IFN-β causes a direct drug-induced TMA in multiple sclerosis patients. Recombinant IFN-β therapy causes a microangiopathy affecting multiple organs in multiple sclerosis patients. (A-B) Magnetic resonance imaging brain scan shows multiple small new lesions consistent with recent microvascular ischemia, identified on diffusion-weighted sequences (white arrows). (C) Admission blood film showing fragmented red blood cells (black arrows). (D) Hematoxylin and eosin stain of renal biopsy from patient shows pathological microvascular changes with endothelial swelling, luminal narrowing, and trapped red blood cells (black arrow; bar represents 25 μm). (E) Patients who developed TMA, including patients from an independent cohort,⁷  received a higher weight-adjusted dose than unaffected multiple sclerosis patients treated with the same IFN-β preparation. *P < .001, Student t test. (F) All UK reports of TMA associated with IFN-β are associated with IFN-β1a dose >50 μg/wk, and 92% are associated with the highest available dose (n = 15 reports). (G-H) Evidence of activation of IFN response in renal biopsy of affected patient (H: MxA immunohistochemistry, red; bar represents 10 μm), with biopsy from patient with TMA not associated with IFN (G: genetic atypical hemolytic uremic syndrome [HUS]) for comparison.