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.