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Amoxicillin And Tlr Agonists Increase The Maturation Of Dendritic Cells From Patients With Non-immediate Allergy To Betalactams
Abstracts AB197
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2
Different Patterns Of IgE Recognition To Amoxicillin In Patients With Immediate Hypersensitivity Reactions A. Ariza1, C. Mayorga1, I. Do~na2, F. Gomez2, E. Perez-Inestrosa3, M. I. Monta~ nez3, J. L. Rodriguez-Bada1, M. A. Guerrero2, M. Blanca2, M. J. Torres2; 1Research Laboratory F-IMABIS, Malaga, SPAIN, 2Allergy Service, Carlos Haya Hospital, Malaga, SPAIN, 3Organic Chemistry Department, Chemistry University, Malaga, SPAIN. RATIONALE: The optimal recognition of penicillin determinants, including amoxicillin, by specific IgE antibodies requires a covalent binding to a carrier molecule. The nature of the carrier and its contribution to the antigenic determinant is not well known. The aim of this study was to evaluate the recognition of different amoxicillin structures by specific IgE antibodies in patients with immediate hypersensitivity reactions. METHODS: Patients (N521) with immediate hypersensitivity reactions to amoxicillin and positive radioallergosorbent test (RAST) were included. RAST was done using benzylpenicillin and amoxicillin bound to poly-Llysine (BPO-PLL and AXO-PLL). RAST inhibition assays used AXOPLL in the solid phase and amoxicillin, amoxicilloic acid, amoxicillin bound to butilamine (AXO-BA), human serum albumin (AXO-HSA) and dendrimers (AXO-DN) in the fluid phase. RESULTS: We observed two clear defined patterns of IgE recognition: A) Cases (N58) with a higher recognition to free amoxicillin being lower to amoxicilloic acid, AXO-BA, AXO-HSA and AXO-DN; B) Cases (N513) which recognize both free and conjugated amoxicillin in similar degree with low recognition to amoxicilloic acid. Group A corresponds to patients with RAST only positive to AXO-PLL and Group B to those positive to BPO-PLL and AXO-PLL. CONCLUSIONS: These results seems to indicate that IgE recognition is influenced by the binding and nature of the carrier molecule (Group A), with others mainly recognizing the amoxicillin structure independently of the nature of the carrier (Group B). The fact that amoxicilloic acid is not optimally recognized in Group B reinforced the need of conjugation to a carrier in this group of patients.
756
Desensitization to Temozolomide H. Mhanna, A. Jimenez Blanco, M. Valdez Tejeda, K. Jukic Beteta, M. Sanchez Gonzalez, C. Fernandez Rodriguez, R. Vives Conesa; Hospital 12 de Octubre, Madrid, SPAIN. RATIONALE: To evaluate the effectiveness of a desensitization protocol to Temozolomide in patients who have allergic symptoms during treatment. MATERIAL AND METHODS: Three patients diagnosed with malignant gliomas (2 men/1 woman, Age range: 35-65 years), presented generalized pruritus and urticaria lesions without other associated symptoms during treatment with Temozolomide. They were treated with corticosteroids and antihistamines with good response. An oral desensitization protocol was performed with an initial dose of 5mg of Temozolomide, increasing it every 30 minutes up to a cumulative therapeutic dose with a total time of administration up to 3 hours. For the next 4 days they daily took a unique dose of Temozolomide PREMEDICATION: Methylprednisolone, Ranitidine, Cetirizine and montelukast, was administrated the night before and 30 min before the begin of the desensitization protocol, also before each diary dose of Temozolomide for the next 4 days of treatment. RESULTS: The protocol of desensitization was a success. Our patients continued with this dose to fulfil the total of 20 courses of treatment with no symptoms. CONCLUSIONS: Desensitization is shown to be safe and effective for patients with adverse reactions to Temozolomide.
757
Amoxicillin And Tlr Agonists Increase The Maturation Of Dendritic Cells From Patients With Non-immediate Allergy To Betalactams S. Lopez1, M. J. Torres2, M. J. Sanchez3, E. Gomez3, A. B. Blazquez3, C. Rondon2, M. A. Guerrero2, M. Blanca2, C. Mayorga3; 1Fundacion IMABIS, Malaga, SPAIN, 2Carlos Haya Hospital, Malaga, SPAIN, 3Fundacion IMABIS-Carlos Haya Hospital, Malaga, SPAIN. RATIONALE: Dendritic cells (DC) are antigen-presenting cells that express toll like receptors (TLR) involved in the maturation process. Amoxicillin and heparins have showed to induce DC maturation in allergic patients to these drugs, although in lower levels. We wanted to analyze whether the combination of amoxicillin with TLR agonists could amplify the DC maturation and trigger T cell response in allergic patients. METHODS: We studied 9 patients with a non-immediate reaction to amoxicillin and 11 tolerant controls. Monocytes-derived-DC were cultured with amoxicillin with/without TLR4, 7, 8 and 9 agonists. For proliferation assays, lymphocytes were cultured with DC at the same combination as above. Studies of the DC maturational status, lymphocyte transformation test (LTT) and cytokines secretions were performed by flow cytometry. RESULTS: In patients, the combination of amoxicillin plus TLR4 and 8 agonists induced higher maturation and higher positivity of LTT than with them alone. The cytokine production in DC after stimulation with amoxicillin, TLR4 or TLR8 agonists showed a Th1 pattern in all of then being lowest in amoxicillin-stimulated-DC. In the LTT, amoxicillin induced a Th0/1 pattern whereas the combination of amoxicillin with TLR4 or TLR8 agonists induced an increase in the Th1 cytokine production being stronger than those produced by each molecule alone. We did not observe any change with TLR7 or TLR9 agonists. CONCLUSIONS: These results show that amoxicillin in combination to TLR4 or TLR8 agonists boost the DC maturation and the specific response towards a Th1 response in patients with non-immediate reaction to this drug.
758
Skin And Drug Provocation Tests In The Diagnosis Of NonImmediate Hypersensitivity Reactions To Iodinated Contrast Media M. J. Torres1, F. Gomez1, A. Rosado2, I. Do~na1, N. Blanca-Lopez3, M. D. Ca~namero1, L. Melendez4, G. Canto3, M. Blanca1; 1Carlos Haya Hospital, Malaga, SPAIN, 2Alcorcon Hospital, Madrid, SPAIN, 3Infanta Leonor Hospital, Madrid, SPAIN, 4Fundacion IMABIS-Carlos Haya Hospital, Malaga, SPAIN. RATIONALE: The frequency of non-immediate hypersensitivity reactions to iodinated contrast media (CM) have increased, and they are usually diagnosed by skin testing. The aim of the study was to evaluate the role of skin testing and drug provocation test (DPT) in the diagnosis of patients with non-immediate reactions to CM. METHODS: Patients (N578) with non-immediate hypersensitivity reactions with skin involvement after CM administration were studied. Intradermal and patch testing with delayed readings were done with different CM (Iobitridol, Iomeprol, Iodixanol, Iohexol, Ioversol, Iopramide and Ioxaglate). If skin-test negative, DPT was done. A skin biopsy was done in patients with positive skin tests and positive DPT. RESULTS: Fifteen subjects (19.2%) had positive delayed intradermal skin tests to at least 1 CM (Iomeprol in 9 cases, Iodixanol in 3, Iobitidol in 2, Ioxaglate in 2, Iopramide in 1 and Iohexol in 1). DPT was done in the 63 patients with negative skin tests, with 22 (34.9%) developing 25 positive episodes to DPT (19 to Iodixanol, 4 to Iomeprol and 2 to Iohexol). We were able to confirm the diagnosis in 37 (47.4%) of the patients evaluated, 40.5% by skin testing and 59.4% by DPT. Considering Iodixanol and Iomeprol, the two most common CM used in our population, Iodixanol was diagnosed significantly more often by DPT. CONCLUSIONS: Skin-test sensitivity with CM is lower than previously thought, with just 40% of the patients being positive; DPT was required in the other 60%. Skin-test sensitivity seems to depend on the CM used and was less with Iodixanol.
MONDAY
755
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2
Different Patterns Of IgE Recognition To Amoxicillin In Patients With Immediate Hypersensitivity Reactions A. Ariza1, C. Mayorga1, I. Do~na2, F. Gomez2, E. Perez-Inestrosa3, M. I. Monta~ nez3, J. L. Rodriguez-Bada1, M. A. Guerrero2, M. Blanca2, M. J. Torres2; 1Research Laboratory F-IMABIS, Malaga, SPAIN, 2Allergy Service, Carlos Haya Hospital, Malaga, SPAIN, 3Organic Chemistry Department, Chemistry University, Malaga, SPAIN. RATIONALE: The optimal recognition of penicillin determinants, including amoxicillin, by specific IgE antibodies requires a covalent binding to a carrier molecule. The nature of the carrier and its contribution to the antigenic determinant is not well known. The aim of this study was to evaluate the recognition of different amoxicillin structures by specific IgE antibodies in patients with immediate hypersensitivity reactions. METHODS: Patients (N521) with immediate hypersensitivity reactions to amoxicillin and positive radioallergosorbent test (RAST) were included. RAST was done using benzylpenicillin and amoxicillin bound to poly-Llysine (BPO-PLL and AXO-PLL). RAST inhibition assays used AXOPLL in the solid phase and amoxicillin, amoxicilloic acid, amoxicillin bound to butilamine (AXO-BA), human serum albumin (AXO-HSA) and dendrimers (AXO-DN) in the fluid phase. RESULTS: We observed two clear defined patterns of IgE recognition: A) Cases (N58) with a higher recognition to free amoxicillin being lower to amoxicilloic acid, AXO-BA, AXO-HSA and AXO-DN; B) Cases (N513) which recognize both free and conjugated amoxicillin in similar degree with low recognition to amoxicilloic acid. Group A corresponds to patients with RAST only positive to AXO-PLL and Group B to those positive to BPO-PLL and AXO-PLL. CONCLUSIONS: These results seems to indicate that IgE recognition is influenced by the binding and nature of the carrier molecule (Group A), with others mainly recognizing the amoxicillin structure independently of the nature of the carrier (Group B). The fact that amoxicilloic acid is not optimally recognized in Group B reinforced the need of conjugation to a carrier in this group of patients.
756
Desensitization to Temozolomide H. Mhanna, A. Jimenez Blanco, M. Valdez Tejeda, K. Jukic Beteta, M. Sanchez Gonzalez, C. Fernandez Rodriguez, R. Vives Conesa; Hospital 12 de Octubre, Madrid, SPAIN. RATIONALE: To evaluate the effectiveness of a desensitization protocol to Temozolomide in patients who have allergic symptoms during treatment. MATERIAL AND METHODS: Three patients diagnosed with malignant gliomas (2 men/1 woman, Age range: 35-65 years), presented generalized pruritus and urticaria lesions without other associated symptoms during treatment with Temozolomide. They were treated with corticosteroids and antihistamines with good response. An oral desensitization protocol was performed with an initial dose of 5mg of Temozolomide, increasing it every 30 minutes up to a cumulative therapeutic dose with a total time of administration up to 3 hours. For the next 4 days they daily took a unique dose of Temozolomide PREMEDICATION: Methylprednisolone, Ranitidine, Cetirizine and montelukast, was administrated the night before and 30 min before the begin of the desensitization protocol, also before each diary dose of Temozolomide for the next 4 days of treatment. RESULTS: The protocol of desensitization was a success. Our patients continued with this dose to fulfil the total of 20 courses of treatment with no symptoms. CONCLUSIONS: Desensitization is shown to be safe and effective for patients with adverse reactions to Temozolomide.
757
Amoxicillin And Tlr Agonists Increase The Maturation Of Dendritic Cells From Patients With Non-immediate Allergy To Betalactams S. Lopez1, M. J. Torres2, M. J. Sanchez3, E. Gomez3, A. B. Blazquez3, C. Rondon2, M. A. Guerrero2, M. Blanca2, C. Mayorga3; 1Fundacion IMABIS, Malaga, SPAIN, 2Carlos Haya Hospital, Malaga, SPAIN, 3Fundacion IMABIS-Carlos Haya Hospital, Malaga, SPAIN. RATIONALE: Dendritic cells (DC) are antigen-presenting cells that express toll like receptors (TLR) involved in the maturation process. Amoxicillin and heparins have showed to induce DC maturation in allergic patients to these drugs, although in lower levels. We wanted to analyze whether the combination of amoxicillin with TLR agonists could amplify the DC maturation and trigger T cell response in allergic patients. METHODS: We studied 9 patients with a non-immediate reaction to amoxicillin and 11 tolerant controls. Monocytes-derived-DC were cultured with amoxicillin with/without TLR4, 7, 8 and 9 agonists. For proliferation assays, lymphocytes were cultured with DC at the same combination as above. Studies of the DC maturational status, lymphocyte transformation test (LTT) and cytokines secretions were performed by flow cytometry. RESULTS: In patients, the combination of amoxicillin plus TLR4 and 8 agonists induced higher maturation and higher positivity of LTT than with them alone. The cytokine production in DC after stimulation with amoxicillin, TLR4 or TLR8 agonists showed a Th1 pattern in all of then being lowest in amoxicillin-stimulated-DC. In the LTT, amoxicillin induced a Th0/1 pattern whereas the combination of amoxicillin with TLR4 or TLR8 agonists induced an increase in the Th1 cytokine production being stronger than those produced by each molecule alone. We did not observe any change with TLR7 or TLR9 agonists. CONCLUSIONS: These results show that amoxicillin in combination to TLR4 or TLR8 agonists boost the DC maturation and the specific response towards a Th1 response in patients with non-immediate reaction to this drug.
758
Skin And Drug Provocation Tests In The Diagnosis Of NonImmediate Hypersensitivity Reactions To Iodinated Contrast Media M. J. Torres1, F. Gomez1, A. Rosado2, I. Do~na1, N. Blanca-Lopez3, M. D. Ca~namero1, L. Melendez4, G. Canto3, M. Blanca1; 1Carlos Haya Hospital, Malaga, SPAIN, 2Alcorcon Hospital, Madrid, SPAIN, 3Infanta Leonor Hospital, Madrid, SPAIN, 4Fundacion IMABIS-Carlos Haya Hospital, Malaga, SPAIN. RATIONALE: The frequency of non-immediate hypersensitivity reactions to iodinated contrast media (CM) have increased, and they are usually diagnosed by skin testing. The aim of the study was to evaluate the role of skin testing and drug provocation test (DPT) in the diagnosis of patients with non-immediate reactions to CM. METHODS: Patients (N578) with non-immediate hypersensitivity reactions with skin involvement after CM administration were studied. Intradermal and patch testing with delayed readings were done with different CM (Iobitridol, Iomeprol, Iodixanol, Iohexol, Ioversol, Iopramide and Ioxaglate). If skin-test negative, DPT was done. A skin biopsy was done in patients with positive skin tests and positive DPT. RESULTS: Fifteen subjects (19.2%) had positive delayed intradermal skin tests to at least 1 CM (Iomeprol in 9 cases, Iodixanol in 3, Iobitidol in 2, Ioxaglate in 2, Iopramide in 1 and Iohexol in 1). DPT was done in the 63 patients with negative skin tests, with 22 (34.9%) developing 25 positive episodes to DPT (19 to Iodixanol, 4 to Iomeprol and 2 to Iohexol). We were able to confirm the diagnosis in 37 (47.4%) of the patients evaluated, 40.5% by skin testing and 59.4% by DPT. Considering Iodixanol and Iomeprol, the two most common CM used in our population, Iodixanol was diagnosed significantly more often by DPT. CONCLUSIONS: Skin-test sensitivity with CM is lower than previously thought, with just 40% of the patients being positive; DPT was required in the other 60%. Skin-test sensitivity seems to depend on the CM used and was less with Iodixanol.
MONDAY
755