title: Delayed hypersensitivity to aminopenicillins is related to major histocompatibility complex genes.
abstract: BACKGROUND
  Although in some cases delayed hypersensitivity may be observed, beta-lactam antibiotics frequently induce immediate allergic IgE-mediated reactions with the specificity localized in the acyl-side chain structure. Generally, delayed immunologic reactions are related to sensitized T lymphocytes and major histocompatibility complex restricted.
  
  
  OBJECTIVE
  To investigate the prevalence of HLA class I and II antigens in patients with delayed hypersensitivity to aminopenicillins in order to evaluate a relationship between major histocompatibility complex immune response genes and aminopenicillins hypersensitivity.
  
  
  METHODS
  We assessed 24 patients with history of delayed hypersensitivity to aminopenicillins using (1) skin test with penicilloyl polylysine, minor determinant mixture, benzylpenicillin, amoxicillin, and ampicillin; (2) patch tests with benzylpenicillin, amoxicillin, and ampicillin; (3) RAST for penicilloyls G and V; and (4) oral challenges with amoxicillin, ampicillin, and penicillin V in 18/24 patients. All patients were typed by microlymphotoxicity standard test for HLA class I and II antigens. Statistical analysis by chi2 test 2 x 2 contingency tables, according to Svejgaard, were used for comparison between patients and random Italian population (522 subjects).
  
  
  RESULTS
  In the patients group we found higher prevalence of HLA A2 (12/24 = 50%, RR = 6.76 P < .001, EF = 0.425), DRw52 (20/24 = 83.3%, RR = 9.28, P < .001, EF = 0.74), and lower frequency of DR4 (3/24 = 12% ns).
  
  
  CONCLUSIONS
  These data suggest that the immune mechanisms involved in adverse reactions to aminopenicillins in vivo are related to genetic markers of immune response and confirms that the presentation of penicillin-hapten determinants to lymphocyte is major histocompatibility complex restricted.
authors.affiliation: Department of Internal Medicine, Catholic University, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Romano
authors.forename: A
authors.initials: A
authors.lastname: De Santis
authors.forename: A
authors.initials: A
authors.lastname: Romito
authors.forename: M
authors.initials: M
authors.lastname: Di Fonso
authors.forename: A
authors.initials: A
authors.lastname: Venuti
authors.forename: G B
authors.initials: GB
authors.lastname: Gasbarrini
authors.forename: R
authors.initials: R
authors.lastname: Manna
mesh_terms: D000293:Adolescent; D000328:Adult; D000628:Aminophylline / Q000009:adverse effects*; D001993:Bronchodilator Agents / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000209:etiology*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology*; D008285:Major Histocompatibility Complex; D008297:Male; D008875:Middle Aged
chemical_list: D001993:Bronchodilator Agents; D000628:Aminophylline