title: In vivo effects of horse and rabbit antithymocyte globulin in patients with severe aplastic anemia.
abstract: 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.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD fengx2@nhlbi.nih.gov.
authors.forename: Xingmin
authors.initials: X
authors.lastname: Feng
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Phillip
authors.initials: P
authors.lastname: Scheinberg
authors.affiliation: Center for Human Immunology, Autoimmunity, and Inflammation, National Institutes of Health, Bethesda, MD.
authors.forename: Angelique
authors.initials: A
authors.lastname: Biancotto
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Olga
authors.initials: O
authors.lastname: Rios
authors.affiliation: Washington University School of Medicine, St. Louis, MO.
authors.forename: Sarah
authors.initials: S
authors.lastname: Donaldson
authors.affiliation: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Colin
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Statistics, the George Washington University, Washington, DC.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sato
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Townsley
authors.affiliation: Center for Human Immunology, Autoimmunity, and Inflammation, National Institutes of Health, Bethesda, MD Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: J Philip
authors.initials: JP
authors.lastname: McCoy
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D006736:Horses; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D011817:Rabbits; D012720:Severity of Illness Index; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D000961:Antilymphocyte Serum; D016207:Cytokines; D007166:Immunosuppressive Agents