Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.

Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300)

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex multi-organ disease, characterised by relapses and remissions. DESIGN: ng a high-quality randomised controlled trial poses many challenges. We have developed evidenced-based recommendations for points to consider in conducting clinical trials in patients with SLE. METHODS: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Initially, the evidence for clinical trial end-points in SLE was evaluated and this has been reported separately. A consensus approach was developed by the SLE Task Force in formulating recommendations for points to consider when conducting clinical trials in SLE. RESULTS: The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not actually been validated in clinical trials, although other forms of validation have been undertaken. The final recommendations for points to consider for conducting clinical trials in SLE address the following areas: study design, eligibility criteria, outcome measures including adverse events, concomitant therapies for SLE and its complications. CONCLUSIONS: Recommendations for points to consider when conducting clinical trials in SLE were developed using an evidence-based approach followed by expert consensus. The recommendations should be disseminated, implemented and then reviewed in detail and revised using an evidence-based approach in about 5 years, by which time there will be further evidence to consider from current clinical trials.

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus: literature based evidence for the selection of endpoints.

OBJECTIVE: To assess available evidence on the use of end-points (outcome measures) in clinical trials in systemic lupus erythematosus (SLE), as a part of the development of evidence-based recommendations for points to consider in clinical trials in SLE. METHODS: The European League Against Rheumatism (EULAR) Task Force on SLE comprised 19 specialists, a clinical epidemiologist and a research fellow. Key questions addressing the evidence for clinical trial end-points in SLE were compiled using the Delphi technique. A systematic search of the PubMed and Cochrane Library databases was performed using McMaster/Hedges clinical query strategies and an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence and agreement on the statements was measured across the 19 specialists. RESULTS: Eight questions were generated regarding end-points for clinical trials. The evidence to support each proposition was evaluated. The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not been formally validated in clinical trials, although some indirect validation has been undertaken. CONCLUSION: This systematic literature review forms the evidence base considered in the development of the EULAR recommendations for end-points in clinical trials in SLE.

Magnetic resonance volumetry of pathological brain foci in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of our study was to determine the volume of pathological foci in the brain tissue of patients suffering from systemic lupus erythematosus (SLE) with or without neuropsychiatric manifestations (NP), and also to find out if that volume depends on the study subjects' data and clinical records. Magnetic resonance (MR) scans of patients with SLE and, in particular, signs of neuropsychiatric involvement, show pathological foci in the cerebral white matter. METHODS: A total of 53 SLE patients, 29 with signs of neuropsychiatric syndromes (NPSLE), 24 without, and 16 healthy controls underwent prospective volumetric magnetic resonance imaging in a flow attenuated inversion recovery (FLAIR) sequence. The disease activity was expressed in terms of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: All the patients in this study were found to have a larger volume of pathological foci in the brain tissue than the healthy controls. The NPSLE subgroup had a larger volume of pathological foci than the SLE patients without NP (p<0.001). The largest volume of such foci was found in the patients with a history of cerebrovascular disease (p<0.05). These were also noted for a correlation between the duration of the disease and the period of time elapsed from the onset of the first signs of neuropsychiatric lupus (p<0.01). Correlation with SLEDAI-rated disease activity was found statistically significant in all the patients (p<0.05) and in those with NPSLE at a level of p<0.01. CONCLUSION: We found that the lesion load was significantly larger in NPSLE than in SLE patients free from NP and controls. Our measurement revealed a positive correlation between the lesion load and SLEDAI in the whole SLE patients group, particularly in the subgroup with NP manifestation. In the future, longitudinal volumetry might conceivably facilitate the therapeutical effect rating.

EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course and prognosis. We sought to develop evidence-based recommendations addressing the major issues in the management of SLE. METHODS: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Key questions for the management of SLE were compiled using the Delphi technique. A systematic search of PubMed and Cochrane Library Reports was performed using McMaster/Hedges clinical queries' strategies for questions related to the diagnosis, prognosis, monitoring and treatment of SLE. For neuropsychiatric, pregnancy and antiphospholipid syndrome questions, the search was conducted using an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence, and agreement on the statements was measured across the 19 specialists. RESULTS: Twelve questions were generated regarding the prognosis, diagnosis, monitoring and treatment of SLE, including neuropsychiatric SLE, pregnancy, the antiphospholipid syndrome and lupus nephritis. The evidence to support each proposition was evaluated and scored. After discussion and votes, the final recommendations were presented using brief statements. The average agreement among experts was 8.8 out of 10. CONCLUSION: Recommendations for the management of SLE were developed using an evidence-based approach followed by expert consensus with high level of agreement among the experts.

Prevalence of antinucleosome antibodies by enzyme-linked immunosorbent assays in patients with systemic lupus erythematosus and other autoimmune systemic diseases.

The objective was to report our experience with the detection of antinucleosome antibodies (anti-Ncs Ab) in a series of systemic lupus erythematosus (SLE) patients, and to compare these results with those of antihistone and anti-double-stranded (ds) DNA antibodies. For this we selected 128 patients (106 females, 22 males, mean age 40 years) including 52 patients with SLE without organ involvement, 14 with lupus nephritis, 8 with neuropsychiatric lupus (NPSLE), 39 with systemic sclerosis (SSc), 15 with Sjögren syndrome (SS), and 51 healthy controls (38 females, 13 males, mean age 42 years). The sera were assayed for the levels of anti-ds DNA (ELISA), antihistone (INNO LIA ANA Update), anti-Ncs Ab (ELISA) and antinuclear antibodies (ANA-indirect immunofluorescence (IIF) on Hep-2 cells). The frequencies of positive anti-Ncs Ab, anti-ds DNA, and antihistone antibodies were in group of patients with SLE: 73%, 63%, and 54%, with SSc: 18%, 8%, 5%, and with SS: 3%, 3% and 0%, respectively. Patients with SLE have significantly increased levels of anti-Ncs Ab in their sera compared to healthy controls, SSc patients, and patients with SS. The concentration of the anti-Ncs Ab was 76 IU/mL in the SLE patients, 139 IU/mL in cases with lupus nephritis, 117 IU in NPSLE patients, 15 IU/mL in the SSc and 8 IU/mL in the healthy controls. All the three autoantibodies were present more frequently in cases with lupus and this correlation was significant in statistical means. Antinucleosome IgG antibodies seem to be a more sensitive marker of SLE than anti-ds DNA.

Opposed independent effects and epistasis in the complex association of IRF5 to SLE.

Genetic variation in the interferon regulatory factor 5 (IRF5) gene affects systemic lupus erythematosus (SLE) susceptibility. However, association is complex and incompletely defined. We obtained fourteen European sample collections with a total of 1383 SLE patients and 1614 controls to better define the role of the different IRF5 variants. Eleven polymorphisms were studied, including nine tag single nucleotide polymorphisms (SNPs) and two extra functional polymorphisms. Two tag SNPs showed independent and opposed associations: susceptibility (rs10488631, P<10(-17)) and protection (rs729302, P<10(-6)). Haplotype analyses showed that the susceptibility haplotype, identified by the minor allele of rs10488631, can be due to epistasis between three IRF5 functional polymorphisms. These polymorphisms determine increased mRNA expression, a splice variant with a different exon 1 and a longer proline-rich region in exon 6. This result is striking as none of the three polymorphisms had an independent effect on their own. Protection was independent of these polymorphisms and seemed to reside in the 5' side of the gene. In conclusion, our results help to understand the role of the IRF5 locus in SLE susceptibility by clearly separating protection from susceptibility as caused by independent polymorphisms. In addition, we have found evidence for epistasis between known functional polymorphisms for the susceptibility effect.

Bias in association studies of systemic lupus erythematosus susceptibility due to geographical variation in the frequency of a programmed cell death 1 polymorphism across Europe.

We obtained eight collections of DNA samples from ethnically matched systemic lupus erythematosus (SLE) patients and controls from five European countries totaling 783 patients and 1210 controls. A highly significant cline in the frequency of the PD1.3 A allele was found among controls but not among SLE patients. The frequency of the PD1.3 A allele increased from the Northeast to the Southwest of Europe. The cline was clearly apparent (P=1.2 x 10(-6)) when data from controls of other five SLE susceptibility studies were included in the analysis. This variation has severely biased SLE association studies owing to the lack of parallel changes in SLE patients. As a consequence, the PD1.3 A allele was more common in SLE patients than in controls in the Northeast and Center of Europe, similar to controls in Southeast Europe, and less frequent than in the controls in the Southwest of the Continent. This dissociation in allele frequencies between SLE patients and controls in different subpopulations indicated that programmed cell death 1 variation and disease susceptibility are not independent but the type of relationship is currently unclear. As allele frequency clines are common in other polymorphisms their impact in genetic epidemiology studies should be carefully considered.

[Prolactin response to stress in patients with systemic lupus erythematodes (SLE), rheumatoid arthritis (RA) and in healthy controls]. / Stresová odezva prolaktinu u nemocnych se systémovým lupus erythematodes (SLE), revmatoidní artritidou (RA) a u zdravých kontrol.

Prolactin is a one of the stress hormones, like the growth hormone, ACTH, cortisol and catecholamins. Among its wide range of functions is the important role of controlling the immune response which is, unlike in the case of cortisol, of stimulatory nature. For this activity, it is monitored as a factor influencing the progress and course of autoimmune diseases. The authors of the paper monitored prolactin response to stress in a normal stress situation, i.e. blood collection. A significant difference was detected between the levels of prolactin in 3 successive blood collections in 30 minute intervals (P < 0.001). Prolactin responded by a prompt increase in the serum level, followed by a relatively fast linear decrease. There was no difference in the response between the SLE and RA patient groups and the healthy population. Therefore we conclude that this is a normal reaction of the organism because acute response to stress in patients with autoimmune diseases is the same as in healthy persons.

Epidemiology of rheumatoid arthritis, juvenile idiopathic arthritis and gout in two regions of the Czech Republic in a descriptive population-based survey in 2002-2003.

OBJECTIVE: To estimate the annual incidence and prevalence of rheumatoid arthritis (RA), juvenile arthritis (JIA) and gout in a population based study in two regions of the Czech Republic with total population of 186,000 inhabitants. METHODS: The study was conducted in the Town of Ceske Budejovice and district of Cheb in the Czech Republic (with a total population of 186,000 inhabitants) in the years 2002 and 2003. Incident cases were registered on condition that the definite diagnosis was confirmed according to existing classification criteria during the study period. Prevalence was studied on the basis of identification of established diagnosis from registers of patients of participating rheumatologists and other specialists. They were asked to report all living patients who had been diagnosed before 1st March 2002. Patients were only included in the study if their permanent address was in the selected study area. RESULTS: Overall, we found 48 incident and 947 prevalent cases of RA among adults (16+ years), 4 incident and 43 prevalent cases of JIA among children (less than 16 years old), and 64 incident and 425 prevalent cases of gout among adults (16+ years). The total annual incidence of RA was 31/100,000 in the adult population aged 16 years and more (95% CI 20 to 42/100,000). The prevalence of RA was 610/100,000 (95% CI 561 to 658/100,000) in the adult population. An annual incidence of gout in adults was 41/100,000 (95% CI 28 to 53/100,000). The prevalence of gout was 300/100,000 (95% CI 266 to 334/100,000). The annual incidence of JIA was 13/100,000 in children less than 16 years old (95%CI 1 to 20/100,000). The prevalence of JIA in children was 140/100,000 (95% CI 117 to 280/100,000). CONCLUSION: This study estimates the annual incidence and prevalence rates of RA, gout and JIA in the first population-based survey in the Czech Republic. The rates of RA and JIA compare well with figures reported from other countries; figures in gout seem to be lower than reported elsewhere.

[Antiphospholipid syndrome--the description of two cases]. / Antifosfolipidový syndrom--popisy dvou prípadu.

Antiphospholipid syndrome (APS) often occurs in young people, it is defined by the presence of venous or arterial thromboses, repeated miscarriages, thrombocytopenias and increased levels of antiphospholipid antibodies. Clinical symptoms are different, there is often experienced the phlebothrombosis of lower limbs, miscarriages or neurological symptoms characterized by transient ischemic attacks (TIA). If APS is associated with other system disease, most often with systemic lupus erythematosus (SLE), it is called secondary APS. We present two cases of secondary APS in the work. In first case we describe synchronous occurrence of SLE with secondary APS, which was clinically manifested by phlebothrombosis of veins of crus. At another elder patient there was stated the diagnosis of non-differentiated disease of bonding agent with secondary APS with cardial, pneumonic and neurological clinical symptoms.

EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis.

OBJECTIVE: To compare the efficacy and side effects of intermittent pulse cyclophosphamide plus methylprednisolone with continuous oral cyclophosphamide plus prednisolone, followed by azathioprine, in patients with proliferative glomerulonephritis caused by systemic lupus erythematosus (SLE). METHODS: A multicentre randomised controlled trial was conducted between June 1992 and May 1996 involving eight European centres. All patients satisfied the American College of Rheumatology criteria for SLE and had biopsy proven proliferative lupus nephritis. All received corticosteroids in addition to cytotoxic drugs, as defined in the protocol, for two years. The trial was terminated after four years as recruitment was disappointing. RESULTS: 32 SLE patients with lupus nephritis were recruited: 16 were randomised to intermittent pulse cyclophosphamide and 16 to continuous cyclophosphamide plus azathioprine. Mean duration of follow up was 3.7 years in the continuous group (range 0 to 5.6) and 3.3 years in the pulse group (range 0.25 to 6). Three patients were excluded from the pulse therapy group as they were later found to have pure mesangial glomerulonephritis. Two patients in the continuous therapy group developed end stage renal failure requiring dialysis, but none in the intermittent pulse therapy (p = 0.488; NS). There were similar numbers of side effects and withdrawals from treatment in both groups. There were three deaths: two in the intermittent pulse therapy group and one in the continuous therapy group. CONCLUSIONS: There was no statistically significant difference in efficacy and side effects between the two regimens. Infectious complications occurred commonly, so careful monitoring is required during treatment.

[Characteristics of foci of increased MR signals in the brain of patients with systemic lupus erythematosus and cerebral involvement]. / Charakteristika lozisek zvýseného MR signálu v mozku u nemocných se systémovým lupus erythematodes s postizením mozku.

The frequency and size of MR hypersignal foci in the white and grey matter in T2 weighted images were evaluated in 50 patients with the definite diagnosis of systemic lupus erythematosus (SLE) with neuropsychiatric symptomatology (neuropsychiatric lupus--NPSLE) and in 50 healthy persons in this study. The lesions were divided according to the size to lesions smaller than 3 mm, lesions of 3-6 mm size and ones greater than 6 mm. Their total and relative number in the brain, the number in cerebral supra- and infratentorial regions and in all cerebral lobes was evaluated. Further their occurrence in the brain in the mediolateral and craniocaudal direction of MR investigation was determined. The study showed that the focal pathology manifests itself in NPSLE patients in 100% of cases with pronounced white matter predominance; the supratentorial occurrence of lesions and their subcortical localization significantly prevailed. As the lesions size is concerned in all patients, the lesions up to 3 mm significantly prevailed, lesions of 3-6 mm size were solitary and lesions greater than 6 mm were present up to 10% of cases. The significant predominance of all size lesions number in frontal and parietal lobes was observed in both groups of investigated persons. The statistically significant difference (p < 0.01) between both followed groups (SLE patients and controls) was found as in absolute and relative numbers of supratentorial lesions up to 3 mm, as in the total brain and in single cerebral lobes. The significant difference was recorded in the same parameters in 3-6 mm lesions and in ones greater than 6 mm. Lesions greater than 6 mm were never observed in controls. This specification of cerebral MR finding in NPSLE patients significantly supports the clinical diagnosis of NPSLE, even though it is not specific.

Effects of stress on serum prolactin levels in patients with systemic lupus erythematosus.

The results of a study of effects of stress on serum prolactin (PRL) levels in patients with SLE reveal statistically significant differences in serum PRL level readings in samples taken over a short period of time, thus corroborating the need to take into account PRL stress induction during sample withdrawals and to interpret the values obtained, especially where moderate idiopathic hyperprolactinemia was detected. To eliminate any external stress factors, it is advisable to take PRL samples repeatedly and in perfectly resting patients.

Hyperprolactinaemia in patients with systemic lupus erythematosus.

OBJECTIVE: To verify the presence of hyper-PRL in SLE patients, its association with high disease activity, specific organ involvement or presence of anti-ds-DNA antibodies. METHODS: The group under study consisted of 80 patients with systemic lupus erythematosus (SLE), 28 patients with rheumatoid arthritis (RA) and 27 healthy controls. PRL serum levels were assayed using standard commercial kits (Immunotech Prague) with the radioimmunometric method for testing three samples of each of the subjects. The samples were taken in the morning hours (9-11 a.m.) of absolute rest 30 minutes after the introduction of the cannula at 30-minute intervals. RESULTS: A significantly higher rate of elevated PRL levels was found in SLE patients (40.0%) compared with the healthy controls (14.8%, p < 0.017). No proof was found of association with the presence of anti-ds-DNA or with specific organ involvement. Similarly, elevated PRL levels were found in RA patients (39.3%). The PRL elevation tended to decline from the 1st to the 3rd sample in the group of patients with SLE and RA but not in healthy controls. CONCLUSION: As follows from our measurements of prolactin serum values in SLE patients they are varriable by definition. According to our opinion further investigations are needed.

[EEG findings in patients with systemic lupus erythematosus]. / EEG nálezy u nemocných se systemovým lupus erythematosus.

We have examined electroencephalography (EEG) and Mini-Mental State Examination (MMSE) in 38 patients with verified diagnosis of systemic lupus erythematosus (SLE). In the clinical neurological finding there were epileptic attacks in 9 patients, 10 patients suffered from stroke, 15 patients from lupus headache, 4 patients from psychosis, in 15 patients cranial neuropathy was present, in one person extrapyramidal syndrome. EEG findings were in 12 patients normal (32%), in 26 patients abnormal (66%). In 3 cases there were focal abnormalities (8%), in 19 cases episodic ones (48%), four times abnormalities were diffuse (10%). Diffuse abnormalities correlated in EEG findings with case history of GM attacks.

Cytokines and adhesion molecules in renal vasculitis and lupus nephritis.

BACKGROUND: Plasma levels of some pro-inflammatory cytokines and soluble adhesion molecules have been suggested to be useful parameters to assess the activity of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis and lupus nephritis. We hypothesized that the renal activity of these diseases is better reflected by the urinary excretion and fractional excretion of these molecules. METHODS: Plasma levels and urinary excretion of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, and the soluble cell adhesion molecules sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 14 patients with ANCA-positive renal vasculitis (eight active, ANCA-A; six in remission, ANCA-R), six patients with active lupus nephritis (LN), 15 patients with IgA nephropathy (IgAN) and nine healthy subjects. Fractional excretion of selected cytokines and adhesion molecules was also calculated. RESULTS: Patients with ANCA-A had increased urinary excretion and fractional excretion of TNF-alpha (9.27 +/- 3.19% vs 0.58 +/- 0.02%, P < 0.01), IL-6 (120.79 +/- 65.83% vs 1.89 +/- 0.34%, P < 0.01) and increased fractional excretion of IL-8 (23.34 +/- 6.38% vs 2.56 +/- 1.07%, P < 0.01) and sVCAM-1 (0.81 +/- 0.33% vs 0.03 +/- 0.02%, P < 0.01) compared with controls. Urinary excretion of TNF-alpha and IL-6 and fractional excretion of TNFalpha, IL-6 and IL-8 were higher in ANCA-A than in ANCA-R. Patients with LN had increased plasma TNF-alpha (20.52 +/- 2.01 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05) and sVCAM-1 (1537.88 +/- 276.36 ng/ml vs 692.26 +/- 44.42 ng/ml, P < 0.05) and increased urinary excretion of TNF-alpha (2.81 +/- 0.51 microg/mol creat vs 0.98 +/- 0.05 microg/mol creat, P < 0.01), IL-8 (35.78 +/- 14.03 microg/mol creat vs 12.46 +/- 5.19 microg/mol creat, P < 0.05) and sVCAM-1 (48.98 +/- 20.20 microg/mol creat vs 2.92 +/- 1.35 microg/mol creat, P < 0.01) compared with controls. Patients with IgAN had, in comparison with controls only increased plasma TNF-alpha (18.10 +/- 0.57 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05). CONCLUSIONS: Urinary excretion and fractional excretion, but not plasma levels, of selected pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-8) were increased in patients with active ANCA-positive renal vasculitis, but not in ANCA positive vasculitis in remission. These parameters may be useful to monitor the activity of this disease.

[Soluble cytokinin receptors in renal vasculitis and lupus nephritis]. / Solubilní receptory pro cytokiny u renální vaskulitidy a lupoidní nefritidy.

BACKGROUND: Activation of various cytokines, e.g. TNF alpha, IL-1 and/or IL-6 may play important role in the pathogenesis of renal vasculitis and lupus nephritis (LN). Systemic effects of these cytokines may be modulated by their circulating soluble receptors. Plasma levels of cytokine receptors may thus be also markers of the activation of these cytokines. METHODS AND RESULTS: Plasma levels of TNF alpha, its soluble receptor p75 (sTNF-RII), IL-6 and soluble IL-6 receptor (sIL-6R) were measured using ELISA in 17 pts with ANCA-positive renal vasculitis (12 active-ANCA-A, 7 in remission ANCA-R), 9 pts with active lupus nephritis (LN) and 5 healthy subjects. Pts with LN had in comparison with controls increased plasma levels of TNF alpha, sTNF-RII, IL-6 and sIL-6R. Pts with ANCA-A had also in comparison with controls increased plasma levels of TNF alpha, sTNF-RII and sIL-6R, but plasma levels of IL-6 were not significantly increased dut to great standard deviation. Pts with ANCA-R had in comparison with controls increased plasma levels of sTNF-RII, but plasma levels of TNF alpha were in ANCA-R significantly lower than in ANCA-A. While the ratio TNF alpha/sTNF-RII was significantly lower in all groups of pts than in controls, the ratio IL-6R/sIL-6R was in comparison with controls significantly increased only in LN. CONCLUSIONS: While increased plasma levels of TNF alpha may be nonspecific marker of the activity of ANCA-positive renal vasculitis and LN, plasma levels of sTNF-RII are increased also in pts with ANCA-positive renal vasculitis in remission. Increased plasma levels of sTNF-RII may interfere with systemic effects of TNF alpha, but may also prolong the lifetime of its active form. Plasma levels of sIL-6R are increased both in ANCA-A and in LN, but their increase is, however, much less pronounced than that of sTNF-RII and cannot effectively block systemic effects of IL-6.