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Systemic lupus erythematosus (SLE) is characterized by the breakdown of self-tolerance, the production of high-affinity pathogenic autoantibodies and derailed B cell responses, which indicates the importance of central players, such as follicular T helper (T

Antiphospholipid syndrome (APS) encompasses a wide spectrum of disease manifestations that may prevail in the form of venous or arterial thrombosis or lead to pregnancy complications in the presence of persisting antiphospholipid antibodies (aPL). Unlike in the case of congenital thrombophilias, in which venous thromboses are more likely to occur as compared with arterial events, aPL may cause thrombosis in both types of vascular systems. Arterial thrombosis in APS is fairly common and often involve coronary or cerebral arteries leading to myocardial infarction (MI) or stroke. In this review, we summarize the complex pathomechanisms leading to aPL‑associated thrombosis and list challenges during the laboratory detection of these antibodies. Specific features of MI in patients with APS are summarized based on a comprehensive literature search of available case reports. Preventive and treatment strategies are discussed based on the current recommendations and most recent evidence. We conclude that the risk of MI in patients with APS is considerable and MI may be the first manifestation of the disease. MI in APS shows specific clinical features including relatively young age at presentation, no sex dominance, often normal coronaries without the sign of atherosclerosis, high risk of recurrent thrombotic events. Treatment of acute MI in patients with APS is often challenging and adverse events, including stent thrombosis, are more frequent as compared with patients without APS. Preventive strategies in APS should be personalized and include strict management of additional cardiovascular risk factors and long‑term anticoagulation with vitamin K antagonists. Current evidence does not support the use of direct oral anticoagulants in the management of patients with APS with arterial thrombosis due to the high risk of recurrent events.

Generally, a reciprocal antagonistic interaction exists between the antiviral type I interferon (IFN) and the antibacterial nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3)-dependent IL-1β pathways that can significantly shape immune responses. Plasmacytoid dendritic cells (pDCs), as professional type I IFN-producing cells, are the major coordinators of antiviral immunity; however, their NLRP3-dependent IL-1β secretory pathway is poorly studied. Our aim was to determine the functional activity of the IL-1β pathway and its possible interaction with the type I IFN pathway in pDCs. We found that potent nuclear factor-kappa B (NF-κB) inducers promote higher levels of pro-IL-1β during priming compared to those activation signals, which mainly trigger interferon regulatory factor (IRF)-mediated type I IFN production. The generation of cleaved IL-1β requires certain secondary signals in pDCs and IFN-α or type I IFN-inducing viruses inhibit IL-1β production of pDCs, presumably by promoting the expression of various NLRP3 pathway inhibitors. In line with that, we detected significantly lower IL-1β production in pDCs of psoriasis patients with elevated IFN-α levels. Collectively, our results show that the NLRP3-dependent IL-1β secretory pathway is inducible in pDCs; however, it may only prevail under inflammatory conditions, in which the type I IFN pathway is not dominant.

Since B-cell hyperactivity and pathologic antibody response are key features in the immunopathogenesis of primary Sjögren’s syndrome (pSS), the role of follicular T helper (TFH) cells as efficient helpers in the survival and differentiation of B cells has emerged. Our aim was to investigate whether a change in the balance of circulating (c)TFH subsets and follicular regulatory T (TFR) cells could affect the distribution of B cells in pSS. Peripheral blood of 38 pSS patients and 27 healthy controls was assessed for the frequencies of cTFH cell subsets, TFR cells, and certain B cell subpopulations by multicolor flow cytometry. Serological parameters, including anti-SSA, anti-SSB autoantibodies, immunoglobulin, and immune complex titers were determined as part of the routine diagnostic evaluation. Patients with pSS showed a significant increase in activated cTFH cell proportions, which was associated with serological results. Frequencies of cTFH subsets were unchanged in pSS patients compared to healthy controls. The percentages and number of cTFR cells exhibited a significant increase in autoantibody positive patients compared to patients with seronegative pSS. The proportions of transitional and naïve B cells were significantly increased, whereas subsets of memory B cells were significantly decreased and correlated with autoantibody production. Functional analysis revealed that the simultaneous blockade of cTFH and B cell interaction with anti-IL-21 and anti-CD40 antibodies decreased the production of IgM and IgG. Imbalance in TFH subsets and TFR cells indicates an ongoing over-activated humoral immune response, which contributes to the characteristic serological manifestations and the pathogenesis of pSS.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by recurrent thrombotic events, pregnancy loss and thrombocytopenia and the presence of antiphospholipid antibodies (APL). The exact pathomechanism of APS is still unknown, thus we investigated the effect of anti-βFor the separation of anti-βIn normal pooled plasma, the anti-βThe anti-β

To detect replicating viruses, dendritic cells (DCs) utilize cytoplasmic retinoic acid inducible gene-(RIG) I-like receptors (RLRs), which play an essential role in the subsequent activation of antiviral immune responses. In this study, we aimed to explore the role of the mammalian target of rapamycin (mTOR) in the regulation of RLR-triggered effector functions of human monocyte-derived DCs (moDCs) and plasmacytoid DCs (pDCs). Our results show that RLR stimulation increased the phosphorylation of the mTOR complex (mTORC) 1 and mTORC2 downstream targets p70S6 kinase and Akt, respectively, and this process was prevented by the mTORC1 inhibitor rapamycin as well as the dual mTORC1/C2 kinase inhibitor AZD8055 in both DC subtypes. Furthermore, inhibition of mTOR in moDCs impaired the RLR stimulation-triggered glycolytic switch, which was reflected by the inhibition of lactate production and downregulation of key glycolytic genes. Blockade of mTOR diminished the ability of RLR-stimulated moDCs and pDCs to secret type I interferons (IFNs) and pro-inflammatory cytokines, while it did not affect the phenotype of DCs. We also found that mTOR blockade decreased the phosphorylation of Tank-binding kinase 1 (TBK1), which mediates RLR-driven cytokine production. In addition, rapamycin abrogated the ability of both DC subtypes to promote the proliferation and differentiation of IFN-y and Granzyme B producing CD8 + T cells. Interestingly, AZD8055 was much weaker in its ability to decrease the T cell proliferation capacity of DCs and was unable to inhibit the DC-triggered production of IFN-y and Granyzme B by CD8 + T cells. Here we demonstrated for the first time that mTOR positively regulates the RLR-mediated antiviral activity of human DCs. Further, we show that only selective inhibition of mTORC1 but not dual mTORC1/C2 blockade suppresses effectively the T cell stimulatory capacity of DCs that should be considered in the development of new generation mTOR inhibitors and in the improvement of DC-based vaccines.

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Background Detection of anti-neutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence assays (IFA) is of diagnostic importance in vasculitides and some other inflammatory diseases. Automation of IFA may be beneficial in high-throughput clinical laboratories. An analytical appraisal of the EUROPattern (EPa) automated microscope and image analysis system has not been reported in a routine clinical laboratory setting testing samples from both vasculitis and non-vasculitis patients. Methods Results of EPa and on-screen ANCA pattern recognition of 568 consecutive routine serum samples were compared to those of conventional visual evaluation. Results Agreement of discrimination between negative and non-negative samples was 86.1% comparing EPa and conventional reading, and it increased to 96.7% after on-screen user validation. Importantly, from the 334 samples classified as negative by EPa 328 (98.2%) were also negative by conventional evaluation. Pattern recognition showed ‘moderate’ agreement between classical microscopic and EPa analysis (κ = 0.446) and ‘very good’ agreement after user validation (κ = 0.900). Misclassification by EPa was dominantly due to the presence of anti-nuclear/cytoplasmic antibodies (incorrect pattern, 80/568) and the lower fluorescence cut-off of the automated microscope (false positives, 73/568). Conclusions Automated ANCA testing by EPa is a reliable alternative of classical microscopic evaluation, though classification of sera needs correction by trained personnel during on-screen validation.

Long-term survival of patients with systemic lupus erythematosus (SLE) improved worldwide; thus, prevention of cumulative organ damage became a major goal in disease management. The aim of our study was to investigate the chronic organ damages and their influence on disease outcome in SLE. We evaluated clinical conditions, laboratory findings and medications of 357 consecutive SLE patients and assessed their impact on Systemic Lupus Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) and disease outcome. We detected one or more SDI scores in 77.87% of patients. Patients with disease duration of more than 10 years and subjects diagnosed at age above 40 had significantly higher SDI values. The most frequent damages were valvulopathies, cognitive dysfunction, angina pectoris and venous thrombosis. Higher cumulative glucocorticoid dose increased SDI, while chloroquin treatment was favourable for patients. Male gender, elevated SDI scores and higher cumulative doses of glucocorticoids increased mortality risk. Our data confirmed that disease duration, age at diagnosis and chronic high-dose glucocorticoid therapy have significant effects on the development of chronic organ damage. Higher SDI score is characterized with worse survival ratios. The most common chronic organ damages affected the cardiovascular or neuropsychiatric system. As long-term survival in SLE improves, it becomes increasingly important to identify the determinants of chronic organ damage. Most of the chronic organ damage occurs in the cardiovascular and the neuropsychiatric systems; thus, regular follow-up, screening and adequate therapy are essential for the best clinical outcome.

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.

Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are systemic autoimmune diseases with complex symptoms and pathogenesis that are still not completely understood. Several studies showed that the trace element homeostasis and also the levels of antioxidant plasma proteins are changed in autoimmune disorders; however, these results are controversial. In this study, the potassium (K), calcium (Ca), magnesium (Mg), copper (Cu), zinc (Zn), and iron (Fe) concentrations of the serum and proteins-immunoglobulin G (IgG), transferrin (Trf), albumin (Alb), and ceruloplasmin (Cp)-separated from serum samples by affinity chromatography were determined in patients with SLE and SS. Ca and K levels were found to be decreased in the case of both disorders compared to the control group, and the competitive antagonism of Cu and Zn was also observed: elevated Cu concentration together with a lower Zn concentration was measured in the sera of patients with autoimmune diseases. After fractionation, the trace element concentration of protein containing fractions altered to that of the control group. In case of the autoimmune disorders, the highest Cu concentration was determined in the Alb-containing protein fractions while the Zn level decreased in the Alb and increased in the Cp as well as in the IgG- and Trf-containing fractions compared to the healthy samples. Changes have also been found in the level and distribution of K and Ca.

The clearance of apoptotic cells has an important role in the maintenance of tissue homeostasis and in the protection of tissues from the inflammatory and immunogenic contents of dying cells. A defect in the recognition and phagocytosis of apoptotic cells contributes to the development of chronic inflammation and autoimmune disorders. We have observed that compared with healthy donors, differentiated macrophages from patients with untreated systemic lupus erythematosus (SLE) showed decreased phagocytosis of apoptotic neutrophils. A TaqMan Low Density Array was designed to determine the mRNA expression levels of 95 apopto-phagocytic genes in differentiated non-phagocytosing and phagocytosing macrophages. In the macrophages of clinically and immunoserologically active SLE patients, 39 genes were expressed at lower levels than in the control macrophages. When inactive patients were compared with those with minor immunoserological abnormalities or patients in an immunoserologically active state, a relationship was observed between the altered gene expression profile and the disease state. In the macrophages of patients with engulfing apoptotic cells, an upregulation of genes involved in inflammation, autophagy, and signaling was observed. These results indicate that novel immune-pathological pathways are involved in SLE and suggest targets for potential therapeutic modulation.

Background The causes of increased cardiovascular risk in systemic lupus erythematosus (SLE) are not understood thoroughly, although presence of traditional cardiovascular risk factors and disease-specific agents were also proposed. In this study, we investigated the quantitative changes in the lipid profile, as well as qualitative characteristics of high-density lipoprotein (HDL) and markers of inflammation and disease activity in SLE patients. Methods Lipoprotein levels were determined in 51 SLE patients and 49 healthy controls, matched in age and gender. HDL antioxidant capacity was determined spectrophotometrically with a cell-free method of hemin-induced low-density lipoprotein (LDL) oxidation. Polyacrylamide gel-electrophoresis was used for HDL subfraction analysis. Human paraoxonase-1 (PON1) activity, apolipoprotein A1 (ApoA1) and oxidized LDL concentrations, as well as interleukin-6, high-sensitivity C-reactive protein, serum amyloid A and monocyte chemotactic protein-1 levels were determined. Results HDL-cholesterol and ApoA1 concentrations decreased significantly in SLE subjects. Also, PON1 arylesterase activity (125.65 ± 26.87 vs. 148.35 ± 39.34 U/L, p = 0.001) and total HDL antioxidant capacity (165.82 ± 58.28 % vs. 217.71 ± 54.36 %, p

Summary Follicular T helper (Tfh) cells have a crucial role in regulating immune responses within secondary lymphoid follicles by directing B cell differentiation towards memory B cells and plasma cells. Because abnormal humoral responses are key features in both primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE), the aim of this study was to profile the pathological connection between peripheral Tfh cells and B cells in the two diseases. Twenty-five pSS patients, 25 SLE patients and 21 healthy controls were enrolled into the study. We determined the ratio of circulating Tfh-like cells, their interleukin (IL)-21 production and different B cell subsets by flow cytometry. We observed higher percentages of naive B cells in both diseases, while non-switched and switched memory B cells showed decreased frequencies. The proportions of double-negative B cells and plasmablasts were elevated in SLE and decreased in pSS. The percentages of transitional B cells and mature-naive B cells were higher in SLE. Patients with more severe disease course had an elevated ratio of TFH-like cells and increased IL-21 production. Moreover, expansion of Tfh-like cells correlated positively with parameters related to antibody secretion, including serum immunoglobulin (Ig)G, immune complexes (ICs) and autoantibodies. Correlation analysis between Tfh-like cells and certain B cell subsets revealed possible defects during B cell selection. In conclusion, our observations on the profound expansion of circulating Tfh-like cells and their IL-21 production, along with the characteristic aberrant peripheral B cell distribution in both pSS and SLE, indicate the prominent role of Tfh cell in the regulation of B cell selection.

Disproportionate vitamin D levels may play an important role in the development of certain systemic autoimmune and rheumatic diseases. The aim of the present study was to investigate the prevalence of vitamin D insufficiency in patients with systemic lupus erythematosus (SLE) and to compare serological and clinical parameters in patients with different vitamin D levels from a single centre registry in Central-Eastern Europe.A total of 177 patients with SLE were enrolled in the study. 25-Hydroxyvitamin D [25(OH)D] levels were measured by chemiluminescent immunoassay (CLIA). Autoantibody profiles, complement 3 (C3) and C4, clinical symptoms, and disease activity (using the SLE disease activity index, SLEDAI) of the patients were assessed.Vitamin D concentration in the total SLE group investigated was 26.88 ± 13.25 ng/mL. Vitamin D levels were normal (≥ 30 ng/mL) in 18.1% of patients, insufficient (15-30 ng/mL) in 44.6%, and deficient (15 ng/mL) in 37.3%. The vitamin levels were significantly reduced in postmenopausal compared to premenopausal patients (p = 0.02). Patients with pericarditis (p = 0.013), neuropsychiatric diseases (p = 0.01), and deep vein thrombosis (p = 0.014) had reduced vitamin D levels. SLEDAI score was significantly increased in patients with reduced vitamin D levels (p = 0.038). Anti-double-stranded (ds)DNA autoantibody concentrations increased from normal to insufficient and further increased from insufficient to deficient patient subsets (p = 0.021). Anti-Smith antigen (anti-Sm) concentrations increased (p0.001), C4 levels decreased (p = 0.027), and immunoglobulin (Ig)G concentration increased (p = 0.034) in patients with reduced vitamin D levels.Our data suggest that vitamin D deficiency in SLE may play a role in perpetuation of the disease.

To analyze the association of antiphospholipid antibodies (aPL) with the development of clinical thrombotic manifestations and to characterize the efficacy of anti-thrombotic therapies used.272 systemic lupus erythematosus (SLE) patients participated in the study. Patient files and a cumulative database were used to collect patients' medical histories. Anti-cardiolipin (aCL), anti-beta2-glycoprotein I (abeta2GPI) antibodies, and lupus anticoagulant (LAC) were measured according to international recommendations. New thrombotic events were registered during follow-up.The patients were prospectively studied for 5 years, of whom 107 were aPL negative (aPL- group). Criteria for antiphospholipid syndrome (APS) were fulfilled by 84 of 165 aPL-positive patients (APS+ group) indicating that SLE patients with aPL have around 50% risk to develop thrombotic complications. The aPL+ group (n = 81) consisted of aPL+ but APS- patients. LAC was the most common aPL (n = 27, 32.1%) in patients with APS. The cumulative presence of aPL further increased the prevalence of thrombotic events. During the follow-up period, aPL developed in 8 of 107 patients (7.5%) from the aPL- group, of whom 3 (2.8%) presented with thrombotic complications. Other types of aPL developed in 7 of 165 (4.2%) aPL+ patients within 5 years. New thrombotic events occurred in 3.7% of aPL+ (n = 3) and 8.3% (n = 7) of the APS group. During follow-up, 52 of 81 aPL+ patients received primary prophylaxis, and 1 (1.9%) had transient ischemic attack (TIA). In the non-treatment group, 2 (6.9%) had stroke. Seventy-nine of 84 of the APS patients received secondary prophylaxis, and myocardial infarction occurred in 2 patients (on cumarine therapy maintaining an international normalized ratio around 2.5-3.0), and 5 suffered a stroke/TIA (1 on aspirin and 4 on aspirin + cumarine).The findings emphasize the importance of determining both aCL and abeta2GPI antibodies and LAC in SLE patients and the need for adequate anticoagulant therapy.

As a result of increasing life expectancy of lupus patients, malignant disorders have become major determinants of morbidity and mortality. The objectives of this study were to analyze cancer-associated morbidity and mortality, the type of malignancies in Hungarian lupus patients, and to analyze association with immune-suppressive therapy, disease duration, and age of the patients. Data from 860 systemic lupus erythematosus (SLE) patients were retrospectively analyzed in a study period between 1970 and 2004. Results were compared to data from age- and sex-matched population obtained from the Health for All database, and also to literature data. A total of 37 patients presented with cancer, reflecting 4.3% cancer-associated morbidity. Patients were 47 (20-73) years old at the onset of malignancy, which appeared 13 (1-45) years later than SLE. Cancer prevalence was the highest in the first 5-10 years of lupus. Breast cancer was the most common malignancy (n = 11) followed by gastrointestinal tumors (n = 9), cervix cancer and hematologic malignancies (n = 5 for both), bronchial cancer (n = 4), bladder, skin, and ovarian cancer (n = 1 for each). Standardized incidence ratio was the highest for non-Hodgkin lymphoma (standardized incidence ratio [SIR] 3.5, 95% CI 0.4-12.5) and cervix cancer (SIR 1.7, 95% CI 0.6-4.1). Although 76% of patients with cancer received immune-suppressive therapy besides corticosteroids, no direct correlation could be confirmed between therapy and malignancy. Out of the 164 patients that expired during the study period, 18 were cancer-related. As such the cancer-associated mortality was 11% (18/164). This peaked during the last 4 years of the study period (8/24, 33%). Lupus patients are at high risk for particular types of malignant disorders, highlighting the importance of screening measures and focused patient examination.

The objective of this study was to analyse whether primary antiphospholipid syndrome (PAPS) may precede and modify the characteristics of systemic lupus erythematosus (SLE). Out of the total 362 SLE patients in our service, 223 patients had antiphospholipid antibodies (aPL), of whom 110 met the criteria of antiphospholipid syndrome. In 26 cases (7.2%) PAPS appeared 5.5 years before the onset of lupus (PAPS+SLE Group). Their clinical findings were compared to lupus patients without (SLE only Group, n = 26) and with secondary APS (SLE+SAPS Group, n = 26). The prevalence of deep venous thrombosis, stroke/TIA, recurrent fetal loss, coronary heart disease and myocardial infarction was significantly higher in PAPS+SLE Group as compared to SLE only Group. The difference in prevalence of fetal loss ( P = 0.014) between PAPS+SLE and SLE+SAPS Groups was also recorded. On comparison to PAPS+SLE Group, patients without APS (SLE only Group) were younger at onset of lupus, with more frequent flares and a higher prevalence of WHO type III/IV nephritis ( P = 0.007), requiring higher doses of cyclophosphamide and corticosteroids. Lupus started in the form of PAPS in 7.2% of our SLE patients, who presented with more thrombotic and less inflammatory complications than in SLE patients without a prior or with a following secondary APS. Considering the long latency between the two diseases, PAPS may be a forerunner of lupus, but it may also coexist with SLE as an independent autoimmune disorder. Lupus (2007) 16 , 324—328.

Systemic lupus erythematosus is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Objectives were to determine endothelial dysfunction with a non-invasive method in lupus patients and to analyse correlation with risk factors and atherosclerotic complications. Sixty-one SLE patients and 26 healthy age- and sex-matched control subjects were entered into the study. The diameters of brachial artery at rest, during reactive hyperaemia, and after glyceril trinitrate administration, as well as the intima-media thickness of the common carotid artery were measured using high-resolution B-mode ultrasonography. Demographic characteristics, lipid profile, paraoxonase activity, concentration of anti-phospholipid antibodies and anti-oxLDL were assessed together with atherosclerotic complications. The endothelium dependent vasodilation (FMD) was significantly impaired in SLE patients as compared to controls. The absolute difference of vessel diameter (Δd) was 0.25 ± 0.15 mm vs. 0.38 ± 0.16 mm ( p = 0.001), and Δd as in percent of the rest diameter was 7.31 ± 5.2% vs. 9.86 ± 3.87% ( p = 0.013) in lupus patients and controls, respectively. Nitrate mediated dilation (NMD) did not differ. FMD negatively correlated with age, systolic and diastolic blood pressure in SLE, but did not show significant correlation with the other examined parameters. However, FMD significantly differed between SLE patients with (5.54 ± 4.36%) and without (8.81 ± 5.28%) cardiovascular complications ( p = 0.01). The determination of flow-mediated vasodilation is a useful method to detect endothelial dysfunction in lupus patients, as reduced capacity of brachial artery may distinguish between SLE patients and healthy subjects, as well as lupus patients with and without atherosclerotic vascular complications.

The discovery of microRNAs (miRNAs) and their critical role in genetic control opened new avenues in understanding of various biological processes including immune cell lineage commitment, differentiation, proliferation and apoptosis. However, a given miRNA may have hundreds of different mRNA targets and a target might be regulated by multiple miRNAs, thus the characterisation of dysregulated miRNA expression profiles could give a better insight into the development of immunological disturbances in autoimmune diseases. The aim of our study was to examine the changes in miRNA expression profiles in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). Eight SLE patients, 8 pSS patients and 7 healthy subjects were enrolled in the investigation. MiRNAs were isolated from peripheral blood mononuclear cells, and expression patterns were determined with Illumina next-generation sequencing technology. Since the immunopathogenesis of pSS and SLE encompasses pronounced B cell hyperactivity along with specific autoantibody production, we paid a special attention on the association between miRNA expression levels and altered peripheral B cell distribution. In SLE patients 135, while in pSS patients 26 miRNAs showed altered expression. Interestingly, the 25 miRNAs including miR-146a, miR-16 and miR-21, which were over-expressed in pSS patients, were found to be elevated in SLE group, as well. On the contrary, we observed the down-regulation of miR-150-5p, which is a novel and unique finding in pSS. Levels of several miRNAs over-expressed in SLE, were not changed in pSS, such as miR-148a-3p, miR-152, miR-155, miR-223, miR-224, miR-326 and miR-342. Expression levels of miR-223-5p, miR-150-5p, miR-155-5p and miR-342-3p, which miRNAs are potentially linked to B cell functions, showed associations with the B cell proportions within peripheral blood mononuclear cells. The observed differences in miRNA expression profiles and the better understanding of immune regulatory mechanisms of miRNAs may help to elucidate the pathogenesis of SLE and pSS.

Although most reported patients with immunoglobulin G4-related disease (IgG4-RD) are from the Far East, we aimed to identify patients suffering from IgG4-RD in our University Centre in Debrecen, Hungary.Serum IgG4 levels were measured at 51 of our 800 patients followed up because of Sjögren's syndrome (SS) if one or more clinical signs during the disease course raised the possibility of IgG4-RD (persisting salivary gland swelling, absence of anti-Ro/SSA and anti-La/SSB antibodies in the serum, and positive salivary gland biopsy, coexistence of autoimmune pancreatitis, autoimmune hepatitis, or primary sclerosing cholangitis, persisting lymphadenopathy). Where available, histological samples of small salivary gland biopsies were revised to detect the particular features of IgG4-RD. Pathologists and surgeons were informed about the disease and asked to refer suspicious cases.Based on our survey, eight patients were identified with IgG4-RD. Pancreatic, salivary gland, aortic, and retroperitoneal manifestations were detected. Of the 51 patients with SS, four appeared to have IgG4-RD, but eventually one was excluded.Although IgG4-RD is not yet well known to physicians of Western countries, it occurs in Caucasians and probably in other races as well. Moreover, our eight cases diagnosed with IgG4-RD demonstrate a relatively large European patient population collected in a single centre. European clinicians, and especially rheumatologists, should be informed and at least certain laboratories should be prepared to investigate patient samples if the suspicion of IgG4-RD is raised. The main clinical significance of an accurate diagnosis is the extreme corticosteroid sensitivity of IgG4-RD.

The objective of the study was to investigate the possibility whether the in vitro treatment with vitamin D3 can restore the impaired expression of protein kinase C (PKC) isoenzymes and IL-2 production in the lymphocytes of patients with systemic lupus erythematosus (SLE). Purified T lymphocytes from 14 patients with SLE and 13 healthy controls were cultured for 48 h in the presence and absence of 1 and 100 nM doses of vitamin D3. The expressions of various PKC isoenzymes were tested by Western blot analysis, and the amounts of various cytokines were detected by ELISA in the culture supernatants. Neither the low (1 nM) nor the high (100 nM) doses of vitamin D3 (1α,-25-dihydroxyvitamin) applied in vitro for 48 h were able to restore the decreased expression of PKC isoenzymes in the T cells of SLE patients. However, 100 nM of vitamin D3 significantly increased the release of IL-10, but suppressed the production of IL-2, IL-6, interferon γ and TNF α in the culture supernatants of both groups. As the low production of IL-2 is one of the main pathologic features of SLE, we recommend to avoid the use of high doses of vitamin D3 for treatment of lupus patients with vitamin D3 deficiency.

MicroRNA-146a (miR-146a) is a microRNA supposed to regulate innate immune, inflammatory response and antiviral pathway negatively. Recently, its potential use as a biomarker for disease diagnosis, prevention and treatment has become widely investigated. In the current study, we measured the expression of miR-146a/b, and their target genes, IRAK1, IRAK4, TRAF6 in the peripheral mononuclear cells of patients with Sjogren's syndrome (n=21) and healthy controls (n=10) by quantitative reverse transcription polymerase chain reaction. We found that both miR-146a and miR-146b, furthermore, the gene of TRAF6 were significantly overexpressed in the Sjogren's patients, whereas the expression of IRAK1 gene was significantly decreased. The expression of IRAK4 did not differ significantly. These results suggest that in the peripheral mononuclear cells of Sjogren's patients, the transcriptional repression of IRAK1 is taking place, whereas the other NF-κB pathway regulating gene, TRAF6 is overexpressed. As IRAK1 has been regarded a crucial gene in the pathogenesis of systemic lupus erythematosus, TRAF6 can be a Sjogren's syndrome specific biomarker, confirming and partly explaining the existance of different pathogenic pathways in the two diseases. These observations, however, need still wider confirmations.

We investigated the association between systemic lupus erythematosus (SLE) and polymorphisms of interleukin-23 receptor (IL23R) gene, which was recently found to be associated with autoimmune diseases, including Crohn's disease, rheumatoid arthritis, psoriasis and ankylosing spondylitis.We analysed 383 SLE patients and 253 controls for rs11805303, rs10889677, rs1004819, rs2201841, rs11209032, 11209026, rs10489629, rs7517847 and rs7530511 variants.The analysis was carried out using PCR-RFLP methods. Logistic regression analysis was used to compare the genotype distributions of the polymorphisms and haplotypes between the SLE patients and healthy controls.We observed no significant difference of the examined variants between the patient and control groups.Our results suggest that neither single nucleotide variants nor haplotypes of IL23R indicate susceptibility to developing SLE in the Hungarian population.

We investigated the genetic background regarding major histocompatibility complex (MHC) II alleles in patients with systemic lupus erythematosus (SLE) only, in patients with SLE with secondary antiphospholipid syndrome (SLE+SAPS), and in patients whose clinical course began as primary antiphospholipid syndrome (PAPS) and subsequently progressed to SLE (PAPS+SLE) in order to explain the phenotypical differences found in our previous study. Those with primary or secondary APS present more thrombotic and less inflammatory activity. Fetal wastage was the highest in the PAPS+SLE group. We performed human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 genotyping in 63 patients (26, 22, and 15 in SLE only, SLE+SAPS, and PAPS+SLE groups, respectively) and in 57 healthy controls, using PCR with sequence-specific primers. We found that, as reported in the literature, the occurrence of DRB1*03 and DQB1*0201 alleles was higher in SLE patients than in controls, but these alleles were rare in the PAPS+SLE group (13% in PAPS+SLE vs. 46% in the SLE only group; P = 0.044). HLA-DRB1*04 alleles were expressed frequently in both primary and secondary APS. DRB1*13, DQB1*06, and DQB1*0302 alleles were present more frequently in the PAPS+SLE patients than in the other groups, while the DQB1*0301 allele was rare. In this study we have shown that the SLE-associated DRB1*03/DQB1*02 alleles occurred frequently in our lupus patients as well as in SLE patients with secondary APS. In patients who started as PAPS and later progressed to SLE, the allele frequency was fundamentally different. Taken together, our results confirmed that the HLA-DRB1 and HLA-DQB1 profile of PAPS and SAPS is different. Therefore it is unlikely that these alleles are responsible for the partly similar phenotype of the two groups.

Lupus anticoagulant (LA) and beta2-glikoprotein I (b2GPI) dependent anti-cardiolipin (aCL) are part of the diagnostic criteria both of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). Anti-phospholipid antibodies (aPL) may also bind to other phospholipids and/or protein co-factors. In the present study, besides aCL and anti-b2GPI, antibodies directed against phosphatidylserine, prothrombin (PT) and annexin V (aANX) were measured in 85 randomly selected SLE patients, 14 suffering from secondary APS. LA was detected by hemostasis tests. Correlations were determined between rare aPLs and clinical manifestations, including thrombotic events. Anti-cardiolipin IgG was positive in 14 patients, aCL IgM in 8, anti-b2GPI IgG in 4 and IgM in 5 patients. LA was detected in nine cases. Seven patients were positive for anti-phosphatidylserine (aPS) IgG, nine for aPS IgM, while anti-PT (aPT) IgG was positive in nine cases. aPT IgM and anti-aANX were negative in all patients. Correlation was found between aPS and aCL antibodies. The frequency and concentration of rare anti-phospholipid/co-factor antibodies was higher in patients with secondary APS. The presence of such rare aPLs cumulated in APS patients, their presence increased the frequency of thrombotic events in the entire study population, furthermore in patients positive for LA or aCL. Rare anti-phospholipid/co-factor antibodies were found in 12% of an un-selected lupus patient population. Their presence was more frequent in patients with secondary APS, and further increased the risk of thrombotic complications.

Some tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected increased production of CA15-3, CA19-9 and CA125 in rheumatoid arthritis (RA). The production of some TAAs may also be increased in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and other connective tissue diseases. Some of these TAAs contain sialylated carbohydrate motifs and they are involved in tumor-associated cell adhesion and metastasis.We assessed levels of TAAs in the sera of SSc, SLE patients, patients with infectious diseases and healthy subjects. Serum TAA levels were correlated with each other, as well as with disease activity markers and organ involvement.TAAs including CEA, CA15-3, CA72-4, CA125 and CA19-9 were assessed by immunoassay in the sera of 92 patients with SSc, 40 patients with SLE, 50 age- and sex-matched healthy controls, as well as with 40 patients with current bacterial or viral infections. Normal upper limits for these TAAs were 3.4 mg/l, 25 kU/l, 6.9 kU/l, 35 kU/l and 34 kU/l, respectively.There were significantly more SSc patients showing abnormally high levels of CA19-9 (8.8% vs 2.0%), CA125 (11.0% vs 6.0%) and CA15-3 (28.4% vs 14.0%) in comparison to controls (p0.05). In SLE, significantly more patients had elevated levels of CEA (32.5% vs 20.0%), CA19-9 (7.5% vs 2.0%), CA125 (15.0% vs 6.0%) and CA72-4 (15.0% vs 8.0%) than did controls (p0.05). The mean absolute serum levels of CEA (6.6+/-1.7 vs 1.8+/-1.4 mg/l) and CA15-3 (22.9 +/- 1.8 vs 18.6 +/- 2.2 kU/l) were also significantly higher in SSc compared to controls (p0.05). We found numerous correlations between the serum levels of different TAAs within the SSc and SLE population. Among SSc patients, serum CEA (R = 0.290; p = 0.005), CA15-3 (R = 0.260; p = 0.020) and CA19-9 (R = 0.257; p = 0.013) correlated with renal involvement. Serum CA15-3 also correlated with joint involvement (R = 0.329; p = 0.003), ANA positivity (R = 0.288; p = 0.010) and CRP levels (R = 0.407; p0.001). Within the SLE population, serum CA72-4 correlated with central nervous involvement (R = 0.624; p = 0.004) and CA125 correlated with the SLEDAI composite activity index (R = 0.666; p = 0.002). Patients with infections exerted serum TAA patterns similar to healthy controls.The concentration of some TAAs may be elevated in the sera of patients with SSc or SLE in comparison to healthy subjects. Pathogenically, most of these TAAs contain carbohydrate motifs and thus they may be involved in inflammation-associated adhesive events. Furthermore, the production of some TAAs may correlate with organ involvement or disease activity in scleroderma or lupus.

Skin vasculitis may be associated with infections and autoimmune diseases. Furthermore, vasculitis may appear as a paraneoplastic symptom. A 19-year-old male patient was examined with swollen joints and papules presented on lower extremitis. Laboratory results showed high erythrocyte sedimentation ratio, positive C reactive protein, increased number of leukocytes and high circulating immune complex level. Histopatology of skin biopsy specimen proved vasculitis. ANCA was not present. No other changes could be observed besides skin involvement. Symptoms disappeared on 0.5-mg/bwkg methylprednisolon therapy. Few weeks later, enlarged cervical lymph nodes developed besides fever and weight loss. Biopsy indicated the presence of mixed cell type Hodgkin lymphoma. Appropriate examinations revealed clinical stage III/B with favorable prognosis (IPS=2). After eight cycles of ABVD therapy complete remission was achieved as confirmed by FDG-PET. As a consequence of the treatment of Hodgkin lymphoma, vasculitis also disappeared. The present case report calls to attention the importance of careful examinations to exclude other diseases, especially malignancies that may remain at the background of cutaneous vasculitis. Treatment of the primary disease also results in the improvement of secondary skin vasculitis.

Excessive lipid peroxidation is a major factor of accelerated atherosclerosis, observed in patients with systemic lupus erythematosus (SLE). We aimed at the present study to determine the paraoxonasel (PON1) and arylesterase activities, and lipid-profile in 37 SLE patients and 30 age-/sex-matched controls. Association was analyzed between PON1 activity and SLEDAI, CRP, anti-oxLDL, and antiphospholipid antibody (aPL) levels, steroid dose, and atherothrombotic events. The age of patients was 40.8 +/- 13.9 year, follow-up time 6.7 +/- 6.2 year, SLEDAI 2 (0-15). PON1 and arylesterase activities were measured spectrophotometrically using paraoxon and phenyl acetate as substrates, respectively. Phenotypic distribution of PON1 was determined by dual substrate method. We measured antioxLDL and aPL levels by ELISA, the CRP by automated immunoassay. PON1 activity (121.9 +/- 65.9 U/mL) was reduced significantly (P < 0.001) in SLE as compared to control (188.1 +/- 78.9 U/mL), but arylesterase activity was not different. A negative correlation was found between PON1 activity and age. PON1 activity did not correlate with other measured parameters. Reduced PON1 activity associated with clinical atherothrombotic complications (P < 0.01). High activity BB phenotype was not present in SLE. Lipid parameters (TC, LDL-C, HDL-C, ApoAI, and ApoB) were within normal range in both groups. Results indicated reduced PON1 activity in lupus patients despite long disease duration and low inflammatory activity, and it was evidenced as a risk for atherosclerotic complications. As the arylesterase activity was normal, further examinations are required to find other mechanisms, such as anti-PON1 antibodies, genetic polymorphisms, and difference in distribution of HDL-subfractions or enzyme abnormalities in HDL remodeling.

The aim of this study was to detect antibodies to vitamin D in systemic lupus erythematosus (SLE) and other autoimmune diseases. The results may shed light to a novel aspect of vitamin D deficiency in autoimmune diseases. Sera from 171 patients with SLE, 56 with antiphospholipid syndrome (APS), and 18 with pemphigus vulgaris (PV) were studied employing an enzyme-linked immunosorbent assay for anti-vitamin D antibodies along with 94 healthy blood donors. In parallel, vitamin D concentrations in the serum were determined by a DiaSorin commercial kit (LIAISON 25 OH vitamin D). Antibody-positive and antibody-negative individuals were compared with respect to demographic variables, SLE disease activity index (SLEDAI) score, autoantibodies profile, and serum vitamin D levels. Anti-vitamin D antibodies were detected in 7 (4%) of 171 patients with SLE, in 2 (3.5%) of 56 of sera from patients with APS, and in 2 (11%) of 18 sera from patients with PV. Vitamin D levels were similar in both SLE groups with and without anti-vitamin D antibodies. Demographic features, organ involvement, SLEDAI score, and autoantibodies did not differ between the groups. Except for anti-dsDNA antibodies, in which anti-vitamin D antibodies were strongly associated with these antibodies in sera from SLE patients (P = 0.0004). Anti-vitamin D antibodies are observed in a subset of patients with SLE, APS, and PV, and are associated with anti-dsDNA antibodies in SLE. Further studies are required to explore the potential diagnostic and prognostic role of these novel antibodies in SLE.

Abnormalities of regulatory T cells may play an important role in the loss of self-tolerance, which is a major characteristic of lupus. The objective of this study was to determine the ratio and the number of natural CD4+CD25highFoxp3+ and inducible CD4+IL-10+ regulatory T cells in lupus patients and to search correlation with disease activity. Seventy-two Hungarian lupus patients were enrolled in the study. Fourty-one age- and sex matched healthy donors served as controls. Flow cytometry was used for the quantification of CD4+CD25high Foxp3+ (nTreg) and CD4+IL-10+ (iTreg) cells. The ratio (3.06 ± 1.45%) and the number (0.019 ± 0.012 × 109/L) of nTreg cells decreased in lupus significantly ( P < 0.001 in both) as compared to normal controls (4.26 ± 1.01% and 0.039 ± 0.017 × 109/L). The ratio of iTreg cells were significantly higher in patients than in controls (20.92 ± 14.02% versus 15.49 ± 11.65%, P < 0.03), but the number of these cell type did not differ in significant manner (0.314 ± 0.236 × 109/L versus 0.259 ± 0.183 × 109/L). The 19 active patients were characterised by significantly higher disease activity index (SLEDAI 8.63 ± 2.95 versus 1.74 ± 1.68, P < 0.001) and anti-DNA concentration (117.85 ± 145.89 versus 37.36 ± 68.85 IU/mL, P = 0.001) as compered to the 52 inactive patients. Furthermore, active patients required higher dose of methylprednisolon than inactive ones (14.8 ± 10.6 versus 4.8 ± 3.4 mg/day, P < 0.001). However, we did not find statistical significant difference in the number and ratio of the examined cell populations regarding to disease activity. Altered ratio and number of both natural and inducible regulatory T cells may play a role in the pathogenesis of lupus. There are small but appreciable difference in the number of regulatory T cells between inactive patients and healthy controls. It suggests that immunoregulatory deficiencies are present in the inactive stage of the disease also. Lupus (2007) 16, 489—496.

Chronic organ damages and complications have become one of the major problems concerning morbidity and mortality in systemic lupus erythematosus.Present study was to examine the frequencies and types of malignancies in a lupus population followed regularly in our department, and to find correlation between cancer-associated mortality and the use of immune suppressants.Authors analysed data 860 lupus patients from 1965 till the end of 2004. During study period 164 patients died, 18 of whom from cancer. The frequency of cancer-associated mortality was 11% that was 2% of the total lupus population. Mortality has increased within 10-year periods reaching the maximum between 2001-2004 (8/24, 33%). Age of the 37 patients affected by malignancy was 47.7 (20-73) years. Cancers appeared 13.4 (1-45) years after the diagnosis of lupus. Breast cancer occurred most frequently (n=11) followed by gastro-intestinal malignancies (n=9), then cervix cancer and different hematologic malignancies (5-5 cases), bronchial cancer (n=4) and skin, ovarian and vesical cancers (1-1-1 cases). Relative risk of non-Hodgkin lymphoma and cervix cancer increased significantly as compared to those of the Hungarian general female population. Before the cancer developed 62.2% of patients received azathioprine and/or cyclophosphamide.Present results describe and analyse for the first time the association between lupus and malignant disorders in a Hungarian population calling the attention for the increased risk for the development of cancers and the importance of regular screening and extended examinations in SLE patients.

Systemic lupus erythematosus is a chronic autoimmune disease with multiple organ involvements. Dup to earlier diagnosis and more effective therapeutic possibilities the survival in lupus has improved significantly in recent decades, however, critical situations may develop.In the present work the authors aimed to summarise critical complications of lupus requiring urgent therapeutic modification, hospitalisation, sometimes at intensive care units.As a systemic autoimmune disorder lupus may involve all vital organs of the human body and as such, it may result in heart failure, respiratory and renal insufficiency, and severe, life-threatening central nervous system complications. These can develop within a short period due to an acute flare, but also as the consequence of chronic progression. Infections, pregnancy, withdrawal of therapy, physical and psychological stress may provoke the worsening of the disease. However, critical situations can be the consequence not only directly of lupus, but due to side-effects of therapy, associating disorders and co-incidence with other severe diseases.Lupus may cause several critical situations that require urgent intervention and/or hospitalisation. The recognition and the solution of these severe lupus crises is a complex, multidisciplinary challenge that should be organised by competent, well-prepared immunologic centres.

The authors discuss the case of a 76-year-old female patient who has been suffering from subacute cutaneous lupus erythematosus since 1983. In 1999 she was diagnosed with systemic lupus erythematosus (SLE) based on her symptoms of malar rash, polyarthritis, leukopenia, autoimmune hemolytic anemia and positive anti-DNA antibody test. For this she received methylprednisolone and cyclophosphamide. After 3 years of remission, symptoms of cutaneous vasculitis appeared in 2004, which transitionally responded to treatment with azathioprin and methylprednisolone. Her cutaneous symptoms, however, progressed quickly along with generalized lymphadenopathy, splenomegaly and thrombocytopenia. Immunohistological evaluation of the lymph node biopsy showed diffuse large B-cell lymphoma. She developed complete remission after treatment with six-cycle R-CHOP (rituximab, and reduced doses of cyclophosphamide, vincristin, adriablastin, methylprednisolone). SLE became inactive and her symptoms of vasculitis resolved. The authors are bringing attention to one of the possible late complications of systemic lupus, and also underscoring that treatment with rituximab (+CHOP) was beneficial not only for the lymphoma but the SLE as well.

Immune-inflammatory processes play important role in the pathogenesis of atherosclerosis. Therefore, increasing attention is focused on rheumatic diseases with chronic inflammation, such as systemic lupus erythematosus. Besides direct influences, inflammation may modify the development of atherosclerosis by other mechanisms.To examine paraaoxonase activity and lipid profile in lupus patients.Authors entered 37 definitive lupus patients and 30 age- and sex-matched normal controls into the present study. Patients' age was 40.8 +/- 13.9 year, follow-up time 6.7 +/- 6.2 year, disease activity index 2.8 +/- 3.4. Lipid parameters (total cholesterol, LDL-C, HDL-C, Apo-AI and ApoB) were determined by an autoanalyser, paraoxonase and arylesterase activities were measured spectrophotometrically. Phenotypic distribution of the enzyme was determined by dual substrate method. Anti-oxLDL was measured by ELISA method, CRP by automatised immunoassay. Statistical analysis was performed by SPSS program.Despite of long disease duration and low inflammatory activity authors found significantly (p0.001) decreased paraoxonase activity (121.9 +/- 65.9 U/mL) (p0.001) in lupus as compared to control (188.1 +/- 78.9 U/mL), which correlated with the presence of atherothrombotic complications (p = 0.009). High activity BB phenotype did not occur in lupus. Lipid parameters and arylesterase activity were within normal range in both groups. No significant correlation was found between paraoxonase activity and disease activity index, dose of corticosteroid therapy, CRP and anti-oxLDL level. Arylesterase activity did not differ in lupus and control groups.Present results suggest that other mechanisms, e.g. antibodies, genetic factors, alteration in the distribution of HDL-subfractions or ensyme abnormalities in HDL remodelling may stand at the background of reduced paraoxonase activity in lupus.

Antiphospholipid syndrome is a multi-organ autoimmune disorder, characterized by arterial and venous thrombotic events, and a well-defined group of recurrent foetal wasteage due to pathologic antibodies against phospholipids and protein co-factors. Antiphospholipid antibodies can be formed in primary antiphospholipid syndrome, but also in other conditions, most often in systemic lupus erythematosus. This may modify the outcome of lupus increasing the risk for thrombotic complications. Less is known about the outcome in primary antiphospholipid syndrome, whether it may precede the development of systemic lupus.Authors hereby describe the case of four patients with primary antiphospholipid syndrome in whom the disease progressed to systemic lupus erythematosus.Lupus followed the primary antiphospholipid syndrome within around a three-year period. It was indicated by the appearance of different antinuclear autoantibodies and clinical complications, such as polyarthritis, nephritis and hematologic disturbances. All of the patients presented cerebrovascular accident as the thrombotic manifestation. All but one, were around forty years old, and had a milder form of lupus. Symptoms of the antiphospholipid syndrome determined the outcome. On the other hand, a typical lupus developed in the youngest patient.According to present cases antiphospholipid syndrome may be considered as the initiative phase of SLE, but APS being a separate entity also may associate to lupus. Present observations indicate the importance of follow-up the patients with APS by immunologic respect. Future prospective, multi-centre studies with larger number of cases are needed to provide further evidence on the fact that patients with APS may acquire other autoimmune disorder.

Systemic lupus erythematosus (SLE) is a multifactorial polysystemic autoimmune disorder. Although life expectance in SLE has been improved by adequate immune suppressive therapy, the importance of chronic renal failure has not been reduced. Among late complications of the disease accelerated atherosclerosis attempts increasing attention. Dyslipoproteinemia and increased concentration of lipoproteins are important risk factors of atherosclerotic cardiovascular complication in SLE. Serum lipid parameters of 50 patients with lupus were examined in the present work. Thirty patients had histologically proven lupus nephritis (LN+), while the other group did not have renal involvement (LN-). Serum triglyceride, total cholesterol, LDL-C and apolipoprotein B (apoB) concentrations were significantly higher in the lupus nephritis (LN+) group. On the other hand, HDL-C and apoAI levels were also elevated in patients with LN. As a consequence of that, LDL-C/HDL-C and the apoB/apoAI ratios did not differ between patients with or without kidney involvement. This concluded the authors to measure the concentration of lipoprotein (a) in SLE patients, as Lp(a) is known to be an independent risk factor of atherosclerosis. Results indicated a significantly increased Lp(a) concentration in patients with lupus nephritis as compared to the LN- group. All but 2 patients without kidney involvement had lower than 100 mg/L Lp(a) concentration, while 27% of patients with lupus nephritis has an Lp(a) level between 100-300 mg/L. Further more, Lp(a) concentration was higher than 300 mg/L in 13% of the LN+ group. In a good correlation of these observations patients with nephritis suffered more frequently from deep venous thrombosis and ischaemic heart disease. The frequencies of hypertension and non-insulin dependent diabetes mellitus were slightly elevated in patients with nephritis. Present results suggest the importance of elevated lipoprotein (a) concentration in patients with lupus nephritis, further increasing the risk of athero-thrombotic cardiovascular complications.