Extracorporeal photopheresis (ECP) involves the reinfusion of autologous peripheral blood lymphocytes rendered apoptotic by in vitro exposure to psoralen and ultraviolet A light. Antigenic determinants presented by apoptotic lymphocytes, primarily T cells, elicit immunomodulatory responses that have shown therapeutic benefit in several conditions, including cutaneous T-cell lymphoma, graft-versus-host disease, and various inflammatory/autoimmune disorders. We treated with ECP a 41-year-old woman diagnosed with cutaneous lupus erythematosus and concomitant hypercholesterolemia, achieving a marked improvement of skin lesions. A study in hypercholesterolemic apolipoprotein E-deficient mice demonstrated that immunization with syngeneic apoptotic thymocytes, a process mimicking ECP, induced the production of IgM antibodies against oxidized low-density lipoproteins (OxLDL) that attenuated atherosclerosis. Thus, we explored whether ECP could similarly induce anti-OxLDL antibodies in our patient. Indeed, over the course of a 14-week ECP treatment we observed a steady increase in circulating IgM antibodies against malondialdehyde-modified LDL, a class of antibodies known to confer atheroprotection in preclinical models. Additionally, we documented an increase in circulating regulatory T cells, which are recognized as suppressing pro-atherogenic immune responses. These findings support the translational potential of a preclinical atheroprotection model and provide a proof of concept for clinical trials evaluating ECP in autoimmune diseases associated with accelerated atherosclerosis, where achieving dual benefits, clinical improvement and reduced cardiovascular risk, may be feasible.
Martini et al. (Fri,) studied this question.