CLIC1 Expression in Skin Biopsies from Patients With Rheumatoid and Psoriatic Arthritis as a Potential Tool to Predict Therapy Response

Abstract

Background/Aim: Chloride intracellular channel protein 1 (CLIC1) activates inflammasomes in rheumatoid (RA) and psoriatic (PsA) arthritis. We studied CLIC1 expression in RA and PsA patients' skin with vasculitis and its variability depending on the therapy used. Materials and Methods: CLIC1 immunoexpression was evaluated in the vascular (CLIC1-V) and stromal (CLIC1-S) compartments of the RA and PsA skin biopsies of patients treated with methotrexate (MTX), leflunomid (LFN), corticotherapy (CT), or biological therapies. Results: MTX significantly reduced CLIC1-S expression (p=0.016), whereas LFN decreased CLIC1-V (p<0.001). LFN therapy duration also correlated with CLIC1-V (p<0.001). CT decreased CLIC1-S expression (p=0.006). CLIC1-S expression persisted in skin biopsies despite of erythrocyte sedimentation rate (ESR, p=0.018) and C reactive protein (CRP, p=0.0026) normalisation. For PsA, CLIC1-S expression significantly related to MTX (p<0.022). Both CLIC1-S (p<0.001) and CLIC1-V (p=0.007) decreased by biological therapies in RA. Conclusion: CLIC1 expression is strongly influenced by the therapy used. Our data strongly support the extensive evaluation of CLIC1 in RA as a potential marker of inflammation and tool to predict therapy response.Chloride intracellular channel protein 1 (CLIC1) is a member of the CLICs family, and one of the most conserved proteins (1). It was first cloned due to its increased expression in activated macrophages (2). CLIC1, also known as NCC27, has an early and variable expression in human fetal tissues, and is found in low levels in human fetal brain but in high levels in the human fetal lung, kidney, and liver (3). During human adult life, expression variability persists among most human tissues (4). The intracellular chloride channels are membrane bound and participate in different pathological processes including inflammation associated with neurodegenerative diseases (5)atherosclerosis (6) ankylosing spondylitis (7) tumor progression, and metastasis of urinary bladder cancer (8) renal cell carcinomas (9) or hepatocellular carcinomas (10). CLIC1 has a high translocation ability between the cytoplasmic and nuclear compartments depending on the functional status and based on this translocation; CLIC1 functions are extremely versatile (11). These versatile functions of chloride channels such as CLIC1 include the regulation of cellular metabolism by acting at the 2559 This article is freely accessible online.

Targeting inflammasome-dependent mechanisms as an emerging pharmacological approach for osteoarthritis therapy

“… 37 High CLIC1 expression in the skin from PsA was involved with increased angiogenesis and might suggest NLRP3 involvement in increased angiogenesis of PsA joints. 38 …”

The Mutually Mediated Chloride Intracellular Channel Protein 1 (CLIC1) Relationship between Malignant Cells and Tumor Blood Vessel Endothelium Exhibits a Significant Impact on Tumor Angiogenesis, Progression, and Metastasis in Clear Cell Renal Cell Carcinoma (ccRCC)

“…In terms of CLIC1 expression in the blood vessel endothelium, our team reported its variability in the inflammatory triggered angiogenic endothelium from non-malignant conditions, such as rheumatoid and psoriatic arthritis, where vascular CLIC1 expression was highly influenced by therapy, as well as by the interrelationship with other stromal components [ 38 ]. For the present study, the capsular and subcapsular vessels with tumor emboli inside were frequently associated with an extensive inflammatory infiltrate, sometimes organized as a tertiary lymphoid tissue.…”

Age, Sex, Metabolic and Pharmacologic Factors May Predict Nonresponse Status to Rheumatoid Arthritis Therapies

“…There are limited studies on the prediction of primary or secondary nonresponse status using demographic, clinical, or psycho-social factors (11). Furthermore, there is a limited number of studies examining other parameters, such as body mass index (BMI), therapy duration, age, or microscopic changes (12)(13)(14). For example, there are only eight studies examining the influence of BMI on the efficacy of certain therapies for RA (15)(16)(17)(18)(19)(20)(21)(22).…”