趋化因子及受体变化与初发系统性红斑狼疮免疫异常的相关性研究

目的初步探讨趋化因子及受体与初发系统性红斑狼疮(SLE)免疫异常的相关性。方法采用酶联免疫吸附试验(ELISA)检测37例初发SLE患者和20名正常对照的巨噬细胞炎症蛋白-la (MIP-1α)、MIP-1β、激活正常T细胞表达和分泌因子(RANTES)以及γ干扰素(IFN-γ)和白细胞介素-4 (IL-4)的血清水平,用流式细胞术检测其中18例初发SLE患者及10名正常对照外周血CD4~ T细胞表面趋化因子受体(CCR)1、CCR3、CCR5的表达情况,分析它们的相关性。结果初发SLE血清MIP-1α、MIP-1β水平较健康对照显著升高(P＜0．01),MIP-1α和MIP-1β呈显著正相关(r=0．609,P＜0．01)；初发SLE组的CD4~ CCR1~ 、CD4~ CCR5~ 细胞百分率显著低于对照组(P均＜0．01),CD4~ CCR1~ 细胞百分率与血清MIP-1α、IFN-γ水平呈显著负相关(r=-0．525,P=0．017；r=-0．442,P=0．045)；CD4~ CCR5~ 细胞百分率与血清IFN-γ水平呈显著负相关(r=-0．645,P=0．001)；CD4~ CCR3~ /CD4~ CCR5~ 比值显著高于对照组(P＜0．01)。结论趋化因子及其受体与细胞因子间相互影响,它们的异常改变可能导致机体免疫紊乱,参与SLE发病。     

Renal function assessment in patients with systemic lupus erythematosus

Few studies have evaluated the glomerular filtration rate (GFR) in patients with systemic lupus erythematosus (SLE). Even though the National Kidney Foundation (NKF) suggests using the equations to estimate GFR, rheumatologists continue using creatinine clearance (CCl). The main objective of our study was the assessment of different equations to estimate GFR in patients with SLE: Simplified MDRD study equation (sMDRD), CCl, Cockcroft Gault (CG), CG calculated with ideal weight (CGi), Mayo Clinic Quadratic (MCQ), and Chronic Kidney Disease Epidemiology Collaboration Equation (CKD-EPI). CKD-EPI was considered as the reference standard, and it was compared with the other equations to evaluate bias, correlation (r), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), percentage of measurement of GFR between 70–130% of GFR measured through CKD-EPI (P30) and to compute the ROC curves. Adequacy of the 24-h urine collection was evaluated. To classify patients into GFR?<?60?ml/min/1.73?m², the best sensitivity and NVP were obtained with sMDRD: the best PPV and specificity with MCQ. P30 was 99.3% with sMDRD, 77.5% CCl, 91.7% CG, 96.7% CGi, and 77.2% with MCQ. The lowest bias was for sMDRD and the highest for CCl. Only 159 (52.6%) urine collections were considered adequate, and when these patients were re-evaluated, the statistical results improved for CCl. CGi was better in general than CG. CCl should not be considered as an adequate GFR estimation. Ideal weight is better than real weight to calculate GFR through CG in patients with SLE.     

Pulmonary function of nonsmoking patients with systemic lupus erythematosus

The pulmonary function of 70 nonsmoking patients with systemic lupus erythematosus (SLE) was evaluated, and the results were compared with those of 70 age- and sex-matched, nonsmoking healthy individuals. Isolated reduction of carbon monoxide diffusing lung capacity (DCO), usually subclinical, was the most commonly detected functional abnormality in the SLE population, whereas it was absent in the comparison group. Isolated small airways disease (SAD) was observed in a relatively high percentage of patients, but not significantly different from that in the healthy people. Restrictive and obstructive patterns were very unusual in the SLE people and absent in the members of the comparison group. Finally, normal lung function was seen in the majority of the latter, but only in one third of the lupus patients. Subclinical respiratory dysfunction, most commonly expressed as diminished DCO, is a common feature of SLE.     

Disorders of hemostatic function in patients with systemic lupus erythematosus

A wide spectrum of hemostatic abnormalities is found in patients with SLE. Thrombocytopenia and qualitative platelet disorder (impaired aggregation to collagen) are probably both due to antiplatelet antibodies, which can be found in most patients with the disease.About 10% of patients with SLE have a circulating anticoagulant. These circulating anticoagulants are broadly heterogeneous. Although most reported cases act at the level of the prothrombin converting complex, 15 of the 74 cases here reviewed had other points of action. The anticoagulants are probably all antibodies; they differ (with rare exceptions) from other naturally occurring circulating anticoagulants in having an immediate rather than a progressive effect, and in acting, not against pre-existing procoagulants, but against unstable complexes. An anticoagulant of the type found in SLE is only rarely observed in the absence of SLE; its presence in a patient is thus of some diagnostic importance.Hypoprothrombinemia is a common second lesion in patients with circulating anticoagulants. Its pathogenesis is obscure.Two patients with acquired von Willebrand's disease have been observed.All the hemostatic abnormalities found in SLE probably have immunologic bases; all respond to glucocorticoid treatment.     

Left ventricular function in patients with stable systemic lupus erythematosus

Echocardiography was used to compare the left ventricular function of 43 female patients with stable systemic lupus erythematosus with 93 healthy females in 3 age groups. Left ventricular systolic function was evaluated by the left ventricular ejection fraction and left ventricular diastolic function was evaluated by the diastolic descent rate of the anterior mitral leaflet (DDR), the ratio of mean systolic velocity to mean diastolic velocity in the left ventricular posterior wall (D/S ratio) and the ratio of peak mitral inflow velocity during the atrial filling period to that in the early filling period (A/E ratio). The left ventricular ejection fraction was not significantly different between patients and normal subjects. However, left ventricular diastolic function evaluated by these indexes in patients was different from normal subjects. These data suggest that left ventricular diastolic function is lower in patients with stable systemic lupus erythematosus than in normal subjects. It appears to deteriorate progressively with age. However, left ventricular systolic function remains normal.     

Serial pulmonary function testing in patients with systemic lupus erythematosus

Previous studies have documented the pulmonary function abnormalities associated with systemic lupus erythematosus (SLE). There are very few data, however, regarding the progression of such changes. To study this question, we evaluated the pulmonary function of a group of 25 patients with SLE from two to seven years after a set of pulmonary function tests had been performed as part of their overall initial assessment. Reductions in diffusing capacity, FVC, and total lung capacity did not change significantly for the group over the period of our study. The mean FEF25-75%, which was initially low, and the mean FEV1/FVC ratio, which was initially normal, both decreased significantly. The observed abnormalities in airway function were not related to smoking history. Other aspects of lupus activity, as measured by serum creatinine levels and clinical activity, did not appear related to progression of lung disease.     

Consensus treatment plans for induction therapy of newly diagnosed proliferative lupus nephritis in juvenile systemic lupus erythematosus

Objective

To formulate consensus treatment plans (CTPs) for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (SLE).

Methods

A structured consensus formation process was employed by the members of the Childhood Arthritis and Rheumatology Research Alliance after considering the existing medical evidence and current treatment approaches.

Results

After an initial Delphi survey (response rate = 70%), a 2‐day consensus conference, and 2 followup Delphi surveys (response rates = 63–79%), consensus was achieved for a limited set of CTPs addressing the induction therapy of proliferative LN. These CTPs were developed for prototypical patients defined by eligibility characteristics, and included immunosuppressive therapy with either mycophenolic acid orally twice per day, or intravenous cyclophosphamide once per month at standardized dosages for 6 months. Additionally, the CTPs describe 3 options for standardized use of glucocorticoids, including a primarily oral, a mixed oral/intravenous, and a primarily intravenous regimen. There was consensus on measures of effectiveness and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology providers treating children with LN, and up to 300 children per year in North America are expected to be candidates for the treatment with the CTPs.

Conclusion

CTPs for induction therapy of proliferative LN in juvenile SLE based on the available scientific evidence and pediatric rheumatology group experience have been developed. Consistent use of the CTPs may improve the prognosis of proliferative LN, and support the conduct of comparative effectiveness studies aimed at optimizing therapeutic strategies for proliferative LN in juvenile SLE.     

Natural killer cell activity in untreated systemic lupus erythematosus

With strictly selected controls natural killer cell activity was evaluated in 10 untreated patients with systemic lupus erythematosus. Natural killer levels of the patients were significantly lower than those of the age- and sex-matched normal controls. Natural killer levels, however, did not correlate with disease activity.     

Ovarian function and disease activity in patients with systemic lupus erythematosus

OBJECTIVE: Menstrual cycle disturbances frequently occur during the onset or in exacerbation periods of systemic lupus erythematosus (SLE), suggesting a possible relationship. The aim of the study is to assess the ovarian function in SLE patients with active disease before the treatment with high doses of glucocorticoids (GC) and cytotoxic agents. METHODS: We evaluated 94 female SLE patients (mean age of 29.2+/-7.0 years). The mean SLEDAI score was 11.4+/-8.1. Seventy-nine patients had a current use of GC with a median dose of 10 mg/day (8-15). The other 15 patients were untreated. After examination and blood sample collection 40% of the patients were treated and high doses of GC (>30 mg/day); 68% from this group of patients were treated GC in combination with cyclophosphamide (CYC). Forty healthy women with the same mean age were evaluated as controls. A careful gynecological history and a gynecological examination were carried out in patients and controls. Hormonal serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol (E2) and progesterone in SLE patients and controls were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Menstrual cycle disorders with oligomenorrhea as dominant aspect were observed in 54% of SLE patients. The hormonal studies showed decreased progesterone level in 52% of patients, reduced E2 concentration in 25% of patients; increased levels of LH, FSH and prolactin were observed with the lower frequency (13%, 9%, 10% respectively). Menstrual cycle disorders and the hormonal unbalance such as decreased progesterone level and hyperprolactinemia were found related significantly to high SLEDAI score (p<0.05, p=0.001, p<0.05). In the group of non-treated SLE patients the menstrual and hormonal disorders were observed in the same spectrum and with the same frequency as in all the examined SLE patients. SLEDAI score was found correlated significantly with the frequency of menstrual cycle disorders in non-treated SLE patients (p<0.05). CONCLUSION: The reported study shows the disease activity as a major factor associated with menstrual cycle disorders in SLE patients before treatment with alkylating agents and high doses of GC. Therefore, SLE women might be considered as a risk group for altered ovarian function.     

Altered coronary vasomotor function in young patients with systemic lupus erythematosus

OBJECTIVE: Accelerated atherosclerosis is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Altered coronary microvascular function may act as a marker of changes that predispose to the development of significant coronary vascular disease. The purpose of this study was to compare coronary flow reserve (CFR) in a group of premenopausal women with SLE and a group of age-, sex-, and race-matched healthy control subjects. METHODS: Coronary flow velocity in 18 premenopausal women with SLE (mean +/- SD age 29.4 +/- 5.9 years) and 19 matched healthy controls (mean +/- SD age 28.2 +/- 4.3 years) was assessed by transthoracic Doppler echocardiography after an overnight fast. The CFR was calculated as the ratio of hyperemic to baseline coronary blood flow velocity in the left anterior descending coronary artery. Hyperemia was induced by intravenous administration of adenosine triphosphate. RESULTS: The mean +/- SD duration of SLE was 8.2 +/- 7.2 years (range 0.25-25 years), and the mean +/- SD score on the Systemic Lupus Erythematosus Disease Activity Index was 11.0 +/- 5.3 (range 4.0-21.0). Adequate recordings of flow velocity in the left anterior descending artery under both conditions were obtained using an ultrasound procedure in all study subjects. CFR was significantly lower in SLE patients as compared with control subjects (mean +/- SD 3.4 +/- 0.8 versus 4.5 +/- 0.5; P < 0.0001). CONCLUSION: These findings provide evidence that coronary vasomotor function is impaired in patients with SLE and support the notion that many of these young patients have subclinical coronary artery disease.     

Brachial endothelial function is impaired in patients with systemic lupus erythematosus

OBJECTIVE: To verify if endothelial function is impaired in pre-menopausal women with systemic lupus erythematosus (SLE) and whether endothelial dysfunction is related to disease duration, cumulative prednisone dose, antimalarial use, anticardiolipin antibody (aCL), hypertension, Raynaud's phenomenon, disease activity score, and vasculitis. METHODS: Using high-resolution ultrasound, we measured the diameter of brachial artery at rest, during reactive hyperemia, and after glyceryl trinitrate (GTN). We compared 69 pre-menopausal female patients with SLE (mean age 29 +/- 8 years) with 35 age and sex-matched controls (mean age 29 +/- 6 years), The mean disease duration was 72 months. RESULTS: There was no significant difference in baseline brachial artery diameter. The flow-mediated dilation (endothelial dependent dilation) was significantly impaired in SLE patients when compared to controls (5.0 +/- 5.0% vs 12.0 +/- 6.0%, p < 0.001), even in the subgroup of patients without coronary artery disease risk factor (4.5 +/- 4.0% vs 12.0 +/- 6.0%, p < 0.001). The GTN induced dilation (endothelial independent dilation) was significantly lower in the aCL positive SLE patients when compared to the controls (11.9 +/- 4.0% vs 16.3 +/- 6.0%, p < 0.05). The endothelium-dependent dilation was not related to disease duration, cumulative prednisone dose, antimalarial use, anticardiolipin antibody, hypertension history, Raynaud's phenomenon, SLE disease activity score or vasculitis. CONCLUSION: This is the first study using brachial artery ultrasound imaging to evaluate endothelium function in SLE. Patients with SLE presented lower flow mediated dilation (endothelium dependent dilation) than sex and age-matched controls, even in patients without traditional cardiovascular risk factors and this may represent an early atherosclerotic process.     

Hyperprolactinaemia in patients with systemic lupus erythematosus

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