Understanding Immune Responses to Surgical Transplant Procedures in Stevens Johnsons Syndrome Patients

Abstract

Stevens Johnsons syndrome (SJS) is a mucocutaneous disorder caused by an autoimmune response most commonly to medications. Unless it is properly managed in the acute setting, this entity can affect the ocular surface causing chronic cicatrizing conjunctivitis with limbal stem cell deficiency and lid anomalies which ultimately result in corneal opacities that may limit patients' visual acuity. When this stage is reached, some patients might need to undergo some form of corneal and/or limbal stem cell transplantation that exposes an already sensitized immune system to a new alloantigen. While the innate immunity plays a role in corneal graft survival, adaptive immune responses play a major part in corneal graft rejection and failure, namely through CD4+ T cell lymphocytes. Hence, the management of the immune response to surgical transplant procedures in SJS patients, involves a dual approach that modulates the inflammatory response to a new alloantigen in the context of an autoimmune sensitized patient. This review will explore and discuss current perspectives and future directions in the field of ocular immunology on how to manage SJS immune responses to ocular surgical procedures, reviewing systemic and local immunosuppressive therapies and protocols to adequately manage this debilitating condition.

Keywords: Stevens Johnsons; corneal transplant; high risk corneal transplantation; immunosuppression; limbal stem cell transplant.

Figure 1

Molecular targets of immunomodulatory medications. Illustration of the mechanism of action and molecular targets of the immunomodulatory agents commonly used in the control of the alloimmune and autoimmune response in Stevens Johnsons Syndrome.

Figure 2

Combination of BET inhibition and T-reg expansion to target immune responses. In response to the presentation of novel antigens, as in the case of an ocular surface transplant, the resident immune cells activate and, through bromodomain-regulated activation of transcription, produce inflammatory cytokines which leads to recruitment of effector cells which carry out non-specific innate immune response. In addition, activated immune cells may also function as antigen presenting cells through MHC-II expression and migrate to draining lymph nodes where activation of antigen specific CD4+ T-cells takes place resulting in cytokine dependent specific immune response activation of the adaptive immune response. Dual therapy using BET-inhibitors mainly targeting the cytokine-dependent innate response along with T-reg expansion therapy targeting the activation of the adaptive response can potentially control immune responses and suppress inflammatory disease. The two modalities have been shown to not interfere with one another and can effectively provide a compound strategy for inflammatory control.