Autoimmune disorders (AID) are chronic conditions that involve the loss of immunological
tolerance to self-antigens, and result in systemic or tissue-specific damage. Current
treatment regimens for AID are often nonspecific and involve long-term administration
of immunosuppressive agents such as corticosteroids, calcineurin inhibitors, and cytotoxic
chemotherapeutics [
[1]
]. While effective, these medications render the patient vulnerable to opportunistic
infections, as well as increasing long-term risk of secondary malignancy [
[2]
]. The optimal treatment for AID would achieve several goals, including targeting the
pathogenic immune cells while leaving the remaining immune system functional, reestablishing
immune tolerance that leads to reduction or discontinuation of other therapies, and
would have low toxicity with few side effects [
[3]
]. Extracorporeal photopheresis (ECP) is a leukapheresis-based immunomodulatory therapy
developed in the 1980 s and is predominantly used in the treatment of erythrodermic
cutaneous T-cell lymphoma, as well as immune-mediated complications of transplantation
such as acute and chronic graft-versus-host disease, cardiac allograft rejection,
and bronchiolitis obliterans syndrome [
[4]
]. Though the exact mechanism remains unclear, the immunomodulatory effects achieved
by ECP suggest a rationale for its use in AID. During ECP, peripheral blood mononuclear
cells (PBMCs) are collected by apheresis, incubated with the photosensitizing agent
8-methoxypsoralen (8-MOP), and exposed to UVA (320–400 nm), resulting in irreversible
crosslinking of DNA and subsequent apoptosis. While only 5–10% of circulating PBMCs
are treated at each session and undergo cell death, it is the downstream immunomodulatory
effects of ECP that are thought to confer the majority of benefits in ECP. Apoptotic
cells then undergo phagocytosis by immature dendritic cells (DCs), stimulating development
of a tolerogenic phenotype that improves peripheral tolerance [
[5]
]. Cytokine profiles are also affected, with tolerogenic DCs producing increased levels
of the anti-inflammatory cytokine IL-10 [
[6]
], and increased secretion of TGF-β through the interaction with antigen presenting
cells with apoptotic leukocytes [
[7]
]. Other immunological changes achieved through ECP therapy include a restoration of
Th1/Th2 balance[
[8]
] and normalization of the CD4/CD8 ratio [
[9]
]. Additionally, ECP is associated with a significant increase in the activity of T-regulatory
cells (Tregs), and a corresponding reduction in the production of T-helper 17 cells, a pro-inflammatory
T-cell subset named for the proinflammatory cytokine IL-17, which induces chemokine
production that recruits monocytes and neutrophils [
[10]
]. Activation of IL-17 signaling is observed in some AID, such as psoriasis [
[11]
], while others such as systemic lupus erythematosus (SLE), inflammatory bowel disease
(IBD), and rheumatoid arthritis (RA) are associated with decreased levels of Tregs [
12
,
13
,
14
]. Therefore, decreased IL-17 signaling, increased Tregs, restoration of Th1/Th2 balance, an enhanced anti-inflammatory cytokine profile,
and induction of peripheral tolerance may all explain the potential benefits of ECP
in the treatment of AID. The current American Society for Apheresis (ASFA) Guidelines
include twelve indications for ECP, six of which are autoimmune conditions. All are
Category III conditions, with variable levels of supporting evidence [
[4]
].To read this article in full you will need to make a payment
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Publication history
Published online: February 24, 2023
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© 2023 Published by Elsevier Ltd.
