Transcriptomic responses of peripheral blood mononuclear cells to cyclosporin and etanercept in a female infant with juvenile generalized pustular psoriasis

Abstract

Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis. An early onset of the diseases is correlated with mutations among IL36RN, CARD14, AP1S3, MPO and SERPINA3 genes. Systemic biological agents including anti‐TNF‐α, anti‐IL‐17, anti‐IL‐12/IL‐23, anti‐IL1R, anti‐IL1β and anti‐IL‐36R act as novel treatment methods for GPP. Herein we report a female infant clinically diagnosed with GPP since she was 10‐month‐old. Results of whole‐exome sequencing (WES) and Sanger sequencing revealed a reported heterozygous IL36RN (c.115+6T>C) and another reported heterozygous SERPINA3 frame‐shifting variant (c.1247_1248del). Initial cyclosporin treatment for the patient led to a partial remission of the symptoms. However, the patient reached nearly total remission of pustules and erythema after anti‐TNF‐α inhibitor etanercept treatment. Results of further RNA sequencing (RNA‐seq) done on peripheral blood mononuclear cells correlated with the clinical responses, showing that cyclosporin suppressed a portion of the neutrophil‐related genes, while most genes associated with neutrophil activation, neutrophil‐mediated immunity and degranulation were downregulated by the subsequent etanercept treatment. We report this case to demonstrate WES and RNA‐seq in combination could come in handy in reaching a precise diagnosis and in evaluating or even predicting the molecular alterations underlying clinical treatment effectiveness.

Characteristics of co-existing psoriatic plaques in generalized pustular psoriasis patients with or without IL36RN mutation

“…CARD14-associated papulosquamous eruption (CAPE) shared features of psoriasis and pityriasis rubra pilaris, which is typi ed by thin plaques [8]. It is also possible for a single GPP patient carrying two pathogenic genes [9].…”

Understanding generalized pustular psoriasis for improved patient care

“…Case series and reports included in this special issue highlight the diverse clinical phenotypes of GPP and underscore the importance of individualized care. They address challenges in accurate diagnosis, explore potential treatments and emphasize the need for medication review to identify potentially triggering agents 7–11 …”