Minor Haptenic Determinant-Specific Reagins of Penicillin Hypersensitivity in Man

Levine, Bernard B.; Redmond, Andrew

doi:10.1159/000230197

Cited by 143 publications

(62 citation statements)

References 13 publications

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“…The penicilloyl antigen can also be formed through binding of the reactive degradation product penicillenic acid (Levine, 1960). Furthermore, drug-protein antigens derive from spontaneous conversion of b-lactam antibiotics into penicilloic acid and penicilloate (Levine and Redmond, 1969). Using novel mass spectrometric methods, we recently characterized b-lactam-albumin conjugates in patient plasma and defined the profile of drug-protein conjugation at specific lysine residues with respect to dose and incubation time Whitaker et al, 2011).…”

Section: The Antigenicity and Immunogenicity Of Directly Reactive mentioning

confidence: 99%

Idiosyncratic Adverse Drug Reactions: Current Concepts

2013

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Section: The Antigenicity and Immunogenicity Of Directly Reactive mentioning

confidence: 99%

Idiosyncratic Adverse Drug Reactions: Current Concepts

2013

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“…In addition, the main population of antibodies in sera from animals immunized with benzylpenicillin, and from patients following penicillin therapy, has specificity for this determinant. A number of other so-called 'minor' determinants [5,13,15] that make up about 5% of administered penicillin have also been implicated as important IgE-binding structures involved in penicillin-induced immediate allergic reactions in some patients.…”

Section: Reaction Of Penicillins With Ige Antibodies and Identificatimentioning

confidence: 99%

IgE and Drug Allergy: Antibody Recognition of ‘Small’ Molecules of Widely Varying Structures and Activities

Baldo

2014

Antibodies

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Abstract:The variety of chemically diverse pharmacologically-active compounds administered to patients is large and seemingly forever growing, and, with every new drug released and administered, there is always the potential of an allergic reaction. The most commonly occurring allergic responses to drugs are the type I, or immediate hypersensitivity reactions mediated by IgE antibodies. These reactions may affect a single organ, such as the nasopharynx (allergic rhinitis), eyes (conjunctivitis), mucosa of mouth/throat/tongue (angioedema), bronchopulmonary tissue (asthma), gastrointestinal tract (gastroenteritis) and skin (urticaria, eczema), or multiple organs (anaphylaxis), causing symptoms ranging from minor itching and inflammation to death. It seems that almost every drug is capable of causing an immediate reaction and it is unusual to find a drug that has not provoked an anaphylactic response in at least one patient. These facts alone indicate the extraordinary breadth of recognition of IgE antibodies for drugs ranging from relatively simple structures, for example, aspirin, to complex molecules, such as the macrolide antibiotics composed of a large macrocyclic ring with attached deoxy sugars. This wide recognition profile is borne out at the molecular level by results of quantitative immunochemical studies where hapten inhibition investigations have identified structural determinants complementary to IgE antibodies in the sera of allergic subjects. Allergenic determinants have been identified on a variety of drugs including neuromuscular blockers, penicillins, cephalosporins, opioids, thiopentone, sulfonamides, trimethoprim, quinolones, chlorhexidine and the non-steroidal anti-inflammatory drug aspirin. It is already clear that IgE can distinguish fine structural differences on a wide variety of molecules, determinants OPEN ACCESSAntibodies 2014, 3 57 may be at least as small as an amino group or encompass the whole molecule, and individual drugs may demonstrate allergenic heterogeneity.

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“…Historically, while PST panels may vary from institution to institution, the haptens that have generally been used include the major determinant penicilloyl-polylysine and a mixture of minor determinants, including penicilloate, penilloate and penicillin G [6,12]. Gadde et al [6] found that 90% of skin test-positive subjects demonstrated sensitivity to penicilloyl-polylysine, whereas 10% displayed sensitivity to the minor determinants alone.…”

Section: Introductionmentioning

confidence: 99%

Penicillin Allergy: Value of Including Amoxicillin as a Determinant in Penicillin Skin Testing

Lin¹,

Saxon²,

Riedl³

2010

Int Arch Allergy Immunol

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Background: Allergy to penicillins remains an important issue. Penicillin skin testing (PST) with major and minor determinants has been shown to be a highly valuable tool for identifying IgE-mediated penicillin allergy. The value of additional testing with side-chain-specific moieties from semisynthetic penicillins such as amoxicillin is not well-established in spite of the widespread use of these medications. Methods: A retrospective review of all consecutive inpatient PST results from 1995 to 2007 comprising 1,068 patients was performed in our institution on individuals with a self-reported history of beta-lactam allergy to assess the importance of including the amoxicillin determinant in a previously validated PST panel. Descriptive statistics were performed. The PST panel included penicilloyl-polylysine, penicillin G, penicilloate, penilloate and amoxicillin. Results: Of 1,068 patients, 243 (23%) had a positive skin test reaction on the PST panel. Testing with amoxicillin was positive in 30.9% of patients, the majority of whom (81%) were also positive to 1 or more standard penicillin reagents. Fourteen of the 243 positive patients (5.8%) had a positive skin test reaction only to amoxicillin. Additionally, the use of penicilloate and penilloate minor determinants in combination with penicillin G identified a greater percentage of penicillin-allergic individuals compared to using only penicillin G (22.6 vs. 6.6%), demonstrating their importance in the PST panel. Conclusions: These data indicate that the inclusion of the amoxicillin determinant appears to identify a small but important group of allergic individuals who may otherwise test negative on a PST panel.

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Minor Haptenic Determinant-Specific Reagins of Penicillin Hypersensitivity in Man

Cited by 143 publications

References 13 publications

Idiosyncratic Adverse Drug Reactions: Current Concepts

Idiosyncratic Adverse Drug Reactions: Current Concepts

IgE and Drug Allergy: Antibody Recognition of ‘Small’ Molecules of Widely Varying Structures and Activities

Penicillin Allergy: Value of Including Amoxicillin as a Determinant in Penicillin Skin Testing

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