title: CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis.
abstract: Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP) that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7), also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics.
authors.affiliation: Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Mott
authors.forename: Alan H
authors.initials: AH
authors.lastname: Lazarus
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D001168:Arthritis / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D018960:Hyaluronan Receptors / Q000276:immunology*; D051379:Mice; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000150:complications / Q000276:immunology*; D013922:Thrombocytosis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors