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Pyrazolones metabolites are relevant for identifying selective anaphylaxis to metamizole.

Ariza A, García-Martín E, Salas M, Montañez MI, Mayorga C, Blanca-Lopez N, Andreu I, Perkins J, Blanca M, Agúndez JA, Torres MJ - Sci Rep (2016)

Bottom Line: Sensitivity of in vitro diagnostic tests is low and this may be due to the incomplete characterization of the structures involved.We studied subjects with confirmed selective immediate hypersensitivity to metamizole and performed BAT with metamizole and its metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4-acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA).BAT results showed an increase of positive results from 37.5% to 62.5% using metamizole plus metabolites as compared with the BAT carried out only with the parent drug, demonstrating that metamizole metabolites have a role in the reaction and can induce specific basophil activation in patients with immediate hypersensitivity to this drug.

View Article: PubMed Central - PubMed

Affiliation: Research Laboratory, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain.

ABSTRACT
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of hypersensitivity reactions, with pyrazolones the most frequent drugs inducing selective reactions. Immediate selective hypersensitivity to pyrazolones is thought to be mediated by specific-IgE. Sensitivity of in vitro diagnostic tests is low and this may be due to the incomplete characterization of the structures involved. Here we investigated whether main metabolites of metamizole (dipyrone) in human could be involved in the immune response using the basophil activation test (BAT). We studied subjects with confirmed selective immediate hypersensitivity to metamizole and performed BAT with metamizole and its metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4-acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA). BAT results showed an increase of positive results from 37.5% to 62.5% using metamizole plus metabolites as compared with the BAT carried out only with the parent drug, demonstrating that metamizole metabolites have a role in the reaction and can induce specific basophil activation in patients with immediate hypersensitivity to this drug. Our findings indicate that pyrazolone metabolites are useful for improving the in vitro diagnosis of allergic reactions to metamizole.

No MeSH data available.


Related in: MedlinePlus

Results of basophil activation inhibition with wortmannin (WTM) after stimulation with 4-methylamino antipyrine (MAA) or positive controls (anti-IgE and fMLP).Bars show the mean value of stimulation index obtained for non-inhibited and WTM inhibited basophil activation. Significant differences (p < 0.05) are indicated in the graph.
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f4: Results of basophil activation inhibition with wortmannin (WTM) after stimulation with 4-methylamino antipyrine (MAA) or positive controls (anti-IgE and fMLP).Bars show the mean value of stimulation index obtained for non-inhibited and WTM inhibited basophil activation. Significant differences (p < 0.05) are indicated in the graph.

Mentions: We tried to confirm the involvement of specific IgE by using a PI3-K inhibitor, WTM. BAT inhibition with WTM was performed with samples from four positive patients to MAA and found a mean percentage of inhibition of basophil activation of 73.96% for MAA and of 85.16%, for the positive control anti-IgE. As expected, no significant inhibition was observed with the positive control N-formyl-Met-Leu-Phe (fMLP), which is a positive control of non-mediated IgE basophil activation (Fig. 4).


Pyrazolones metabolites are relevant for identifying selective anaphylaxis to metamizole.

Ariza A, García-Martín E, Salas M, Montañez MI, Mayorga C, Blanca-Lopez N, Andreu I, Perkins J, Blanca M, Agúndez JA, Torres MJ - Sci Rep (2016)

Results of basophil activation inhibition with wortmannin (WTM) after stimulation with 4-methylamino antipyrine (MAA) or positive controls (anti-IgE and fMLP).Bars show the mean value of stimulation index obtained for non-inhibited and WTM inhibited basophil activation. Significant differences (p < 0.05) are indicated in the graph.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814906&req=5

f4: Results of basophil activation inhibition with wortmannin (WTM) after stimulation with 4-methylamino antipyrine (MAA) or positive controls (anti-IgE and fMLP).Bars show the mean value of stimulation index obtained for non-inhibited and WTM inhibited basophil activation. Significant differences (p < 0.05) are indicated in the graph.
Mentions: We tried to confirm the involvement of specific IgE by using a PI3-K inhibitor, WTM. BAT inhibition with WTM was performed with samples from four positive patients to MAA and found a mean percentage of inhibition of basophil activation of 73.96% for MAA and of 85.16%, for the positive control anti-IgE. As expected, no significant inhibition was observed with the positive control N-formyl-Met-Leu-Phe (fMLP), which is a positive control of non-mediated IgE basophil activation (Fig. 4).

Bottom Line: Sensitivity of in vitro diagnostic tests is low and this may be due to the incomplete characterization of the structures involved.We studied subjects with confirmed selective immediate hypersensitivity to metamizole and performed BAT with metamizole and its metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4-acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA).BAT results showed an increase of positive results from 37.5% to 62.5% using metamizole plus metabolites as compared with the BAT carried out only with the parent drug, demonstrating that metamizole metabolites have a role in the reaction and can induce specific basophil activation in patients with immediate hypersensitivity to this drug.

View Article: PubMed Central - PubMed

Affiliation: Research Laboratory, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain.

ABSTRACT
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of hypersensitivity reactions, with pyrazolones the most frequent drugs inducing selective reactions. Immediate selective hypersensitivity to pyrazolones is thought to be mediated by specific-IgE. Sensitivity of in vitro diagnostic tests is low and this may be due to the incomplete characterization of the structures involved. Here we investigated whether main metabolites of metamizole (dipyrone) in human could be involved in the immune response using the basophil activation test (BAT). We studied subjects with confirmed selective immediate hypersensitivity to metamizole and performed BAT with metamizole and its metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4-acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA). BAT results showed an increase of positive results from 37.5% to 62.5% using metamizole plus metabolites as compared with the BAT carried out only with the parent drug, demonstrating that metamizole metabolites have a role in the reaction and can induce specific basophil activation in patients with immediate hypersensitivity to this drug. Our findings indicate that pyrazolone metabolites are useful for improving the in vitro diagnosis of allergic reactions to metamizole.

No MeSH data available.


Related in: MedlinePlus