Autoantibodies to thrombopoietin and the thrombopoietin receptor in patients with immune thrombocytopenia

Summary Autoantibodies to thrombopoietin ( TPO , also termed THPO ) or the TPO receptor ( cM pl, also termed MPL ) could play a pathological role in immune thrombocytopenia ( ITP ). In this study, we tested for autoantibodies against TPO , cM pl, or the TPO / cM pl complex in ITP and other thrombocytopenic disorders. Using an inhibition step with excess TPO in fluid‐phase to improve binding specificity, the prevalence of anti‐ TPO autoantibodies was: active ITP : 9/32 (28%); remission ITP : 0/14 (0%); non‐immune thrombocytopenias: 1/10 (10%); and healthy controls: 1/11 (9%). Similarly, using an inhibition step with excess cM pl, the prevalence of specific anti‐ cM pl autoantibodies was: active ITP : 7/32 (22%); remission ITP : 1/14 (7%); non‐immune thrombocytopenias: 3/10 (30%); and healthy controls: 0/11 (0%). Two active ITP patients had autoantibodies against the TPO / cM pl complex, but not against TPO or cM pl alone. Anti‐ TPO or anti‐ cM pl autoantibodies were found in 44% of ITP patients, and in 40% of patients with other thrombocytopenic disorders. These autoantibodies did not correlate with ITP disease severity or number of ITP treatments received; however, in this cohort, 3 patients failed to respond to TPO receptor agonist medications, and of those, 2 had anti‐ TPO autoantibodies. This suggests that anti‐ TPO and anti‐ cM pl autoantibodies are associated with thrombocytopenia, and may be clinically relevant in a subset of ITP patients.