Practice question

Alemtuzumab humanized IgG1 mAb 150 kDa directed CD52 glycopeptide 21-28 kDa GPI-anchored highly expressed 500k copies normal malignant B T lymphocytes monocytes macrophages eosinophils dendritic cells but absent HSC permitting immune reconstitution after depletion absent neutrophils limiting neutropenia. CD52 function incompletely understood proposed T-costimulation binding Siglec-10 inhibitory modulating migration L-selectin. Binding clusters GPI protein lipid rafts inducing proximity Fc enabling C1q multivalent binding activating classical complement C4 C2 cleavage forming C3 convertase C4b2a opsonizing C3b membrane attack complex C5b-9 osmotic lysis. Simultaneously Fc gamma RI CD64 macrophages Fc gamma RIIIa CD16a NK engage triggering ADCC perforin granzyme B caspase-3 phagocytosis clearing circulating lymphocytes within hours profound lymphopenia <0.1e9/L lasting months >year. Repopulation B cells returning 6 months CD8 12 months CD4 longer regulatory T dominance inducing tolerance. Indications B-CLL previously and relapsing multiple sclerosis as induction immune reset therapy requiring monitoring thyroid autoimmunity due reconstitution aberration and anti-GBM disease risk managed REMS program.