Mass spectrometric characterization of circulating and functional antigens derived from piperacillin in patients with cystic fibrosis.

نویسندگان

  • Paul Whitaker
  • Xiaoli Meng
  • Sidonie N Lavergne
  • Sabah El-Ghaiesh
  • Manal Monshi
  • Caroline Earnshaw
  • Daniel Peckham
  • Jimmy Gooi
  • Steve Conway
  • Munir Pirmohamed
  • Rosalind E Jenkins
  • Dean J Naisbitt
  • B Kevin Park
چکیده

A mechanistic understanding of the relationship between the chemistry of drug Ag formation and immune function is lacking. Thus, mass spectrometric methods were employed to detect and fully characterize circulating Ags derived from piperacillin in patients undergoing therapy and the nature of the drug-derived epitopes on protein that can function as an Ag to stimulate T cells. Albumin modification with piperacillin in vitro resulted in the formation of two distinct haptens, one formed directly from piperacillin and a second in which the dioxopiperazine ring had undergone hydrolysis. Modification was time and concentration dependent, with selective modification of Lys(541) observed at low concentrations, whereas at higher concentrations, up to 13 out of 59 lysine residues were modified, four of which (Lys(190), Lys(195), Lys(432), and Lys(541)) were detected in patients' plasma. Piperacillin-specific T lymphocyte responses (proliferation, cytokines, and granzyme B release) were detected ex vivo with cells from hypersensitive patients, and analysis of incubation medium showed that modification of the same lysine residues in albumin occurred in situ. The antigenicity of piperacillin-modified albumin was confirmed by stimulation of T cells with characterized synthetic conjugates. Analysis of minimally modified T cell-stimulatory albumin conjugates revealed peptide sequences incorporating Lys(190), Lys(432), and Lys(541) as principal functional epitopes for T cells. This study has characterized the multiple haptenic structures on albumin in patients and showed that they constitute functional antigenic determinants for T cells.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Isolation and Genetic Fingerprinting of Pseudomonas aeruginosa from Iranian Patients with Cystic Fibrosis Using RAPD-PCR

Sixty four Iranian patients with cystic fibrosis (CF) were studied for colonization with Pseudomonasaeruginosa. The patient’s age ranged between 2 months to 18 years old. Twenty one patients werecolonized, 15 with non-mucoid and 6 with mucoid strains of P. aeruginosa. The colonization rateincreased with age and the mucoid phenotype was only recovered from the older patients. A...

متن کامل

Genetic Profiling of Pseudomonas aeruginosa Isolates from Iranian Patients with Cystic Fibrosis Using RAPD-PCR and PFGE

Objective(s) Pseudomonas aeruginosa is the most important cause of chronic lung infections and death in patients with cystic fibrosis. Determining the distribution of specific strains within patient populations is important in order to examine the epidemiology of the disease and the possibility of cross infection among patients. Materials and Methods Forty six Iranian patients with cystic fib...

متن کامل

Appendicovesical fistula presenting as a bladder mass in a girl with cystic fibrosis: a case report

Background: Appendicovesical fistula in patients suffering from cystic fibrosis is a rare condition. Although this situation is so rare it should be considered in the differential diagnosis, dealing with a patient with cystic fibrosis and chronic abdominal pain with no response to primary management. To the best of our knowledge, this is the third case of appendicovesical fistula in a patient w...

متن کامل

Antibiotic resistance properties and molecular characterization of Pseudomonas aeruginosa strains from patients with cystic fibrosis (CF) referred to Gholhak Pathobiology Laboratory in Tehran city during 2016-2018

Background and Objectives: Pseudomonas aeruginosa isolates from the lungs of cystic fibrosis (CF) patients are often heterogeneous and antibiotic resistant strains. Our work therefore focused on the antibiotic resistance properties of these P. aeruginosa strains isolated from Iranian patients, as well as the genetic diversity analysis by a repetitive-element-based molecular assay. Methods: This ...

متن کامل

Characterization of the antigen specificity of T-cell clones from piperacillin-hypersensitive patients with cystic fibrosis.

β-Lactam antibiotics provide the cornerstone of treatment and reduce the rate of decline in lung function in patients with cystic fibrosis, but their use is limited by a high frequency of delayed-type allergic reactions. The objective of this study was to use cloned T-cells expressing a single T-cell receptor from five piperacillin-hypersensitive patients to characterize both the cellular patho...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of immunology

دوره 187 1  شماره 

صفحات  -

تاریخ انتشار 2011