Natural anticoagulants in systemic lupus erythematosus. Deficiency of protein S bound to C4bp associates with recent history of venous thromboses, antiphospholipid antibodies, and the antiphospholipid syndrome.

The association of thrombosis with antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE) could be due to their interference with natural phospholipid dependent anticoagulant mechanisms. We studied antigenic protein C (APC), functional protein C (FPC), free protein S (FPS), protein S bound to C4 binding protein (C4bp-S), antithrombin III (ATIII), as well as IgG and IgM anticardiolipin antibodies (aCL) in 38 patients with SLE with a history of thromboses and 70 patients with SLE without such history. We found a high frequency of deficiencies of natural anticoagulants in both groups of patients with SLE but, because of patient selection, we could not determine the actual prevalence of these defects. Patients having had a venous thrombosis in the previous year had low C4bp-S more frequently than patients with older or no thromboses. When we divided our patients with SLE into those who had a definite, probable, questionable or no antiphospholipid syndrome (aPS) we found the frequency of C4bp-S deficiency to be significantly higher in those with definite aPS than in those without aPS. Intermediate proportions were found in patients with probable and questionable aPS. The levels of C4bp-S decreased as the levels of aCL, particularly IgG, increased. Stepwise discriminant analysis of natural anticoagulants selected deficiencies of C4bp-S and FPC with increased ATIII as a set of variables with highest predictive power for classification of patients with and without aPS. Thus, deficiencies of natural anticoagulants may occur frequently in patients with SLE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thromboembolism in paediatric lupus patients

Paediatric patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL), specifically lupus anticoagulants (LAC) are at high risk of developing thromboembolic events (TE). Our objectives were to determine the prevalence of TE in paediatric SLE patients with LAC and to determine if anticoagulation was effective to decrease morbidity, and prevent recurrent TE. We reviewed data on 149 paediatric SLE patients treated over 10 years. In all, 24 patients (16%) were LAC positive, and 21 TE occurred in 13 of these LAC positive patients (54% incidence of TE in LAC positive patients). The events were cerebral venous thrombosis (9), arterial stroke (3), deep venous thrombosis (4), pulmonary embolism (2), other venous event (1) and other arterial events (2). The median duration between SLE diagnosis and first TE was 15.2 months (range 0-62), and the median age at first TE was 15.1 years (range 11.4-18.4). Long-term anticoagulation was prescribed, and eight patients (62%) were transferred to adult care on lifelong oral warfarin; four (31%) remain under our care on lifelong warfarin, and one patient died of causes unrelated to her TE. No patient has been identified with deficiencies of protein C, protein S or antithrombin III. One patient is heterozygous for Factor V Leiden, and one is heterozygous for both the Prothrombin 20210A mutation and the MTHFR (methylene tetrahydrofolate reductase) mutation. Four patients had recurrent TE (31%), and three were not anticoagulated at the time of their second event. One patient had two recurrences on therapeutic anticoagulation. Thromboembolic events are prevalent in the LAC positive paediatric SLE population, and consideration for lifelong anticoagulation must occur after an initial TE.     

Plasma concentrations of total/free and functional protein S are not decreased in systemic lupus erythematosus patients with lupus anticoagulant and/or antiphospholipid antibodies

Summary We conducted an investigation to clarify whether or not the levels of total, free, and functional protein S and C4-binding protein (C4bp) in plasma are decreased in systemic lupus erythematosus (SLE) patients, especially those with antiphospholipid antibody (aPL), which is known to be a causative factor of such complications as habitual abortion and arteriovenous thrombosis. Fifty patients with SLE were recruited as subjects of the study. Serum aPL (anticardiolipin, antiphosphatidyl serine, antiphosphatidyl inositol, and antiphosphatidic acid antibodies) were measured by ELISA. Lupus anticoagulant was determined by aPTT, KCT, and diluted RVVT. Furthermore, plasma concentrations of total, free, and functional protein S and C4bp were measured. There were no significant differences in the mean levels of total, free, or functional protein S and C4bp between aPL-positive, aPL-negative SLE patients, and the healthy controls. From these results, we concluded that the protein S level is not the sole factor causing complications, and that other factor(s) may be involved in the induction of such complications in this clinical setting.     

Serum apolipoprotein H levels in systemic lupus erythematosus are not influenced by antiphospholipid antibodies.

Anticardiolipin antibodies (aCL) were recently discovered to recognize a complex consisting of phospholipids and apolipoprotein H (apo H). In this study, we determined the serum apo H levels in 36 systemic lupus erythematosus (SLE) patients with or without antiphospholipid antibodies (aPL), including aCL and lupus anticoagulants, to clarify the possible effects of aPL on apo H levels in vivo. The apo H levels were low in SLE patients as compared with 22 healthy controls. However, no associations were found between apo H levels and circulating aPL or clinical features of the antiphospholipid antibody syndrome. A secondary hyperlipidemic state, which probably related to lupus nephritis (proteinuria) and/or prednisolone treatment, increased apo H levels in SLE patients.     

The fibrinolytic response to venous occlusion and the natural anticoagulants in patients with antiphospholipid antibodies both with and without systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE) have an increased risk of thrombosis and this is increased in the presence of antiphospholipid antibodies (APA). These APA are also associated with thrombosis in patients who do not have SLE. We compared haemostatic parameters in SLE patients with and without APA, and also compared patients who had APA but not SLE with healthy normal controls. No relationships between the natural anticoagulants, antithrombin III, heparin cofactor II, protein C and protein S, and the presence of APA were found. In the patients with SLE both tissue plasminogen activator antigen and plasminogen activator inhibitor (PAI) were increased, but these changes were not due to APA which had no effect on fibrinolysis in these patients. In the patients with APA who did not have SLE the fibrinolytic response to venous occlusion was reduced due to raised levels of PAI; similar changes have, however, been reported in some patients with idiopathic thrombosis.     

Regulation of coagulo-fibrinolytic activity and lupus anticoagulants in systemic lupus erythematosus

We determined the following coagulo-fibrinolytic activities in 24 patients with systemic lupus erythematosus (SLE) and 20 healthy adults: prothrombin time (PT), activated partial thromboplastin time (A-PTT), factor VIII: coagulant activity), von Willebrand factor antigen (vWF: Ag), antithrombin-III (AT-III), plasminogen (PLG), alpha 2 plasmin inhibitor (alpha 2 PI), alpha 2-plasmin inhibitor-plasmin complex (PIC), protein C (PC: activity and antigen concentration), and protein S (PS: total PS and free PS). PLG, AT-III, PC antigen concentration and total PS were significantly decreased in ten female controls as compared with ten male controls. Therefore, we used the ten healthy females as controls and excluded two male SLE patients in the analysis of the correlations of coagulo-fibrinolytic activities with lupus anticoagulant (LA), clinical and laboratory features in 22 female patients with SLE. In the SLE patients, PT was significantly shortened, while A-PTT was prolonged. PLG, PC activity and antigen, and total PS were significantly increased, and free PS levels were decreased in SLE. The shortened PT and decreased free PS suggest hypercoagulable states in SLE patients. A significant prolongation of A-PTT and a decrease of F VIII activity were observed in the six LA-positive SLE patients, and the results were considered as known effects of LA. Furthermore, vWF: Ag, AT-III and PC antigen levels were significantly increased in the LA-positive patients as compared with LA-negative patients. These changes indicate both vascular endothelial cell damages and a compensatory increase in coagulation inhibitors in the LA-positive patients.     

Bilirubin levels in patients with systemic lupus erythematosus: increased or decreased?

The aim of this study was to investigate the serum bilirubin levels in SLE patients and their associations with clinical and laboratory characteristics of SLE. There were 198 SLE patients in this study, of whom 7 cases with tobacco smoking or alcohol intake were excluded. Some clinical and laboratory characteristics of the patients were obtained by medical record review. In addition, 154 age- and sex- matched healthy volunteers with no histories of SLE, liver diseases, and other autoimmune or inflammatory diseases were randomly recruited into this study. The serum bilirubin levels were lower in SLE patients without liver diseases than in healthy controls (P?=?0.000). Univariate logistic analysis demonstrated that hypertension, lupus renal involvement, positive anti-dsDNA antibody, C3, C4, hsCRP, and albumin remained as impact factors of total bilirubins; lupus renal involvement, ESR, IgG, globulin, and ALT, as impact factors of direct bilirubins; and lupus renal involvement, positive anti-dsDNA antibody, C3, C4, hsCRP, and albumin, as impact factors of indirect bilirubins. However, multivariate logistic analysis showed that only hsCRP remained as an independent positive impact factor of total bilirubins, lupus renal involvement as an independent negative impact factor of direct bilirubins, and hsCRP and albumin as independent positive impact factors of indirect bilirubins. In conclusion, serum bilirubin levels are decreased in SLE and the decreased bilirubin levels could be associated with inflammatory process and lupus renal involvement of SLE.     

Thrombosis in systemic lupus erythematosus: congenital and acquired risk factors

OBJECTIVE: To investigate the thrombotic tendency in patients with systemic lupus erythematosus (SLE) by evaluating congenital or acquired abnormalities associated with an increased risk of venous and/or arterial thrombosis. METHODS: A total of 57 patients with SLE were included in the study. Twenty-one patients (37%) had a history of arterial and/or venous thrombosis and 36 patients (63%) did not have such a history. Sera from 50 healthy controls were examined. Protein C, protein S, antithrombin, D-dimer, fibrinogen, homocysteine, anticardiolipin antibodies (aCL), lupus anticoagulant (LAC), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T gene mutation were evaluated. RESULTS: Protein C, antithrombin, fibrinogen, D-dimer, and homocysteine levels were significantly higher in patients with SLE than in controls. A prothrombin mutation was observed in 2 (4%) of 50 controls and in 6 (11%) of 57 patients. A significantly higher prevalence (P = 0.036) of MTHFR homozygous mutation was observed in patients with SLE (14 [25%] of 57) in comparison with controls (4 [8%] of 50). IgG-aCL and IgM-aCL levels were significantly higher in patients with SLE than in controls (P < 0.0001). The presence of medium-high (> or = 20 IgG phospholipid units/ml) IgG-aCL antibody titers was significantly higher (P = 0.005) in patients with thrombosis (11 [52%] of 21) than in patients without (5 [14%] of 36) thrombosis. LAC was present in 22 (38.5%) of 57 patients and in none of 50 controls. CONCLUSION: In this study, we confirm the association between thrombosis and IgG-aCL at medium-high titers and suggest that the coexistence of other risk factors can affect the expression of thrombosis in patients with SLE.     

IgG reactivity to phospholipid-bound beta(2)-glycoprotein I is the main determinant of the fraction of lupus anticoagulant activity quenched by addition of hexagonal (II) phase phospholipid in patients with the clinical suspicion of antiphospholipid-antibody syndrome.

BACKGROUND AND OBJECTIVE: Autoantibodies to beta(2)-glycoprotein I (beta(2)-GPI) and/or prothrombin (FII) have been involved in the expression of lupus anticoagulant (LA) activity, an in vitro phenomenon associated with an increased risk of arterial and/or venous thromboembolic events. However, LA activity sustained by anti-FII antibodies has a much weaker association with thrombosis than LA activity sustained by anti-beta(2)-GPI antibodies. Because assays aimed at detecting LA activity are now commercially available, we evaluated the relative sensitivity to anti-FII and anti-beta(2)-GPI antibodies of a commercial LA assay in a consecutive series of patients with the clinical suspicion of anti-phospholipid antibody (APA) syndrome. DESIGN AND METHODS: One hundred and ten consecutive patients with the clinical suspicion of APA syndrome (primary in 39) and 36 healthy controls were evaluated for the presence of LA activity (LA, Staclot, Stago), anticardiolipin antibodies (Quanta Lite aCL IgG, IgM, Inova Diagnostics), and IgG binding to solid-phase and/or phospholipid (PL)-bound beta(2)-GPI and FII by ELISA assays developed an optimized in our laboratory. Odds ratios for the association of IgG binding activity with LA and the aCL IgG status were calculated. In LA patients, dependency of LA potency (as assessed by clotting time prolongation in absence or presence of hexagonal phospholipid) on autoantibody titers was analyzed by the generalized linear model. Total IgG fractions were purified from selected patients to evaluate their ability to inhibit prothrombin activation at low FII concentration. RESULTS: Anticardiolipin antibodies (aCL) of the IgG or IgM type were found in 64 and 23 patients and LA activity in 49 patients. Anti-beta(2)-GPI and anti-FII (solid-phase and PL-bound) IgG titers exceeding by more than 3 standard deviations the mean values observed in control subjects were found in 46 and 47 patients and in 56 and 30 patients respectively, with the highest titers detected in the subgroup of patients with both LA and aCL IgG. The relative risk of LA for patients free of anti-FII and/or anti-beta(2)-GPI IgG was 0.03 after stratification for the aCL IgG status. Anti-beta(2)-GPI (solid-phase and PL-bound) IgG (RR 34.4 and 12.6) and anti-FII (solid-phase) IgG (RR 6.33) were all associated with LA activity. However, when taking into account co-existence of anti-FII and anti-beta(2)-GPI IgG in the same patients, the relative risk of LA for patients with isolated anti-FII IgG (solid-phase and/or PL-bound) was 0.50, whereas it ranged from 4.24 to 8.70 for all the antibody combinations including anti-beta(2)-GPI IgG. Anti-beta(2)-GPI (PL-bound) and aCL IgG titers were the only significant predictors of LA potency determined in absence phospholipid (anti-beta(2)-GPI IgG) or in presence of hexagonal phospholipid (aCL IgG). Total IgG fractions purified from 12 patients (6 with anti-FII IgG) did not significantly inhibit factor II activity up to a 150-fold molar excess. INTERPRETATION AND CONCLUSIONS: These results highlight the high prevalence of anti-FII and anti-beta(2)-GPI IgG in patients with the clinical suspicion of APA syndrome and particularly in the subgroup of patients with LA activity. The fraction of LA activity which can be quenched by addition of hexagonal phospholipid is, however, only dependent on IgG directed to PL-bound beta(2)-GPI. Other antibodies associated with anticardiolipin IgG may explain residual clotting time prolongation observed in the presence of hexagonal phospholipid.     

Increased levels of serum protein oxidation and correlation with disease activity in systemic lupus erythematosus

OBJECTIVE: To examine protein oxidation in systemic lupus erythematosus (SLE) and to correlate levels of protein oxidation products with disease activity. METHODS: Serum was collected from SLE patients and healthy control subjects. Protein-bound carbonyls and the pro-oxidant enzyme myeloperoxidase (MPO) were quantified by enzyme-linked immunosorbent assay. Protein thiols were quantified using 5,5'-dithionitrobenzoic acid. Protein-bound amino acids and methionine, tyrosine, and phenylalanine oxidation products were quantified by acid hydrolysis and high-performance liquid chromatography. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Levels of anti-double-stranded DNA (anti-dsDNA) antibodies were measured by radioimmunoassay. RESULTS: Compared with control subjects, SLE patients exhibited elevated levels of protein carbonyls (0.108 +/- 0.078 versus 0.064 +/- 0.028 nmoles/mg of protein; P = 0.046), decreased levels of protein thiols (3.9 +/- 1.1 versus 4.9 +/- 0.7 nmoles/mg of protein; P = 0.003), decreased levels of protein-bound methionine (P = 0.0007), and increased levels of protein-bound methionine sulfoxide (P = 0.0043) and 3-nitrotyrosine (P = 0.0477). SLE patients with high SLEDAI scores or elevated anti-dsDNA antibody levels exhibited increased oxidation compared with patients with low SLEDAI scores or low antibody levels. Serum MPO levels were decreased in SLE patients (P = 0.03), suggesting that this enzyme is not responsible for the enhanced protein oxidation. CONCLUSION: We found elevated levels of multiple markers of protein oxidation in sera from SLE patients compared with controls, and these levels correlated with disease activity. The findings suggest that protein oxidation may play a role in the pathogenesis of chronic organ damage in SLE.     

Serum thrombopoietin levels and anti-thrombopoietin antibodies in systemic lupus erythematosus

Thrombocytopenia is a common phenomenon in patients suffering from systemic lupus erythematosus (SLE). The cause of thrombocytopenia in SLE, however, is poorly understood. In this study, 100 patients with SLE were evaluated for serum thrombopoietin levels, anti-thrombopoietin antibodies and routine laboratory parameters such as peripheral blood counts, parameters of blood chemistry and immunologic parameters of SLE. The median platelet count of SLE patients was 230 g/l and 19 were thrombocytopenic (range 8-148 g/l). Thrombopoietin levels in SLE patients were found to be significantly higher than in healthy controls (n = 96; median, 117 pg/ml vs 64 pg/ml, P < 0.01). When excluding thrombocytopenic SLE patients, thrombopoietin levels in SLE were still above controls (111 pg/ml, P < 0.01). The thrombopoietin levels were correlated to erythrocyte sedimentation rate and ECLAM score of disease activity, and inversely correlated to complement factor C4, but not to the platelet count. Anti-thrombopoietin antibody reactivity was found in 23% of SLE patients. Interestingly, these patients had lower platelet counts than SLE patients without anti-thrombopoietin antibodies (median 174 g/l and 253 g/l, respectively, P < 0.01), but thrombopoietin levels were not significantly different. Taken together, thrombopoietin levels are significantly higher in the sera of SLE patients than in healthy controls and anti-thrombopoietin antibodies are frequently found.     

The prevalence and clinical associations of the lupus anticoagulant in systemic lupus erythematosus

To determine the prevalence and clinical associations of the lupus anticoagulant (LAC) in patients with systemic lupus erythematosus (SLE), we studied 74 patients with SLE, 6 with lupus-like disease and a heterogeneous group of 45 patients with various autoimmune diseases. LAC was demonstrated in 19 SLE patients (26%), 5 patients with lupus-like disease (83%) and in none of the other patients. Statistically significant associations were found between LAC and a history of thromboembolic events (p less than 0.001), fetal loss (p less than 0.001), thrombocytopenia (p less than 0.01), biologically false-positive VDRL test (p less than 0.02) and convulsions (p less than 0.05). A negative correlation was found between LAC and a history of butterfly rash (p less than 0.01) and the presence of antibodies against extractable nuclear antigen (p less than 0.01). No significant difference was found between LAC-negative SLE patients and patients with other autoimmune diseases with respect to the prevalence of thromboembolic events or fetal loss. We conclude that LAC is a useful marker to identify a subset of patients with SLE or lupus-like disease at risk of thromboembolic events, fetal wastage, and thrombocytopenia.     

Resistance to activated protein C in healthy women taking oral contraceptives

Summary. Resistance to activated protein C (APC) is at present considered the most frequent laboratory abnormality in patients with deep-vein thrombosis. An increased risk for venous thrombosis is associated to the use of oral contraceptives (OC).
We studied APC sensitivity in 50 healthy women taking OC and in 50 healthy controls, matched for age, smoking habit, educational and social levels, and the main biochemical routinary parameters. Subjects with a personal or familial history of thrombosis and also with chronic or acute diseases were excluded. Protein C, protein S, antithrombin III and lupus anticoagulant activity (LAC) were also evaluated. Increased fibrinogen and protein C levels, decreased protein S, and shortened PT and APTT were also observed in women taking OC. APC sensitivity ratio (APC-SR) was significantly lower in the OC group than in a control group (2.6 ± 0.38 v 2.81 ±0.35, P <0.01). Seven of eight women with APC ratio ≤ 2 (APC resistant) were OC users: the difference of prevalence was statistically significant (chi-squared test, P <:0'05). Only two out of eight women were found heterozygous for the Leiden factor V mutation. Two APC-resistant women without the Leiden mutation subsequently discontinued OC and both then normalized their APC-SR. We conclude that acquired factors, i.e. oral contraceptives, may play an important role in determining plasma APC resistance.     

Complement degradation product C3d in urine: marker of lupus nephritis

OBJECTIVE: To examine whether serum and urine C3d, a degradation product of C3, correlate with renal and extrarenal lupus activity. METHODS: Serum and urinary C3d levels were measured by ELISA in 15 healthy individuals and 24 patients with systemic lupus erythematosus (SLE) (8 with inactive disease, 7 with active but nonrenal disease, 9 with active lupus nephritis). Disease activity variables like serum C3, C4, and anti-dsDNA antibodies were also measured. RESULTS: The median serum C3d levels were significantly higher (p < 0.01) in patients with active (26 arbitrary units/ml; AU/ml) and inactive SLE (27 AU/ml) compared to healthy controls (11.25 AU/ml); levels were comparable in patients with active renal and extrarenal SLE. On the other hand, urine C3d was elevated only in patients with active SLE; its level was highest in patients with active lupus nephritis (0.87 AU/ml) compared to patients with active extrarenal diseases (0.31 AU/ml; p < 0.05), to patients with inactive lupus nephritis (0.06 AU/ml; p < 0.001), or to levels in healthy individuals (0.06; p < 0.001). Urine C3d showed stronger correlation with disease activity score (SLE Disease Activity Index) than serum C3, C4, anti-dsDNA antibodies, and serum C3d. CONCLUSION: Urine C3d is a good index of active lupus, particularly lupus nephritis.     

The inflammation and coagulation cross-talk in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder with a high prevalence of cardiovascular disease due to accelerated atherosclerosis, as well as an increased risk of venous thromboembolism. Many of these clinical features have been attributed to the high prevalence of autoantibodies that are directed against phospholipid-bound antigens and that induce prothrombotic effects and disturb endothelial cell function. We conducted a case-control study in a cohort of female patients with SLE and in age-matched and sex-matched normal individuals. Patients had significantly higher levels of plasma inflammatory markers, but their overall coagulation status assessed by prothrombin fragment 1 + 2 and D-dimer plasma levels was not different from controls. Resistance against activated protein C (APC), assessed by a thrombin generation-based as well as an activated partial thromboplastin time-based method, however, was increased in patients. This defect was neither due to factor V Leiden carriership or to the use of oral contraceptives. This acquired form of APC resistance was due to proinflammatory changes associated with lower plasma levels of free protein S. In conclusion, acquired APC resistance may be an important determinant of the risk of thrombosis in patients with SLE, probably due to an active cross-talk between inflammation and coagulation systems.     

Impaired control of the tissue factor pathway of blood coagulation in systemic lupus erythematosus

Thrombosis is a frequent manifestation in patients with systemic lupus erythematosus (SLE), although precise mechanisms remain unclear. This study investigated whether the major physiological trigger of blood coagulation, the tissue factor (TF) pathway, was altered in SLE patients. Furthermore, we investigated potential associations between the TF pathway, the presence of antiphospholipid (APL) antibodies and other abnormalities present in SLE. A total of 101 participants (40 SLE patients and 61 age- and sex-matched controls) were recruited from Tasmania, Australia. Markers of the TF pathway, hypercoagulability, inflammation and endothelial cell damage were measured in plasma. Serum levels of APL antibodies (anti-cardiolipin antibodies [ACL], lupus anticoagulants [LAC], anti-beta2-glycoprotein-1 [anti-β2GP1] and anti-prothrombin antibodies) were also determined. Despite similar TF and TF pathway inhibitor (TFPI) total antigen levels, SLE patients had significantly increased levels of TFPI free antigen (patients vs controls; mean ±?SD) (11.6 ± 0.9 ng/mL vs 6.4 ± 0.4 ng/mL; p?相似文献   

系统性红斑狼疮抗活化的蛋白C研究

目的　了解抗活化的蛋白C(APCR)在系统性红斑狼疮 (SLE)患者中的发生情况 ,并进一步探讨SLE患者发生血栓的机制。方法　采用APC KPTT法 ,ELISA法和PTT LA法分别对5 0例SLE患者及 2 0例正常对照 (NC)进行APCR、抗心磷脂抗体 (ACA)和狼疮抗凝物 (LA)检测。结果　SLE患者APCR阳性率 ( 5 8% )明显高于NC组 ( 5 % ) (P <0 0 0 5 ) ,APCR阳性患者中血栓发生率( 2 7 6% )明显高于APCR阴性患者 ( 4 8% ) (P <0 0 1) ,患者LA阳性率 ( 2 2 % )明显高于对照组 ( 0 /10 ) (P <0 0 5 ) ,患者ACA IgG及IgM明显高于对照组 (P <0 0 5 ) ,而IgA与对照组差异不显著 (P >0 0 5 ) ,LA阳性组中的APCR阳性率 ( 90 9% )明显高于LA阴性组 ( 5 3 8% ) (P <0 0 5 ) ,ACA阳性组中的APCR阳性率 ( 64 7% )与ACA阴性组 ( 60 6% )未发现明显相关性 (P >0 0 5 )。结论　APCR在国人SLE患者中有较高的发生率且与LA有明显相关性 ,APCR可能是SLE患者诱发血栓的主要原因之一。     

High circulating levels of interleukin-18 binding protein indicate the severity of glomerular involvement in systemic lupus erythematosus

In systemic lupus erythematosus (SLE), glomerular involvement often progresses with the activity of the disease. Immune complexes and abnormal secretion of cytokines are thought to be involved in the central mechanism of the development of lupus nephritis. We investigated serum levels of interleukin 18 (IL-18), a proinflammatory cytokine, and its natural antagonist IL-18 binding protein (IL-18 BP) in 45 patients with lupus nephritis. IL-18 levels were significantly increased in patients with Class II, Class III, and Class IV lupus nephritis compared with the level in a healthy control group. However, the levels stayed within the non-significant range in Class V. IL-18 BP levels were significantly increased in patients with Class III and Class IV lupus nephritis, in which histological activity and chronicity are severe. However, IL-18 BP levels stayed within the non-significant range in Class II and Class V, in which histological markers are mild. We also compared the levels of IL-18 and IL-18 BP in patients with and without glomerular infiltration of inflammatory cells. IL-18 was increased regardless of glomerular infiltration. However, IL-18 BP was increased only in patients with glomerular infiltration. These data suggest that IL-18 levels indicate the extent of the offending inflammatory response not only in the bloodstream but also in renal tissue, and that high IL-18 BP levels indicate the severity of existing glomerular injury.     

系统性红斑狼疮患者外周血基质金属蛋白酶-3检测及其临床意义

目的　检测系统性红斑狼疮 (SLE)患者外周血清基质金属蛋白酶 3 (MMP 3)水平并探讨其临床意义。方法　MMP 3检测采用ELISA方法。结果　SLE患者血清MMP 3水平为99 86ng/ml(中位数 ,下同 )显著高于正常对照组 2 7 82ng/ml (P <0 0 0 1)。SLE患者中 ,发生神经精神性狼疮者MMP 3水平显著高于非神经精神性狼疮患者 (P <0 0 1) ,发生狼疮肾炎者MMP 3亦明显高于无肾损害者 (P <0 0 5 ) ,而发生多发性关节炎和颊部皮疹 /光敏感患者分别与无多发性关节炎和颊部皮疹 /光敏感患者的MMP 3水平差异无显著性 (P >0 0 5 ) ;出现抗dsDNA抗体阳性、低补体C3血症、低白蛋白血症、高IgG血症及血肌酐升高者血清MMP 3水平均分别显著高于无上述表现者 (P <0 0 5 ) ,SLE患者血清MMP 3水平与SLEDAI呈正相关关系 (P <0 0 5 )。结论　SLE患者血清中MMP 3水平显著升高 ,可作为狼疮活动的参考指标之一。MMP 3参与SLE的病理生理过程 ,与SLE的某些临床检验异常表现及狼疮脑、肾等脏器损害有关     

Decreased serum erythropoietin and its relation to anti-erythropoietin antibodies in anaemia of systemic lupus erythematosus

OBJECTIVE: This study was performed to assess erythropoietin levels and anti-erythropoietin antibodies in patients with systemic lupus erythematosus (SLE). METHODS: The sera of 100 patients with SLE were investigated for serum erythropoietin levels and the presence of anti-erythropoietin antibodies by ELISA. Routine laboratory parameters such as peripheral blood count, relevant parameters of blood chemistry, and immunological parameters of SLE were recorded. RESULTS: Erythropoietin levels were significantly decreased in SLE patients when related to individual haemoglobin and haematocrit values (P<0.001), suggesting an inadequate erythropoietin response in SLE. Anti-erythropoietin antibodies were found in 46% of SLE patients, and erythropoietin levels (but not haemoglobin or haematocrit values) were significantly decreased in these patients compared with patients without anti-erythropoietin antibodies. Serum erythropoietin concentration as determined by ELISA was reduced in the presence of anti-erythropoietin antibodies. Furthermore, anti-erythropoietin antibodies also correlated with younger age, decreased serum levels of complement factors C3 and C4 and elevated anti-double-stranded DNA antibodies. CONCLUSIONS: We conclude that the anaemia of SLE is characterized by an inadequate erythropoietin response. Anti-erythropoietin antibodies are frequently present in SLE and interfere with the measurement of serum erythropoietin level. However, these antibodies are not associated with increased severity of SLE-associated anaemia.