Microthrombotic renal involvement in an SLE patient with concomitant catastrophic antiphospholipid syndrome: the beneficial effect of rituximab treatment.

Antiphospholipid syndrome is characterized by multiple arterial and/or venous thrombotic events, recurrent fetal losses in the presence of antiphospholipid antibodies (aPL). Catastrophic antiphospholipid syndrome is a life-threatening, rare subset of antiphospholipid syndrome when the thrombotic events affect at least three organs, and clinical manifestations develop simultaneously or within a week. Diagnostically, small vessel occlusions can be detected by histopathology in the presence of aPL. Our case report describes an 18-year-old man who has been treated for antiphospholipid syndrome associated with systemic lupus erythematosus (SLE) since 2011. The clinical findings were dominated by recurrent deep vein thrombosis, and severe proteinuria caused by lupus nephritis, accompanied by mild serological and laboratory findings. The patient was hospitalized in March 2014 because of severe thrombocytopenia and infective diarrhoea. At this time the renal functions deteriorated rapidly. Simultaneously, left upper extremity paresis was observed; computed tomography showed ischaemic lesions in the territory of the middle cerebral artery. Abdominal discomfort and pain occurred. On computed tomography scan ischaemic lesions were seen in the spleen, the right kidney and the coeliac trunk. Laboratory and serological findings verified the presence of aPL and anti-DNA antibodies, anaemia and thrombocytopenia. Based on the above-mentioned clinical and laboratory findings, the diagnosis of catastrophic antiphospholipid syndrome was established. Anticoagulation, corticosteroids and plasma exchange treatment, as well as haemodiafiltration were initiated. Although the thrombotic cascade decelerated following these interventions, we could not see an improvement in the renal function. Rituximab treatment was started, leading to a significant improvement in renal function. After 5 weeks of treatment the patient was discharged from hospital.

Three-year longitudinal clinical trial of arterial function assessed by a oscillometric non-invasive method in comparison with carotid sclerosis and transferrin kidney-transplanted patients.

Chronic kidney disease remains one of the main risk factors of cardiovascular disease. However, patients with kidney transplantation have better life expectancy and better quality of life compared with patients on dialysis. In patients with a well-functioning graft, the main cause of death is cardiovascular in origin. Metabolic pathways have complex effects on arterial function that can be monitored by conventional ultrasonography and with the assessment of arterial stiffness by oscillometric non-invasive technique. Forty-one primer cadaver kidney-transplanted patient were involved in a 3-year longitudinal clinical trial (21 female, 20 male; average age, 40.16 ± 12.56 years). Arterial stiffness parameters referring to rigidity of the arterial wall (pulse wave velocity [PWV], augmentation index, and pulse pressure) were investigated. Correlation between stiffness, and laboratory parameters (serum creatinine, urea, hemoglobin, albumin, cholesterine, triglycerides, transferrin, uric acid, glomerular filtration rate, and C-reactive protein) were analyzed. A non-invasive oscillometric method--Tensiomed Arteriograph--was applied to assess the arterial stiffness parameters. Statistical analysis was performed with the use of Statistica for Windows, version 8.0. A value of P < .05 was considered statistically significant for all statistical tests. We found a positive correlation between PWV and left ventricular wall thickness and a negative correlation between PWV and ejection fraction. We also found a positive significant correlation between serum level of transferrin and PWV. There was simultaneous significant progression concerning PWV and carotid artery sclerosis in a 3-year follow-up. There was no fatal cardiovascular event during the study period among our patients. All of our patients involved in this study are still alive. Our findings suggest that arterial stiffness monitoring is a reliable method to assess global cardiovascular risk among kidney-transplanted patients. The oscillometric method is convenient, fast, painless technique to monitor arterial function, which, in the case of pathological findings, proposes more frequent cardiovascular control.

The beneficial effect of plasmapheresis in mixed connective tissue disease with coexisting antiphospholipid syndrome.

The authors report a rare case of a female patient with mixed connective tissue disease (MCTD) with coexisting antiphospholipid syndrome (APS). Five years after the diagnosis of MCTD high concentrations of anticardiolipin (anti-CL) and anti-ß2-glycoprotein (anti-ß2GPI) autoantibodies were present in the patient's serum without thrombotic events. Epstein-Barr virus (EBV) reactivation provoked APS, with the clinical manifestations of livedo reticularis, digital gangrene and leg ulcers. Skin biopsy from the necrotic area showed multiple fibrin microthrombi in the superficial vessels. Corticosteroid pulse therapy, and plasma exchange in combination with synchronized cyclophosphamide was administered, which led to improvement of the digital gangrenes, while no new lesions developed. The number of CD27high plasma cells decreased, and the previous high levels of autoantibodies also normalized in the peripheral blood. In the case of MCTD with coexisting APS combination therapy, including plasmapheresis has beneficial effects.

Decreased flow-mediated dilatation with increased arterial stiffness and thickness as early signs of atherosclerosis in polymyositis and dermatomyositis patients.

Several autoimmune rheumatic diseases have been associated with accelerated atherosclerosis or other different types of vasculopathy depending on the underlying disease, leading to increased cardio- and cerebrovascular disease risk. Polymyositis (PM) and dermatomyositis (DM), members of idiopathic inflammatory myopathies (IIMs), a group of systemic autoimmune diseases are also associated with elevated risk of cardiovascular diseases (CVD). Up until now, no specific data is known on the mechanisms, risk factors, or possible vasculopathy leading to increased CVD risk. The aims of the present study were to assess the flow-mediated dilatation of the brachial artery by a TensioClinic arteriograph and to measure the thickness of carotid artery intima-media, the augmentation index, and the pulse wave velocity using high-resolution ultrasonography in a cohort of PM and DM patients. We also investigated the correlation of these parameters with the traditional risk factors of atherosclerosis and overall cardiovascular status within PM and DM patients. Twenty-seven patients (21 females, six males) with IIMs were enrolled in this study, and 38 healthy individuals matched for sex and age served as controls. We found a decreased flow-mediated dilatation in the brachial artery (6.36 vs. 8.39 %) with increased arterial stiffness and carotid artery thickness in our patients compared to healthy controls. We found significantly decreased flow-mediated dilatation of the brachial artery (5.57 vs. 8.39 %) in DM patients. We also detected a correlation between these parameters and the traditional cardiovascular risk factors, as well as hypertriglyceridemy, hypertension, and peripheral arterial disease. In DM, overall, more vascular abnormalities were found than in PM. Our findings suggest that flow-mediated dilatation of the brachial artery, arterial stiffness, and carotid artery thickness measurements could be beneficial for predicting the CVD risk in myositis patients. Further investigations need to find the potential differences and role of inflammation and immune mechanisms in atherosclerotic processes in DM and PM.

Noninvasive perioperative monitoring of arterial function in patients with kidney transplantation.

Development of atherosclerosis is accelerated in kidney transplant recipients. Impaired metabolic pathways have a complex effect on the arterial wall, which can be measured by noninvasive techniques. Few data are available on the change of stiffness parameters in the postoperative course, so in this study we analyzed the stiffness parameters of kidney transplant recipients during the perioperative period. Seventeen successful primary kidney transplant patients with uneventful postoperative period (7 woman, 10 men; 46.16 ± 12.19 years) were involved in our short-term prospective longitudinal study. We analyzed the correlation between noninvasively assessed stiffness parameters (pulse wave velocity [PWV], augmentation index [AIx], pulse pressure [PP], systolic area index, diastolic area index, diastolic reflection area), ankle-brachial index (ABI), and laboratory parameters (creatinine, glomerular filtration rate, urea, haemoglobin, C-reactive protein). Stiffness parameters were measured with a Tensiomed Arteriograph. These parameters were assessed before the transplantation, and 24 hours, and 1 and 2 weeks after surgery under standard conditions. We found that creatinine (P = .0008) and C-reactive protein (P = .006) serum levels decreased, and glomerular filtration rate increased significantly (P = .0005). We revealed that PWV (P = .0075) and AIx (P = .013) improved significantly. There was no significant change in ABI, PP, and the other monitored parameters. Along with the available data in the literature, our findings suggest that kidney transplantation has a positive effect on the arterial function.

Prospective study of changes in arterial stiffness among kidney-transplanted patients.

BACKGROUND: Chronic kidney disease is one of the main risk factors for cardiovascular disease. Changes in stiffness parameters can predict the higher risk of the development of cardiovascular disease. METHODS: Cadaveric donor kidney transplant patients (n=184) were followed in a cross-sectional single-center study. Arterial stiffness parameters were measured by arteriography. We analyzed the correlation between stiffness parameters and immunosuppressive therapy, the main operation parameters, patient age, elapsed time since transplantation, carotid artery stenosis, and septual wall thickness. We enrolled 24 patients in a 3-year longitudinal study to analyze changes in stiffness parameters. RESULTS: Our cross-sectional study showed pulse wave velocity (PWV) to be significantly related to the age of the patient (P=.0001; r=0.41). There was no significant correlation between the stiffness parameters and type or dosage of immunosuppressive drugs and number of transplantations. We noted significant correlations between pulse pressure (PP) and pulse wave velocity (PWV), and augmentation index (AI) (P=.01). Patients with abnormal PWV (>12 m/s) showed significantly higher systolic blood pressures, body mass indexes, PP, and AI (P<.01). Our 3-year longitudinal study revealed a significant elevation in PWV. CONCLUSIONS: Improving endothelial function and prevention of atherosclerosis may help to reduce cardiovascular complications. Among chronic kidney disease patients, early transplantation is a possible way to prevent cardiovascular events. It is better to perform the transplantation at as early an age as possible.

Assessment of IgG antibodies to oxidized LDL in patients with acute coronary syndrome.

OBJECTIVES: Circulating IgG antibodies to oxidized low-density lipoprotein (anti-oxLDL) have been implicated in the development of atherosclerotic plaques. In this study, we investigated the prognostic value of IgG anti-oxLDL antibodies in patients with acute coronary syndrome (ACS). METHODS: In total 54 patients with ACS and 41 matched healthy controls were involved in this prospective study. Serum IgG anti-oxLDL levels were assessed by ELISA. RESULTS: Higher IgG anti-oxLDL levels were found in patients with ACS versus controls (22.8 ± 23.3 vs. 7.5 ± 5.27 EU/ml, p < 0.0001). IgG anti-oxLDL concentrations were significantly higher in ACS patients with unstable clinical complications (circulatory insufficiency, malignant arrhythmias, recurring ischaemic pain, positive stress-test, need for urgent coronary intervention or sudden cardiac death) versus those without such complications (30.0 vs. 11.7 EU/ml, p < 0.001). Twelve patients (22%) were taking statins. Patients on statins had a significant reduction in clinical complications (33%) versus patients not receiving statin therapy (61%). IgG anti-oxLDL levels were also different in these two groups (11.4 vs. 25.8 EU/ml, respectively; p = 0.03). Serum IgG anti-oxLDL levels correlated with the subsequent development of unstable coronary events. Levels of anti-oxLDL significantly decreased in response to statin therapy, independently of its lipid-lowering effect. CONCLUSIONS: Anti-oxLDL antibodies are involved in ACS. The association of anti-oxLDL with unstable clinical complications may indicate the role of this antibody in plaque destabilization.

Clinical and immunoserological characteristics of the transition from primary to overlap antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a distinct clinical entity characterized by arterial and venous thromboembolic events, recurrent fetal loss and the presence of antiphospholipid antibodies in the patients' sera. In primary APS, there is no detectable underlying disease, while overlap APS is associated with clinical syndromes including systemic autoimmune diseases, infections, or malignancies. We carried out a retrospective analysis of serological and clinical manifestations as well as assessed outcome-measures in 165 patients with primary APS. Thrombotic manifestations and possible signs of autoimmune diseases were determined at the time of the diagnosis, followed by the analysis of recurrent thrombotic events and effects of therapy during the follow-up period. Among the 165 patients with primary APS at onset, 105 patients (63%) remained primary APS after a mean 5.2 years of follow-up. In 14% of the patients, subsequently APS became associated with various characteristics of undifferentiated connective tissue disease. Finally 23% of patients evolved into a definitive systemic autoimmune disease during a mean 9.75 years of follow-up. Recurrent thrombotic events were registered in 24% of patients. Our results suggest that primary APS may be considered as a potential early phase of a dynamic transition towards a well-defined systemic autoimmune disease.

Immunological parameters, including CXCL8 (IL-8) characterize cerebro- and cardiovascular events in patients with peripheral artery diseases.

The most commonly occurring atherosclerotic manifestations are peripheral artery diseases (PAD). Immune-mediated processes contribute to the development of atherosclerosis, and affect the diseases outcome. The aim of the present study was to assess various immune-competent cells, cytokines and chemokines in patients with PAD and to evaluate whether the base immunological values reflect the subsequent development of cardio/cerebrovascular symptoms. One hundred sixty patients with PAD were followed-up for 42 months. At the time of enrolment, we determined blood lymphocyte subpopulations, both T-helper (Th)1/Th2-type intracytoplasmic cytokines and soluble cytokines, chemokines. Intracellular cytokines were measured on phorbol-myristate-acetate- and ionomycine- stimulated cells. Lymphocyte subgroups were quantified by flow cytometry, soluble cytokines by ELISA and intracellular cytokine levels were measured by flow cytometry. The ankle-brachial index (ABI), indicator of atherosclerosis, was also evaluated. The clinical results were correlated with the immune-parameters to assess the input of immune-inflammatory events in the propagation of vascular manifestation. CD4(+) T-cell proportions in patients with PAD with cerebro- cardio-vascular manifestations were decreased, which further reduced in patients with fatal outcome. Of circulating chemokines, IL-8 (CXCL-8) was increased in patients with subsequent cerebro- cardio-vascular manifestations, compared to those without the symptoms, and further raised in patients with fatal outcome. The percentage of interferon (IFN)-gamma positive cells showed clear negative correlation with ABI. We conclude that altered peripheral lymphocyte subsets and cytokine/chemokine imbalance play important roles in the proinflammatory cascade and reflect disease severity in patients with PAD.

Immunological features of primary anti-phospholipid syndrome in connection with endothelial dysfunction.

OBJECTIVES: To describe how certain peripheral immune parameters reflect the inflammatory alterations in patients with primary APS. METHODS: Twenty-eight patients with newly diagnosed primary APS were studied. The control group included 26 patients with stable coronary disease and 38 healthy individuals. Peripheral blood lymphocyte subgroups were quantified, intracellular cytokines were measured by flow cytometry, soluble cytokines and auto-antibodies were assessed using ELISA. Endothelial dysfunction was evaluated by measuring endothelium-dependent (flow-mediated; FMD) vasodilation. Carotid duplex ultrasound was performed to quantify the carotid artery intima-media thickness (IMT). Stiffness parameters, augmentation index (AIx) and pulse wave velocity (PWV) were assessed by TensioClinic technology. RESULTS: Serum IL-4 and IL-6 levels were significantly higher in APS. CD4+IL10+ and CD8+IL10+ cell percentages in APS were significantly increased compared with controls. Th 0 and T cytotoxic 0 cell percentages were significantly decreased in patients compared with controls. FMD in APS was significantly lower, while IMT was higher than that of controls. FMD showed strong association with stiffness parameters, AIx and PWV. A significant negative linear correlation was detected between PWV and CD8+IL10+ cell percentages and significant positive linear correlation was found between PWV and CD8+IL10- cell percentage. CONCLUSION: In APS, the orchestrated pro-inflammatory cascade can eventually result in endothelial dysfunction, leading to the characteristic vascular abnormalities of the disease.

The severity of systemic lupus erythematosus negatively correlates with the increasing number of CD4+CD25(high)FoxP3+ regulatory T cells during repeated plasmapheresis treatments of patients.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased pathologic autoantibody production. A decrease in the number of CD4+CD25(high)FoxP3+ regulatory T cells can play a key role in the loss of tolerance to self antigens. Our aim was to determine the absolute number of peripheral CD4+CD25(high)FoxP3+ T cells in 44 patients with SLE, furthermore, to measure the changes in the number of CD+CD25(high)FoxP3+ T cells in 5 patients with severe SLE treated with repeated plasmapheresis for 4-6 days in comparison to the changes in the activity of disease (SLEDAI). Percent of CD4+CD25(high)FoxP3+ T cells were measured by flow cytometry. The absolute number of peripheral CD4+CD25(high)FoxP3+ T cells was significantly decreased in the 44 patients with SLE compared to the healthy controls n = 32 (0.012 +/- 0.006 vs. 0.038 +/- 0.017 G/L, p < 0.05). In the 5 patients with severe SLE the repeated plasmapheresis treatments increased the peripheral number of CD4+CD25(high)FoxP3+ T cells. As the number of CD4+CD25(high)FoxP3+ T cells increased during the treatment, the activity of disease (the value of SLE activity index) decreased. In the peripheral blood of SLE patients not only the ratio was decreased (as it was published earlier) but also the absolute number of these regulatory T cells. The repeated plasmapheresis treatments of SLE patients induced a significant increase in the number of peripheral CD4+CD25(high)FoxP3+ T cells in parallel to the decrease in the values of SLEDAI (the activity of disease). This phenomenon is, among others, possibly due to the elimination of interpheron-alpha and lymphocytotoxic antibodies during plasmapheresis.

Impaired endothelial function and increased carotid intima-media thickness in association with elevated von Willebrand antigen level in primary antiphospholipid syndrome.

Primary antiphospholipid syndrome (APS) is characterized by venous or arterial thrombotic events and/or recurrent abortions, fetal death, preeclasmpsia, eclampsia in the presence of anticardiolipin antibodies or lupus anticoagulant, in the absence of accompanying diseases. Antiphospholipid antibodies can activate endothelial cells, and were recently implicated in atherosclerosis. To assess potential endothelial impairment and early signs of atherosclerosis, flow-mediated (endothelium-dependent) and nitrate-mediated (endothelium independent) vasodilation, as well as von Willebrand factor antigen level and carotid artery intima-media thickness (IMT) were measured in patients with primary antiphospholipid syndrome and in healthy controls. Flow-mediated vasodilation in patients with primary APS was significantly lower than that of controls (3.43 +/- 2.86% versus 7.96 +/- 3.57%; P < 0.0001). We also found significantly higher von Willebrand antigen levels in patients with primary APS than in the control group (157.91 +/- 52.45% versus 125.87 +/- 32.8%; P = 0.012). Moreover, carotid artery IMT was significantly larger in the primary APS group compared to controls (0.714 +/- 0.2 mm versus 0.58 +/- 0.085 mm; P = 0.0037). Our results reflect ongoing endothelial damage and accelerated atherosclerosis in patients with primary APS, and suggest that vasoprotective therapy may be beneficial in the treatment of these patients.

Endothelial dysfunction precedes atherosclerosis in systemic sclerosis--relevance for prevention of vascular complications.

OBJECTIVES: The pathogenesis of systemic sclerosis (SSc) includes vasculopathy with endothelial dysfunction. The aim of this study was to investigate endothelium-dependent, flow-mediated dilatation (FMD), as well as endothelium-independent, nitroglycerin-mediated dilatation (NMD) of the brachial artery and to assess common carotid intimal-medial thickness (ccIMT) in SSc patients compared with healthy controls. METHODS: FMD and NMD of the brachial artery were determined using high-resolution ultrasound imaging and the values were expressed as percentage change from baseline in 29 SSc patients and 29 healthy controls. The two groups were very similar regarding sex, age and traditional cardiovascular risk factors. In addition, common carotid arteries were assessed by duplex colour ultrasound, ccIMT determined using high resolution ultrasound and expressed in mm thickness in the same patients and controls. Correlations between FMD, NMD, ccIMT, age and the SSc subtype (diffuse or limited form) were analysed. RESULTS: In the 29 SSc patients (mean age: 51.8 yrs), the FMD was significantly lower (4.82 +/- 3.76%) in comparison with the controls (8.86 +/- 3.56%) (P < 0.001). No difference was found in NMD between patients (19.13 +/- 17.68%) and controls (13.13 +/- 10.40%) (P > 0.1). There was a tendency of increased ccIMT in SSc patients (0.67 +/- 0.26 mm) compared with healthy subjects (0.57 +/- 0.09), but this difference was not significant (P = 0.067). A significant, positive correlation between ccIMT and age in SSc (r = 0.470, P = 0.013) was detected, as well as in healthy controls (r = 0.61, P = 0.003), but no correlation was found between FMD and age. In addition, ccIMT, but not FMD and NMD, displayed significant correlation with disease duration (r = 0.472, P = 0.011). NMD displayed significant inverse correlation with the age in SSc patients (r = -0.492, P = 0.012), but not in controls. We did not find any correlation between FMD, NMD, ccIMT and SSc subtype. CONCLUSIONS: There is an impairment of endothelium-dependent vasodilatation indicated by low FMD in SSc. At the same time, the endothelium-independent dilatation assessed by NMD is still preserved giving an opportunity of nitroglycerine therapy. Carotid atherosclerosis indicated by ccIMT may occur at higher ages and after longer disease duration. Thus, the assessment of FMD in the pre-atherosclerotic stage may have a beneficial diagnostic, prognostic and therapeutic relevance.

TH1/TH2 imbalance, measured by circulating and intracytoplasmic inflammatory cytokines--immunological alterations in acute coronary syndrome and stable coronary artery disease.

To describe how peripheral immune-parameters reflect the inflammatory alterations of the atherosclerotic plaques in coronary atherosclerosis. We measured general inflammatory markers C-reactive protein (CRP) and granulocyte activity, lymphocyte subpopulations and their state of activation, evaluated circulating Th1/Th2-type cytokines, and specific intracytoplasmic cytokines. We investigated the association of immune-parameters with disease outcome and mortality. Thirty-three patients with acute coronary syndrome (ACS), 62 with stable coronary artery disease (CAD) and 58 healthy controls were studied. Peripheral blood lymphocyte subgroups were quantified by flow cytometry, soluble cytokines and autoantibodies were assessed using enzyme-linked immunosorbent assay (ELISA), while intracellular cytokine levels were measured by flow cytometry after intracellular staining. We found elevated levels of CRP and granulocyte activity in ACS versus CAD (P < 0.001, P = 0.017, respectively). Natural killer (NK) cell percentages were elevated, while percentage of T cells to the total lymphocyte count was slightly decreased in ACS compared to controls (P < 0.0001, P = 0.012, respectively). Both forms of coronary atherosclerosis showed significantly higher percentages of activated T cells than controls when stained for the activation markers HLA-DR3 and CD69(+) (ACS: P < 0.0001, P = 0.002, CAD: P < 0.0001, P = 0.018, respectively). IL-1, IL-4 and IL-10 proved significantly higher in ACS versus controls (P = 0.036, P = 0.01, P < 0.0001 respectively). Th1 to Th2 ratio shifted towards a Th1 dominance in both diseases. Both general proinflammatory markers and activated T cells signify CAD. The orchestrated proinflammatory cascade eventually leads to the development of the disease.

Clinical and immunoserological characteristics of mixed connective tissue disease associated with pulmonary arterial hypertension.

We investigated the clinical characteristics and immunoserological alterations in patients with mixed connective tissue disease (MCTD) associated with pulmonary arterial hypertension (PAH). Anti-U1RNP autoantibodies, anti-endothelial cell antibodies (AECA) and serum thrombomodulin (TM) as well as von Willebrand factor antigen (vWFAg) concentrations were measured in 25 patients with MCTD associated with PAH and in 154 MCTD patients without PAH. The results showed that the probability of survival was lower in MCTD patients with PAH than in the 154 MCTD-non-PAH patients (5-year survival rate in MCTD with PAH: 73%, versus 96% in MCTD-non-PAH; P < 0.01). AECA were more frequently present in the sera of MCTD patients with PAH than in MCTD-non-PAH (P < 0.001). Serum TM and vWFAg levels were higher in MCTD-PAH patients than in MCTD-non-PAH patients (TM: P < 0.001; vWFAg: P < 0.001). Significant correlation was noticed between the quantity of AECA and TM level (r = 0.466) as well as the quantity of AECA and vWFAg level (r = 0.550). In conclusion, our results suggest that in MCTD the presence of AECA and endothelial cell activation may play a role in the development of PAH and in the maintenance of obliterative vascular processes.

Antiphospholipid antibodies in acute coronary syndrome.

Antiphospholipid (aPL) antibodies entailing anticardiolipin (aCL) and anti-beta2 glycoprotein I (anti-beta2GPI) antibodies may be involved in a number of vascular diseases including coronary artery diseases (CAD) or stroke. Here we assessed the presence of aPL antibodies in acute coronary syndrome (ACS). The frequency of anti-beta2GPI antibodies was significantly higher (14.4%) in ACS in comparison to control healthy subjects (2%). In addition, serum concentrations of anti-beta2GPI antibodies were also increased in ACS. Anti-beta2GPI antibodies of the IgA isotype might be the most relevant for the onset and outcome of ACS. Regarding subclasses of ACS, anti-beta2GPI IgA antibodies were elevated in unstable angina (UA) and myocardial infarction with ST elevation (STEMI), but not in myocardial infarction without ST elevation (NSTEMI). The involvement of anti-beta2GPI antibodies in ACS was more pronounced in men than women, and in younger rather than older patients. Finally, anti-beta2GPI antibodies in ACS were associated with previous stroke, but not with hypertension or previous myocardial infarction. Thus, anti-beta2GPI antibodies may be involved in the thrombotic events underlying ACS.

Evaluation of clinical and laboratory features of antiphospholipid syndrome: a retrospective study of 637 patients.

We retrospectively analysed the data of 1519 antiphospholipid antibody (APLA) positive patients between 1986 and 1999. Among them 637 were considered to have antiphospholipid syndrome (APS) based on the 1999 preliminary classification criteria, while 704 patients had no clinical signs of the syndrome. Our aim was to compare the autoantibody profile and clinical characteristics of primary and secondary APS, moreover to evaluate the associations between different APLA and specific symptoms attributable to APS. In our results, the APLA profiles for primary and SLE-associated secondary APS were similar. Among the evaluated clinical symptoms, cerebrovascular thrombosis was found to be more frequent in the SLE-associated, than in the primary APS group (P = 0.04). We identified important differences in the clinical profile of patient populations with various types of APLA. Venous thrombosis occurred more frequently in subjects withlupus anticoagulant (LA), than in those with IgG or IgM type ACLA (P < 0.0001), while coronary, carotid and peripheral artery thrombosis occurred more often in subjects with IgG or IgM ACLA (P < 0.0001). These findings may support the role of antibodies to cardiolipin or its cofactor, beta2glycoprotein I (beta2-GPI) in the initiation and progression of atherosclerosis. Cerebrovascular thrombosis was detected in larger proportion of LA or IgG ACLA-positive patients compared with to IgM ACLA-positive subjects, while the occurrence of foetal loss was similar in all three groups.

[The effect of plasmapheresis and other immunomodulating therapies on the course of severe Guillain-Barré syndrome]. / Plazmaferézis és kombinált immunmoduláns terápia hatása súlyos tünetekkel járó Guillain-Barré-szindrómás betegek kórlefolyására.

Clinical datas of 20 patients with severe Guillain-Barre syndrome were evaluated retrospectively. The diagnosis was established on the electrophysiological and histopathological examinations (electroneurography, electromyography, sural nerve and muscle biopsy) and the analysis of the cerebrospinal fluid. All of the patients were treated with plasma exchange and some of them with other immunomodulant therapies (intravenous immunoglobuline, steroid, cyclophosphamide), too. To judge the clinical state correctly we used the modified Rankin scale. The patient's follow up went on for maximum 4 years. The improvement was satisfactory in 7 cases (35%) and good in 6 patients (30%). The last 6 patients had pure motor neuropathy. Six patients (30%) remained in severe residual condition. All of them had long-term course of disease, serious sensory symptoms and predominantly axonal degeneration of the peripheral nerves. One patient had died. The plasma exchanges were well tolerated, without any serious adverse event. This therapy would be safe and effective help in Guillain-Barre syndrome.

Antiprothrombin and antiannexin V antibodies imply risk of thrombosis in patients with systemic autoimmune diseases.

OBJECTIVE: To investigate the relationship between antiprothrombin (aPT) and antiannexin V (aANX) autoantibodies of IgG isotype and thrombosis in patients with systemic autoimmune diseases. To compare the clinical relevance of these antibodies to that of anticardiolipin (aCL), anti-beta2-glycoprotein I antibodies (anti-beta2-GPI), and lupus anticoagulant (LAC). METHODS: Serum IgG aPT, aANX, aCL, and anti-beta2-GPI levels were measured by solid phase enzyme immunoassay in the sera of 70 patients with systemic autoimmune diseases, 35 with antiphospholipid syndrome (APS) and 35 without APS. Medical records were analyzed, and associations of the antibodies with clinical features of APS were assessed. RESULTS: Patients with APS had higher frequency of aPT (p = 0.001) and aANX (p = 0.002) compared to patients without APS. Thrombotic events occurred more frequently in those with aPT or aANX than those without (p = 0.005, p = 0.006, respectively). The presence of aPT and aANX was found to be highly specific for APS. CONCLUSION: Measurement of aPT and aANX antibodies may be of value in confirming the diagnosis of APS, and in evaluating risk of venous and arterial thrombosis in patients with systemic autoimmune diseases.

Catastrophic antiphospholipid syndrome in cancer.

Antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies resulting in arterial and venous thromboembolism. Apart from primary cases, this syndrome is often associated with autoimmune diseases. Around 50 cases of catastrophic antiphospholipid antibody syndrome have been reported as yet. Authors describe the first case of catastrophic antiphospholipid syndrome associated with gastric cancer. Apart from presenting the clinical case, authors also discuss the possible pathomechanism of this associated disorder including the role of immunological factors, as well as antiphospholipid antibodies.