Anticardiolipin Antibodies in Juvenile Rheumatoid Arthritis and Systemic Lupus Erythematosus

Background: Antiphospholipid antibody syndrome (APS) can either occur as a primary syndrome or associated with other autoimmune diseases such as systemic lupus erythematosus (SLE). Anticardiolipin antibody (aCL) of IgG and/or IgM isotype in blood, measured by a standardized ELISA is the most acceptable laboratory criteria. APS IgG isotype, particularly IgG2 subclass is more strongly associated with thrombosis. Objectives: This study was done to determine the prevalence of IgG aCL and its subclasses in relation to APS symptoms, in a group of juvenile rheumatoid arthritis (JRA) and juvenile systemic lupus erythematosus (SLE) patients.   Methods: In this prospective study, 28 JRA and 16 SLE patients, aged 3-18 years, were enrolled. IgG aCL was assayed by standard aCL ELISA. IgG subclasses were also assayed by ELISA on sera with medium to high titers of aCL. ACL assay was performed on at least two occasions for each patient, over 3-6 months period of follow up.   Results: 29% (8/28) of JRA patients and 44% (7/16) of SLE patients had aCL. Six of SLE patients displayed APS related manifestations: hemolytic anemia, thrombocytopenia, arterial occlusion, valvular heart disease, livedo reticularis and pulmonary hypertension, but none of them had persistant medium or high titer of aCL. The lack of association of high titer of aCL with APS related symptoms was observed in two patients. The IgG subclasses were primarily IgG1 and IgG3.   Conclusion: The prevalence of IgG aCL in this group of pediatric SLE and JRA is not uncommon but it’s relation to clinical manifestations is not clear. IgG1 and IgG3 subclasses were not associated with thrombosis, which is in agreement with previous studies.     

Immunological profile and dyslipidemia in Egyptian Systemic Lupus Erythematosus patients

Aim of the work

To study the relation of the immune profile to dyslipidemia in a cohort of Egyptian Systemic Lupus Erythematosus (SLE) patients.

Adenosine Deaminase Activity and its Isoenzyme Pattern in Patients with Juvenile Rheumatoid Arthritis and Systemic Lupus Erythematosus

Adenosine deaminase (ADA) is involved in purine metabolism and plays a significant role in the mechanisms of the immune system. The aim of this study was to investigate the activity of total ADA (tADA) and its isoenzymes ADA1 and ADA2 in serum and peripheral blood lymphocytes (PBLs) of children with juvenile rheumatoid arthritis (JRA) and systemic lupus erythematosus (SLE) in different phases of the diseases. The study comprised 34 patients with rheumatic disease, 24 with JRA and 10 with SLE, and 64 healthy controls. The tADA activity and its isoenzymes were measured in serum and PBLs of all patients by the method of Giusti and by the presence or absence of EHNA (erythro-9-(2-hydroxy-3-nonyl)adenine) during the active phase of the disease (before treatment), as well as during remission and relapse. Our data show that increased tADA activity in the serum and PBLs of patients with JRA and SLE is correlated mainly to increased levels of ADA2 activity in serum and ADA1 activity in PBLs. It also closely correlates with clinical disease activity and relapse. The cause of this increased tADA/ADA2 activity in serum and tADA/ADA1 activity in PBLs in JRA and SLE remains to be elucidated. Nevertheless, it may be noted that the measurement of tADA activity, together with ADA2 activity in serum and tADA with ADA1 activity in PBLs, could offer a biochemical approach to the assessment of the pathophysiology of JRA and SLE. Also, tADA and its isoenzymes could be used as alternative parameters representing disease activity. Received: 31 July 2000 / Accepted: 5 June 2001     

The Influence of Fibronectin on Cryoprecipitate Formation in Rheumatoid Arthritis and Systemic Lupus Erythematosus

Fibronectin, a human fibroblast surface and plasma protein, is present in cryoprecipitates of synovial fluids and/or sera from patients with rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and mixed essential cryoglobulinemia. Fibronectin was shown to be capable of influencing cryoprecipitate formation. No antibodies to fibronectin could be detected, thus ruling out the possibility that it was directly involved in the formation of cold-insoluble antigen—antibody complexes. Fibrinogen or fibrinogen degradation products were frequently present in synovial fluid cryoprecipitates but rarely in serum cryoprecipitates. Since complexes of fibronectin—fibrin—fibrinogen are known to be cold-insoluble, such interactions could occur in synovial fluids and contribute to the formation of cryoprecipitates. In serum, however, this is not likely to occur, and the mechanism by which fibronectin influences cryoprecipitate formation remains to be elucidated.     

Increased Insulin Resistance and Glucagon Levels in Mild/Inactive Systemic Lupus Erythematosus Patients Despite Normal Glucose Tolerance

Objective

To assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT).

Methods

In this cross‐sectional study, 33 adult females with mild/inactive SLE (SLE group) and 16 age‐ and body mass index–matched female healthy controls (CTRL group) underwent an MTT and were assessed for insulin sensitivity and beta cell function. Skeletal muscle protein expressions of total and membrane insulin‐dependent glucose transporter 4 (GLUT‐4) were also evaluated (SLE group: n = 10, CTRL group: n = 5); muscle biopsies were performed after MTT. Further measurements included inflammatory cytokines, adipocytokines, physical activity level, body composition, and food intake.

Results

SLE and CTRL groups showed similar fasting glucose, glucose response, and skeletal muscle GLUT‐4 translocation after MTT. However, the SLE group demonstrated higher fasting insulin levels (P = 0.01; effect size [ES] 1.2), homeostatic model assessment insulin resistance (IR) (P = 0.03; ES 1.1), insulin‐to‐glucose ratio response to MTT (P = 0.02; ES 1.2), fasting glucagon levels (P = 0.002; ES 2.7), glucagon response to MTT (P = 0.0001; ES 2.6), and a tendency toward lower Matsuda index of whole‐body insulin sensitivity (P = 0.06; ES ?0.5) when compared with the CTRL group. Fasting proinsulin‐to‐insulin ratio and proinsulin‐to‐insulin ratio response to MTT were similar between groups (P > 0.05), while the SLE group showed a higher insulinogenic index when compared with the CTRL group (P = 0.02; ES = 0.9).

Conclusion

We have identified that SLE patients had a bi‐hormone metabolic abnormality characterized by increased IR and hyperglucagonemia despite normal glucose tolerance and preserved beta cell function and skeletal muscle GLUT‐4 translocation. Strategies capable of ameliorating insulin sensitivity to reduce the risk of type 2 diabetes mellitus and cardiovascular disease in SLE may require more than targeting IR alone.

     

Antibodies to Native Type I and II Collagens Detected by an Enzyme linked Immunosorbent Assay (ELISA) in Rheumatoid Arthritis and Systemic Lupus Erythematosus

Anti-native type I and/or type II collagen antibodies measured by an immunoenzymatic immunosorbent assay were found to be present in 22.2'0/o of the rheumatoid arthritis cases studied, 27.5 °/o of systematic lupus erythematosus patients and 28.6:0/o of patients with Overlap Syndrome. These antibodies were not associated with any particular clinical or radiological form of rheumatoid arthritis. Nevertheless, antibodies to native type I and/or type II collagens were associated with seropositive rheumatoid arthritis and antibodies to native type II collagen with rheumatoid arthritis which have antinuclear antibodies. In addition antibodies to native type I collagen were especially present in rheumatoid arhritis with extraarticular symptoms. Antibodies to native collagens disappear or are diminished after corticosteroid treatment. Unlike gold, D-penicillamine or non-steroid antiinflammatory drugs have no effect on levels of antibodies to native type I and II collagens.     

Elevation of Serum Soluble Tumour Necrosis Factor Receptors in Patients with Polymyositis and Dermatomyositis

The aim of the study was, to examine the relationship between serum levels of soluble tumour necrosis factor receptors (sTNF-R) and the gene expression of two types of receptor for TNF (TNF-R), a 55 kDa receptor (TNF-R1) and a 75 kDa receptor (TNF-R2), in peripheral blood mononuclear cells (PBMC) from patients with polymyositis and dermatomyositis (PM/DM). Soluble tumour necrosis factor receptor 1 (sTNF-R1) and soluble tumour necrosis factor receptor 2 (sTNF-R2) levels in sera from patients were measured by enzyme-linked immunosorbent assay. Expression of TNF-R1 and TNF-R2 mRNAs in PBMC was analysed by Northern blotting. Serum sTNF-R1 and sTNF-R2 levels were elevated significantly in 25 patients with active-stage PM/DM, compared to those in 18 patients with inactive-stage PM/DM and 32 normal controls. Serum concentrations of sTNF-R1 and sTNF-R2 were correlated with PM/DM disease activity. TNF-R1 gene expression was enhanced in freshly isolated PBMC from patients with active-stage PM/DM. In contrast, TNF-R2 mRNA was expressed constitutively in patients with active-stage PM/DM and in normal controls. The expression of TNF-R1 and TNF-R2 mRNAs in PBMC and elevation of their soluble forms in the sera of patients with active-stage PM/DM suggest increased proteolytic cleavage of cell surface TNF-R from PBMC in patients with active-stage PM/DM, and that sTNF-R may regulate TNF-α-mediated muscle fibre damage in PM/DM. Received: 25 June 1999 / Accepted: 18 January 2000     

系统性红斑狼疮患者热休克蛋白90和白细胞介素18的表达及意义

目的:研究系统性红斑狼疮(SLE)患者热休克蛋白90(HSP90)和血浆白细胞介素18(IL-18)的表达水平及与疾病活动的关系。方法:运用Westernblot技术检测SLE患者外周血单个核细胞HSP90的表达,ELISA方法检测血浆中的IL-18水平,并与SLE疾病活动指数(SLEDAI)进行相关性分析。结果:⑴SLE患者HSP90的表达水平在活动期组(0.82±0.10)和稳定期组(0.54±0.09)与正常对照组(0.37±0.11)比较均具有显著性差异(分别P<0.01),且活动期组较稳定期组增高更明显(P<0.01);⑵SLE患者血浆IL-18水平在稳定期组(327.82±101.45pg/ml)和活动期组(459.79±134.08pg/ml)均显著高于正常对照组(252.32±76.45pg/ml)(分别为P<0.05,P<0.01);⑶SLE患者的HSP90和IL-18水平与SLEDAI评分之间呈正相关(分别为r=0.80,P<0.01;r=0.49,P<0.01)。结论:SLE患者外周血单个核细胞HSP90和血浆IL-18水平均显著增高,并且与SLE的病情活动密切相关,可能在SLE的发病机制中发挥重要作用。     

Proteus IgG Antibodies and C-Reactive Protein in English, Norwegian and Spanish Patients with Rheumatoid Arthritis

The distribution of Proteus antibody levels was compared in English, Norwegian and Spanish patients with rheumatoid arthritis (RA). Using an indirect immunofluorescence method, the IgG antibody titre against Proteus mirabilis was measured in the sera of 27 English, 53 Norwegian and 34 Spanish patients with RA and divided into active and inactive disease groups according to the serum C-reactive protein (CRP) level (≥10 mg/l). Serum samples were also collected from 25 English, 30 Norwegian and 14 Spanish healthy individuals who served as controls. The levels of Proteus IgG antibodies were significantly higher in the sera of active RA patients (p<0.001) when compared with the corresponding healthy controls, whether these groups belonged to the English, Norwegian or Spanish populations. Furthermore, active RA patients from each country showed significantly higher levels of Proteus antibodies when compared with inactive English (p<0.01), Norwegian (p<0.001) or Spanish (p<0.001) RA patients. Finally, a significant correlation was observed between Proteus IgG antibody levels and the CRP concentrations in RA patients whether each population was tested individually or all together (p<0.001). The increased levels of Proteus antibodies in RA patients from three different European countries support the concept of a possible aetiopathogenetic role for Proteus microorganisms in the development of RA. Received: 20 October 1997 / Accepted: 14 October 1998     

Serum Cyr61 is Associated With Clinical Disease Activity and Inflammation in Patients With Systemic Lupus Erythematosus

Our previous studies have shown that secreted extracellular matrix-associated protein Cysteine rich angiogenic inducer 61 (Cyr61), a novel proinflammatory factor, is involved in the pathogenesis of rheumatoid arthritis (RA). However, whether Cyr61 has any effect in systemic lupus erythematosus (SLE) remains unknown. This study aims to assess the level of serum Cyr61 and to investigate the association of serum Cyr61 and clinical disease activity in SLE. We found the level of serum Cyr61 in patients with SLE was significantly higher than healthy controls (P < 0.001), and Cyr61 was high expressed in renal tubule of lupus nephritis compared to control. The sensitivity of Cyr61 in diagnosis of SLE was 47.3%. In receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.830, with a 95% confidence interval (CI) from 0.776 to 0.885. Cyr61 was present in 60.0%, 54.5%, and 41.5% of anti-double stranded DNA (dsDNA), anti-antinuclear antibodies (ANA), and anti-Sm negative SLE patients, respectively. Serum Cyr61 levels were significantly higher in high systemic lupus erythematosus disease activity index (SLEDAI) group than that in low SLEDAI group (P = 0.003). Correlation analyzes showed a significant negative correlation between serum Cyr61 and complements (C3) (P = 0.015), C4 (P = 0.04). Moreover, increased Cyr61 level in SLE was associated with serum level of TNF-α, interleukin 6 (IL-6), and IL-17. In conclusion, serum Cyr61 was increased in patients with SLE which was associated with clinical disease activity and inflammation in SLE, suggesting Cyr61 may be a novel potential auxiliary marker for the diagnosis of SLE.This work was supported by grants from the “National Natural Science Foundation of China" (81401340) and “Youth Foundation of Fujian Provincial Health and Family Planning Commission" (2014-1-52).