Anna Sysa-Jędrzejowska

Chloroquine treatment influences proinflammatory cytokine levels in systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex pathogenesis. Published data have revealed that serum levels of proinflammatory cytokines are increased in SLE patients. The aim of our study was to evaluate whether monotherapy with chloroquine phosphate affects IL- 1β, IL-6, IL-18 and TNF-α serum levels in SLE patients. The study group consisted of 25 SLE patients with mild or moderate disease activity and 25 age- and sex-matched healthy control subjects. In SLE patients the cytokine levels were measured just before and three months after starting chloroquine treatment at a dose of 125 mg twice daily. Although the majority of SLE patients had a low systemic lupus activity measure (SLAM) index, the levels of IL-6, IL-18 and TNF-α were significantly higher than in the control group. After three-months of chloroquine therapy the mean level of IL-6, IL-18 and TNF-α decreased significantly. Minimal erythema doses (MEDs) were significantly increased in SLE patients after three months of chloroquine therapy. The results indicate that chloroquine treatment lowers some proinflammatory cytokines and may provide a photoprotective effect.

Vitamin D effects in atopic dermatitis

BACKGROUND Because vitamin D has immunomodulatory properties and immunologic mechanisms play a role in the pathogenesis of atopic dermatitis (AD), it is possible that vitamin D may influence the activity of AD. OBJECTIVE The aim of the study was to correlate vitamin D concentrations in patients who had AD with clinical, immunologic, constitutional, and environmental factors, and to determine if vitamin D supplementation affects the clinical manifestations of AD. METHODS Clinical and laboratory parameters of 95 patients with AD and 58 control subjects were measured. Severity of AD was assessed with the SCORAD index. RESULTS The mean serum concentration of 25(OH)D3 in patients with AD was not statistically different from control subjects. The frequency of bacterial skin infections was higher in patients with AD who had lower 25(OH)D₃ levels. No statistical associations between vitamin D levels and other multiple laboratory and clinical parameters were found. After supplementation both mean objective SCORAD and SCORAD index were significantly lower (P < .05). LIMITATIONS All study patients were Caucasians and only one supplemental vitamin D dose and treatment duration were assessed. CONCLUSION The results from this study indicate that vitamin D supplementation may help ameliorate clinical signs of the disease and can be considered as a safe and well-tolerated form of therapy.

Vitamin D status in systemic lupus erythematosus patients and its association with selected clinical and laboratory parameters

Objectives: To identify relationships between vitamin D serum levels and the presence of autoantibodies directed against vitamin D and levels of interleukin(IL)-17 and IL-23 in patients with systemic lupus erythematosus (SLE). Methods: The study included 49 patients with SLE. Serum concentrations of 25(OH)D3 were measured with electrochemiluminescence immunoassay (ECLIA). Enzyme-linked immunosorbent assays (ELISA) were used to determine antibodies directed against 1,25(OH)2D3 and levels of IL-17 and IL-23 in serum of SLE patients. In evaluation of vitamin D status, the control group consisted of 49 age and gender matched healthy individuals, whereas in assessment of anti-vitamin D antibodies the control group comprised 30 sera from blood donors. Results: Serum concentration of 25(OH)D3 in SLE patients during the warm season was 18.47 ± 9.14 ng/ml, which was significantly decreased as compared with that of the control group – 31.27 ± 12.65 ng/ml (p = 0.0005). During the cold season a trend toward lower concentration of 25(OH)D3 in SLE patients was revealed; however, it did not reach statistical significance (11.71 ± 7.21 ng/ml vs. 16.01 ± 8.46 ng/ml; p = 0.054). Results within the recommended range for vitamin D (30–80 ng/ml; 70–200 nmol/l) were observed only in three patients. The 25(OH)D3 concentration was decreased in SLE patients with renal disease or leucopenia as compared with the levels in patients who did not have either problem (p = 0.006 and p = 0.047, respectively). The cold season was found to be a risk factor for vitamin D deficiency (<20 ng/ml) (odds ratio = 9.25; p = 0.005). Autoantibodies directed against 1,25(OH)2D3 were detected in three SLE patients. No significant difference in 25(OH)D3 serum concentrations was found between SLE patients with and without these autoantibodies. No link was shown between the existence of autoantibodies against 1,25(OH)2D3 and clinical or laboratory findings, including IL-17 and IL-23 levels. However, serum concentrations of IL-23 were lower in patients with vitamin D deficiency (p = 0.037). Conclusions: SLE patients, especially those with leucopenia or renal involvement, are at high risk of vitamin D deficiency and require vitamin D supplementation. Some SLE patient sera contained 1,25(OH)2D3 antibodies, but these antibodies do not appear to affect vitamin D levels.

Quality of life and satisfaction with life in SLE patients—the importance of clinical manifestations

To assess the correlation between quality of life (QoL) and satisfaction with life (SL) in SLE patients and correlate both with clinical symptoms of the disease. The study was performed in 83 patients. QoL was assessed by Short Form 36, and SL was assessed by the Satisfaction with Life Scale. Clinical manifestations presented at the time of examination were taken into consideration. SLE patients assessed their QoL and SL as rather low. Those with photosensitivity as well as neurological symptoms presented lower QoL in particular domains, while those with renal manifestation of SLE assessed their QoL as higher. Similar observations were made for SL only in relation to neurological symptoms. Moreover, our findings show that although SL is a part of QoL, both these parameters should be distinguished in order to fully assess the state of the patient.

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.

Effect of chloroquine phosphate treatment on serum MMP-9 and TIMP-1 levels in patients with systemic lupus erythematosus

Antimalarials are widely used for the treatment of systemic lupus erythematosus. However, their mechanisms of action have not been fully elucidated. Literature data indicate that matrix metalloproteinases may play a role in the immune response and tissue damage that occur in autoimmune skin diseases. The aim of this study was to determine the effect of 3 months of chloroquine treatment on serum levels of MMP-9 and TIMP-1 in patients with systemic lupus erythematosus. The study group consisted of 25 patients with systemic lupus erythematosus and 25 sex- and age-matched healthy volunteers. Before drug administration, serum levels of MMP-9 and TIMP-1 were determined by enzyme-linked immunosorbent assay. The same procedure was performed after chloroquine treatment. We found significantly higher median serum levels of MMP-9 in patients with systemic lupus erythematosus before therapy (57.20 ng/ml) when compared with controls (44.50 ng/ml) (p < 0.001). After chloroquine therapy the median MMP-9 serum level of systemic lupus erythematosus patients decreased significantly (43 ng/ml; p < 0.001). Before treatment the median TIMP-1 serum level in the patients with systemic lupus erythematosus was significantly higher than in the control group (500 vs. 200 ng/ml; p < 0.001), and after therapy it increased significantly (750 ng/ml TIMP-1; p < 0.001). The results suggest that chloroquine treatment may affect the matrix metalloproteinase network, and this effect may contribute to the immunoregulatory and anti-inflammatory properties of antimalarials.

Lupus vulgaris: report of two cases

Although there has been a steady decline in the incidence of tuberculosis in recent years, it persists in some regions, and where AIDS is especially prevalent, the number of new cases has been increasing. 1–3 Thus, cutaneous tuberculosis has re‐emerged in areas with a high incidence of HIV infection and multidrug‐resistant pulmonary tuberculosis. Lupus vulgaris has been and remains the most common form of cutaneous tuberculosis. 1 Cutaneous manifestations of disseminated tuberculosis are unusual, being seen in less than 0.5% of cases. 4 Scrofuloderma, tuberculosis verrucosa cutis and lupus vulgaris comprise most cutaneous tuberculosis cases. 2

Circulating angiogenesis inhibitor endostatin and positive endothelial growth regulators in patients with systemic lupus erythematosus

Serum concentrations of three angiogenic cytokines: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-18 (IL-18) and antiangiogenic factor endostatin in the serum of 52 patients with systemic lupus erythematosus (SLE) and 20 healthy subjects were investigated. The possible association between serum levels of these proteins and SLE activity as well as correlation between the concentrations of angiogenic cytokines and the level of endostatin was also analyzed. VEGF and IL-18 were detectable in all SLE patients and healthy control group. bFGF was measurable in 71.2% of patients with SLE and 65% of healthy persons. Endostatin was detectable in 94.2% of SLE patients and 95% of normal subjects. The serum levels of endostatin and bFGF were not significantly different in SLE and healthy control (P > 0.05). The median concentration of VEGF was higher in active SLE (238.4pg/ml) than in inactive disease (118.1pg/ml, P < 0.05) or in control group (133.5pg/ml, P < 0.04). The median serum level of IL-18 was higher in the SLE patients (595.2pg/ml) than in the control group (252.7pg/ml) (P < 0.001). The correlations between the levels of angiogenic cytokines and endostatin with clinical features, laboratory abnormalities and also with the type of treatment were analysed. We found a positive correlation between VEGF serum concentration and SLE activity according to SLAM score (r=0.275, P < 0.05). The significant positive correlation was also found between IL-18 and endostatin (r=0.289, P < 0.04). In contrast, the correlation between bFGF and endostatin was significantly negative (r=7 0.299, P < 0.04). In conclusion, serum levels of the angiogenic and antiangiogenic factors may play an important role in SLE pathogenesis.

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.

The influence of antimalarial treatment on IL-1β, IL-6 and TNF-α mRNA expression on UVB-irradiated skin in systemic lupus erythematosus

Background  There are very few data addressing the mechanisms of antimalarial treatment benefit locally within the skin of patients with lupus erythematosus, at the level of cytokine messenger RNA (mRNA) expression.