Elżbieta Waszczykowska

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.

Auditory function in patients with systemic lupus erythematosus

OBJECTIVE Patients with systemic lupus erythematosus (SLE) may develop hearing and balance disorders as a result of the immune-mediated inner ear damage due to vasculitis or ototoxicity of drugs used in SLE treatment. The aim of the study was evaluation of the hearing organ disorders in patients with SLE with particular regard to their prevalence and relationship to duration and severity of disease. The severity was assessed from involvement of organs that resulted in poorer SLE outcome, i.e. kidneys and central nervous system (CNS), and from the presence of antibodies associated with unfavourable SLE prognosis. METHODS Thirty-five unselected, consecutive patients (33 women, two men, mean age 47.8 years) with SLE diagnosed in compliance to the international diagnostic criteria of the American Rheumatism Association (1982) were enrolled into the study. The control group consisted of 30 otologically healthy persons matched to the SLE group for age and sex. Case history was recorded for all patients from questionnaire data and laryngological examinations were performed, followed by pure-tone, speech and impedance audiometry and auditory brainstem response audiometry (ABR). RESULTS In the anamnesis 71.4% of patients reported vertigo, 62.9% headaches, 40% tinnitus, 25.7% hyperacusis, 17.1% hearing loss and 2.9% ear fullness. It was found that SLE patients had a significantly poorer mean hearing thresholds than the control group for all frequencies, except for 500; 2000 and 4000 Hz. Longer ABR latency averages were observed in the group of SLE patients compared to control. Ten patients (28.6%) developed high-frequency and symmetric sensorineural hearing loss (SNHL). Significant positive correlation between mean air-conduction hearing thresholds and SLE duration (r = 0.46, p < 0.001) was found. After taking age into consideration, hearing acuity in SLE was related to duration of disease in younger patients. Furthermore, no relation was seen between hearing level and severity of disease. CONCLUSIONS Auditory system involvement ought to be considered as one of elements of the clinical picture of systemic lupus erythematosus while determination of its character, original or secondary, requires further research.

Correlation of Endostatin and Tissue Inhibitor of Metalloproteinases 2 (TIMP2) Serum Levels With Cardiovascular Involvement in Systemic Sclerosis Patients

Fibrosis of oesophagus, lungs, heart, and kidney in the course of systemic sclerosis (SSc) may lead to dysfunction of the above organs or even patients death. Recent studies point out the role of angiogenesis and fibrosis disturbances in the pathogenesis of SSc. Heart fibrosis is one of the most important prognostic factors in SSc patients. So, the aim of our study was to examine cardiovascular dysfunction in SSc patients and its correlation with serum levels of vascular endothelial growth factor (VEGF), endostatin, and tissue inhibitor of metalloproteinase 2 (TIMP2). The study group comprised 34 patients (19 with limited scleroderma (lSSc) and 15 with diffuse scleroderma (dSSc)). The control group consisted of 20 healthy persons, age and sex matched. Internal organ involvement was assessed on the basis of specialist procedures. Serum VEGF, endostatin, and TIMP2 levels were evaluated by ELISA. We found cardiovascular changes in 15 patients with SSc (8 with lSSc and 7 with dSSc). The observed symptoms were of different characters and also coexisted with each other. Higher endostatin serum levels in all systemic sclerosis patients in comparison to the control group were demonstrated (P < .05). Also higher serum levels of endostatin and TIMP2 were observed in patients with cardiovascular changes in comparison to the patients without such changes (P < .05). The obtained results support the notion that angiogenesis and fibrosis disturbances may play an important role in SSc. Evaluation of endostatin and TIMP2 serum levels seems to be one of the noninvasive, helpful examinations of heart involvement in the course of systemic sclerosis.

Elevated exhalation of hydrogen peroxide in patients with systemic sclerosis

Background Systemic sclerosis is accompanied by an influx of activated phagocytes into distal airways. These cells release H2O2, which may evaporate from the airways surface and be detected in expired breath condensate. We tested whether patients with systemic sclerosis exhale more H2O2 than healthy subjects and whether breath condensate H2O2 levels correlate with some clinical parameters.

Prevalence of ocular manifestations in systemic sclerosis patients.

Introduction Systemic sclerosis (scleroderma, SSc) is a severe chronic connective tissue disease caused by immune system disorders and changes in the structure and functions of blood vessels, which consequently leads to enhanced tissue fibrosis. The aim of the study was to evaluate changes in the organ of vision in systemic sclerosis patients. Material and methods Overall the study involved 27 patients with systemic sclerosis. The control group comprised 27 age- and gender-matched healthy individuals. All the study subjects underwent complete ophthalmological examination that in systemic sclerosis patients additionally involved fluorescein angiography. Results Ophthalmological examination revealed higher incidence of the following abnormalities in the study group, compared to the control: symptoms of dry eye syndrome (19 eyes, p < 0.02), astigmatism(in 30 eyes, p < 0.01), posterior subcapsular cataract (10 eyes, p < 0.05), increased intraocular pressure (> 21 mm Hg were observed in 11 eyes, p < 0.002) and vascular abnormalities within fundus in fluorescein angiography (20 eyes). Conclusions In patients with systemic sclerosis numerous abnormalities within the vision of organ may be found. Regular ophthalmological examinations are essential among the mentioned group. The examination should be particularly focused on the presence of retinal vascular abnormalities.

IL-17 Expression in Dermatitis Herpetiformis and Bullous Pemphigoid

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although cytokines are critical for the inflammatory process, there are single findings concerning concentration of IL-17 in bullous diseases. The goal of this study was to assess IL-17 expression in DH and BP patients. Skin biopsies were taken from 10 DH, 14 BP patients and from 10 healthy subjects. The localization and expression of IL-17 was studied by immunohistochemistry and the serum concentration was measured by immunoassays. Expression of IL-17 in the epidermis and in influxed cells in dermis was detected in skin biopsies. Expression of IL-17 was statistically higher in epidermis and infiltration cells in specimens from BP than from DH patients. Examined interleukin expression was detected in perilesional skin of all patients but it was much lower than in lesional skin. The expression of IL-17 was not observed in biopsies from healthy people. Serum level of IL-17 was statistically higher in BP and DH groups as compared to control group. Our results provide the evidence that IL-17 may play an essential role in activating and recruiting eosinophils and neutrophils, which ultimately contribute to the tissue damage in DH and BP.

The imbalance between metalloproteinases and their tissue inhibitors is involved in the pathogenesis of dermatitis herpetiformis.

Dermatitis herpetiformis (DH) is a subepidermal autoimmune disease characterized by skin and intestinal lesions consistent with coeliac disease. There are also some data that metalloproteinases (MMPs) are involved in the development of skin lesions in DH, however their exact role in this process is not fully understood. The aim of the study was to investigate whether MMPs and their inhibitors are involved in pathogenesis of DH. Skin biopsies were taken from 13 patients with active DH and from 10 healthy subjects. The localization and expression of MMPs and TIMPs were examined by immunohistochemistry. MMPs expression was detected in basal keratinocytes and in the whole epidermis in all of the DH subjects. Neutrophils in microabscesses and in blister fluid were also positive for MMPs. Expression of TIMPs was moderate or weak in all examined biopsies. Our results allow us to conclude that imbalance between these enzymes takes an important role in the pathogenesis of DH.

The impact of the CYP2D6 gene polymorphism on the risk of pemphigoid

Studies concerning the etiopathogenesis of numerous diseases emphasize the involvement of genetically determined impairments of xenobiotic metabolism. Nowadays, more attention has been drawn to the role of cytochrome P450 and its isoenzymes in the course of dermatological diseases, including pemphigoid, the most frequently occurring autoimmune bullous disease, whose etiopathogenesis has not been completely elucidated.

Correlation between IL-36α and IL-17 and Activity of the Disease in Selected Autoimmune Blistering Diseases

Dermatitis herpetiformis (DH), bullous pemphigoid (BP), and pemphigus vulgaris (PV) are autoimmune bullous skin conditions with eosinophilic and neutrophilic infiltrations. While cytokines are crucial for the affinity and activation of different leukocyte cells in the inflammation and blister formation, there are no studies concerning a role of IL-36. The goal of the study was to analyze whether interleukin 36 is involved in pathogenesis of DH, BP, and PV. And the second aim of the study was the estimation of correlation between Il-36 and IL-17 and titers of specific antibodies in these diseases. Expression of IL-36 and IL-17 was detected in serum in all DH, BP, and PV samples. Serum levels of IL-36 and IL-17α were statistically higher in DH, BP, and PV groups as compared to the control group. IL-36α levels were statistically higher in DH patients, as compared to patients with PV and BP. Our results showed that IL-36 may be helpful in the diagnostic and monitoring of the activity of the disease. IL 36 may play a relevant role of enrolling eosinophils and neutrophils in DH, BP, and PV and finally provoke tissue injury.

Mediators of Mast Cells in Bullous Pemphigoid and Dermatitis Herpetiformis

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are skin diseases associated with inflammation. However, few findings exist concerning the role of mast cells in autoimmune blistering disease. Skin biopsies were taken from 27 BP and 14 DH patients, as well as 20 healthy individuals. Immunohistochemistry was used to identify the localization and mast cell expression of TNFα and MMP9 in skin lesions and perilesional skin. The serum concentrations of TNFα, MMP9, chymase, tryptase, PAF, and IL-4 were measured by immunoassay. TNFα and MMP9 expression in the epidermis and in inflammatory influxed cells in the dermis was detected in skin biopsies from patients. Although these mediators were found to be expressed in the perilesional skin of all patients, the level was much lower than that in lesional skin. Increased serum PAF levels were observed in BP patients. Mast cells may play an essential role in activating inflammation, which ultimately contributes to the tissue damage observed in BP and DH. Our findings suggest that differences in the pattern of cytokine expression directly contribute to variations in cellular infiltration in DH and BP.