Obstructive uropathy as the only manifestation of flare in a patient with systemic lupus erythematosus and anti-phospholipid syndrome

Chronic interstitial cystitis and ureteral stenosis has occasionally been reported in systemic lupus erythematosus, mostly associated with gastrointestinal symptoms. We report a case of obstructive uropathy associated to chronic interstitial cystitis as the only manifestation of lupus flare in a patient with SLE and anti-phospholipid syndrome (APS) who had been in remission for many years. The development of chronic interstitial cystitis in patients with SLE and APS has not been previously reported. Histopathological study of her urinary bladder and ureteral meatus showed chronic inflammatory infiltrate in the subepithelium. Lack of significant lower urinary tract symptoms and gastrointestinal involvement were some of the factors that could have prevented an earlier diagnosis. Obstructive uropathy and renal insufficiency initially improved with immunosuppressive treatment and endoureteral protheses, but poor compliance to the therapy led to ominous ending.     

Atherosclerosis in premenopausal women with antiphospholipid syndrome and systemic lupus erythematosus: a controlled study

OBJECTIVE: To evaluate whether premenopausal women with antiphospholipid syndrome (APS) or systemic lupus erythematosus (SLE) have increased prevalence of atherosclerosis after adjustment has been made for known cardiovascular risk factors. METHODS: We evaluated premenopausal women with APS in comparison with age-matched groups of patients with SLE [positive or negative for anticardiolipin (aCL) antibodies] or rheumatoid arthritis (RA), and healthy subjects. Thirty-three subjects in each group were assessed for cardiovascular risk factors, including a detailed lipid profile. Ultrasonography of carotid and femoral arteries assessed the intima-media thickness (IMT) and the presence of atherosclerotic plaque. RESULTS: Atherosclerotic plaques were detected in 5, 2, 4, 1 and 1 subject in the five groups respectively. APS patients had significantly more affected vessels than RA patients and healthy controls (P=0.042 and P=0.016, respectively), but not compared with SLE patients. No consistent differences in IMT, traditional cardiovascular risk factors or lipid parameters were detected among the five groups. The odds for atherosclerosis independently increased 1.19-fold per year of increasing age [95% confidence interval (CI) 1.08-1.31; P=0.001), 1.019-fold per 1 mg/dl increase in low-density lipoprotein (LDL) (95% CI 1.003-1.036; P=0.020), 1.035-fold per additional 1 g of methylprednisolone equivalent cumulative corticosteroid dose (95% CI, 0.996-1.074; P=0.074), and 4.35-fold in the presence of APS or SLE (95% CI 0.75-25.2; P=0.10). Neither aCL nor anti-beta(2)GPI antibodies were associated with atherosclerosis. CONCLUSION: Premenopausal APS and SLE women have an increased prevalence of carotid and femoral plaque that is not accounted for by other predictors of atherosclerosis, including age, lipid parameters and cumulative steroid dose.     

Preclinical vascular disease in systemic lupus erythematosus and primary antiphospholipid syndrome

OBJECTIVE: To determine the prevalence of preclinical vascular disease and associated risk factors in patients with systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). METHODS: We consecutively studied 70 SLE patients and 25 primary APS patients without clinical coronary artery disease. The control group included 40 healthy women. Carotid ultrasound was performed and the intima-media wall thickness (IMT) and presence of plaque was investigated in all patients and controls. Traditional vascular risk factors and SLE-disease and treatment related factors were also analysed. RESULTS: SLE patients had a higher prevalence of traditional atherosclerosis risk factors: hypertension (P<0.005) and dyslipidaemia (P<0.05) and higher levels of total cholesterol (P = 0.03), triglycerides (P = 0.004) and apolipoprotein B (P = 0.04). The prevalence of carotid plaque was higher and appeared earlier in SLE patients than in the primary APS patients or controls (P<0.001). The IMT was similar in the three groups. SLE patients with secondary APS had a higher prevalence of carotid plaque than patients with primary APS (37.5% vs 8%, P = 0.03). The presence of plaque in SLE patients was associated with a higher SLICC score (2.40 +/- 1.78 vs 1.02 +/- 1.18, P = 0.002), higher ECLAM score (3.10 +/- 2.32 vs 1.84 +/- 1.59, P = 0.02) and older age (47.3 +/- 8.44 vs 37.38 +/- 11.28, P = 0.003) at the time of carotid ultrasound study. CONCLUSION: Plaque prevalence in patients with primary APS is similar to that of controls and inferior to that of SLE patients with secondary APS. SLE patients have a high prevalence of early carotid atherosclerosis that is associated with cumulative disease damage and disease activity.     

Cardiovascular Disease in Systemic Lupus Erythematosus: The Role of Traditional and Lupus Related Risk Factors

Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). SLE is an autoimmune disease that may affect any organ. Premature coronary heart disease has emerged as a major cause of morbidity and mortality in SLE. In addition to mortality, cardiovascular morbidity is also markedly increased in these patients, compared with the general population. The increased cardiovascular risk can be explained only partially by an increased prevalence of classical risk factors for cardiovascular disease; it also appears to be related to inflammation. Inflammation is increasingly being considered central to the pathogenesis of atherosclerosis and an important risk factor for vascular disease. Recent epidemiologic and pathogenesis studies have suggested a great deal in common between the pathogenesis of prototypic autoimmune disease such as SLE and that of atherosclerosis.We will review traditional risk factors for CVD in SLE. We will also discuss the role of inflammation in atherosclerosis, as well as possible treatment strategies in these patients.Key Words: Cardiovascular disease, systemic lupus erythematosus, atherosclerosis.     

Early atheroma in primary and secondary antiphospholipid syndrome: an intrinsic finding

OBJECTIVES: The relationship between atherosclerosis and the antiphospholipid syndrome (APS) is unclear. This study compared intima-media thickness (IMT), arterial stiffness, and presence of plaques in APS patients and controls to evaluate the risk of atherosclerosis in this patient population. The study also explored the relationship between these parameters and cardiovascular risk factors. METHODS: Carotid and femoral IMT and stiffness were measured in 58 APS patients and 58 controls. In addition, antiphospholipid antibodies and cardiovascular risk factors were investigated and other systemic lupus erythematosus (SLE)-related serologic parameters were measured. Details of the patients' previous medical history and information regarding disease treatment were analyzed. RESULTS: A significant difference was found between IMT, arterial stiffness, and the presence of plaques in patients and controls (P<0.05). All of these parameters were independent of cardiovascular risk factors. No differences in these parameters were found between patients with primary APS and those with secondary APS, or between patients with thrombosis and those with obstetric manifestations. There was no correlation between SLE disease activity and atheroma. Patients with plaques had taken a lower total dose of corticosteroids and/or hydroxychloroquine. CONCLUSIONS: Some markers of early atherosclerosis could be detected in both primary and secondary APS, irrespective of clinical manifestations. These data suggest that atherosclerosis might be an intrinsic finding in APS patients, independent of cardiovascular risk factors, and that immunosuppressive treatment may prevent atherosclerosis.     

Oxidativ modifizierte Lipoproteine und deren Antikörper bei Patienten mit Antiphospholipidsyndrom und Systemischem Lupus erythematodes

The antiphospholipid syndrome (APS) with its typical clinical manifestations of recurrent thrombosis and fetal loss is biochemically defined by the presence of circulating antiphospholipid antibodies (aPL). The disease pattern has raised special interest as a possible link between autoimmunity and atherosclerosis. aPL, oxidized low density lipoproteins (oxLDL), and antibodies to oxLDL (Anti-oxLDL) are suggested to play an important role in atherogenesis. In the present study we compared the serum levels of oxLDL and Anti-oxLDL in APS patients (20 subjects with primary APS; 14 subjects with secondary APS) and nonAPS subjects (24 phenotypically healthy controls samples and 12 patients with systemic lupus erythematosus [SLE]) and investigated associations of the above mentioned parameters with the intima-media thickness (IMT), a clinical surrogate parameter of atherosclerosis.SLE patients with and without APS showed significantly increased levels of Anti-oxLDL as compared to the controls group (p = 0.038 and p = 0.007, respectively). In contrast, oxLDL levels were not significantly different between the controls group and patients. The Anti-oxLDL levels correlated significantly with anticardiolipin (p = 0.002) and beta(2)-glycoprotein I antibodies (p < 0.048), both from IgG isotype. Only SLE patients without APS revealed a significantly elevated production of reactive oxygen species indicating an increased proatherogenic oxidative stress in the circulation (p < 0.002). In the patient groups, the circulating levels of oxLDL and Anti-oxLDL showed no association with atherosclerosis as estimated by IMT. In conclusion, our experimental data do not support the concept of oxidative stress-induced accelerated atherosclerosis in APS patients.     

Carotid and femoral atherosclerosis in antiphospholipid syndrome: Equivalent risk with diabetes mellitus in a case–control study

BackgroundAntiphospholipid syndrome (APS) may carry a worse prognosis for vascular complications when co-existing with subclinical atherosclerosis; however, the association between the two conditions remains ambiguous.MethodsWe evaluated ultrasonographic markers of subclinical atherosclerosis in carotid and femoral arteries of 86 patients with thrombotic APS [43 primary APS (PAPS), 43 systemic lupus erythematosus-associated APS (SLE/APS)], 86 patients with diabetes mellitus (DM) and 86 healthy controls, individually matched for age and gender, and investigated their associations with traditional and disease-related factors in APS.ResultsCarotid plaques were found in 28% of PAPS, 23% of SLE/APS, and 30% of DM patients versus 9% of controls (p = 0.006). Femoral plaques were found in 33% of PAPS, 19% of SLE/APS, 20% of DM, and 9% of controls (p = 0.032). Multivariate regression-derived relative risk estimates for atherosclerotic plaques in any location were 2.72 for PAPS, 2.63 for SLE/APS, and 1.98 for DM (p = 0.004, 0.009, and 0.032 respectively), after adjusting for age, gender, hypertension, dyslipidemia, smoking, BMI, and family history of coronary disease. Among patients with APS, atherosclerotic plaques were associated with the number of traditional CVD risk factors in both PAPS (RR = 2.75, p < 0.001) and SLE/APS (RR = 1.84, p < 0.001), and with IgG anti-beta2-glycoprotein I antibodies in SLE/APS.ConclusionsPatients with PAPS and SLE/APS have a nearly 2.5-fold risk of atherosclerotic plaques in carotid and femoral arteries compared to healthy controls, similar to DM patients. Atherosclerotic plaques are associated with the number of traditional risk factors in both APS and SLE/APS, and with IgG anti-beta2-glycoprotein I antibodies in SLE/APS.     

Lipoprotein(a) oxidation and autoantibodies: a new path in atherothrombosis

Lipoprotein(a) (Lp(a)) is considered a vascular pathogen of outstanding importance. High plasma levels of this lipoprotein are associated with premature arterial disease; however, the mechanisms involved have not been clarified. The atherosclerotic process is increasingly regarded as a chronic inflammatory reaction in the arterial wall where oxidation-mediated endothelial injury involving modified forms of low-density lipoprotein (LDL) seems to be a key event. Autoimmune pathways are involved in the progression of atherosclerosis and humoral response to oxidatively modified LDL can be considered among these pathways. A number of factors can be encountered in the pathogenesis of the accelerated arterial disease seen in patients with antiphospholipid (Hughes) syndrome (APS) and systemic lupus erythematosus (SLE). Among these, high levels of Lp(a) have been described in both and increasing evidence indicates that patients with antiphospholipid antibodies (aPL) are under oxidative stress. Recent studies suggest that the so-called 'oxidation theory of atherosclerosis' may also be applied to Lp(a). This fact makes this lipoprotein potentially suitable as a target of the immune system and antibodies reacting against oxidatively-modified Lp(a) by malondialdehyde have been recently described in APS and SLE. It is therefore likely that an immune response to the oxidized moiety of Lp(a) might be influential in the pathogenicity of this lipoprotein and, subsequently, of atherosclerosis.     

Antiphospholipid syndrome in patients with systemic lupus erythematosus treated by autologous hematopoietic stem cell transplantation

Systemic lupus erythematosus (SLE) is the most common disease associated with antiphospholipid syndrome (APS). We, therefore, evaluated 46 patients with refractory SLE treated by autologous hematopoietic stem cell transplantation (HSCT) for a history of APS prior to transplantation. The prevalence of SLE-related APS in our patient population was 61% (28 of 46 patients with refractory SLE). Nineteen of 28 patients with APS had lupus anticoagulant (LA) or high titers of anticardiolipin antibodies (ACLAs), either immunoglobulin (Ig)G or IgM, when evaluated at study entry. Six of 8 evaluable LA+ patients became and remained LA-; 5 of 7 initially ACLA IgG+ patients and 9 of 11 ACLA IgM+ patients demonstrated normalization of ACLA titers when followed after HSCT. Eighteen of 22 patients refractory to chronic anticoagulation discontinued anticoagulation therapy a median of 4 months after transplantation; 78% of them remained free of thrombotic events and in complete SLE remission for up to 78 months (median, 15 months) after HSCT. There was no treatment-related mortality. Autologous HSCT may be performed safely in patients with APS and appears to be effective therapy for eliminating ALPAs and preventing thrombotic complications in patients with SLE.     

Systemic lupus erythematosus and antiphospholipid syndrome in children and adolescents

Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) can be associated with significant morbidity in children and adolescents. Renal involvement in SLE appears to be more severe and more frequent in the pediatric age group, with the major predictors for poor outcome being the severity of histopathologic lesions, severity of renal impairment at diagnosis, and hypertension. In addition to currently recognized cardiovascular and pulmonary involvement, accelerated atherosclerosis is of increasing concern in young individuals with SLE, because of both disease effects and medication usage. Neuropsychiatric SLE seen in childhood ranges from subtle cognitive dysfunction to severe central nervous system involvement; however, there is controversy over the value of different diagnostic studies. APS in children may be associated with SLE, idiopathic, or associated with viral infections. Systemic anticoagulation is recommended for patients with thrombotic events, but long-term management has not been well studied in children.     

Antibodies to high-density lipoprotein and beta2-glycoprotein I are inversely correlated with paraoxonase activity in systemic lupus erythematosus and primary antiphospholipid syndrome

OBJECTIVE: To determine the prevalence of anti-high-density lipoprotein (anti-HDL) antibodies and to establish a possible relationship between anti-HDL, anticardiolipin antibodies (aCL), anti-beta(2)-glycoprotein I (anti-beta(2)GPI), and paraoxonase (PON) activity in patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). METHODS: Thirty-two patients with SLE and 36 with primary APS were enrolled in a cross-sectional study. Twenty age- and sex-matched healthy subjects were used as controls. Serum levels of IgG and IgM aCL, anti-beta(2)GPI, and antiprothrombin antibodies and IgG anti-HDL were measured by enzyme-linked immunosorbent assay. Total cholesterol, HDL cholesterol, HDL(2), and HDL(3) were determined by standard enzymatic techniques. PON activity was assessed by quantification of nitrophenol formation, and total antioxidant capacity (TAC) by chemiluminescence. RESULTS: Levels of total HDL, HDL(2), and HDL(3) were reduced in patients with SLE compared with controls (mean +/- SD 0.51 +/- 0.3, 0.37 +/- 0.3, and 0.14 +/- 0.1 mmoles/liter, respectively, versus 1.42 +/- 0.9, 1.01 +/- 0.7, and 0.40 +/- 0.2). Patients with SLE and primary APS had higher titers of anti-HDL antibodies and lower PON activity than controls. In the SLE population, PON activity was inversely correlated with IgG anti-HDL titers (r = -0.48, P = 0.005) whereas in the primary APS population, IgG anti-beta(2)GPI was the only independent predictor of PON activity (r = -0.483, P = 0.003). In the SLE group, anti-HDL was inversely correlated with TAC (r = -0.40, P < 0.02), and PON activity was positively correlated with TAC (r = 0.43, P < 0.02). CONCLUSION: IgG anti-HDL and IgG anti-beta(2)GPI antibodies are associated with reduced PON activity in patients with SLE and primary APS. Since the physiologic role of PON is to prevent low-density lipoprotein oxidation with its attendant atherogenic effects, the reported interactions may be relevant to the development of atherosclerosis in SLE and primary APS.     

Foetal loss, liver necrosis and acute lupus erythematosus in a patient with antiphospholipid antibody syndrome.

The antiphospholipid antibody syndrome (APS) is characterized by arterial or venous thromboses and recurrent foetal loss. It occurs as primary disease, but also in the context of systemic lupus erythematosus (SLE). Whereas primary APS induces a thrombotic microangiopathy without significant inflammatory reaction, secondary APS in SLE is usually associated with vasculitis. Here we report a patient with APS who presented with acute diarrhoea and then developed a HELLP-like syndrome characterized by a spontaneous abortion, multifocal hepatic necroses and thrombocytopenia. Thereafter an acute flare of SLE with arthralgias, pleuritis, skin rash and glomerulitis occurred. Clinical amelioration was only achieved by combining curettage, anticoagulation and immunosuppression, a treatment taking into account the pathogenesis of HELLP-like disease, APS and SLE. To our knowledge this is the first reported case of APS associated with combined acute manifestations of these three syndromes triggered by a presumable intestinal infection.     

Anti-beta2-glycoprotein I antibodies in pediatric systemic lupus erythematosus and antiphospholipid syndrome

OBJECTIVE: To determine whether serum beta2-glycoprotein I antibody (anti-beta2GPI) detection improves identification of pediatric subjects at risk for antiphospholipid syndrome (APS). METHODS: Serum antiphospholipid antibodies (aPL) were identified by anticardiolipin enzyme-linked immunosorbent assay (ELISA), lupus anticoagulant assays, and syphilis screening in children with primary APS, systemic lupus erythematosus (SLE), or SLE plus APS. Anti-beta2GPI level and isotype were determined by beta2GPI ELISA and correlated with clinical manifestations and other aPL assays. RESULTS: One hundred-ten subjects under 22 years of age and of mixed ethnicity were evaluated. Fifty-seven had SLE (including 14 with APS), 25 had primary APS, 16 had SLE-like APS, 6 were healthy children with aPL detected incidentally, 4 had other rheumatic diseases and 2 had other conditions. Anti-beta2GPI were detected in 48% of SLE subjects and did not improve aPL detection over standard tests. Anti-beta2GPI were associated with stroke (P = 0.014), but not with other APS manifestations, and were rarely detected in primary APS. Among subjects with APS manifesting as chronic thrombocytopenia, anti-beta(2)GPI distinguished subjects with SLE from those with primary APS. CONCLUSIONS: With the exception of stroke, anti-beta2GPI detection does not improve identification of pediatric APS over that of traditional aPL assays. Anti-beta2GPI are rare in pediatric primary APS, but may predict evolution of chronic thrombocytopenia to SLE.     

Primary antiphospholipid syndrome as the forerunner of systemic lupus erythematosus

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

The prevalence of antibodies to anionic phospholipids in patients with the primary antiphospholipid syndrome, systemic lupus erythematosus and their relatives and spouses

OBJECTIVES: Antiphospholipid antibodies (aPL) have been associated with syndromes involving thrombosis, fetal loss and thrombocytopenia. Genetic and environmental conditions are among the factors attributed to the cause of autoimmune diseases such as the antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). The aim of this study was to determine whether these factors determine the prevalence of aPL. METHODS: Three groups of patients were tested for the presence of IgG, IgM and IgA anticardiolipin (aCL), antiphosphatidylinositol (aPI), antiphosphatidylglycerol (aPG) and antiphosphatidylserine (aPS) antibodies: (i) patients with primary APS (PAPS); (ii) patients with SLE and secondary APS; and (iii) patients with SLE without APS. First-degree relatives and spouses of patients with SLE/APS were also tested for circulating aPL. RESULTS: IgG aPL were particularly prevalent in patients with PAPS. IgG aPI and aCL were more prevalent in patients with PAPS than the IgM equivalents (P < 0.0001). Notably, none of the patients with PAPS had IgA aPL. A significantly higher number of relatives of patients with SLE/APS possessed IgG aPL than the normal controls. Except for aPG (P < 0.03), the prevalence of these antibodies in the relatives was not significantly different from patients with SLE/APS. The relatives also had significantly higher prevalence of IgG aPI, aPS and aCL antibodies than IgM aPL antibodies. In contrast, the prevalence of IgG aPL in the spouses was no different than in the healthy controls. CONCLUSIONS: Genetic factors, shared by patients and their relatives, seem to have some effect on the prevalence of aPL in the subjects studied, while environmental factors shared by spouses appear to have no influence.     

Increased level of tumor necrosis factor-�� in patients with antiphospholipid syndrome: marker not only of inflammation but also of the prothrombotic state

Connections between inflammation and thrombosis are intriguing, especially in a condition such as an antiphospholipid syndrome (APS), a disease characterized by immune-mediated thrombosis. Tumor necrosis factor alpha (TNF-α) is a cytokine which shares proinflammatory and prothrombotic actions, while a soluble form of interlukin-2 receptor (sIL-2R) is considered a typical marker of (auto)immune inflammation with not known direct links to thrombosis. The differences in the pathogenesis of APS as compared to other autoimmune diseases might be connected with different serum levels of both mediators. To answer this question, we studied 147 patients with systemic lupus erythematosus (SLE), 21 with SLE-like syndrome (SLE-LS), 20 with isolated APS (primary antiphospholipid syndrome, PAPS), and 32 healthy controls. Thirty-six patients from the SLE group fulfilled the updated APS criteria (secondary APS, SAPS). In comparison to healthy subjects, TNF-α concentration was increased in all patients, while sIL-2R rose significantly in the SLE group only. APS (both SAPS and PAPS) was characterized by the highest levels of TNF-α. Moreover, patients with lupus anticoagulant or elevated levels of IgG anticardiolipin or IgG anti-β₂-glycoprotein I antibodies had higher TNF-α levels than patients without the presence of any type of antiphospholipid antibodies (aPL). In conclusion, the presence of aPL is associated with higher TNF-α level, whereas increased level of sIL-2R is rather connected with definite SLE where inflammatory processes prevail. It might be hypothesized that TNF-α plays a major role in pathogenesis of APS thrombotic phenomena.     

系统性红斑狼疮合并抗磷脂综合征患者外周血CD1d的表达

目的通过检测系统性红斑狼疮(SLE)合并抗磷脂综合征(APS)患者外周血单个核细胞(PBMC)CD1d表达,探讨CD1d分子和APS疾病和实验室指标的相关性。方法利用流式细胞分析方法对20例合并APS患者,30例SLE对照,23名正常对照PBMC CD1d表达进行分析,并与患者临床资料和实验结果进行相关分析。结果SLE合并APS组PBMC中CD1d表达高于正常对照组,和SLE对照组比较差异无统计学意义。SLE合并APS组单核细胞群中CD1d表达高于正常对照组,和SLE对照组比较差异无统计学意义。CD1d和SLE疾病活动指数(SLEDAI)评分显著相关,和补体明显呈负相关。结论CD1d表达异常与SLE发病相关,并可作为评价SLE活动的指标。     

Acute acalculous cholecystitis induced by mesenteric inflammatory veno-occlusive disease (MIVOD) in systemic lupus erythematosus

A 43-year-old woman with systemic lupus erythematosus (SLE) was treated for lupus pleurisy. During the course of her illness, she abruptly suffered severe right hypochondriac pain and high-grade fever. Abdominal ultrasonography revealed a thickening of the gallbladder wall without cholelithiasis, and she was diagnosed with acute acalculous cholecystitis (AAC). Laparoscopic cholecystostomy was performed. Pathological examination revealed lymphocytic venulitis without arteritis. Antiphospholipid antibodies were not demonstrated during the course of illness. From these findings, the cause of AAC was revealed as a mesenteric inflammatory veno-occlusive disease (MIVOD), which is a novel venopathy mainly affecting the mesenteric vein and/or its branches, causing serious ischemic complications. MIVOD should be considered as a possible cause of AAC.Abbreviations AAC Acute acalculous cholecystitis - APS Antiphospholipid syndrome - APTT Activated prothromboplastin time - CRP C-reactive protein - LC Lupus anticoagulant - MVT Mesenteric venous thrombosis - MIVOD Mesenteric inflammatory veno-occlusive disease - SLE Systemic lupus erythematosus     

Cross-reactivity between anti-cardiolipin,anti-high-density lipoprotein and anti-apolipoprotein A-I IgG antibodies in patients with systemic lupus erythematosus and primary antiphospholipid syndrome

OBJECTIVES: Atherosclerosis is an important complication of patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). One suggested mechanism may be the action of autoantibodies directed against plasma lipoproteins. We studied the presence and patterns of cross-reactivity between antibodies directed against cardiolipin, high-density lipoprotein (HDL) and apolipoprotein A-I (Apo A-I) in patients with SLE and APS. METHODS: Sera from 50 patients (25 SLE and 25 APS) and 10 healthy controls together with three human immunoglobulin G anti-cardiolipin (CL) monoclonal antibodies (IS4, CL1 and CL24) were assessed for the presence of autoantibodies binding cardiolipin, HDL and Apo A-I. Classical inhibition assays were performed to study interference by HDL and Apo A-I in the binding of the human monoclonal antibody to CL. To determine the cross-reactivity patterns between these autoantibodies, sera from 12 patients were incubated on ELISA plates coated with the three different molecules and the captured antibodies were then tested for their activity towards each of the other antigens. RESULTS: All three monoclonals bound to CL. IS4 and CL1 also bound to HDL but only IS4 bound to Apo A-I. Anti-cardiolipin titres were higher in patients with APS than SLE and in healthy controls (P<0.03 and P<0.009 respectively). Titres of antibodies to HDL were higher in patients with SLE and APS than in controls (P<0.009 and P<0.03 respectively). There were no significant differences with respect to the presence of antibodies binding to Apo A-I. In the SLE population, anti-HDL antibody titres correlated with anti-Apo A-I (r=0.563, P<0.004), but not in patients with APS. In the cross-reactive assay, 11/12 (91.7%) of the samples containing isolated anti-CL antibodies reacted to HDL and 2/12 (16.7%) to Apo A-I. Samples containing isolated anti-HDL antibodies also reacted with CL and Apo A-I (7/12 and 3/12 respectively). All samples collected after incubation with Apo A-I bound to HDL and 6/12 (50%) to CL. There were no differences in the cross-reactivity patterns between patients with SLE and APS. CONCLUSIONS: Patients with SLE and APS have antibodies directed against HDL and Apo A-I. A high percentage of these antibodies cross-react with CL, suggesting the presence of different groups of antibodies with different targets. The study of the interaction between the immune response and the lipoprotein components and the correct characterization of the reactivity patterns of autoantibodies may be of relevance in the study of atherosclerosis in patients with SLE and APS.     

Antiphospholipid Syndrome in Systemic Lupus Erythematosus: Is the Whole Greater Than the Sum of Its Parts?

This article compares the manifestations of systemic lupus erythematosus (SLE) in the presence and absence of antiphospholipid antibodies (aPLs), the hallmark autoantibodies of antiphospholipid syndrome (APS). The combination of SLE and APS appears to be of greater concern than either entity alone. APS complicates SLE by adding a vaso-occlusive factor to the inflammatory component that adversely affects the prognosis of those who have lupus and aPLs. The increase in both morbidity and mortality when both are present has significant therapeutic implications. Anticoagulation may be a safer and more appropriate therapeutic option than instituting a regimen of corticosteroids and immunosuppressive agents with all their attendant adverse effects. It falls upon the physician to clearly define the disease entity and fully evaluate the disease process.