Enhanced CCR9 expression levels in psoriatic skin are associated with poor clinical outcome to infliximab treatment

Abstract

Infliximab is an anti-tumor necrosis factor (TNF)-α antibody drug that suppresses TNF-α and its associated inflammatory responses. Although infliximab therapy generally results in a 75% or greater improvement in the Psoriasis Area and Severity Index from baseline in psoriasis patients, there is the heterogeneity of therapeutic efficacy in psoriasis patients among patients of a similar PASI baseline score. However, there are few published reports about the predictors of the clinical response among psoriasis patients who undergo biologic therapies. We thus evaluated the possible existence of biologic markers that would indicate poor prognosis of infliximab using skin biopsy specimens. This was because we assumed that the inhibitors for upregulated chemokine/chemokine receptors in non-responders may have the ability to reduce the occurrence of psoriatic eruptions. PCR array analyses identified that the levels of various chemokines and chemokine receptors were increased in non-responders in comparison to responders. Immunohistochemical analyses revealed that upregulation of the CCR9 protein levels was not associated with the pretherapeutic PASI score, but with poor response to infliximab. Our results indicated that the expression levels of CCR9 in lesional skin may be a useful biologic marker of the clinical efficacy of infliximab therapy in psoriasis patients.