Joanna Narbutt

The Effect of Chronic Ultraviolet Radiation on the Human Immune System

A single or a limited number of UVR exposures is recognized to suppress cell‐mediated immunity in human subjects. The complex pathway leading from the absorption of photons by chromophores in the skin to the generation of T regulatory cells has been, at least partially, elucidated. However, the effect of repeated UV exposures on immune responses and associated mediators is not well studied, particularly to assess whether they lead, first, to the development of photoprotection so that these immune changes are reduced or no longer occur, and, secondly, to the development of photoprotection against the normal downregulation of immunity induced by a high UV dose. For almost all the parameters evaluated in this review—epidermal DNA damage/erythema, urocanic acid, Langerhans and dendritic cells, natural killer cells, macrophages, mast cells, contact and delayed hypersensitivity responses—none, aside from epidermal DNA damage/erythema and macrophage phagocytic activity, show convincing evidence of photoadaptation or, where appropriate, photoprotection. It is concluded that repeatedly irradiating individuals with UVR is likely to continue to result in downregulation of immunity.

Combined occurrence of filaggrin mutations and IL‐10 or IL‐13 polymorphisms predisposes to atopic dermatitis

Background:  Although filaggrin mutations are presently believed to play a key role in the development of atopic dermatitis (AD), obviously also immunological factors involved in acquired immune response are important for the development of allergic inflammation.

Estimation of SLE activity based on the serum level of chosen cytokines and superoxide radical generation

We estimated the serum levels of IL-6, TNF-alpha and IL-10, and generation of superoxide radicals, as well as their mutual dependence, in 63 SLE patients at various stages of disease activity. Our results indicate a statistically significant increase of the serum levels studied, and an increase of superoxide anion generation by granulocytes, in correlation with SLE activity. These results indicate that oxygen metabolism and the examined cytokines play an important role in pathogenesis of SLE. The assessment of these parameters can be useful in the estimation of disease activity.

Repeated low-dose ultraviolet (UV) B exposures of humans induce limited photoprotection against the immune effects of erythemal UVB radiation

Background  Exposure of human subjects to ultraviolet (UV) B radiation causes immunosuppression. Most experiments to date have not tested the effects of low daily doses of UVB radiation.

Long-term results of topical PUVA in necrobiosis lipoidica

The aim of our study was to evaluate the long‐term results of topical psoralen ultraviolet A (PUVA) in patients with necrobiosis lipoidica (NL), in whom conventional methods (pentoxifylline, vitamin E, tretinoin, and topical or intralesional corticosteroids) had failed. The study comprised 10 women (age range 17–44 years), six of whom were insulin‐dependent diabetics and four were diabetes‐free. Duration of NL ranged from 3 to 10 years. The patients were treated with a 0.005% aqueous solution of 8‐methoxypsoralen, applied topically for 30 min, and subsequently irradiated with UVA three times weekly. All the patients experienced almost complete remission (softening of skin lesions, no hyperpigmentation, lack of lesion progression) after a mean of 47 sessions (mean UVA cumulative dose 69.5 J/cm2). They were followed up for 12–24 months, during which time two recurrences, both in diabetic patients, were observed after 8 and 12 months of treatment cessation, which further resolved after another course of topical PUVA. We conclude that topical PUVA is well tolerated by NL patients and may serve as an alternative therapeutic regimen.

The Role of T‐Regulatory Cells and Toll‐Like Receptors 2 and 4 In Atopic Dermatitis

Regulatory T cells (Tregs), toll‐like receptors (TLRs) and interleukin‐17 (IL‐17) play important role in inflammatory diseases; however, their relevance in atopic dermatitis (AD) pathogenesis is not clear. The aim of study was to evaluate the number of circulating Tregs and peripheral blood mononuclear cells (PBMC) expressing TLR2 and TLR4 receptors in patients with AD. PBMC and CD4+/CD25high+ Tregs were isolated from the whole blood of 32 AD patients and 36 healthy volunteers. Expression of CD4+CD25+, TLR2 and TLR4 receptors and IL 17+ was assessed with the flow cytometry. In the peripheral blood of AD patients, the percentage of Tregs was significantly higher when compared with the controls (P = 0.0003). The number of TLR2+PBMC and TLR4+ PBMC in AD patients was significantly lower than in the controls (P = 0.035; P = 0.001, respectively). Also the percentages of Tregs with expression of both TLR2+ and TLR4+ in AD patients were significantly lower than in the control (3.85 versus 21.6, P < 0.0001; 2.2 versus 17.6, P < 0.0001, simultaneously). The percentage of CD4+/CD25high+/FOXP3+ Treg lymphocytes with expression of IL‐17 was significantly higher in AD group than in healthy subjects (0.3% versus 0.06%; P = 0.011). Distinct number of Tregs and various distribution of TLR2 and TLR4 expression on PBMC in AD patients suggest their contribution in the pathogenesis of AD.

Interleukin 6 and 8 Levels in Plasma and Fibroblast Cultures in Psoriasis

Fibroblasts have been implicated in psoriatic inflammatory processes. The aim of the study was to evaluate soluble interleukin 2 receptor (sIL-2R), interleukin 6 (IL-6), and interleukin 8 (IL-8) plasma levels in psoriatic patients and IL-6 and IL-8 levels in fibroblast culture supernatants. Cytokines levels in plasma and supernatants were measured by ELISA. Plasma sIL-2R, IL-6, and IL-8 levels were higher before the treatment in comparison to healthy controls (P < 0.001) and decreased after treatment. Fibroblasts from healthy controls, psoriatic lesional skin, and noninvolved psoriatic skin, when stimulated with tumor necrosis factor alpha, released considerable amounts of IL-6 and IL-8. No significant difference between healthy controls and psoriatic fibroblasts was observed. Monitoring plasma sIL-2R levels could be employed as a reliable method of psoriasis activity. IL-8 and IL-6 plasma levels seem to reflect psoriasis activity, and treatment response, respectively. Fibroblasts are not a major source of increased IL-6 and IL-8 production in psoriasis.

An enhanced risk of basal cell carcinoma is associated with particular polymorphisms in the VDR and MTHFR genes

Background:  Vitamin D and folate are influenced by ultraviolet radiation (UVR), and both are implicated in skin carcinogenesis. Polymorphisms in the genes involved in the metabolism of these two compounds may alter the risk of basal cell carcinoma (BCC).

Serum Concentration of Interleukin-6 Is Increased Both in Active and Remission Stages of Pemphigus Vulgaris

As most studies on pemphigus vulgaris (PV) pathogenesis concern its active stage, we aimed to evaluate the serum concentration of TNF-α, IL-1, and IL-6 in PV patients in clinical remission. The study group consisted of sera from 19 PV patients in active stage and from 24 patients in clinical remission. 19 sera taken from healthy subjects served as the controls. Serum IL-6 concentrations in PV active and PV remission group were significantly higher when compared to the controls (P < .05). In patients in active stage of PV, a significant correlation between serum IL-1 and IL-6 concentrations was found (r P = 0.46; P < .05). We also found a negative correlation between TNF-α level and pemphigus antibodies titer in the patients from the remission group (r S = −0.47303; P < .02). Our data suggest that IL-6 and TNF-α may be involved in maintaining immunological disturbances in remission stage of PV.

Tumour necrosis factor-alpha polymorphism as one of the complex inherited factors in pemphigus.

The aim of our study was to analyse a significance of tumour necrosis factor (TNF)-alpha promoter gene polymorphisms in relation to the HLA-DR locus in genetic predisposition to pemphigus. TNF-alpha gene polymorphisms in position -238 and -308 were identified using a modified polymerase chain reaction-restriction fragment length polymorphism method in 53 patients with pemphigus (38 with pemphigus vulgaris, 15 with pemphigus foliaceus) and 87 healthy controls. The HLA-DRB1 locus was typed using the polymerase chain reaction SSO method in all the patients and 152 population controls. Carriers of the TNF-alpha polymorphic -308 A allele were found to be more frequent in the pemphigus foliaceus group in comparison with the control group (odds ratio (OR) = 8.12; p = 0.0005). A significant association between HLA-DRB1*04 (OR = 3.86; pcor = 0.0001) and DRB1*14 (OR = 8.4; pcor = 0.0001) and pemphigus vulgaris was found. In this group of patients a decreased frequency of HLA-DRB1*07 (OR = 0.08; pcor = 0.006) was also identified. We have shown for the first time a positive association of TNF-alpha polymorphism in position -308 with pemphigus foliaceus.