Frequency Of Cross-reactivity Research Articles

Immediate Hypersensitivity to Fluoroquinolones: A Cohort Assessing Cross-Reactivity.

BackgroundFluoroquinolones are the second-most prescribed antimicrobial and are frequently associated with causing hypersensitivity reactions. Existing evidence regarding cross-reactivity of fluoroquinolones is limited, offering clinicians little guidance in understanding the implications of selecting an in-class alternative among patients with histories of allergic reactions to fluoroquinolones. The aim of this study was to compare the frequency of immediate hypersensitivity reactions to ciprofloxacin, levofloxacin, and/or moxifloxacin among patients with a history of immediate hypersensitivity to a different fluoroquinolone.MethodsThis retrospective chart review included adult patients with a history of an immediate hypersensitivity reaction to ciprofloxacin, levofloxacin, and/or moxifloxacin and a documented prescription for a different fluoroquinolone. The primary outcome was documentation of a hypersensitivity reaction upon second fluoroquinolone exposure.ResultsA total of 321 cases met inclusion criteria. Of these cases, 2.5% experienced an immediate hypersensitivity reaction after second fluoroquinolone exposure to ciprofloxacin, levofloxacin, and/or moxifloxacin. Within the ciprofloxacin, levofloxacin, and moxifloxacin index allergy cohorts, the frequency of cross-reactivity was 2.5%, 2.0%, and 5.3%, respectively.ConclusionsOur data suggest that patients with a history of immediate hypersensitivity reaction to ciprofloxacin, levofloxacin, and/or moxifloxacin are at low risk of experiencing a cross-reaction when exposed to a different fluoroquinolone. Avoidance of all fluoroquinolones in this patient population may not be warranted.

Evaluation of Suspected Macrolide Allergies in Children

Objective:Macrolides are often accepted as safe antibiotics due to their low allergenicity. However, studies on macrolides, particularly studies evaluating cross-reactivity in macrolides, are highly rare in children. This study aimed to evaluate the clinical manifestations, confirmation rate, and frequency of cross-reactivity in children admitted with suspicious clarithromycin or azithromycin allergy.Materials and Methods:A total of 61 children suspected of macrolide antibiotic allergy (clarithromycin, n = 39 and azithromycin, n = 22) were evaluated. Allergy work-up including drug provocation tests were performed in all patients to confirm drug allergy.Results:Macrolide allergy was confirmed in 9.8% (n = 6) of patients (azithromycin, 18.2% [n = 4] and clarithromycin, 5.1% [n = 2]). There was no significant difference between the confirmation rate of clarithromycin and azithromycin (P = .117). Cross-reaction with clarithromycin was confirmed in 2 (33.3%) patients with azithromycin allergy.Conclusion:Drug skin tests are not capable of confirming or ruling out macrolide allergy, and oral provocation tests are essential for a definitive diagnosis. Cross-reactivity, albeit rare, can occur between clarithromycin and azithromycin, which are the most frequently used macrolides in children.

Evaluation of Suspected Macrolide Allergies in Children.

Macrolides are often accepted as safe antibiotics due to their low allergenicity. However, studies on macrolides, particularly studies evaluating cross-reactivity in macrolides, are highly rare in children. This study aimed to evaluate the clinical manifestations, confirmation rate, and frequency of cross-reactivity in children admitted with suspicious clarithromycin or azithromycin allergy. A total of 61 children suspected of macrolide antibiotic allergy (clarithromycin, n = 39 and azithromycin, n = 22) were evaluated. Allergy work-up including drug provocation tests were performed in all patients to confirm drug allergy. Macrolide allergy was confirmed in 9.8% (n = 6) of patients (azithromycin, 18.2% [n = 4] and clarithromycin, 5.1% [n = 2]). There was no significant difference between the confirmation rate of clarithromycin and azithromycin (P = .117). Cross-reaction with clarithromycin was confirmed in 2 (33.3%) patients with azithromycin allergy. Drug skin tests are not capable of confirming or ruling out macrolide allergy, and oral provocation tests are essential for a definitive diagnosis. Cross-reactivity, albeit rare, can occur between clarithromycin and azithromycin, which are the most frequently used macrolides in children.

Cefazolin Use in Patients with Penicillin Allergy

The frequency of cross-reactivity between cephalosporins and penicillin is reported to be about 10%, although many experts believe it is much lower.

The frequency of cross-reactivity with various avian eggs among children with hen’s egg allergy using skin prick test results: fewer sensitizations with pigeon and goose egg

Introduction and objectivesA high rate of cross-reactivity has been reported between the specific proteins of hen’s egg with proteins of various avian eggs by quantitative immunoelectrophoretic techniques. The aim of this study was to assess the clinical cross-reactivity of different birds’ eggs in children with hen’s egg allergy based on skin prick test results. Material and methodsThis cross-sectional study enrolled 52 infants with hen’s egg allergy and 52 healthy infants with no history of food allergy from October 2018 to April 2019. Skin prick tests were performed in both patient and control groups with fresh extract of white and yolk related to pigeon, duck, goose, turkey, quail, and partridge. ResultsFifty (96.1%) children with hen’s egg allergy showed positive sensitization to at least one of the avian eggs. The most frequent positive skin tests were related to quail’s white (36 = 69.2%) followed by duck’s white (34 = 65.5%), and sensitization was the least frequent in pigeon’s yolk (23 = 44.2%). Skin tests of the control group were negative to all the tested extracts. ConclusionBecause of fewer sensitizations to some avian eggs, further research should clarify starting oral immunotherapy with the yolk of goose and pigeon in children with hen’s egg allergy.

No Evidence for Cross-reactivity of Virus-specific Antibodies With HLA Alloantigens.

Antibodies directed against HLA can develop through pregnancy, blood transfusions, or organ transplants. Anecdotal evidence suggests that virus-specific antibodies may have the capacity to cross-react with HLA, a phenomenon called heterologous immunity, which is well described for T-cell alloreactivity. To determine whether antibody cross-reactivity between viral antigens and HLA is common, we tested 51 virus-specific human monoclonal antibodies (mAbs) specific for human immunodeficiency virus, varicella zoster virus, cytomegalovirus, and parvovirus, for reactivity against HLA class I and class II in single-antigen bead assays. In addition, we tested the reactivity of 41 HLA-specific human mAbs against common viral antigens of cytomegalovirus, varicella zoster virus, human immunodeficiency virus, Epstein-Barr virus, and BK polyomavirus. No cross-reactivity of any of the virus-specific mAbs with either HLA class I or class II molecules, as well as no cross-reactivity of any of the HLA-specific mAbs with any of the viral antigens was observed. These findings indicate that the frequency of cross-reactivity on the antibody level between viral antigens and HLA, if present at all, is low. The emergence of HLA antibodies upon viral infection or vaccination is therefore probably due to bystander activation of dormant HLA-specific memory B cells.

Analysis of cross-reactivity among radiocontrast media in 97 hypersensitivity reactions

Results Ninety-seven patients were included. CR occurred between ionic monomers (IMs) in 2 cases, between non-ionic monomers (NIMs) in 93 cases, between an ionic dimer (ID) and an IM in 1 case, between NIMs and IMs in 38 cases, between NIMs and IDs in 29 cases, between non-ionic dimers (NIDs) and IMs in 9 cases, between IDs in 13 cases, and between NIMs in 65 cases. Multiple correspondence analyses identified two subgroups of RCM in which CR was frequent: Group A (iodixanol, iopamidol, iomeprol, iohexol, ioversol), which share two identical N-(2, 3-dihydroxypropyl) carbamoyl side chains that could be the antigen determinant (also present in other drugs), and Group B (ioxaglate, iobitridol). Conclusion From this largest study of CR between RCM, we demonstrate that frequent CR between RCM does not follow the current chemical classification. Thus, we propose reclassifying RCM, and also suggest re-challenging sensitized patients with RCM from a different CR subgroup than that of the RCM initially involved.

The risk for cross-reactions after a cutaneous delayed-type hypersensitivity reaction to heparin preparations is independent of their molecular weight: a systematic review

Heparins are a widely used class of drugs known to cause delayed-type hypersensitivity (DTH) reactions. Recent publications indicate that the incidence of these may be higher than previously thought. To date, patient-related but no drug-related risk factors for the development of DTH reactions to heparins have been identified, although molecular weight is discussed as a potentially relevant parameter. To address this, a systematic review was conducted on the frequency of cross-reactions after DTH reactions to heparin preparations. We electronically searched MEDLINE and EMBASE, hand-searched selected journals and references, and contacted experts for unpublished data. Sixty-six publications and unpublished data of 14 patients resulted in 198 patients with 1084 tests for cross-reactivity. The primary causative agents were mostly unfractionated heparin (50%) and low molecular weight heparins (49.5%). Cross-reactions were more likely after an initial DTH reaction to unfractionated heparin than after an initial DTH reaction to low molecular weight heparin. Our findings also indicate that molecular weight does not correlate with the risk for cross-reactivity, which is in line with recent observations, indicating that different heparins have to be individually considered. The available data demonstrated the lowest overall risk for cross-reactions for pentosan polysulfate (36.4%) and fondaparinux (10.4%). In the clinical context, fondaparinux is recommended as the current best alternative when a DTH reaction occurs.

Immediate reactions following iodinated contrast media injection: A study of 38 cases

Objectives To investigate the pathomechanisms involved in cases of immediate hypersensitivity reactions occurring after the administration of iodinated contrast media. Materials and methods Patients having presented clinical signs of immediate hypersensitivity suggesting allergy after iodinated contrast medium were investigated. Histamine and tryptase concentrations were measured, and/or skin tests were performed. Patients with positive skin tests to the culprit contrast agent were classified as IgE-mediated allergic hypersensitivity (Group I) and patients with negative skin tests as non-allergic hypersensitivity (Group II). Results 38 patients were included. Most reactions appeared after non-ionic ( n = 32). Reactions were more frequently severe following ionic than non-ionic ( p = 0.014). Skin testing was not performed in 11 patients. Skin tests with the culprit contrast agent were negative in 26% of the patients (Group II, n = 7) whereas they were found positive with the contrast agent in 73% of the patients (Group I, n = 19). Latex-induced reaction was diagnosed in one patient, and was consequently excluded from the cohort. In Group I, the frequency of cross-reactivity with the other commercialized iodinated contrast media was low (7%). Cardiovascular signs were present in Group I (52.6%, n = 10), and absent in Group II ( p = 0.023). Histamine and tryptase concentrations were higher in patients who had cardiovascular signs ( p < 0.02). Conclusion Immediate reactions with clinical signs suggesting allergy along with positive skin tests with the administered contrast agent confirm immediate allergic hypersensitivity (anaphylaxis) to this agent. Consequently, the culprit contrast agent should be definitely avoided as well as cross-reactive ICM in order to prevent further recurrences.

Antibody detection and cross-reactivity among species and serogroups of Legionella by indirect immunofluorescence test

The purpose of the present study was to determine possible cross-reactivity between different serogroups or between different species by means of bacterial smears of individual L. pneumophila serogroups and several non- pneumophila Legionella spp. Using BIOCHIP slide we found a considerable frequency of cross-reactions with L. pneumophila serogroup 12 (88.4%) therefore BIOCHIP slide proved as useful method for identification of cross-reactivity between members of the Legionnellaceae.

Upgrading the flow-cytometric analysis of anti-Leishmania immunoglobulins for the diagnosis of American tegumentary leishmaniasis

We have previously described a flow cytometry-based assay to detect anti-live Leishmania (Viania) braziliensis promastigote antibodies (FC-ALPA) with prominent performance of FC-ALPA to diagnosis American tegumentary leishmaniasis (ATL). However, the laboriousness to work with live parasites represented the major drawback for using FC-ALPA in routine clinical laboratory. Herein, we have presented an upgraded technology using fixed Leishmania (Leishmania) amazonensis promastigotes as antigen (FC-AFPA). Our data demonstrated that FC-AFPA-IgG displays outstanding performance for ATL diagnosis with high sensitivity (99%) and specificity (100%). Moreover, Likelihood Ratio indicated that positive results (LR+) has an infinite times more chance to come from ATL than from non-infected individuals (NI). Despite the high frequency of cross-reactivity with putative ATL co-endemic diseases, including visceral leishmaniasis, Chagas disease and malaria, FC-AFPA-IgG showed remarkable potential for differential diagnosis with other dermatological illnesses such as leprosy and sporotrichosis. FC-AFPA-IgG subclasses analysis revealed that LTA is characterized by IgG1>IgG3>IgG2 = IgG4 anti-L. amazonensis profiling, electing FC-AFPA-IgG1 and IgG3 with better performances to diagnosis ATL diagnosis. Additionally, FC-AFPA-IgG3 showed to be a better diagnostic tool in endemic areas for malarial disease. Despite the substantial advance to work with fixed promastigotes that contributes to its higher sensitivity, the lower specificity of FC-AFPA represented the major flaws as compared to FC-ALPA, suggesting that further improvement is still required to minimize the cross-reactivity with trypanosomatidae infections. Perspectives for using a flow cytometry multiplex based methodology to simultaneously assess anti-L. amazonensis, anti-L. chagasi and anti-Trypanosoma cruzi IgG reactivity is currently under investigation.

Diagnostic and predictive value of skin testing in platinum salt hypersensitivity

Hypersensitivity reactions to platinum salts are potentially lethal adverse events in chemotherapy, and often require its discontinuation. Several preventive procedures have been proposed: premedication, desensitization regimens, or replacement with a different platinum salt. We therefore assessed the value of skin tests with platinum salts. A positive result would confirm their responsibility in hypersensitivity reaction, whereas a negative result would identify candidates for continuation of therapy using a different platinum salt. Patch tests, prick tests, and intradermal tests with cisplatin, carboplatin, and oxaliplatin were performed in 21 patients. Skin tests were positive in 14 of 21 cases. Prick tests were positive in 5 cases with the suspected platinum salt. Intradermal tests were positive in 12 of 19 cases, always when the hypersensitivity occurred less than 2 hours after infusion. Cross-reactions were observed in 4 cases. Delayed readings of skin tests at 24 hours and 48 hours were positive in 3 patients. Patch tests were negative in all the 21 patients tested. Replacement with another platinum salt was performed in 13 patients using one that gave a negative skin test. A relapse of symptoms occurred in 1 patient. Intradermal tests are particularly indicated for the diagnosis of immediate hypersensitivity reaction. Their good negative predictive value allows safe retreatment by detecting a potential cross-reaction. The frequency of cross-reactions among cisplatin, carboplatin, and oxaliplatin has not been clearly established. Skin tests allow different platinum salts to be given and avoid discontinuation of chemotherapy.

A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients

Purpose of the Study. The American Academy of Pediatrics, in their evidence-based guidelines for treatment of otitis media and sinusitis, endorse the use of cephalosporin antibiotics for patients with reported allergies to penicillin. Many physicians, however, remain reluctant to prescribe such agents. This article reviews evidence in support of the American Academy of Pediatrics recommendations for administration of cephalosporins to penicillin-allergic children. Study Population and Methods. The author reviewed data from published studies related to penicillin and cephalosporin allergies in children and adults and in animal models. Results. Included in this review is an examination of the types and incidence of reactions to penicillins and cephalosporins, the frequency of cross-reactivity between these 2 groups of agents, and a thorough discussion of the clinical guidelines related to penicillin and cephalosporin allergy. Experimental and clinical studies that suggest that side chain–specific antibodies predominate in the immune response to cephalosporins, thereby explaining the lack of cross-sensitivity between most cephalosporins and penicillins. Specific recommendations for the treatment of patients on the basis of their responses to previously prescribed agents are summarized. Conclusions. The author concludes that there is a low but measurable (0.5%) attributable risk associated with administration of a first-generation or selected second-generation cephalosporin to a patient with penicillin allergy. This increased risk is not present for third- or fourth-generation cephalosporins or for second-generation molecules with non–cross-reactive side chains. Reviewer Comments. This is a very careful, comprehensive, and clinically useful review article. I recommend this article to physicians who would like to understand the evidence base and immunologic concepts underlying the use of cephalosporins in penicillin-allergic individuals.

A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients

The American Academy of Pediatrics, evidence-based guidelines endorse the use of cephalosporin antibiotics for patients with reported allergies to penicillin, for the treatment of acute bacterial sinusitis and acute otitis media. Many physicians, however, remain reluctant to prescribe such agents. Although such concern is understandable, lack of consistent data regarding exactly what constitutes an initial penicillin-allergic reaction and subsequent cross-sensitivity to cephalosporins may be preventing many patients from receiving optimal antibiotic therapy. This article reviews evidence in support of the American Academy of Pediatrics recommendation. Included is an examination of the types and incidence of reactions to penicillins and cephalosporins; the frequency of cross-reactivity between these 2 groups of agents; experimental and clinical studies that suggest that side chain-specific antibodies predominate in the immune response to cephalosporins, thereby explaining the lack of cross-sensitivity between most cephalosporins and penicillins; the role of skin testing; and the risks of anaphylaxis. Specific recommendations for the treatment of patients on the basis of their responses to previously prescribed agents are summarized.

Use of Live Cultures for Serotyping Campylobacter jejuni II. Further Experience and Use in an Epidemiological Study

Summary The results of a five year (1983–1987) study have confirmed that the use of live cultures for vaccination and slide agglutination is a generally available, reproducible and sensitive method for serotyping Campylobacter jejuni. Strains from 312 patients were typed by 25 antisera. Eleven serovars occurred most frequently, occasionally with a marked geographical prevalence. An identical serovar was found to persist in convalescents for 2–3 weeks or longer. Serovars associated with human disease were also found in domestic animals and persons living in close contact with patients. Simultaenous infection of two family members was found in 10 families; in 3 of these the serovars were identical, in 7, different. Occasional interhuman transmission of the bacterium could not be ruled out. Untypability due to autoagglutination of the suspension was rare, as was the frequency of cross reactions with diluted sera. The association of expressed markers can be utilized as typing characteristics. The dominant markers seem to be consistent with predominantly thermolabile epitopes of the abundant antigenic endowment of live bacteria. The procedure appears to be suitable for studying the epidemiology of the bacterium. Comparative studies with other serotyping techniques were not performed.

Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. III. Cross‐reactivity of bystander idiotopes on allergen‐specific IgE antibodies

Rabbits were inoculated with affinity-purified human antibodies to the common house dust mite Dermatophagoides pteronyssinus (DPT) to produce anti-idiotypic (Id) antibodies. The Id carried by human IgE antibodies were studied in a radioimmunoassay in which specific anti-DPT IgE were first insolubilized on rabbit F(ab')2 fragments against human Fc epsilon. In a single individual specific anti-DPT IgE antibodies shared bystander idiotopes (i.e. idiotopes located outside the antigen-binding site) with IgG antibodies of the same specificity, since the adsorption on insolubilized anti-DPT IgG almost completely eliminated the binding of anti-Id antibodies to IgE. This differed from our previous observations (J.-M. R. Saint-Remy et al., Eur. J. Immunol. 1986. 16: 575) wherein distinct paratope-associated idiotopes were identified on IgG and IgE anti-DPT antibodies. The frequency of cross-reactions between idiotopes of anti-DPT IgE antibodies observed in ten unrelated individuals was less than 10% for bystander idiotopes. This finding confirmed the private character of the above idiotopes that we found earlier on anti-DPT IgG antibodies. However, one anti-Id antibody preparation was found to react with bystander idiotopes of anti-DPT IgE of most individuals, thereby suggesting the existence of a recurrent idiotope. The low frequency of inter-individual bystander idiotope cross-reactivity contrasted with the public character of paratope-associated idiotopes.

How probable are antibody cross-reactions?

Antibodies to polypeptides are increasingly being used in research. Their specificity and tight but reversible binding make them ideal for applications such as identification of proteins, immunological quantification or purification, and peptide mapping. Antibodies are also used in medicine to deliver loads to specific sites in tissues, and in electron microscopy as heavy metal conjugates to locate antigens in thin sections. While these techniques depend on specificity of antibody binding, it is occasionally observed that cross-reactions occur. These cross-reactions are attributed to the existence of one or more antibody binding sites common to both polypeptides. It is important to know whether these cross-reactions are expected due to chance alone, or if they are improbable and likely due to some causative agent. Examples of such causative agents might include gene duplication events or convergence due to functional constraints. At the present time, good methods for predicting the probability and therefore the frequency of cross-reactions are unavailable. In this paper we apply some recently reported mathematical results to address the following questions: (1) What is the probability that polyclonal or monoclonal antibodies raised against a given polypeptide will cross-react with another polypeptide due to chance alone? (2) What is the probability that polyclonal or monoclonal antibodies raised against a given polypeptide will cross-react with one or more polypeptides in a pool of polypeptides? Approximate answers to these questions are presented for cases where amino acid compositions of linear polypeptides are known or unknown, but the amino acid sequence of one or more of the polypeptides is not known. Implications of the results for antibody use in protein research are discussed.

Sensitization potency of some phenolic compounds--with special emphasis on the relationship between chemical structure and allergenicity.

AbstractSkin irritability and sensitization potency of 14 phenolic compounds were studied on guinea pigs. When 10% preparations of each compound were used for induction, and 1% preparations were used for the challenge, the sensitization frequencies were 80% for isoeugenol and isosafro eugenol, 67% for isohomogenol, 40% for acetyl isoeugenol, 20% for eugenol, and 5% for dihydro eugenol. No animals were sensitized by methyl eugenol, acetyl eugenol, methyl isoeugenol or benzyl isoeugenol. The sensitization frequency was 80% for catechol, 89% for guaethol, 14% for p‐n‐propyl phenol, and 0% for phenol.The frequency of positive allergic reactions to patch tests on patients with cosmetic dermatitis was 2.6% for eugenol and 5.2% for isoeugenol. The frequency of cross reactions on patients sensitive to isoeugenol was also studied.The relationship between chemical structures and sensitization potencies as well as other factors influencing the results of patch tests on patients are discussed.

Schistosomiasis: assessment of the sensitivity, specificity and reproducibility of serological methods for the diagnosis of schistosomiasis in Nigeria

Three groups of sera were tested by indirect fluorescent antibody (IFA), complement fixation (CF) and counter-current immunoelectrophoresis (CCIE) techniques; 56 (10.1%) of 554 sera from Nigerians were anticomplementary and so could not be tested by the CF. Crude antigen extract of adult Schistosoma mansoni was used in the CF and CCIE tests and cercarial antigen in the IFA test. IFA was the most sensitive test and CF the most specific. The reproducibility of both these tests was good. The CCIE was the least sensitive and specific, and its reproducibility was poor. The IFA test was the most suitable for Nigerian conditions. Cross-reactions to S. haematobium antibodies were consistently present in all three tests and it was not possible to differentiate serologically S. mansoni from S. haemotobium. The interpretations of the results presented some difficulties because of the frequency of cross-reactions and false-positives, but the data fell within the infection prevalence rate of 50% reported earlier from south-western Nigeria. The IFA test was more specific and is considered ideal for serodiagnosis.