Soluble CD40 ligand in systemic lupus erythematosus and antiphospholipid syndrome

AIM: To investigate a clinical role of soluble (s) CD40 ligand in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). MATERIAL AND METHODS: A serum concentration of sCD40 ligand was measured with enzyme immunoassay (Bender Medsystems, Austria) in 21 patients with primary antiphospholipid syndrome (PAPS), in 25 patients with secondary APS (SAPS) associated with SLE, in 92 SLE patients and in 16 healthy donors. RESULTS: A sCD40 ligand concentration in sera of SAPS and SLE patients was significantly higher than in donors. Significant differences by the ligand level between the above patients were not seen. In PAPS sCD40 ligand concentration was normal. Elevated serum concentration of the ligand was observed in 9.5% patients with PAPS, 54.0%--with SAPS, 73.9%--with SLE. This rise in SLE and SAPS was not related with the disease activity or renal damage. Hyperexpression of the ligand in APS was associated neither with thromboses nor with a high concentration of IgG/IgM antibodies to cardiolipin. A direct correlation occurred between sCD40 ligand level and platelet count. In SLE and SAPS elevation of the ligand level correlated with increased thickness of carotid artery intima-media complex, hypercholesterinemia and diastolic dysfunction of left ventricular myocardium. CONCLUSION: Hyperexpression of sCD40L in SLE and SAPS is associated with developing cardiovascular diseases and atherosclerosis.     

Soluble adhesion molecules in antiphospholipid syndrome associated with systemic lupus erythematosus and in primary antiphospholipid syndrome

AIM: To evaluate clinical implications of measurements of the level of soluble cell molecules of adhesion (sCMA) in systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS) and primary APS (PAPS). MATERIAL AND METHODS: Serum levels of sP-selectine, sE-selectine, sVCAM-1 were determined with enzyme immunoassay (R&D, USA) in 23 SLE with APS, 15 SLE patients free of APS and 19 patients with PAPS. RESULTS: Mean levels of sE-selectine and sVCAM-1 in SLE patients with APS, PAPS and SLE was higher than in donors. Elevated mean levels of sP-selectine were observed only in SLE patients free of APS. These patients also showed a correlation between sVCAM-1 level and the disease activity (p < 0.01). CONCLUSION: The development of immunopathological process in APS is associated with increased concentration of sCMA.     

The role of hyperhomocysteinemia in systemic lupus erythematosus and antiphospholipid syndrome

AIM: To assess the role of hyperhomocysteinemia (HHC) in development of vascular complications in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). MATERIAL AND METHODS: A total of 125 participants (24 males and 101 females aged 38 +/- 13 years) were divided into three groups: group 1--SLE patients (n=51); group 2--SLE+APS patients (n=49); group 3--primary APS patients (n=25). The patients had the disease for 14 +/- 11 years. Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) marked APS serologically. Homocystein (HC) was assayed by high performance liquid chromatography. HHC (HC > 15 mcg/l) was diagnosed in 82 of 125 (66%) patients: in 59% patients of group 1, 67%--of group 2 and 76%--of group 3. There was a relationship between HHC and digital necrosis (DN): 80% of DN patients had HHC while HHC was diagnosed in 57% patients free of DN (chi-square = 4.76, p = 0.03). Development of occlusions in APS was associated with HHC. Elevated levels of HC in blood was registered in 43 of 55 (78%) APS patients with thromboses vs. 9 of 19 (47%) patients with APS free of thromboses (p = 0.03). HHC occurred significantly more frequently in patients with arterial thromboses (in all 14 patients) than in patients with venous thromboses (in 16 of 23--69.6%, p = 0.03) and in the absence of thromboses (in 9 of 19, 47.4%, p = 0.04). HHC was associated with thromboses of cerebral, peripheral arteries (90 vs. 47% in patients without thrombosis, p = 0.005; 84 vs. 47%, p = 0.04, respectively), coronary vessels (79 vs. 47%, p = 0.04). In APS patients having arterial thromboses with duration of postthrombocytic period (PTP), estimated as time from thrombosis to entering the trial, less than 2 months, HC concentration was significantly higher (22.9 +/- 7.0 mcg/l) compared to patients with PTP more than 2 years (16.6 +/- 3.7 mcg/l (p = 0.04). CONCLUSION: More than 50% patients with SLE and APS, irrespective of APS variants, had an elevated HC level in the blood. Correlation between HHC and development of thromboses, primarily arterial, in APS gives grounds for the role of HHC in development of vascular complications in SLE and APS.     

Serum nitrates in patients with systemic lupus erythematosus and antiphospholipid syndrome

AIM: To elucidate clinical implications of nitrates (NO3) concentration as an indicator of nitric oxide (NO) level in blood serum of patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (PAPS). MATERIAL AND METHODS: Blood serum concentration of NO3 was measured by high-performance liquid chromatography in a total of 41 patients with SLE (n = 17), PAPS (n = 14) and secondary APS (n = 9). Sera from 10 healthy subjects (donors) served as control. NO3 concentration > 40 mcmol/l was stated high. SLE activity was assessed by V. A. Nasonova's scale and SLEDAI index (SLEDAI > 9 indicated SLE exacerbation). Patients with PAPS were divided into two groups depending on clinical symptoms: 7 patients with significant thrombosis or history of more than two thrombotic complications (group 1); 7 patients with the history of two or less thromboses (group 2). RESULTS: The mean serum nitrate concentration in the SLE group was 43.59 mcmol/l (range 17.06-113.22). The nitrate level of the sAPS + SLE group was 49.81 +/- 27.54 and did not significantly differ from APS (33.67 +/- 14.70). By univariate standard analyses, serum nitrate concentration was significantly higher in patients with high disease activity (57.31 +/- 25.12 vs. 25.62 +/- 6.96, Mann-Whitney test, p < 0.01). The Spearman correlation coefficient of nitrate level with SLEDAI was 0.8 (p < 0.001). CONCLUSION: A nitrate level is increased in patients with active SLE and in APS patients with severe thrombotic complication.     

Atheroscleotic vascular lesion in systemic lupus erythematosus and antiphospholipid syndrome in men

The aim of the study was to determine the prevalence of various clinical and subclinical manifestations of atherosclerosis (AS) in men with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APLS), as well as to evaluate correlations between vascular atherosclerotic lesions, risk factors, and the levels of C-reactive protein (CRP) and cardiolipin antibodies (CLA). The subjects of the study were 62 patients (mean age 35.7 +/- 11.6 years, disease duration 129 +/- 102 months). Conventional and disease-related risk factors were analyzed. Carotic ultrasonography (CU) was performed in order to reveal vascular atherosclerotic lesions. Serum CRP levels were measured by the high-sensitive immunonephelometric technique. IgG and IgM CLA were studied by solid-phase immunoenzyme assay. CU found carotic arterial involvement in 58% of the patients; clinical manifestations of AS were revealed in 42% of the patients. The patients were divided into two groups: group I included 19 patients with APLS signs, group II consisted of 43 patients without APLS symptoms. The disease duration and lesion index were higher in group I. The study revealed a significant correlation between CRP level and intima-media complex (IMC) thickness in patients suffering from SLE with or without APLS (p < 0.05). Patients with AS displayed higher levels of IgG CLA, although the difference was insignificant. The study demonstrates that men suffering from SLE with or without APLS have a high risk of AS. An increase in CRP level is associated with an increase in IMC thickness.     

Clinical and morphological characteristics of lupus nephritis in systemic lupus erythematosus with antiphospholipid syndrome

AIM: To ascertain clinical and morphological features of lupus nephritis (LN) in systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome (APS). MATERIAL AND METHODS: Immunological markers of SLE and APS, clinical picture, urine indices were examined in 138 patients with SLE, APS and renal dysfunction. RESULTS: LN associated with APS is characterized with marked arterial hypertension, such patients had arterial thromboses more frequently than patients with isolated LN. Patients with anticardiolipin antibodies have arteriolosclerosis, in APS - diffuse interstitial sclerosis. CONCLUSION: Renal impairment in SLE may run not only with LN but also with thrombotic microangiopathy modifying clinical symptoms and course of the disease.     

系统性红斑狼疮合并抗磷脂综合征患者的临床分析

目的 研究系统性红斑狼疮合并抗磷脂综合征(SLE-APS)患者的临床特点.方法 对39例SLE-APS患者的临床和实验室资料进行回顾性分析.结果 39例患者中,有31例共发生了48次血栓栓塞事件,以深静脉血栓及脑梗死为主.26例已婚有生育史女性患者中,有12例发生病态妊娠.28例抗心磷脂抗体阳性;16例狼疮抗凝物阳性.24例患者先确诊SLE,平均9.5年后又出现APS样表现;12例先出现反复病态妊娠或血栓事件,平均4.8年后演变为SLE;3例一发病便同时符合SLE和APS的分类标准.有5例在发生血栓事件或病态妊娠时的狼疮活动指数<5分.结论 SLE-APS患者血栓事件及病态妊娠发生率增多.APS可出现于SLE之前、之后或同时.狼疮患者可以在病情稳定期出现APS的表现.详细询问病史、常规检测抗心磷脂抗体,有助于发现SLE-APS的高危因素,积极预防APS的发生.     

False-positive tests for heparin-induced thrombocytopenia in patients with antiphospholipid syndrome and systemic lupus erythematosus

Summary.  Background : Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy that can be associated with arterial or venous thrombosis and is caused by antibodies against platelet factor 4 (PF4)–heparin complex. Patients with antiphospholipid syndrome (APS) have been reported with positive tests for PF4–heparin complex antibodies by antigen assay. Whether such patients can be treated with heparin is a dilemma. Objectives : To determine the incidence and nature of the HIT immune reaction in patients with APS and/or systemic lupus erythematosus (SLE). Methods : Antibodies against PF4–heparin complex were assayed by particle gel immunoassay (PaGIA), or enzyme immunoassay (EIA) with or without an excess of heparin. EIA for PF4 alone was also performed. Functional assays for HIT, that is, heparin-induced platelet activation (HIPA) and heparin-induced platelet aggregation, were also performed. Results : In 32 of 42 patients (76.2%) with APS, APS and SLE, SLE, or SLE with antiphospholipid antibodies, EIA IgG or PaGIA for PF4–heparin complex antibodies were positive. Of these 32 samples, 26 (81.3%) tested positive for anti-PF4 antibodies. All 24 samples that were positive for PF4–heparin complex by EIA IgG were also positive for EIA IgG in the presence of heparin excess, and all were negative by the HIPA and heparin-induced platelet aggregation tests. Conclusion : A large proportion of patients with APS and/or SLE give false-positive HIT antigen test results that are presumably related to autoantibodies against PF4, which can be distinguished from true HIT antibodies by EIA for PF4–heparin complexes tested with heparin excess, and by functional assays.     

Leiden, G20210A mutations in prothrombin gene and antiphospholipid antibodies in systemic lupus erythematosus and antiphospholipid syndrome

AIM: To estimate incidence rate of Leiden mutation in factor V gene, prothrombin gene mutation responsible for replacement of G for A in position 20210 (G20210A) of its 3'-end noncoding part in patients with systemic lupus erytheamtosus (SLE) and antiphospholipid syndrome (APS) and their relationships with antiphospholipid antibodies (aPL): lupus anticoagulant (LA) and anticardiolipin antibodies (aCL). MATERIALS AND METHODS: The trial included 33 patients (2 males and 31 females) aged 20-62 years (mean age 32.7 +/- 9.8 years). 29 patients suffered from SLE, 17 of them had also APS (criteria by G. R. V Hudhes). 3 patients had primary APS, 1 female had hemorrhagic vasculitis. IgG and IgM-aCL were detected by enzyme immunoassay. In revealing mutation, DNA was used isolated from peripheral blood by standard methods based on polymerase chain reaction (PCR). Primary screening of Leiden mutation was made according to Bertina et al. with Mnl I restrictase. The mutation was confirmed by an original technique with allele-specific primers. G20210A mutation in the prothrombin gene was determined with restrictase Taq I after introduction of artificial restriction site in PCR product. The patients were divided into 2 groups. Group 1 incorporated 12 patients with SLE without APS. Group 2--21 patients with APS (17 with SLE + APS, 3 with primary APS and 1 with hemorrhagic vasculitis). RESULTS: Patients of group 1 had neither thrombotic complications nor Leiden mutation. Two patients of group 2 had heterozygous Leiden mutation. Both females were aPL-positive and had previously recurrent thrombophlebitis. One of them had also recurrent disorders of cerebral circulation. None of the examinees had any G20210A mutations in the prothrombin gene. CONCLUSION: Detection of genetic defects in APS provide arguments in the dispute about the necessity, duration and choice of anticoagulant therapy. If patients with APL syndrome appeared to have besides aPL also genetic defects in coagulation, this will enable identification of patients at high risk of thrombosis which need permanent administration of anticoagulants among which only low-molecular ones or glycosaminoglycanes are indicated. Mutation in gene of factor V is absolute contraindication to phenilin and quamarines.     

1例系统性红斑狼疮伴抗磷脂综合征病人的护理

抗磷脂综合征(APS)是反复发生动脉、静脉血栓形成,习惯性流产和血小板减少等症状为主要表现的自身免疫性疾病.有文献报道,系统性红斑狼疮(SLE)合并APS的发生率为20%[1].部分病例病情进展迅速,造成多器官功能衰竭甚至死亡.我科于2008年1月收治1例SLE合并APS的病人,经过精心治疗及护理,效果满意.现将护理报告如下.     

Small vessel thrombosis without major thrombotic events in systemic lupus erythematosus patients with antiphospholipid syndrome

Antiphospholipid syndrome has been defined by the presence of antiphospholipid antibodies or lupus anticoagulant in association with certain clinical events, including recurrent arterial or venous thromboses and recurrent fetal loss. It comprises two separate clinical entities: simple, characterized by large vessel occlusions, and catastrophic, with multiple occlusive events predominantly affecting small vessels. Three patients with systemic lupus erythematosus and permanently increased IgG anticardiolipin antibody levels are being described. Only postmortem histopathological examination revealed microangiopathic thrombotic changes in different organs, which were clinically silent in early stages of the disease and misinterpreted later in its course because of a peculiar clinical picture. All patients presented features of catastrophic antiphospholipid syndrome in the final stage of the disease.     

The shrinking lungs syndrome in systemic lupus erythematosus

A comprehensive review of the literature on shrinking lungs syndrome (SLS) in systemic lupus erythematosus involved a MEDLINE search (1965-1997) of case reports and clinical series of patients with the diagnosis of SLS. A total of 49 well-documented cases of SLS were reviewed. Shrinking lungs syndrome is characterized by unexplained dyspnea, a restrictive pattern on pulmonary function test results, and an elevated hemidiaphragm. The cause of SLS remains controversial, with several authors attributing the disorder to diaphragmatic weakness and others suggesting that chest wall restriction accounts for the clinical syndrome. No definitive therapy exists. Corticosteroids have been reported to lessen symptoms and improve pulmonary function in some patients with SLS, but other methods of treatment have occasionally been found to be helpful. Clinical presentation, method of diagnosis, pathogenesis, and treatment modalities are summarized in this review. An uncommon complication of systemic lupus erythematosus, SLS causes significant morbidity and, occasionally, mortality.