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.

Abnormal portal vein waveform as an indicator of constrictive pericarditis - a case report.

We report a case of a 17-year-old patient referred to our outpatient Doppler Department due to clinical suspicion of liver cirrhosis. The patient presented with non-specific symptoms, such as malaise, pain in the right subcostal region, peripheral oedema. Until then, diagnostic imaging, including echocardiography was inconclusive. We performed the Doppler sonography of the portal system, which revealed normal diameter of the portal vein with abnormal, phasic and markedly pulsatile waveform. Hepatic veins distention with pathological reverse flow during systole was reported. Additionally, inferior vena cava was dilated and remained unchanged through the respiratory cycle. Basing on the above image a heart disease, which had not been taken into differential diagnosis before, was suggested. The following echocardiography, together with computed tomography, enabled a diagnosis of constrictive pericarditis. Successful pericardiotomy was performed. Such a complicated diagnostics happened to demonstrate an uncommon example of the use of portal vein waveform in making the proper cardiologic diagnosis.

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.

Post-Lyme disease syndrome.

About 10% of patients with Lyme disease continue to experience musculoskeletal pain and cognitive dysfunction after recommended antibiotic treatment. This condition is called post-Lyme disease syndrome (PLDS) or post-treatment Lyme disease syndrome. These two terms are used interchangeably. The pathogenesis of PLDS has been controversial. The hypothesis that patients with PLDS may harbor hidden reservoirs of Borrelia burgdorferi after their initial antibiotic treatment is difficult to accept. The prospective, double-blind studies contradict this point of view. Also, recently published research applying xenodiagnosis to PLDS supports the opinion that PLDS most likely has an autoimmune background. Lengthy courses of antibiotics are not justified in patients with PLDS because of the lack of benefit, and they are fraught with hazards. Most patients with PLDS recover from persistent symptoms with time. However, it can take months before they feel completely well.

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.

Ultrasonography of the tongue in macroglossia - a case report.

This paper is an attempt to assess the usefulness of ultrasonography in the diagnosis of the enlargement of the tongue (macroglossia). The role of sonography in diagnosing local pathologies of the tongue, such as neoplasms, abscesses or granulomas, has been well-established for 20 years. Rarely is its usefulness considered with respect to diagnosing macroglossia with concomitant systemic diseases. The starting point of these considerations was the presented case of a 59-year-old patient with considerably enlarged tongue. The patient had difficulty speaking and ingesting meals. Moreover, he complained about swelling and pain in the carpal and proximal interphalangeal joints. Tongue ultrasound examination revealed blurred lingual structure with evident, irregular vascular pattern in the color Doppler. The obtained image helped to rule out local pathology of the tongue and directed our diagnostic considerations towards immunoglobulin-related diseases (deposition diseases). We believe that the presented ultrasound image of the tongue was helpful in the diagnostic process. Establishing the final, correct diagnosis was a particularly strenuous process. The suspicion of a deposition disease had been rejected during two previous stays in two hospitals. This was the consequence of a negative diagnostic test of staining tissue deposits with Congo red. An accurate diagnosis occurred to be a rare form of a deposition disease: lambda light chain disease with symptoms of amyloidosis. Such a diagnosis was based on a thorough hematological analysis. A high level of free lambda light chains in the serum was detected and the bone marrow biopsy showed 13% of plasma cells. The patient underwent chemotherapy.

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.

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.

Selected angiogenic cytokines in systemic lupus erythematosus patients.

The objective of this study was to determine the serum concentration of angiogenic factors (vascular endothelial growth factor, VEGF; transforming growth factor beta, TGF-beta1; hepatic growth factor, HGF; basic fibroblast growth factor, bFGF; tumor necrosis factor alpha, TNF-alpha; soluble vascular endothelial growth factor receptor 1, sVEGF-R1; soluble vascular endothelial growth factor receptor 2, sVEGF-R2), the relationships among them and to assess the relation of their levels with the applied therapy in 48 females with systemic lupus erythematosus (SLE; 37 long-term treated +11 newly diagnosed). The control group consisted of 24 healthy women. A statistically significant increase of sVEGF-R2 and significant decrease of sVEGF-R1 were observed in the subgroup of newly diagnosed SLE patients as compared to the control subjects. No significant differences were found between serum angiogenic factors in the long-term treated subgroup and the control, the long-term treated subgroup and the newly diagnosed SLE patients after a 3-month treatment, and the subgroup of newly diagnosed SLE patients before therapy and after a 3-month treatment. The significant decrease in the serum of sVEGF-R2 was revealed in the subgroup treated for a long-time as compared to the subgroup of newly diagnosed untreated SLE patients. The analysis of relationships between serum concentration of sVEGF-R1 and other cytokines levels revealed positive correlation with concentration of VEGF and TNF-alpha in the total group of patients. In the newly diagnosed untreated subgroup, a strong positive correlation between concentration of sVEGF-R1 and bFGF was observed. Furthermore, a moderate positive correlation between concentration of sVEGF-R1 and the level of VEGF was revealed in the long-term treated patients. The association between sVEGF-R2 and HGF was also noted in this subgroup. The obtained data suggest the necessity of further investigations to determine the importance of angiogenic factors in pathogenesis and therapy of SLE.

Selected growth factors and diffusing capacity of the lung for carbon monoxide in patients with systemic lupus erythematosus.

The purpose of the study was to evaluate serum concentrations of selected growth factors and the diffusing capacity of the lung for carbon monoxide (DLCO) in 21 females treated for systemic lupus erythematosus. The control group consisted of 24 healthy women. Based on the high-resolution computed tomography (HRCT), patients were allocated to a subgroup of 11 subjects (HRCT-negative) and a subgroup of 10 with pulmonary abnormalities (HRCT-positive). In HRCT-negative patients a significantly higher level of TNF-α as compared with the control was observed and positive correlation between TNF-α and bFGF was revealed in this subgroup and in the total group of patients. DLCO was below the predicted value in 13 patients. No correlations between DLCO and growth factors concentrations were observed. DLCO reduction in asymptomatic, with respect to the respiratory system, SLE patients suggests a need for long-term monitoring of this parameter. The role of TNF-α in these patients requires further investigations.

Erythrocyte antioxidant parameters in workers occupationally exposed to low levels of ionizing radiation.

It has been postulated that ionizing radiation generates reactive oxygen species (ROS). ROS are annihilated by an intracellular enzymatic system composed mainly of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Workers of X-ray departments are occupationally exposed to long-term low levels of ionizing radiation, which may affect their antioxidant status. Erythrocyte activities of SOD, CAT and GPx were measured in 45 workers of X-ray departments and 30 persons who constituted the control group. Subgroups with respect to sex and cigarette smoking were selected. Colorimetric method was used for determination erythrocyte activities of SOD, CAT and GPx. A significant decrease of GPx, SOD and CAT activity in workers as compared to controls was observed. Lower activity of SOD and GPx in female and GPx in male subgroup was found. SOD was significantly more elevated in smoking workers than in the non-smoking staff. Moreover non-smoking employees showed lower SOD and GPx activity in comparison to the non-smoking control. GPx decrease was found in smoking workers in comparison to the smoking control. Additionally, smoking workers showed lower activity of GPx and CAT compared to non-smoking control.

Vasculopathy and vasculitis in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease, where vascular lesions are one of the typical symptoms. The pathological process often involves skin vessels, renal glomeruli, the cardiovascular system, brain, lung alveoli, and gastrointestinal tract vessels. This review presents possible adverse mechanisms underlying the cause and effect relationship of various factors causing vascular lesions in SLE patients. The generally accepted hypothesis links vascular damage in SLE with the deposition of immune complexes in the vascular endothelium. The anti-endothelial cell antibodies (AECA), antiphospholipid antibodies and anti-double stranded DNA antibodies present in SLE, that directly or indirectly affect endothelial cells, causing inflammatory damage to the vessel wall, and their role, have been discussed. It has been stressed that although the suggested role of AECA in vasculitis pathogenesis has not been fully established, evidence, however, has demonstrated that AECA is a factor causing endothelial damage in SLE patients. On the other hand, issues concerning cellular adhesion molecules which enable leukocyte adhesion and rolling along the endothelial cell surface, and their extravascular migration, focus on the role they may be playing in SLE patients with vasculitis. A potential role of soluble forms of adhesion molecules, pentraxin 3, medications, infections in the pathogenesis of this disease has also been shown. Special attention has been given to the role of type 3 hepatitis virus in vascular damage in SLE.

Expression of cellular isoform of prion protein on the surface of peripheral blood lymphocytes among women exposed to low doses of ionizing radiation.

Ionizing radiation affects the expression of adhesive and co-stimulatory molecules in lymphocytes. The physiological function of cellular isoform of prion protein (PrPc) is little known. Evidences indicate a link between lymphocytes activation and PrPc expression on their surface; however, no direct effect of radiation on PrPc level in these cells was investigated. The objective of this study was to determinate the effect of low doses of ionizing radiation on the expression of PrPc on the surface peripheral blood lymphocytes in the women operating X-ray equipment. In 36 female workers and 30 persons of the control group the PrPc expression on CD3 (T lymphocytes), CD4 (T helper), CD8 (T cytotoxic) and CD19 (B lymphocytes), as well as the percentage of lymphocytes with PrPc on their surface, were tested. Subgroups with respect to age and length of employment were selected. A significant increase was observed in PrPc expression on CD3 and CD4 with lowered PrPc level on CD8 and percentage of CD8 cells with PrPc in workers compared to control. The PrPc level did not show significant changes in subgroups in relation to age (below and over 40 years old) both in the investigated and control groups, whereas a lower percentage of PrPc expressing CD19 cells showed in employed women below 40 years of age. A significant decrease was found in PrPc expression on the surface of CD3, CD4 and CD8 cells in the subgroup employed for over 10 years than in the subgroup with less than 10 years of employment.

Kikuchi-Fujimoto disease: a case report.

Kikuchi-Fujimoto disease is a rare benign cervical lymphadenopathy, which often affects young adult women. Its etiology and pathogenesis are unknown. We present the case of Kikuchi-Fujimoto disease in the Polish population and analyse the difficulties in differentiating this disease from the systemic lupus erythematosus.

Assessment of blood serum immunoglobulin and C-reactive protein concentrations in workers of x-ray diagnostics units.

OBJECTIVES: Workers of x-ray departments are occupationally exposed to long-term low levels of ionizing radiation. The aim of the study was to investigate the influence of occupational exposure of low-level x-ray radiation on immunoglobulin and C-reactive protein (CRP) concentrations in radiology workers. MATERIALS AND METHODS: In the study group of 41 x-ray department workers and the control group composed of 32 persons, immunoglobulins (IgM, IgG, IgA) and CRP concentrations were analyzed. The study group was subdivided by gender and smoking habit. RESULTS: A significant decrease in IgG level was found in the workers and the female subgroup. The same observation was made when smokers and nonsmokers of both groups were compared. Smoking workers showed lower concentrations of IgA than non-smokers. The remaining results of immunoglobulin and CRP concentrations did not show significant differences. CONCLUSIONS: Occupational exposure to low levels of ionizing radiation is associated with suppressive influence on the immunoglobulin production, especially IgG. In addition, smoking decreases the production of IgA in radiology workers.

HLA-DRB1 and -DQB1 alleles and gene polymorphisms of selected cytokines in systemic lupus erythematosus.

OBJECTIVE: The objective of this study was to evaluate the genetic profiles of selected cytokines (transforming growth factor beta 1, tumor necrosis factor alpha, interleukin-6, interferon gamma, and interleukin-10) in systemic lupus erythematosus and the contributions of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles to susceptibility for this disease. PATIENTS AND METHODS: The study was carried out in 24 SLE patients and 36 healthy controls (from Upper Silesia) using polymerase chain reaction methods. All persons were of Caucasoid origin. Standard association analysis was used to compare the HLA alleles and frequency of cytokine gene polymorphisms between these groups. RESULTS: Only the frequency of HLA-DRB1*07 allele was higher in SLE patients than controls (odds ratio 2.92, 95% confidence interval 1.16-7.33), but the difference did not reach statistical significance when Bonferroni's adjustment procedure was performed. No other significant associations were noted between class II alleles (DR1-DR6, DR8-DR10, DQ1-DQ4) and SLE. The frequency of the interleukin-6 GG and GC genotypes was significantly higher in SLE patients than in controls, and a significantly higher percentage of the G vs C alleles between patients and controls was revealed (odds ratio 2.53, 95% confidence interval 1.37-4.65, chi-squared test 8.16, P < 0.05). The most significant association of increased frequency of the G allele with SLE was more commonly noted in HLA-DRB1*07-positive patients (odds ratio 10.29, 95% confidence interval 5.34-19.83, P < 0.001). These data indicate that this combination could contribute toward determining the susceptibility to SLE, but its possible significance will require confirmation by further studies.