Susceptibility to UVB Light in Cultured Keratinocytes of Cutaneous Lupus erythematosus

Furukawa, Fukumi; Kanauchi, Hideo; Imamura, Sadao

doi:10.1159/000246922

Cited by 24 publications

(14 citation statements)

References 13 publications

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“…The cytotoxicity of cultured keratinocytes was significantly higher in cells from LE patients and normal adult controls than from neonatal foreskins when the viability was determined 24 h after UVB (100 mJ/cm 2 ) irradiation (Table 1); this was compatible with our previous report [14]. Among the cells cultured from patients and adult controls, cells from SLE patients were the highest in cytotoxicity ( P < 0.001 versus cells from adult controls), and the cytotoxicity in cells from SCLE and DLE was significantly higher than that from adult controls (0.001 < P < 0.01).…”

Section: Resultssupporting

confidence: 91%

“…The binding of these antibodies on the keratinocytes is dependent on UVB dose and glycosylation, but independent of the cell cycle [10]. In addition, we have previously shown that the binding of anti‐SS‐A/Ro antibodies to the surface of epidermal cells is an important inducer of antibody‐dependent keratinocyte damage in photosensitive cutaneous LE [14]. These experiments are mostly performed by using cultured keratinocytes from normal human foreskins.…”

Section: Introductionmentioning

confidence: 99%

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Keratinocytes from patients with lupus erythematosus show enhanced cytotoxicity to ultraviolet radiation and to antibody-mediated cytotoxicity

Furukawa

Itoh

Wakita

et al. 1999

Clinical and Experimental Immunology

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SUMMARYKeratinocyte cytotoxicity is an important component of the immunopathology of photosensitive lupus erythematosus, and antibody-dependent cell-mediated cytotoxicity (ADCC) has been shown to be an important mechanism by which autoantibodies, especially those specific for SS-A/Ro, can induce keratinocyte damage in models of photosensitive lupus. We provide further evidence that keratinocytes from patients with photosensitive lupus show significantly greater ultraviolet radiation (UVR)-induced cytotoxicity, and that ADCC of these targets is especially enhanced by autologous patient's serum or by anti-SS-A/Ro þ sera. Keratinocytes from normal uninvolved skin of 29 patients with cutaneous lupus erythematosus (LE) were grown in cell culture and tested as targets in cytotoxicity experiments in vitro. Cultured keratinocytes from patients with systemic lupus erythematosus (SLE) and subacute cutaneous lupus erythematosus (SCLE) showed significantly greater cytotoxicity following UVR treatment than did keratinocytes from normal adult controls or from neonatal foreskins (P < 0·01). The same cultures also showed greater UVR-induced binding of IgG from fractionated anti-SS-A/Ro þ preparations. ADCC experiments were also performed using keratinocytes cultured from patients with SLE, SCLE, discoid lupus erythematosus (DLE), and normal controls. When keratinocytes were incubated in autologous serum plus a standard mononuclear cell effector population, the percentage of ADCC observed was significantly greater in cultures containing keratinocytes and sera from the SLE and SCLE patients (P < 0·001). When cultured keratinocytes were added to different IgG antibody probes, plus standard mononuclear effector populations, greater ADCC was seen using the anti-SS-A/Ro probe and keratinocytes from patients with SLE or SCLE. With normal human neonatal keratinocyte targets, the anti-SS-A/Ro probe induced greater ADCC than that seen with anti-ssDNA or normal human serum. We have shown that keratinocytes from patients with some forms of lupus erythematosus (SLE and SCLE) show greater cytotoxicity in vitro when irradiated with UVR, and greater susceptibility to ADCC whether the antibody source is their own serum or an anti-SS-A/Ro probe.

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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Keratinocytes from patients with lupus erythematosus show enhanced cytotoxicity to ultraviolet radiation and to antibody-mediated cytotoxicity

Furukawa

Itoh

Wakita

et al. 1999

Clinical and Experimental Immunology

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“…The usage of this kind of monoespecific sera has many disadvantages, like 1) not being completely representative of a SAP's patient 2) having the monoespecificity tested against only a few well-known autoantigens and 3) the usage of serum instead of pure Aabs, implying that other antibodies (not tested in the "monoespecificity assay") could be present in those monoespecific sera and interacting with the irradiated keratinocytes. Those assays were also performed on patients' own keratinocytes, and it has been shown that keratinocytes from cutaneous LE patients showed a higher susceptibility to a singledose UVB light irradiation compared to keratinocytes from normal controls, and that the binding of Aabs was more up-regulated when cultured keratinocytes were reacted with autologous sera [29]. Anyhow, experiments were always performed using sera and we suggest that, according to our results, there might be other Aabs implicated in the pathogenesis of CP that are not essentially anti-Ro Aabs, and that those Aabs could be the anti-Sm ones, due to the fact that we-and also other authors- [24,27,43] have previously found a statistically significant direct positive association between CP and high reactivity anti-Sm Aabs.…”

Section: Discussionmentioning

confidence: 99%

“…Anyhow, beyond all this controversy the actual mechanism which triggers CP has not been fully elucidated yet, though the relationship between CP and anti-Ro/SS-A Aabs has been studied focusing on different aspects. These include the expression of autoantigens in the skin [28], the presence of certain Aabs [21] and also the relation with apoptotic cell death induced by UVr [29], but the study of the above mentioned association using purified anti-Ro/SS-A Aabs has been poorly explored.…”

Section: Introductionmentioning

confidence: 99%

Two Approaches to the Study of a Controversial Relationship: Cutaneous Photosensitivity and Anti-Ro/SS-A Autoantibodies

Paz¹,

Maiten²,

Ferrari³

et al. 2014

OJRA

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Background: Autoantibodies (Aabs) are the hallmark of numerous systemic autoimmune pathologies (SAPs), for instance anti-Ro/SS-A Aabs are usually found in Systemic Lupus Erythematosus (SLE) and Sjögren's Syndrome. Cutaneous photosensitivity (CP) is found in most forms and subsets of LE and consists of a skin rash as a result of unusual reaction to sunlight. There are many theories which relate specifically the presence of circulating antiRo/SS-A Aabs with the CP phenomenon, though there are several studies which are in disagreement. Results: In this study we analyzed the relationship between CP and anti-Ro Aabs by means of two approaches. The first one included an in vitro model where we evaluated by flow cytometry the binding capacity of affinity-purified Aabs to autoantigens relocalized on apoptotic keratinocyte's surface. We found that there was no relationship between the binding capacity of serum from 10 selected patients or their corresponding purified anti-Ro52 and anti-Ro60 Aabs, and the presence or absence of CP, neither with the SAPs. The in vivo model consisted of Hairless SKH:1 mice which were induced to produce anti-murine Ro52 and/or Ro60 Aabs and were subsequently irradiated with UVB light. We evaluated the skin histology and also the epidermal production of TNF-α. We found no differences between the groups in neither of the parameters evaluated. Conclusions: These results agree with some studies on the role of the Aabs in CP, considering anti-Ro Aabs not as the only responsible for the manifestation; and disagree with many other authors, who believe in the strong association between these two events.

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“…Subacute cutaneous lupus erythematosus and NLE have been proposed as models for ADCC of keratinocytes (93,103,104), in which antibodies to Ro induced keratinocyte cytotoxicity mediated by macrophage and/or lymphocyte effectors (105). Although keratinocyte cytotoxicity is observed in the epidermis in both DLE and SCLE, it is unknown whether these cells are dying by apoptosis or necrosis.…”

Section: The Spectrum Of Photosensitive Lupusmentioning

confidence: 99%

The Influence of Ultraviolet Light on Immunological Cytotoxicity in the Skin

Norris

Whang²,

David-Bajar

et al. 1997

Photochem & Photobiology

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Susceptibility to UVB Light in Cultured Keratinocytes of Cutaneous Lupus erythematosus

Cited by 24 publications

References 13 publications

Keratinocytes from patients with lupus erythematosus show enhanced cytotoxicity to ultraviolet radiation and to antibody-mediated cytotoxicity

Keratinocytes from patients with lupus erythematosus show enhanced cytotoxicity to ultraviolet radiation and to antibody-mediated cytotoxicity

Two Approaches to the Study of a Controversial Relationship: Cutaneous Photosensitivity and Anti-Ro/SS-A Autoantibodies

The Influence of Ultraviolet Light on Immunological Cytotoxicity in the Skin

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