The Impact of the IL-10 Gene Polymorphism on mRNA Expression and IL-10 Serum Concentration in Polish Lupus Patients.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies against a lot of nuclear components. Despite many studies on the genetic background of this disease, the pathogenesis remains unclear. The aim of the study is to comprehensively evaluate the polymorphism of the IL-10 promoter gene, its mRNA expression, and the serum IL-10 concentration of SLE female patients and females age-matched controls. Analyzing the association between the level of the tested cytokine and the polymorphism genotype-1082; -819; -592, we found statistically higher serum IL-10 levels in SLE patients compared to in healthy controls (11.9 ± 2.2 pg/mL vs. 9.4 ± 1.7 pg/mL, accordingly; p < 0.0001). We did not find statistically significant differences in the gene polymorphism of IL-10 among SLE patients and controls. The most significant observation derived from our study is that IL-10 mRNA transcripts are upregulated in SLE patients compared to in healthy controls (p < 0.0001). According to our results, the presence of the IL-10 genetic polymorphism has no clinical significance for the development of SLE, and subsequent differences in mRNA and IL-10 concentration results from the influence of other factors which should be the subject of further research.

The impact of anti-endothelial cell antibodies (AECAs) on the development of blood vessel damage in patients with systemic lupus erythematosus: the preliminary study.

Vascular injury represents one of the most frequent lesions in systemic lupus erythematosus (SLE). The aim of the study was to assess the influence of anti-endothelial cell antibodies (AECAs) on the development of endothelial cell (EC) activation, dysfunction and subsequent vasculitis in women with SLE. Fifty six women with SLE were divided into 2 subgroups, i.e. subjects with positive AECAs (+) and those with negative AECAs (-). The control group consisted of 25 healthy women. Clinical characteristics, routine laboratory tests and circulating markers of EC activation/dysfunction, i.e. monocyte-chemotactic protein-1 (MCP-1), soluble E- and P-selectin, vascular and intercellular adhesion molecule-1 (sVCAM-1, sICAM-1), von Willebrand factor (vWF), pentraxin 3 (the marker of vasculitis) the indicator of procoagulant activity i.e. prothrombin fragment 1 + 2 (F1 + 2) were detected using ELISA and compared between patients with AECA (+), AECA (-) and control subgroups. Serum concentrations of AECAs in AECA(+), AECA(-) and control groups were 4.58 ± 2.97, 0.92 ± 0.50 and 0.72 ± 0.28 AU/ml, respectively (p < 0.001). The study showed significant increases in EC activation markers, i.e. MCP-1, sE-selectin, sVCAM-1 and F1 + 2 in SLE AECA(+) compared to SLE AECA(-) and control groups. However, the indicator of vasculitis (PTX3) was significantly lower in SLE AECA(+). Moreover, multivariate analysis of variance showed a positive correlation between AECAs and sE-selectin and sVCAM-1 levels, but not with PTX3. AECAs were involved in the initial stages of vascular damage in SLE, i.e. in EC activation and dysfunction. However, they did not play a role in the development of vasculitis.

Addison's Disease in the Course of Recurrent Microangiopathic Antiphospholipid Syndrome-A Clinical Presentation and Review of the Literature.

The article presents a male patient with adrenocortical insufficiency in the course of antiphospholipid syndrome (APS). It also describes recurrent exacerbations of his clinical status, characteristic of microangiopathic antiphospholipid syndrome (MAPS) which had been misdiagnosed as a disseminated intravascular coagulopathy (DIC) syndrome due to sepsis with multi-organ failure, including heart, kidneys, and liver. Issues related to pathogenesis, clinical symptoms, differential diagnosis, and treatment of APS in the context of presently distinguished subtypes of this syndrome have been addressed. The role of vascular endothelial cell activation and the influence of coagulation patterns on the development of APS continuum clinical symptoms have also been mentioned. In addition, this paper highlights that the diagnosis of APS should be considered in patients with adrenal insufficiency and abdominal pain, even without any prior history of thromboembolic diseases, as well as in the course of DIC, especially without predisposing factors.

[Listeriosis of central nervous system in patients with ulcerative colitis - case study].

In the recently an increase morbidity inflammatory bowel disease, including ulcerative colitis was observed. The use of purine analogs and their metabolites are associated with a higher incidence of infections in this group of patients. Listeriosis is an infectious disease caused by a relatively anaerobic gram-positive bacteria - Listeria monocytogenes. Common symptoms include fever, nausea, vomiting and diarrhea, but these pathogens can also cause myocarditis, central nervous system infections, including brain abscesses and sepsis. Since the incidence of Listeria monocytogenes is higher in patients with inflammatory bowel disease than in the general population, it is important to pay special attention to this group of patients (in prophylaxis as well as treatment) as these infections are serious and often fatal among them.

[Description of the case of Cogan syndrome]. / Opis przypadku zespolu Cogana.

Cogan syndrome is a persistent disease with the autoimmunologic background connected with vasculitis. It can be diagnosed by symptoms such as interstitial keratitis, optic nerve dysfunction and nervus acusticus dysfunction with subsequent hearing impairment or deafness. In its course, such systemic symptoms frequently occur: exhaustion, weight loss and joint pain. Due to the rare occurrence of Cogan syndrome and vast obstacles in diagnosing it, the case of34 years old patient with Cogan syndrome is discussed.

Pentraxin 3 as a biomarker of local inflammatory response to vascular injury in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disorder with organ injury related to vasculitis. Inflammation of blood vessels results from auto-immunological activation of endothelial cells. The pentraxin 3 (PTX3), might act as an indicator of vasculitides in many diseases. The aim of this study was to determine whether PTX3 might be useful as a marker of vascular injury in SLE. This study was carried out in a group of 56 SLE women, and in the 28 female volunteers control group. All participants' plasma and serum samples were collected to estimate concentrations (ELISA) of PTX3, soluble thrombomodulin, soluble E-selectin (sE-selectin), soluble P-selectin (sP-selectin), soluble form of vascular cell adhesion molecule 1 (sVCAM-1), soluble inter-cellular adhesion molecule-1 (sICAM-1), soluble platelet endothelial cell adhesion molecule 1, monocyte chemotactic protein-1 (MCP-1) and von Willebrand factor (vWF) activity. Anthropometric, demographic and lifestyle characteristics of SLE patients were also performed. The SLE patients had higher PTX3, vWF, MCP-1, sE-selectin and sVCAM-1 levels than the controls (1.82 ± 1.56 ng/mL, 237 ± 101%, 70.05 ± 18.31 ng/mL, 111.16 ± 49.15 ng/mL and 978.78 ± 462.35 ng/mL vs. 0.86 ± 0.40 ng/mL, 138 ± 43%, 58.56 ± 13.91 ng/mL, 66.04 ± 27.18 ng/mL and 499.07 ± 125.67 ng/mL, respectively). The independent factors affecting PTX3 expression included Systemic Lupus Erythematosus Disease Activity Index, prednisone dose and anemia severity. Moreover, the PTX3 areas under the curve-receiver operating characteristics curves 0.717 ± 0.056 with cut-off level of 1.96 ng/mL was comparable to vWF, MCP-1, sE-selectin, sP-selectin and sICAM-1. PTX3 and sVCAM-1 were the only factors related to SLE activity. Other vascular injury indicators associated with PTX3 were vWF and sVCAM-1. In conclusion, PTX3 concentrations in SLE patients might serve as a indicator of the activation/dysfunction of vascular endothelium.

Assessment of selected B cells populations in the workers of X-ray departments.

OBJECTIVES: Workers of X-ray departments are occupationally exposed to long-term low levels of ionizing radiation (LLIR), which may affect their humoral immunity. The aim of the study was to assess the influence of LLIR on the number and proportion of B cells (CD19+), B1 cells (CD5+CD19+) and memory B cells (CD27+CD19+) in peripheral blood of such workers. MATERIALS AND METHODS: In the study group of 47 X-ray departments workers and the control group consisting of 38 persons, the number and percentage of CD19+, CD5+CD19+, CD27+CD19+ cells as well as CD5+CD19+/CD19+ and CD27+CD19+/CD19+ cell ratios were assessed using flow cytometry. Additionally, the study group was divided into 2 groups by the length of employment below and over 15 years and analysis adjusted for age and smoking habit was performed. RESULTS: The total number of CD19+ cells showed significant increase in the group of workers in comparison with the persons from the control group, whereas the percentage of CD5+CD19+ cells as well as CD27+CD19+/CD19+ and CD5+CD19+/CD19+ cell ratios were lower. Percentage, number of CD5+CD19+ cells and CD5+CD19+/CD19+ cell ratio were significantly lower in the workers with length of employment longer than 15 years in comparison with those employed below 15 years. Moreover, we found positive associations between the number of CD19+ cells and employment as well as smoking habit, whereas the number of CD5+CD19+ cells was positively associated with cigarette smoking alone. Percentage of CD5+CD19+ cells as well as CD5+CD19+/CD19+ and CD27+CD19+/CD19+ cell ratios were negatively correlated with employment. CONCLUSIONS: The study suggests association between the suppressive influence of low level ionizing radiation on circulating in peripheral blood, especially of B1 cells as well as of memory B cells, in workers of X-ray units, which is adverse in relation to microbiological threat.

A comparative clinical study on five types of compression therapy in patients with venous leg ulcers.

The aim of this study was to compare five types of compression therapy in venous leg ulcers (intermittent pneumatic vs. stockings vs. multi layer vs. two layer short stretch bandages vs. Unna boots). Primary study endpoints were analysis of changes of the total ulcer surface area, volume and linear dimensions inside observed groups. The secondary end points were comparisons between all groups the number of completely healed wounds (ulcer healing rates), Gilman index and percentage change of ulcer surface area. In total, 147 patients with unilateral venous leg ulcers were included to this study. Participants were randomly allocated to the groups: A, B, C, D and E. After two months the healing rate was the highest in group A (intermittent pneumatic compression) - 57.14%, 16/28 patients, B (ulcer stocking system) - 56.66%, 17/30 patients and C (multi layer short stretch bandage) - 58.62%, 17/29 patients. Significantly much worse rate found in group D (two layer short stretch bandages) - only 16.66%, 5/30 patients and E (Unna boots) - 20%, 6/30 patients. The analysis of changes of the percentage of Gilman index and wound total surface area confirmed that intermittent pneumatic compression, stockings and multi layer bandages are the most efficient. The two layer short - stretch bandages and Unna boots appeared again much less effective.

A randomized, controlled clinical pilot study comparing three types of compression therapy to treat venous leg ulcers in patients with superficial and/or segmental deep venous reflux .

Compression therapy--including inelastic, elastic, and intermittent pneumatic compression--is the standard of care for venous ulcers (VLUs) and chronic venous insufficiency, but there is no consensus in the literature regarding the most effective type of compression therapy. A prospective, randomized, clinical pilot study was conducted among 70 patients with unilateral VLUs treated in a hospital dermatology department in Poland to compare three types of compression therapy (intermittent pneumatic compression, stockings, and short-stretch bandages) in persons with superficial deep venous reflux alone or combined with the segmental variety. Study endpoints were change in ulcer dimensions and proportions healed. Patients with superficial or combined superficial and deep vein insufficiency were randomly allocated to receive one of the three therapies (one of each vein type for each treatment option, six groups total). All patients received saline-soaked gauze dressings along with micronized purified flavonoid fraction, diosmin, hesperidin, and Daflon 500 once daily. Compression treatments were changed or pneumatic compression provided daily for 15 days. Wound size reduction and percentage of wounds healed were significantly higher in groups receiving intermittent pneumatic compression or stockings than in groups using short-stretch bandages (for percentage change of ulcer surface area, P = 0.02; for healing rates P = 0.01). These results warrant additional randomized controlled clinical studies with a larger sample size and longer patient follow-up.

[Serum level of selected chemokines in systemic lupus erythematosus patients taking into consideration the peripheral blood leukocyte counts]. / Stezenie wybranych chemokin u chorych na toczen rumieniowaty ukladowy z uwzglednieniem liczby leukocytów we krwi obwodoweJ.

UNLABELLED: Chemokines promote leukocyte traffic into the site of inflammation. It depends on the repertoire of chemokines synthesized locally, and the temporal expression of chemokine receptors on leukocytes among them lymphocytes B and T which play crucial role in the pathogenesis of autoimmune diseases for example in systemic lupus erythematosus (SLE). RANTES (regulated upon activation in normal T cells expressed and secreted) is chemokine influencing T cells and BLC 1 (B-lymphocyte chemoattractant 1) is chemokine which affects B cells. The aim of the study was to evaluate serum concentration of the above mentioned chemokines in treated SLE patients and to analyze the relationships between their concentration in patients group and the control one. Another aim of our study was to assess the relationships between serum levels of these chemokines and the total peripheral blood leukocyte count and between serum levels of these chemokines and absolute peripheral blood counts of the individual forms of these cells in SLE patients. MATERIAL AND METHODS: Serum levels of RANTES and BLC 1 were determined in 48 treated women with SLE and mild-to-moderate disease severity. The results were compared between the total SLE group and the control (29 healthy women). The correlation between chemokines and between their levels and peripheral blood leukocyte count were evaluated. The relationships between the analyzed chemokines were also determined in the control group. RESULTS: Lower level of RANTES in serum was revealed in patients with SLE compared to the control and the tendency to higher concentration of BLC 1 in serum was observed. No relationships were observed between the levels of these chemokines both in the SLE patients and in the control group. Whereas the negative correlations between BLC 1 and total leukocyte count and BLC 1 and absolute number of neutrophils were found without such correlation between BLC 1 the subgroup of patients with concomitant neutropenia. CONCLUSION: We suggest that in treated patients with SLE lowered level of RANTES and tendency to higher level of BLC 1 is observed which have not any connections with the peripheral blood leukocyte counts and individual forms of these cells counts.

Serum levels of selected chemokines in systemic lupus erythematosus patients.

Chemokines promote leukocyte traffic into the site of inflammation. Serum levels of monocyte chemotactic protein 1 (MCP-1), stromal cell-derived factor-1 (SDF-1), interferon-gamma-inducible protein 10 (IP-10), and interleukin-8 (IL-8) were evaluated in 48 treated women with systemic lupus erythematosus (SLE) and mild-to-moderate disease severity. The results were compared between the whole SLE group and the control (29 women). The relationships between chemokines, their concentrations, and peripheral blood leukocyte count and between the chemokines and individual leukocyte populations (polymorphonuclear leukocytes-PMNs, lymphocytes-Ls, monocytes-Ms, eosinophils) counts were determined. The relationships between the analyzed chemokines were also determined in the control. SLE subjects had significantly higher MCP-1, SDF-1, IP-10, and lower IL-8 concentrations compared to the control. Moderate, positive correlations between MCP-1/SDF-1, SDF-1/IP-10 and a negative correlation between MCP-1/IL8 were observed in the patient group. Moderate, negative correlations were found between SDF-1/total leukocyte count, SDF-1/absolute number of PMNs as well as between IP-10/total leukocyte count, IP-10/absolute PMNs, Ls, and Ms counts in peripheral blood of SLE group. We suggest that the obtained results and correlations observed between the examined parameters might be used to monitor SLE course and progression. However, further randomized clinical studies should be carried out on in untreated and treated patients with SLE.

Long pentraxin 3 (PTX3) in the light of its structure, mechanism of action and clinical implications.

Pentraxins are a group of evolutionarily conserved ancient proteins. Depending on their structure, pentraxins are divided into short and long pentraxin families. Pentraxin 3 (PTX3) is the prototype of the long pentraxin group. PTX3 synthesis is stimulated by a variety of molecules involved in the inflammatory process. The inflammatory mediator is typically produced at inflammatory sites; however, it can also be released at the sites remote from the original inflammatory insult. Although mainly expressed by vascular endothelium and smooth muscle cells, PTX3 is also synthesized by myeloid dendritic cells, mononuclear macrophages/phagocytes, vascular endothelial and smooth muscle cells, fibroblasts, adipocytes, cumulus oophorus cells mesangial cells, synovial cells and chondrocytes. PTX3 binds to several ligands including complement component C1q, factor H, ficolin-1 (M-ficolin), mannose-binding lectin, fibroblast growth factor 2, P-selectin, matrix protein TSG6 and Klebsiella pneumoniae; it is also known to play a role in humoral innate immunity as well as in degenerated and apoptotic cells clearance. PTX3 acts as a modulator of inflammatory processes, modifies angiogenesis and atherosclerotic lesion development, and participates in extracellular matrix formation. Due to the fact of PTX3 being primarily produced and released by vascular wall cells, it might be used as a sensitive and independent inflammatory marker.

A sequence of pathologic events in a patient after thymectomy for myasthenia gravis.

The case of a rare coexistence of myasthenia gravis (MG) with systemic lupus erythematosus (SLE) is described. MG was diagnosed prior to SLE which developed after thymectomy. The patient was affected by HCV viremia. Therefore, there were therapeutic problems. Metylase treatment was continued for several years and dopamine receptor agonist was effectively administered as adjunctive therapy in SLE.

Annexin A5 and anti-annexin antibodies in patients with systemic lupus erythematosus.

Plasma levels of annexin A5 (ANX A5) and anti-annexin A5 (aANX A5) antibodies were evaluated in 51 women with systemic lupus erythematosus (SLE). The results were compared between the total SLE group, subgroups on/without immunosuppressive therapy and the control (28 women). The relationships between ANX A5/aANX A5 antibodies levels and laboratory variables (anti-cardiolipin antibodies-aCL, total cholesterol, thrombocyte count, activated partial thromboplastin time-APTT, prothrombin time, international normalized ratio-INR) were performed in the total SLE group and in the patient subgroups identified as the arithmetic mean of ANX A5 concentration in the control plus 1-4 standard deviations (SD). The whole SLE group and the subgroup on immunosuppression showed significantly higher ANX A5 and IgG aANX A5 antibodies concentrations. A weak positive correlation was found between ANX A5 and thrombocyte count, a moderate one between IgG and IgM aANX A5 antibodies, a weak negative correlation between IgG aANX A5 and APTT in the whole SLE group. SLE subgroups with ANX A5 concentrations higher than the control mean plus 3 or 4 SD showed a weak/moderate negative correlation of this parameter with aANX A5 antibodies, moderate one with IgG aCL antibodies levels, a moderate positive correlation with cholesterol concentration, moderate/high positive correlations with thrombocyte count. The association between plasma ANX A5/IgG aANX A5 levels and severity of disease was noticed. The role of aANX A5 and IgG aCL antibodies as causative factors of increased ANX A5 levels was suggested, and the relationship between ANX A5 and thrombocyte count was revealed.

[Development of systemic lupus erythematosus after thymectomy performed in a patient with myasthenia gravis]. / Rozwój tocznia rumieniowatego ukladowego po wykonanej tymektomii u chorej z nuzliwoscia miesni prazkowanych.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, with not fully understood, complex origin. Several factors are suspected of involvement in the development of the disease. Genetic predisposition, environmental factors, some drugs, estrogens, cigarette smoking and ultra violet radiation seems to be the most important among them. The case of a patient with myasthenia gravis (MG) followed by thymectomy and lupus erythematosus (SLE) diagnosed one year later presented in this study.

[Can drugs used in type 2 diabetes therapy induce acute pancreatitis?]. / Czy preparaty stosowane w leczeniu cukrzycy typu 2 moga indukowac ostre zapalenie trzustki?

The increased number of subjects with type 2 diabetes and putting into clinical practice further new hypoglycemic agents and also aspiring to achieve the bettest glycemic control using a few medications may cause that undesirable actions of these agents may be observed more frequently. One undesirable effect of hypoglycemic drugs is acute pancreatitis; therefore the aim of the present paper is to review data concerning the development of this complication during type 2 diabetes pharmacotherapy.

[Diagnostic value of antineutophil cytoplasmic antibodies]. / Znaczenie diagnostyczne przeciwcial przeciw cytoplazmie granulocytów obojetnochlonnych.

Antineutrophil cytoplasmic antibodies (ANCA) constitute a family of auto-antibodies directed against various components of the neutrophil cytoplasm. The indirect immunofluorecence assays detected three fluorescent staining patterns: cANCA--cytoplasmic; pANCA--perinuclear and aANCA--atypical. Occurence ANCA is mainly associated with Wegener's granulomatosis and vasculitis, but they are also detected in autoimmune diseases (eg. in systemic lupus erythematosus, in rheumathoid arthritis, Sjögren's syndrome, in dermatomyositis) and in inflamatory bowel diseases (Crohn disease, colitis ulcerosa). Presence of ANCA was found also in primary sclerosing cholangitis, in chronic infections and in person using some kinds of drugs. The aim of the study was to review recent investigations concerning prevalence of ANCA and their diagnostic value not only for vasculitis but also for the other disease in which they are detected.

[The thyroid functional tests, antithyroid antibodies and the level of prolactin in treated patients with systemic lupus erythematosus]. / Testy czynnosciowe tarczycy, przeciwciala przeciwtarczycowe i stezenie prolaktyny u leczonych chorych na toczen rumieniowaty ukladowy.

UNLABELLED: The relationships between different autoimmune diseases and among them the connections between systemic lupus erythematosus (SLE) and autoimmune thyroid diseases have been reported for a few years. The aim of this study is the assessment of the laboratory tests findings which are applied in the evaluation of the thyroid function and prolactin (PRL) concentration in serum in women with SLE during therapy. MATERIAL AND METHODS: In 41 women with SLE treated in the period of a few months to several years the following laboratory tests were performed: the concentration of thyroid stimulating hormone (TSH), PRL and free triiodothyronine (fT3) and free thyroxine (fT4) levels were measured by chemiluminescence technique, anithyroid antibodies (anti-thyroperoxidase - anti-TPO, and anti-thyroglobulin - anti TG) were tested by immunofluorescence assay. The control group consisted of 17 healthy women of a similar age to the SLE patients. RESULTS: The levels of fT3 and fT4 were statistically significantly lower in SLE patients comparing to the controls but the arithmetic means for the whole investigated patients were within the range of laboratory limits for these hormones. Considering other parameters no statistical differences between the mean values were observed. CONCLUSIONS: The results indicate that fT3 and fT4 concentrations are lower in SLE treated women with small and mild disease activity compared to the controls with the mean arithmetic values for the total group of patients which is within the laboratory limits for these hormones. Furthermore, the results seem to support the tendency of connections between the detection of antithyroid antibodies with higher level of serum PRL in SLE treated patients.

[Chronic fatigue syndrome with special focus on systemic lupus erythematosus]. / Zespól przewleklego zmeczenia ze szczególnym uwzglednieniem tocznia rumieniowatego ukladowego.

Chronic fatigue is an ailment frequently reported in the course of several pathologies. When fatigue clearly predominates over other symptoms, it is referred to as chronic fatigue syndrome (CFS). Initial CFS definition and diagnostic criteria were published in 1988, and have been several times modified since that time. In 1994, Fukuda et al. presented precise guidelines for the evaluation and study of CFS. The etiopathogenic mechanisms of CFS have not yet been satisfactorily clarified although immune and hormonal responses as well as a decline in neurotransmitter concentrations have been implicated in the development of the disorder. Systemic lupus erythematosus (SLE) is an autoimmune disease, with chronic fatigue as a very common symptom observed in as many as 80% of the patients. Owing to its obscure pathogenesis, therapy for CFS remains a difficult and complex issue consisting mostly of the treatment of the underlying disease. Appropriate lifestyle and physical activity should be emphasized. Medications include antidepressants and glucocorticosteroids. Psychological counseling has also been recommended. Complex etiopathogenesis and the involvement of the immune and neurohormonal systems suggest that CFS might be a primary and not secondary disorder. Hence a significant role of medical professionals in the diagnosis and treatment of chronic fatigue syndrome.