances in the study of drug hypersensitivities in general, and ongoing research regarding severe cutaneous adverse reactions in particular, careful study of the subgroup of patients with demonstrated immunological basis of MDH has enabled the generation of possible pathogenetic hypotheses. Together with the studies (despite their limitations) to estimate the prevalence of this syndrome in adult and paediatric patients these emerging data need confirmation through larger studies with well defined populations. Bringing together the experience of groups involved in the field of drug allergy should help to move knowledge regarding this peculiar form of drug hypersensitivity forward.

Update in drug allergy: novel drugs with novel reaction patterns

In the last years, many novel drugs have been introduced, generating new patterns of drug hypersensitivity. There are also novel clinical and biologic techniques that have enabled us to understand the mechanisms and diagnosis of reactions to old used drugs. This review summarizes current knowledge on the epidemiology, mechanisms, and clinical and in-vitro diagnosis of these reactions. Traditional and complementary alternate medicines are also causes of adverse drug reactions, and many of them are cataloged as allergy. Research in the field of skin and drug provocation test to antibiotics such as beta-lactams and carbapenems, and iodinated and gadolinium contrast media has allowed the understanding of cross-reactivity reactions and permitted the use of well tolerated alternate drugs in cases of proper negative drug allergy work-up. Many unique cases have been reported, including diverse drugs as infliximab, succinylcholine, hydroxychloroquine, that widen the spectrum of clinical manifestations of drug hypersensitivity to various drugs. Several studies have been published in the field of in-vitro diagnosis, including basophil activation tests, radioallergosorbent test, Immuno-Cap, ELISA, enzyme-linked immunospot assays, and T-cell proliferation tests allowing novel approaches to assess drug allergy. As new and old drugs continue to be used, new reports regarding new and known drug hypersensitivity manifestations are made. Advances in mechanisms are enhanced by the use of new in-vitro techniques to detect specific antibodies or T cells. Research in the field of skin and provocation tests has allowed the use of well tolerated alternate drugs in individuals with proven drug allergy.

Management of the Patient with Multiple Food Allergies

Food allergies affect 6% of children and 3% to 4% of adults in the United States. Although several studies have examined the prevalence of food allergy, little information is available regarding the prevalence of multiple food allergies. Estimates of prevalence of people allergic to multiple foods is difficult to ascertain because those with allergy to one food may avoid additional foods for concerns related to cross-reactivity, positive tests, or prior reactions, or they may be reluctant to introduce foods known to be common allergens. Diagnosis relies on an accurate history and selective IgE testing. It is important to understand the limitations of the available tests and the role of cross-reactivity between allergens. Allergen avoidance and readily accessible emergency medications are the cornerstones of management. In addition, a multidisciplinary approach to management of individuals with multiple food allergies may be needed, as avoidance of several food groups can have nutritional, developmental, and psychosocial consequences.

Mongrelised genetics of H1N1 virus: A bird′s eyeview

H1N1 influenza, also known as "novel H1N1 virus" has led to a "global outcry." This virus is more virulent when compared with other seasonal flu viruses. Virulence may change as the adaptive mutation gene increases within the virus. A study at the US Centre for Disease Control and Prevention published in May 2009 found that children had no preexisting immunity to the new strain as they showed no cross-reactive antibody reaction when compared with adults aged 18-64 years, who showed a cross-reactive antibody reaction of 6-9% and older adults with 33% immunity. This review article depicts H1N1 virus, its virulence with genetic evolution potential and preventive protocol for the dental professionals. This would allow us to comprehend the changes in the disease process and contribute in its prevention as "prevention is better than cure."