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Published on: October 14, 2021
Similar Molecular Features in Two Cases of CARD14-Associated Papulosquamous Eruption
Yumeng Wang1,2,3, Bing Wang1,2,3, Jiawen Chen1,2,3
1Dermatology Center, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Insights
CARD14 gene variants are linked to psoriasis and pityriasis rubra pilaris (PRP). This study identified new CARD14 variants in two CAPE cases, revealing distinct inflammatory patterns and epidermal changes.
Area of Science:
- Dermatology
- Genetics
- Immunology
Background:
- CARD14 variants are associated with papulosquamous conditions like psoriasis and PRP.
- CARD14-associated papulosquamous eruption (CAPE) presents with overlapping clinical features of both diseases.
- Understanding the genetic and molecular basis of CAPE is crucial for diagnosis and treatment.
Purpose of the Study:
- To diagnose two cases of CAPE.
- To investigate the underlying pathogenic mechanisms of CAPE, focusing on inflammatory markers and epidermal differentiation.
- To explore differential features and potential therapeutic targets.
Main Methods:
- Whole-exome sequencing and Sanger sequencing were used to identify CARD14 variants.
- Analysis of inflammatory markers (IL-17A, IL-23A) in skin lesions and serum.
- Histopathological examination of skin lesions to assess epidermal differentiation and signaling pathways (NF-κB).
Main Results:
- A novel CARD14 variant (c.2768T>C) and a recurrent variant (c.467T>C) were identified in two unrelated CAPE patients.
- Both patients exhibited incomplete penetrance of CARD14 variants.
- Increased IL-17A in skin lesions (not serum) and aberrant epidermal differentiation with active NF-κB signaling were observed.
- One patient showed increased serum IL-23A.
Conclusions:
- Genetic variants in CARD14 are confirmed in CAPE, with novel and recurrent mutations identified.
- Localized IL-17A elevation in skin lesions may explain treatment resistance to certain therapies.
- Aberrant epidermal differentiation and NF-κB activation are key pathogenic features of CAPE.
Abstract:
Subjects carrying variants in the caspase recruitment domain family member 14 (CARD14) gene can exhibit characteristics of psoriasis and pityriasis rubra pilaris (PRP). The term 'CARD14-associated papulosquamous eruption (CAPE)' is used to describe individuals presenting with symptoms of both conditions. This study aimed to diagnose two cases of CAPE and explore the pathogenic mechanisms, including inflammatory trends and differential features. Whole-exome sequencing and Sanger sequencing identified a novel variant, c.2768T>C and a recurrent variant, c.467T>C, in CARD14 in two unrelated individuals, both exhibiting incomplete penetrance. Both of patients exhibited increased IL-17A in skin lesions, but not in serum, potentially explaining the reported cases with low response rate to secukinumab. One patient also exhibited increased IL-23A in serum. Additionally, the epidermis of lesions showed aberrant late differentiation and active NF-κB signalling.
