Apoptotic signal molecules in skin biopsies of cutaneous lupus erythematosus: analysis using tissue microarray

Abstract

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease. Different pathogenetic mechanisms, including the accumulation of apoptotic keratinocytes in CLE, have been reported. Therefore, we investigated whether CLE and other inflammatory skin diseases differ with regard to the epidermal expression of molecules that are crucial for the initiation and regulation of apoptosis. In this study, 241 skin biopsies from patients with CLE, psoriasis (PSO), lichen planus (LP) and healthy controls (HCs) were analysed immunohistochemically using the tissue microarray (TMA) technique. The TUNEL assay and anti-activated caspase-3 antibodies revealed a significant increase of apoptotic keratinocytes in CLE lesions compared with HCs. Furthermore, we detected a significant increase in the epidermal expression of CD95 in CLE specimens compared with PSO, LP and HCs. These data suggest that the accumulation of apoptotic keratinocytes in CLE might be due to the increased epidermal expression of CD95, resulting in increased activity of the extrinsic apoptotic pathway in the disease.

Apoptosis of keratinocytes and serum DNase I activity in patients with cutaneous lupus erythematosus: relationship with clinical and immunoserological parameters

“…18,19 Previous reports have found extensive apoptosis in nearly all the epidermis in CLE patients, with the exception of LE profundus 11 and higher apoptotic index (AI) in more acute forms of LE (subacute CLE (SCLE) and acute CLE (ACLE). 18 Toberer et al 21 found a significant increase in the TUNEL-and antiactivated caspase-3-positive keratinocytes in CLE and suggested an increased activity of the extrinsic apoptotic pathway in CLE.…”

Eradication of damaged keratinocytes in cutaneous lichen planus forms demonstrated by evaluation of epidermal and follicular expression of CK15, indices of apoptosis and regulatory protein S100

“…Analysis of the literature data on the TUNEL evaluations suggests that a higher number of apoptotic keratinocytes was demonstrated in LP compared with healthy controls, but lower when LP is compared with other inflammatory diseases (psoriasis and cutaneous lupus erythematosus) [74,75,76]. Our findings regarding psoriatic skin samples studied are in accordance with the aforementioned literature data suggesting that psoriasis is characterized by aberrant differentiation and arrest of natural apoptotic process; to some extent, TUNEL positivity can be associated with hyperproliferation, in which actively replicating DNA is more abundant or accessible to detection.…”

Cutaneous lupus erythematosus: updates on pathogenesis and associations with systemic lupus

“…UV induces keratinocyte apoptosis, inflammatory cytokine production, and autoantigen exposure [23]. CLE lesions highly express Fas (CD95), which activates the extrinsic apoptotic pathway [24]. It is unclear whether UV drives enhanced apoptosis in lupus vs. control skin as two studies addressing this question have disparate findings[25, 26].…”