We recently reported that
rabbit antithymocyte globulin was markedly inferior to horse
antithymocyte globulin as a primary treatment for severe
aplastic anemia. Here we expand on our findings in this unique cohort of patients.
Rabbit antithymocyte globulin was detectable in plasma for longer periods than horse
antithymocyte globulin;
rabbit antithymocyte globulin in plasma retained functional capacity to bind to lymphocytes for up to 1 month, horse
antithymocyte globulin for only about 2 weeks. In the first week
after treatment there were much lower numbers of neutrophils in patients treated with
rabbit antithymocyte globulin than in patients receiving horse
antithymocyte globulin. Both
antithymocyte globulins induced a "
cytokine storm" in the first 2 days after administration. Compared with horse
antithymocyte globulin,
rabbit antithymocyte globulin was associated with higher levels of
chemokine (C-C motif)
ligand 4 during the first 3 weeks. Besides a much lower absolute number and a lower relative frequency of CD4(+) T cells,
rabbit antithymocyte globulin induced higher frequencies of CD4(+)CD38(+), CD3(+)CD4(-)CD8(-) T cells, and B cells than did horse
antithymocyte globulin.
Serum sickness occurred around 2 weeks after infusion of both types of
antithymocyte globulin. Human anti-
antithymocyte globulin antibodies, especially of the
IgM subtype, correlated with
serum sickness, which appeared concurrently with clearance of
antithymocyte globulin in blood and with the production of
cytokines. In conclusion, rabbit and horse
antithymocyte globulins have very different pharmacokinetics and effects on neutrophils, lymphocyte subsets, and
cytokine release. These differences may be related to their efficacy in suppressing the immune system and restoring hematopoiesis in
bone marrow failure. Clinicaltrials.gov identifier: NCT00260689.