Mast Cell Carboxypeptidase as a Confirmatory and Predictive Marker in Allergic Reactions to Drugs

RATIONALE: Allergic drug hypersensitivity presents a serious and increasingly common problem in the perioperative setting, but there are few reliable laboratory aids for confirming a reaction has occurred or for evaluating which patients may be susceptible. We have investigated carboxypeptidase, a major product of mast cell activation, as a diagnostic biomarker in drug-induced reactions. METHODS: Blood and saliva were collected from patients with suspected allergic reactions to antibiotics, non-opioid analgesics, opioids and other drugs (n=33) before and following skin prick and intradermal testing with the drug implicated. The severity of reactions elicited following provocation testing as well as on previous occasions was recorded. Levels of carboxypeptidase and also of tryptase and angiotensin converting enzyme (ACE) were determined in samples using specific ELISA techniques. RESULTS: Levels of carboxypeptidase were increased in saliva (but not serum) following a positive reaction in drug challenge (p=0.025). Alterations in levels of the other markers were not observed. Drug allergic patients who experienced symptoms on drug challenge had greater baseline levels of carboxypeptidase in both serum and saliva than in those who were asymptomatic (p=0.022). Baseline carboxypeptidase concentrations in serum were also higher in patients who historically had suffered severe reactions (involving cardiovascular or respiratory compromise) than in those with mild (p=0.0012) or moderate reactions (p=0.004). Associations between symptoms and the corresponding levels of tryptase or ACE were not observed. CONCLUSIONS: High levels of mast cell carboxypeptidase may be helpful in confirming perioperative reactions to drugs, and baseline levels in serum and saliva may be predictive of symptom severity.