von Willebrand factor antigen and plasminogen activator inhibitor in giant cell arteritis.

Sixty three patients (51 women, 12 men) with giant cell arteritis were studied by serial analyses of von Willebrand factor antigen (vWF: Ag) concentration and plasminogen activator inhibitor activity. Their mean age at the time of diagnosis was 71 years. Two hundred and one randomly selected subjects from the general population, aged 75 years, served as controls. The mean concentration of vWF:Ag in the patients with giant cell arteritis before the start of corticosteroid treatment was 2.63 (SD 1.35) IU/ml compared with 1.71 (0.69) IU/ml in the general population. The vWF:Ag concentration slowly decreased and reached the control range about 18 months after the diagnosis. The vWF:Ag did not correlate with the clinical group of giant cell arteritis nor with the results of temporal artery biopsy. Flare ups and vascular complications were not indicated by the vWF:Ag. Plasminogen activator inhibitor activity in the patients was not significantly different from that of the general population at any time. It was concluded that the determination of vWF:Ag and plasminogen activator inhibitor activity is of limited clinical value in the diagnosis, prognosis, and monitoring of steroid treatment in patients with giant cell arteritis.     

血管性血友病因子及其裂解酶与系统性红斑狼疮的关系

目的检测系统性红斑狼疮(SLE)患者血浆血管性血友病因子(VWF)水平及VWF裂解酶(VWF-CP)活性,探讨VWF及VWF-CP在SLE中的临床意义。方法采用残余胶原结合实验法及ELISA法分别对30例SLE患者血浆VWF-CP活性及VWF:AG水平进行检测。结果SLE患者血浆VWF:AG(114.6±16.3)%显著高于正常对照组(71.3±49.5)%(P<0.01),而血浆VWF-CP活性水平(57.7±16.3)%显著低于正常对照组(86.6±1.8)%(P<0.01),狼疮性肾炎(LN)组(130.1±40.6)%血浆VWF:AG水平显著高于非LN组(97.6±27.6)%(P<0.05),而VWF-CP活性显著降低(P<0.05),血浆VWF-CP活性水平与狼疮活动指数(SLEDAI)呈负相关(R=-0.4316,P<0.05)。18例肾活检的LN患者中,Ⅳ型VWF水平最高,VWF-CP活性最低,其余3型之间无差别。30例初发SLE患者综合治疗4周后血浆VWF:AG水平显著下降,VWF-CP活性水平在治疗后SLEDAI评分≥9分者,无显著性升高,SLEDAI评分<9分者,有显著性升高(P<0.05)。结论SLE的血浆VWF升高,VWF-CP活性低下,参与SLE尤其是LN的发生发展,内皮损伤和自身抗体可能是致SLE患者VWF升高,VWF-CP活性低下的原因。     

Increased fibrinogen,von Willebrand factor and tissue plasminogen activator levels in insulin resistant South Asian patients with ischaemic stroke

The aim of this study was to determine differences in atherothrombotic risk factors in South Asian subjects with a history of ischaemic stroke and South Asian subjects free from personal and family history of clinically detectable stroke. Eighty South Asian patients with ischaemic stroke (confirmed on cranial computerised scan) and 80 South Asian controls with similar age and gender distributions were recruited at random. The frequency of hypertension (P=<0.0001), myocardial infarction (P=0.003) and diabetes mellitus (<0.0001) were significantly higher in stroke patients. Stroke patients had lower high-density lipoprotein cholesterol (0.95 vs. 1.1 mmol/l, P=<0.0001), higher plasma glucose (8.1 vs. 6.6 mmol/l, P=0.01) and trendwise higher HBA(1C) (6.4 vs. 6.0%, P=0.09). There was no difference in insulin levels but insulin resistance was significantly higher in stroke patients (3.75 vs. 2.66, P=0.01). Stroke patients showed elevated levels of fibrinogen (3.78 vs. 3.41 mg/dl, P=0.02), von Willebrand factor (1.78 vs. 1.50 IU/ml, P=0.006) and tissue plasminogen activator (12.8 vs. 11.3 ng/ml, P=0.04), but the differences did not persist after adjustment for glucose, triglycerides, HDL, WHR, and BMI. Higher levels of fibrinogen, von Willebrand factor and t-PA in South Asian stroke patients disappeared after adjustment for features of insulin resistance syndrome but persisted after adjustment for presence of diabetes, confirming that these changes are essentially dependant on features of insulin resistance syndrome. A prospective study would be required to elucidate the role of thrombotic risk factors in South Asians with ischaemic stroke.     

Clinical significance of plasma presepsin levels in patients with systemic lupus erythematosus

Objectives: Presepsin (PSEP: soluble CD14 subtype) is produced from bacteria-stimulated monocytes or neutrophils, thus recognized as a biomarker of sepsis. Aberrant functions in monocyte or neutrophils are increasingly recognized in systemic lupus erythematosus (SLE). We investigated whether plasma PSEP reflects disease activity in patients with SLE.

Methods: This retrospective study comprised 35 patients with SLE and 72 with non-SLE autoimmune diseases who visited our facility during the period from August 2012 to September 2015. Plasma PSEP levels and laboratory data were compared between SLE and non-SLE. Clinical markers of SLE disease activity, including SLE disease activity index 2000 (SLEDAI-2K), serum complement concentrations and serum anti-ds-DNA antibodies were assessed in correlation with plasma PSEP levels.

Results: Plasma PSEP levels in SLE were higher than those in non-SLE. This phenomenon holds true when comparing SLE and non-SLE patients in the absence of infection (p?=?.0008). Plasma PSEP levels in SLE patients negatively correlated with C3 (r =?–0.4454, p =?.0430), CH50 (r =?–0.4502, p =?.0406) and positively with SLEDAI-2K (r =?0.4801, p =?.0237).

Conclusion: Elevated plasma PSEP levels were correlated with disease activity of SLE, suggesting inappropriate monocyte or neutrophil activation in the pathophysiology of SLE exacerbation.     

Effect of total-body cold exposure on plasma concentrations of von Willebrand factor, endothelin-1 and thrombomodulin in systemic lupus erythematosus patients with or without Raynaud's phenomenon.

The effect of total-body cold exposure on plasma concentrations of von Willebrand factor (vWF), endothelin-1 (ET) and thrombomodulin (TM), all of which are considered to be generated from the endothelium, was studied in systemic lupus erythematosus (SLE) patients with and without Raynaud's phenomenon. The plasma levels of vWF, ET and TM in SLE patients, irrespective of the presence of Raynaud's phenomenon, were significantly higher than in normal controls even before the cold provocation test. After the cold provocation test, plasma levels of vWF and ET were significantly higher in SLE patients with Raynaud's phenomenon than in those without and in normal controls. No significant increase in TM was observed in either the SLE patients or the controls. These results suggest that SLE patients, regardless of the presence of Raynaud's phenomenon, are in a hypercoagulable state and that this state may be further intensified by cold exposure. Hence, it is concluded that we should consider antithrombotic therapy for SLE patients, especially those with Raynaud's phenomenon, to prevent unwanted activation of the coagulation system and possible endothelial damage.     

Clinical significance of substantially elevated von Willebrand factor antigen levels in patients with advanced chronic liver disease

BackgroundVon Willebrand factor antigen (VWF) is a non-invasive marker for clinically significant portal hypertension (HVPG≥10 mmHg) and confers HVPG-independent prognostic information. While quantification of increased VWF-levels is not relevant in the context of von Willebrand disease, highly elevated VWF may be of clinical significance in ACLD. Thus, we have modified our analytical approach to quantify very high VWF-levels (i.e.,>420%) and investigated their prognostic value.MethodsPatients undergoing HVPG-measurement at the Vienna Hepatic Hemodynamic Lab with evidence of ACLD and information on VWF were considered. Clinical stages (CS) were defined as follows: Probable compensated ACLD (cACLD): LSM≥10kPa&HVPG<6 mmHg; 0: cACLD&6–9 mmHg; 1: cACLD&HVPG≥10 mmHg; 2: bleeding; 3: non-bleeding decompensation; 4: ≥2 decompensations.Results124 (16%) of 793 patients had VWF>420%. The proportion of VWF>420% increased with disease severity (probable cACLD-0: 5(4%) vs. 1: 22(10%) vs. 2–4: 97(23%),p ≤ 0.001) as well as across HVPG (<6mmHg: 1(2%) vs. 6–9: 6(6%) vs. 10–15: 17(9%) vs. ≥16: 100(22%),p ≤ 0.001) and MELD (<10: 17(6%) vs. 10–14: 27(10%) vs. ≥15: 79(32%),p ≤ 0.001) strata. In patients with VWF>420%, median VWF was 533 (IQR:466–611)% and VWF was unrelated to HVPG (Spearman's ρ=0.139,p = 0.123), but showed direct correlations of weak/moderate strength with MELD (ρ=0.336,p < 0.001) and CRP (ρ=0.286,p = 0.001). In the subgroup with VWF>420%, VWF was predictive of decompensation/liver-related mortality (VWF per 10%; hazard ratio (HR): 1.02(95% confidence interval (95%CI): 1.01–1.04),p = 0.008, even after adjusting for other factors (VWF per 10%; adjusted HR: 1.02(95%CI: 1.00–1.05),p = 0.031).ConclusionThe proportion of patients with substantially elevated VWF values steadily increases with disease progression. While VWF is not reflective of HVPG in these patients, it is correlated with hepatic dysfunction and systemic inflammation. Importantly, quantification of high values provides prognostic information.     

Circadian variation of tissue plasminogen activator and its inhibitor, von Willebrand factor antigen, and prostacyclin stimulating factor in men with ischaemic heart disease.

OBJECTIVES--To determine whether plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor antigen, and prostacyclin stimulating factor and plasminogen activator inhibitor activity show circadian variation in men with ischaemic heart disease. DESIGN--Blood samples were obtained every four hours for 24 hours from 10 men with ischaemic heart disease. The men were ambulant from 08:10 until 00:00 when they went to bed and they remained in bed until 08:00 the following morning. PATIENTS--Ten men with positive diagnostic exercise tolerance tests with no significant past history, who were not regularly taking any medical treatment except for glyceryl trinitrate. RESULTS--There was significant circadian variation in plasminogen activator inhibitor activity (p = 0.001) (peak value 04:00 and trough value 20:00), but not in plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor, or prostacyclin stimulating factor. CONCLUSION--Men with ischaemic heart disease showed a significant circadian variation in fibrinolysis. The combination of peak values of plasminogen activator inhibitor activity and failure of plasma concentrations of tissue plasminogen activator antigen to increase in the early morning must predispose to thrombosis at this time. The circadian variation in fibrinolysis may contribute to the increased incidence of myocardial infarction in the morning.     

The prevalence and clinical significance of autoantibodies to plasminogen activator inhibitor 1 in systemic lupus erythematosus

We have recently described the novel autoantigen plasminogen activator inhibitor (PAI-1) in systemic lupus erythematosus (SLE). The aim of this study was to determine the prevalence and clinical significance of anti-PAI-1 autoantibodies in patients with SLE. Autoantibodies to recombinant PAI-1 were measured in retrospective sera of 48 lupus patients by immunoassay in order to assess their clinical significance. This showed that 71% of sera from 48 lupus patients had significantly elevated anti-PAI-1 autoantibodies as compared with normal control subjects (P < 0.0001). There was a weak but significant (P < 0.043) correlation with anti-dsDNA autoantibodies. In longitudinal studies, autoantibodies against PAI-1 correlated with clinical parameters measured by the BILAG disease activity index including global clinical score. Our study demonstrates the high frequency of novel autoantibodies to PAI-1 in patients with lupus. The serial clinical correlations with anti-PAI-1 autoantibodies also support the hypothesis that these autoantibodies may play a pathogenic role in lupus.     

Clinical significance of a single test for anti-cardiolipin antibodies in patients with systemic lupus erythematosus

PURPOSE: Clinicians have difficulty interpreting results of tests for anti-cardiolipin antibodies (aCL) because of conflicting reports of the clinical associations of these antibodies in patients with systemic lupus erythematosus (SLE). We therefore decided to evaluate the clinical associations of aCL in an effort to facilitate interpretation of single reports of either positive or negative test results. We also assessed the role of estrogen on the development of aCL. PATIENTS AND METHODS: The study population consisted of 85 consecutive outpatients with SLE and 40 control subjects. Serum samples and clinical and laboratory data were obtained from each patient and control. Testing for aCL was performed using a standardized enzyme-linked immunoabsorbent assay developed at an international workshop. RESULTS: The presence of aCL was documented in 42.4 percent of patients with SLE and 7.5 percent of control subjects. In patients with SLE, these antibodies were significantly associated with thrombosis, fetal loss, and thrombocytopenia, but not with other manifestations. Measurement of all isotypes optimized clinical correlations. Titers did not add clinical utility. Fluctuations of levels of aCL occurred, making it difficult to interpret a single negative result. Among control subjects, the presence of aCL was not significantly more common in women who used oral contraceptives. CONCLUSION: Our findings suggest that positive results of testing for aCL correlate with a predisposition for thrombosis, fetal loss, and thrombocytopenia in patients with SLE; however, the test is not predictive for other clinical manifestations of SLE, including activity and severity of disease. We believe that measurement of all isotypes of aCL should be performed in patients with SLE considering pregnancy, to identify those with a high risk of fetal loss, and in SLE patients with a thrombotic episode.     

Circulating thrombomodulin as a novel endothelial cell marker: comparison of its behavior with von Willebrand factor and tissue-type plasminogen activator.

Circulating thrombomodulin is a novel endothelial cell marker, which may reflect the endothelial injury. Plasma levels of thrombomodulin were quantitated by an enzyme-linked immunosorbent assay (ELISA) in patients with hematological malignancies, liver disease, diabetes mellitus, collagen disease, thrombotic disease, and disseminated intravascular coagulation (DIC), and the thrombomodulin values were compared with those of von Willebrand factor antigen (vWf:Ag) and tissue-type plasminogen activator (t-PA) which are released from stimulated or damaged endothelial cells. The mean plasma concentrations of thrombomodulin in these disease states were elevated as compared with healthy subjects. A relatively high mean thrombomodulin level was observed in DIC, liver disease, and collagen disease. Abnormally high thrombomodulin values (greater than normal mean value + 3 SD) were found in 32.3% of patients with hematological malignancies, 57.7% of patients with liver disease, 39.3% of patients with diabetes mellitus, 30.0% of patients with collagen disease, 23.1% of patients with thrombotic disease, and 69.0% of patients with DIC. Plasma concentrations of both vWf:Ag and t-PA were also elevated in these patients. On the whole, the plasma thrombomodulin concentration was positively correlated with vWf:Ag (r = 0.441, P less than 0.001) and t-PA (r = 0.398, P less than 0.001). These findings indicate that the elevation of plasma thrombomodulin is frequently seen in a variety of diseases and circulating thrombomodulin is possibly useful for evaluating the endothelial damage in selected disease states.     

Clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus patients

The aim of this study was to investigate the clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus (SLE) patients. IgG antinucleosome antibodies were detected by a qualitative enzyme immunoassay (immunodot) in the sera of SLE patients at onset of disease. The patients were divided into two groups according to the result of the antinucleosome antibodies test: positive (group A) and negative (group B). The two groups were also evaluated for clinical and biological parameters. Of 84 patients with SLE, 66 (78.6%) had antinucleosome antibodies. Among 21 patients negative for anti-double-stranded DNA (anti-dsDNA), 5 (23.8%) were antinucleosome positive. The most common initial features were haematological disorders (80.1%) and arthritis or arthralgias (79.8%). Renal disorders, observed in 59.5% of SLE patients, were more common in group A compared to group B (65 vs 38%) (p=0.04). The European Consensus Lupus Activity Measurement (ECLAM) mean score was higher in group A (6.42) than in group B (4.44) (p=0.002). Antinucleosome antibodies were positive in nearly one-fourth of SLE patients negative for anti-dsDNA. We found a correlation between antinucleosome antibodies, nephritis and SLE disease activity. Therefore, the determination of circulating antinucleosome antibodies could be a useful parameter for early diagnosis and follow-up of SLE patients.     

Clinical significance of anticentromere antibodies in patients with systemic lupus erythematosus

OBJECTIVE: To clarify the clinical significance of anticentromere antibodies (ACA) in patients with systemic lupus erythematosus (SLE). METHODS: Two hundred sixteen patients with SLE who were treated in our department were surveyed cross sectionally for the presence of ACA using indirect immunofluorescence on HEp-2 cell lines. ACA were identified by their discrete speckled pattern. Antibodies to the major centromere protein, CENP-B, were also studied with ELISA. Serial determinations of anti-CENP-B were carried out using stored serum samples, if available. RESULTS: ACA were recognized in 12 (5.6%) patients with SLE. All patients were receiving steroid therapy, with a mean dose of prednisolone of 14.4 mg/day. These patients also tested positive for anti-CENP-B with high titers despite the low serological disease activity in most. Three or more CREST features were observed in 2 patients and 2 others had no such features. Both patients without CREST features had a relatively short disease duration. The age at onset of SLE was significantly higher and Raynaud's phenomenon was more frequent in patients with ACA than in patients without ACA. In 8 of 10 patients tested, retrospective analysis using stored sera revealed no consistent change in anti-CENP-B titers over time. CONCLUSION: The presence of ACA in patients with SLE is apparently more frequent than previously believed. Patients with SLE with ACA may be a distinct subgroup. A longterm followup is warranted to fully determine the clinical significance of ACA in patients with SLE.     

系统性红斑狼疮合并静脉血栓栓塞症临床相关危险因素分析

目的探讨系统性红斑狼疮（SLE）合并发生静脉血栓栓塞症（VTE）的临床相关危险因素。方法回顾性连续收集2008年1月至2012年2月期间在解放军总医院住院治疗的27例SLE并发VTE的患者入血栓组,并募集同期27例与血栓组性别、年龄、体质量指数（BMI）、生活方式等环境因素相匹配的不伴有VTE的SLE患者作为对照组,利用单因素统计学分析两组患者的静脉血栓形成相关临床危险因素（血小板计数、免疫功能、补体、合并低蛋白血症、狼疮肾炎、肾功能不全、肾病综合征、肾性高血压、蛋白尿、血尿等）及实验室诊断指标[C-反应蛋白（CRP）、D-二聚体,白细胞计数、活化部分凝血活酶时间（APTT）、血浆凝血酶原时间（PT）、血浆纤维蛋白原（FIB）1的差异。结果与对照组相比,血栓组合并低蛋白血症（70．37％）、狼疮肾炎（74．07％）、肾功能不全（70．37％）、肾病综合征（55．56％）、肾性高血压（66．67％）的发生率均显著升高（P值分别为0．003,0．000,0．000,0．027,O．029）。血栓组患者的实验室检测指标CRP（7．19±9．23）mg／L和D．二聚体（6．32±5．75）mg／L均显著高于对照组（P值分别为0．004,0．000）。结论低蛋白血症、狼疮肾炎、肾功能不全、肾病综合征及肾性高血压可能是SLE合并VTE的临床相关危险因素;CRP及D-二聚体可能成为SLE合并VTE的实验室诊断指标。     

Clinical significance of hemostatic markers and thrombomodulin in systemic lupus erythematosus: evidence for a prothrombotic state

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with overwhelming thrombotic states. The precise pathogenetic mechanisms underlying the prethrombotic state in SLE is not fully understood, but interactions between the antiphospholipid antibodies and antigen targets on the coagulation components have been incriminated to play fundamental roles. To evaluate this issue, 34 women with antiphospholipid antibody negative SLE were investigated for molecular markers of blood coagulation and fibrinolytic activity: prothrombin fragment1+2 (PF1+2), thrombin-antithrombin complex (TAT), plasmin-alpha2-antiplasmin inhibitor complex (PAP), and tissue factor pathway inhibitor (TFPI). We also analysed plasma soluble thrombomodulin (sTM) levels. SLE disease activity was determined using the SLE Disease Activity Index (SLEDAI). Concentrations of TAT, PAP, PF1+2 and sTM were significantly elevated (P<0.0001, P=0.0002, P<0.0001, and P<0.0001, respectively), while TFPI antigen levels were found to be reduced (P<0.0001) in patients with SLE compared to the control group. In patients with active SLE, anti-ds DNA levels were correlated positively with plasma TAT (P<0.05), PF1+2 (P<0.05), and sTM (P<0.01) concentrations and negatively with plasma TFPI levels (P<0.05). SLEDAI scores were correlated positively with plasma TAT (P<0.01), PF1+2 (<0.01), and sTM (P<0.01) levels. This study illustrates that both a prethrombotic state and a compensatory fibrinolytic process secondary to subclinical intravascular coagulation might coexist in SLE with elevated sTM levels, indicating impaired endothelial functions.     

Clinical significance of plasma D—dimer and von Willebrand factor levels in patients with ulcer colitis

AIM：To investigate the levels of D-dimer(DD)and von Willebrand factor(vWF)and the relationship between DD and vWF in ulcerative colitis(UC)patients. METHODS:A total of 29 plasma specimens were obtained form patients with ulcerative colitis(male 13,female 16),aged21-47years(33&#177;11),diseases activity was assessed by truelove-Writeria.Patients with a score of above 5 were regarded as having active colitis.Twenty healthy people (male 12,female8)aged 19-53 years(31&#177;14),served as normal controls.Blood samples were taken from an antecubital vein puncture .Blood(1.8mL) was injected into the tubes containing sodium citrate(0.13)mmol/L,The plasma was obtained by centrifugation of 3000r.min^-1 for 10 min,and stored at-80℃until assayed by ELISA&gt;RESULTS:The mean plasma levels of DD and vWF in active UC patients were significantly higher than those of the controls(0.69&#177;0.41vs 0.27&#177;0.11,P&lt;0.01,143&#177;46vs 103&#177;35,P&lt;0.01),The mean plasma levels of DD in the patients with active disease were higher than those with inactive disease(0.69&#177;0.41vs 0.48&#177;0.29,P&lt;0.05),The levels of vWF were not different between active and inactive patients.DD levels wrer positively related to vWF levels(r=0.574.P&lt;0.01).There was no significant difference between levels of DD and vWF and the scope of disease and sex of the patients.CONCLUSION.vWF is an important feature and a good marker of UC;intravascular thrombus and endothelial cell dysfunction were found in UC patients;and the combined test of DD and vWF is helpful to distinguish the activity of the UC patients.     

Relationship between elevated cerebrospinal fluid levels of plasminogen activator inhibitor 1 and neuronal destruction in patients with neuropsychiatric systemic lupus erythematosus

Objective

A homeostatic imbalance between coagulation and fibrinolysis might occur intrathecally in neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no published data on levels of fibrinolytic factors in the cerebrospinal fluid (CSF) of patients with NPSLE. The present study was undertaken to assess CSF levels of fibrinolytic molecules, including urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), D‐dimer, and plasminogen activator inhibitor 1 (PAI‐1), in SLE patients with clinically verified neuropsychiatric involvement and to compare these levels with those in SLE patients without neuropsychiatric involvement and in healthy subjects.

Methods

Levels of uPA, tPA, and PAI‐1 were assessed in CSF from 94 patients with SLE (33 who had NPSLE, 56 who did not have NPSLE, and 5 who were positive for antiphospholipid antibody [not included in the NPSLE or non‐NPSLE group]) and from 53 age‐matched controls. Patients were evaluated clinically, with magnetic resonance imaging of the brain, analyses of neuronal/glial degradation products in CSF, and neuropsychiatric testing.

Results

In the group of patients with NPSLE, intrathecal PAI‐1 levels were significantly elevated compared with levels in SLE patients without overt neuropsychiatric involvement (P < 0.05) and in healthy controls (P < 0.001). In contrast, intrathecal levels of uPA did not differ significantly. Intrathecal levels of PAI‐1 correlated significantly with CSF levels of interleukin‐6 (IL‐6) (r = 0.34, P < 0.001) and IL‐8 (r = 0.33, P < 0.001). Importantly, increased PAI‐1 and D‐dimer levels were observed in SLE patients who had pathologically elevated levels of glial fibrillary acidic protein, neurofilament triplet protein, and tau protein in CSF.

Conclusion

Intrathecal release of PAI‐1 is increased in patients with NPSLE. This results in impaired fibrinolysis, which might contribute to neuronal and astrocytic damage in NPSLE.

     

Clinical significance of IgG anti-Sm antibodies in patients with systemic lupus erythematosus

Free Sm was purified by gel filtration and anti-Sm affinity chromatography. Using this purified antigen, an ELISA for anti-Sm was performed. Three hundred and fifty patients with various rheumatic diseases were studied with respect to immunoglobulin classes of anti-Sm by ELISA. A high frequency of IgG anti-Sm was specifically detected in patients with systemic lupus erythematosus (SLE), but IgA and IgM anti-Sm showed a low frequency and also was detected in other diseases. In patients with SLE, anti-Sm significantly correlated with lung fibrosis and pericarditis. In our longitudinal study, there were increases in titer of IgG anti-Sm preceding central nervous system exacerbation and serositis. IgG anti-Sm was found to be not only a diagnostic marker but also a reliable measure of disease activity in SLE.     

Clinical significance of anti-annexin V antibodies in patients with systemic lupus erythematosus

Annexin V has a calcium-dependent binding affinity for anionic phospholipids and activated platelets, and prevents prothrombinase activity. We investigated the clinical significance of IgG anti-annexin V antibodies in patients with SLE. The study population consisted of 140 patients with SLE. Sera were examined for IgG anti-annexin V antibodies by ELISA. IgG anti-annexin V antibodies were detected in 27 of 140 patients (19%). Significantly higher incidences of arterial or venous thrombosis, intrauterine fetal loss, and prolonged activated partial thromboplastin time were found in patients with anti-annexin V antibodies than in those without anti-annexin V antibodies. Three patients with thrombosis were found not to have anticardiolipin antibodies, but to show sustained serological reactions for anti-annexin V antibodies, irrespective of prednisolone administration. These results indicated the clinical characteristics of SLE patients with anti-annexin V antibodies, and that these antibodies may be associated with the pathogenesis of thrombotic events. Am. J. Hematol. 54:209–213, 1997 © Wiley-Liss, Inc.