Antithymocyte globulins


Antithymocyte globulins are the preferred treatment for patients with aplastic anemia and in prevention and treatment of renal, cardiac, kidney, and bone marrow graft rejection. Several commercial preparations from different animal serums exist (horse, rabbit, murine).
 
Incidence
Anaphylaxis < 1% of treatments.
 
Risk factors
Allergy to horses, rabbits, or murine species.
 
Clinical manifestations
Anaphylactic shock
 
Bronchospasm, A.R.D.S.
 
Cutaneous eruptions, periorbital edema.
 
Diagnostic methods
Skin tests must be performed before use of antithymocyte globulins in order to detect at-risk patients.
 
Intradermal skin tests give false positive results.
 
Skin prick-tests with dilutions to 1/1000 to pure have a better predictive value.
 
Mechanisms
IgE-mediated hypersensitivity (immediate reactions).
 
Circulating immune complexes (serum sickness).
 
Management
Skin prick-tests must be performed in all patients treated with heterologous antisera.
 
For patients with positive skin prick-tests:
  • use a preparation from other mammalian origin (horse <—> rabbit).
     
  • Desensitization may be performed:

0.02 ml intradermal 5 µg/ml, 50 µg/ml, 500 µg/ml, 5 000 µg/ml at ten minutes intervals then

0.5 ml subcutaneous 50 µg/ml, 100 µg/ml, 300 µg/ml, 1 000 µg/ml,
3 000 µg/ml,
 
5 000 µg/ml at ten minutes intervals then
 
0.5 mg/min, 1 mg/min, 2 mg/min intravenous for ten minutes each with the therapeutic dose of ATG at 15 mg/kg constantly infused over 24 hours.

References

  1. Bielory L, Wright R, Nienhuis A.W, Young N.S, Kaliner M.A, "Antilymphocyte globulin hypersensitivity in bone marrow failure patients", JAMA. 1988; 260 (21): 3164-7
  2. Cunningham E, Chi Y, Brentjens J, Venuto R, "Acute serum sickness with glomerulonephritis induced by antithymocyte globulins", Transplantation. 1987; 43 (2): 309-12
  3. Gartner J, Earl H, Carrington D, Jiang C.L, Sullivan T, "Reactions to antilymphocyte globulins", J. Allergy. Clin. Immunol., 1987; 79 (1): 237

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.