long-term ß-lactam antibiotic are the cornerstone for management of respiratory exacerbations, but unfortunately their application is restricted due to delayed-type hypersensitivity reactions. Reactions develop at a higher frequency when compared to the general population (greater than 30% of adult patients with cystic fibrosis experience hypersensitivity) (1, 2). Patients present with rashes, fixed drug eruptions, arthralgia and drug fevers. antibiotics interact with and bind covalently to specific lysine residues on protein β-lactam generating an antigen that may activate cellular immune responses in susceptible patients. We have recently focused on three commonly used drugs in patients with cystic fibrosis, piperacillin, meropenem and aztreonam and found that each forms a distinct haptenic structure on albumin resulting in activation of drug-specific CD4+ T-lymphocytes isolated from hypersensitive patients (3-5). T-cell cross-reactivity with the different drugs was not observed. The absence of detectable drug-specific T-cells in tolerant patients exposed to several drug courses suggests that T-cells are directly involved in the disease pathogenesis. Drug protein adducts might also activate B-cells promoting hapten-specific immunoglobulin production (6-8). Once activated B-cells differentiate they are able to acquire a memory phenotype characterized by expression of cell surface receptors such as CD27+ (9). Memory B-cells reside primarily in peripheral blood and secrete immunoglobulin following to antigen. activation of memory B-cells following mitogen or In vitro antigen stimulation can be visualized using an IgG ELIspot or increases in CD27 expression (10, 11). Antigen-specific memory B-cells can be detected in the presence or absence ex vivo of circulating serum IgG; hence, it is important to measure memory B-cell activation alongside serum antibodies to obtain a more detailed analysis of the antigen-specific humoral immune response.
long-term ß-lactam antibiotic are the cornerstone for management of respiratory exacerbations, but unfortunately their application is restricted due to delayed-type hypersensitivity reactions. Reactions develop at a higher frequency when compared to the general population (greater than 30% of adult patients with cystic fibrosis experience hypersensitivity) (1, 2). Patients present with rashes, fixed drug eruptions, arthralgia and drug fevers. β-lactam antibiotics interact with and bind covalently to specific lysine residues on protein generating an antigen that may activate cellular immune responses in susceptible patients. We have recently focused on three commonly used drugs in patients with cystic fibrosis, piperacillin, meropenem and aztreonam and found that each forms a distinct haptenic structure on albumin resulting in activation of drug-specific CD4+ T-lymphocytes isolated from hypersensitive patients (3-5). T-cell cross-reactivity with the different drugs was not observed. The absence of detectable drug-specific T-cells in tolerant patients exposed to several drug courses suggests that T-cells are directly involved in the disease pathogenesis. Drug protein adducts might also activate B-cells promoting hapten-specific immunoglobulin production (6-8). Once activated B-cells differentiate they are able to acquire a memory phenotype characterized by expression of cell surface receptors such as CD27+ (9). Memory B-cells reside primarily in peripheral blood and secrete immunoglobulin following to antigen. In vitro activation of memory B-cells following mitogen or antigen stimulation can be visualized using an IgG ELIspot or increases in CD27 expression (10, 11). Antigen-specific memory B-cells can be detected ex vivo in the presence or absence of circulating serum IgG; hence, it is important to measure memory B-cell activation alongside serum antibodies to obtain a more detailed analysis of the antigen-specific humoral immune response.
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