Interference of antimodified C-reactive protein autoantibodies from lupus nephritis in the biofunctions of modified C-reactive protein

Autoantibodies against modified C-reactive protein (mCRP) are frequently found in patients with lupus nephritis and are associated with disease activity, suggesting their pathogenic role in lupus nephritis. The aim of this study was to investigate the influence of anti-mCRP autoantibodies from patients with lupus nephritis on the biofunctions of mCRP. mCRP plays important roles in the clearance of apoptotic cells and immune complex-mediated injuries via binding to C1q and factor H and acting as an opsonin. In this study, we confirmed that mCRP could bind to C1q and factor H, and the binding between mCRP and C1q was mainly via the collagen-like region of C1q by enzyme-linked immunosorbent assay and surface plasmon resonance. mCRP could significantly enhance the phagocytosis of late apoptotic cells in the presence of normal human serum. Autoantibodies against mCRP, purified from immunoglobulin G fractions of 3 patients with lupus nephritis by affinity chromatography, could significantly inhibit the binding between mCRP and C1q or factor H and reduce the clearance of late apoptotic cells enhanced by mCRP. Our observations suggest that anti-mCRP autoantibodies from patients with lupus nephritis might be pathogenic in systemic lupus erythematosus and lupus nephritis through interfering with the biofunctions of mCRP.     

Elevated serum anti-endothelial cell autoantibodies titer is associated with lupus nephritis in patients with systemic lupus erythematosus.

BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease associated with endothelial dysfunction and the existence of multiple species of autoantibodies. However, the association between endothelial dysfunction and renal manifestations remains unclear in Taiwanese SLE patients. METHODS: Serum samples were collected from SLE patients with biopsy-proven lupus nephritis (n = 32), stable SLE patients (n = 32) and healthy controls (n = 32). The SLE Disease Activity Index (SLEDAI) of SLE patients was scored, and levels of anti-endothelial cell antibodies (AECA) and anti-endothelial activities in serum samples were measured by cell-enzyme-linked immunosorbent assay and crystal violet assay, respectively, using cultured human endothelial EA.hy926 cells. RESULTS: Significantly higher AECA (p<0.001) and anti-endothelial activities (p<0.001) were found in sera from patients with lupus nephritis compared with that from stable SLE patients or controls. Moreover, AECA titers (p<0.001) and anti-endothelial activities (p<0.001) were strongly correlated with SLEDAI scores in these patients. CONCLUSION: The strong correlations of AECA and anti-endothelial activity with lupus nephritis activity support an endothelial origin for renal complications in Taiwanese SLE patients.     

Correlation between the renal C1q deposition and serum anti-C1q antibody: a potential role of anti-C1q antibody in lupus nephritis

The anti-C1q antibody has been shown to be associated with lupus patients with renal involvement. We conducted a study to determine the relationship between the serum anti-C1q titer and the renal deposition of C1q. The serum anti-C1q was measured in 26 healthy controls and 47 systemic lupus erythematosus (SLE) patients who were divided into 2 groups as non-nephritis and nephritis SLE. We analyzed the relationship between the anti-C1q titers and SLE, renal C1q staining and the WHO classification for lupus nephritis. The result revealed that the serum anti-C1q was present in 50.8% of the SLE patients, that its levels in those with renal involvement were significantly higher than in the normal control group (61.540 +/- 87.720 U/ml vs 15.750 +/- 2.530 U/ml, p = 0.005). Besides, the serum anti-C1q levels were higher in the patients with lupus nephritis with C1q deposition in the kidney tissue (66.038 +/- 91.141 U/ml vs 16.652 +/- 3.097 U/ml, p < 0.01). There seems to be evidence supporting that the autoantibody anti-C1q might play a pathogenic role in lupus nephritis.     

抗核抗体系列检测对狼疮性肾炎进行鉴别诊断的临床意义

目的探讨抗核抗体(ANA)系列指标在狼疮性肾炎(LN)患者中的表达情况及临床意义.方法对406例系统性红斑狼疮(SLE)患者(其中LN 122例)和74例其他自身免疫病患者及120例健康体检者采用间接免疫荧光法测定ANA,应用欧蒙印迹法测定ANA系列.结果 SLE患者ANA阳性率为94.49%,其他自身免疫病组ANA阳...     

Anti-C1q autoantibodies from active lupus nephritis patients could inhibit the clearance of apoptotic cells and complement classical pathway activation mediated by C1q in vitro

Anti-C1q antibodies are prevalent in patients with active lupus nephritis and were found to be closely associated with renal involvement and predictive for a flare of nephritis. However, the pathogenesis of anti-C1q antibodies involved in human lupus nephritis remains unclear. C1q, which plays a key role in apoptotic cell and immune complex removal, is a very important functional molecule in the pathogenesis of SLE. The aim of this study was to investigate the influence of anti-C1q autoantibodies from active lupus nephritis patients on the bio-functions of C1q in vitro. We purified IgG autoantibodies against C1q from lupus nephritis patients, and found that they could recognize C1q bound on early apoptotic cells at 30 μg/ml, and could significantly decrease the phagocytosis by macrophages of early apoptotic cells opsonized by 50 μg/ml C1q in comparison with normal IgG. Levels of circulating immune complexes of the ten patients were measured by a circulating immune complexes (CIC)-C1q Enzyme Immunoassay Kit. Anti-C1q autoantibodies affinity purified by microtiter plates could significantly inhibit the deposition of C3c on CIC-C1q in a dose dependent manner in comparison with IgG from 10 healthy blood donors. The binding of opsonized immune complexes to RBCs was significantly inhibited by anti-C1q autoantibodies purified by microtiter plates in a dose dependent manner. Our observations suggest that serum anti-C1q autoantibodies from active lupus nephritis patients could interfere with some biological function of C1q in vitro.     

Urinary TWEAK and the activity of lupus nephritis

The TNF superfamily cytokine TWEAK induces mesangial cells, podocytes, and endothelial cells to secrete pro-inflammatory chemokines including MCP-1, IP-10 and RANTES, which are crucial in the pathogenesis of lupus nephritis (LN). As TWEAK regulates the secretion of these inflammatory mediators, we studied whether urinary TWEAK (uTWEAK) levels might be predictive and/or diagnostic in LN. In a cross-sectional study of a large, multi-center cohort of systemic lupus erythematosus (SLE) patients, uTWEAK levels were higher in patients with active as compared to never or non-active nephritis (median (IQR): 16.3 (9.9-23.0) versus 5.5 (2.3-16.8) pg/mg creatinine, p=0.001), and levels of uTWEAK correlated with the renal SLE disease activity index (rSLEDAI) score (r=0.405, p<0.001). uTWEAK levels were higher in patients undergoing a flare as compared to patients with chronic stable disease (11.1 (8.1-18.2) and 5.2 (2.3-15.3) pg/mg creatinine, respectively; p=0.036). Moreover, uTWEAK levels were significantly higher in patients undergoing a renal flare, as opposed to a non-renal flare (12.4 (9.1-18.2) and 5.2 (3.0-11.9) pg/mg creatinine, respectively; p=0.029). An accurate, non-invasive method to repeatedly assess kidney disease in lupus would be very helpful in managing these often challenging patients. Our study indicates that urinary TWEAK levels may be useful as a novel biomarker in LN.     

Lupus-specific kidney deposits of HSP90 are associated with altered IgG idiotypic interactions of anti-HSP90 autoantibodies

Previous studies have shown that autoantibodies to heat shock protein 90 (HSP90) are elevated in a significant proportion of patients with systemic lupus erythematosus (SLE) who are more likely to have renal disease and a low C3 level. Using samples from 24 patients, we searched for glomerular deposits of HSP90 in renal biopsy specimens from seven patients with lupus nephritis and 17 cases of glomerulonephritis from patients without SLE. Positive glomerular immunofluorescent staining for HSP90 was observed in six of seven cases of SLE and positive tubular staining in two of seven SLE patients. The staining for HSP90 was granular in nature and was located in subepithelial, subendothelial and mesangial areas. None of the non-SLE renal biopsies revealed positive staining for HSP90 deposition. Further we showed the presence of anti-HSP90 IgG autoantibodies in IgG from sera of patients with SLE as well as in normal human IgG (IVIg). In normal IgG this autoreactivity could be adsorbed almost completely on F(ab')2 fragments from the same IgG preparation, coupled to Sepharose and could be inhibited by the effluent obtained after subjecting normal IgG to HSP90 affinity column. These findings indicate that anti-HSP90 natural autoantibodies are blocked by idiotypic interactions within the IgG repertoire. Unlike natural autoantibodies, anti-HSP90 IgG from SLE patients' sera were only moderately adsorbed on F(ab')2 fragments of normal IgG. These results demonstrate that immunopathogenesis of lupus nephritis is associated with HSP90 (as an autoantigen) and that the pathology is associated with altered idiotypic regulation of the anti-HSP90 IgG autoantibodies.     

Measurement of autoantibodies using multiplex methodology in patients with systemic lupus erythematosus

Autoantibodies are central to the diagnosis and assessment of systemic lupus erythematosus (SLE). A recent technique for the measurement of autoantibodies utilizes addressable laser bead immunoassay technology (BioPlex 2200) which permits the simultaneous detection of multiple autoantibodies and improved efficiency due to the shorter time to perform the assay and low volume of test samples and reagents. In the current study we have compared this technique to more traditional measures of autoantibody detection. The clinical and laboratory data and stored serum samples from the enrollment visit into a long-term lupus registry at a single academic medical center were used. Sera were examined for a panel of autoantibodies using the BioPlex ANA screen. The results were compared to the historical data on autoantibody profiles using indirect immunofluorescence (IIF) and ELISA. The association with global and organ specific SLE disease activity (nephritis) was also examined. The study consisted of 192 patients who were predominantly female (87%) and Caucasian (91%) with mean disease duration of 8.8 years. The frequency of ANA and anti-dsDNA by IIF and ELISA was 81.3% and 46.6% respectively and was higher than that found with BioPlex (75.5% and 31.8%). The latter detected a higher proportion of patients with autoantibodies to Sm (7.5% vs 16.7%), RNP (21.8% vs 24.0%), Ro (37.4% vs 41.7) and La (13.9% vs 23.4%). Overall agreement between assays varied between 71.4% and 92.5%. Additional autoantibodies identified by BioPlex were anti-chromatin antibodies which were similar in frequency to anti-dsDNA antibodies (33.9% and 31.8% respectively). There was a low frequency of anti-ribosomal P (6.8%), anti-Scl-70 (5.2%), anti-centromere B (3.7%) and anti-Jo-1 (0.5%). Several autoantibodies revealed significant associations with SLEDAI scores but in a multivariate analysis the only autoantibodies that approached statistical significance were anti-Sm (p = 0.094) measured by ELISA and anti-dsDNA (p = 0.082) measured by BioPlex. There was no association between any of the autoantibodies regardless of the method of detection and cumulative organ damage scores. Fifty-three patients (27.6%) had lupus nephritis of which 17 (32%) had active nephritis at the time of autoantibody determination. There was no significant association between a positive ANA (IIF) and any autoantibodies detected by ELISA with either the cumulative occurrence of lupus nephritis or active nephritis. In contrast, there was an association between BioPlex detected anti-dsDNA with the cumulative occurrence of nephritis (p = 0.074) which reached statistical significance with active nephritis at the time of antibody testing (p = 0.012). This was confirmed by multivariate analysis (p = 0.047). These results suggest reasonable agreement between the detection of lupus autoantibodies by ELISA and BioPlex. The latter demonstrated a better correlation with lupus nephritis.     

Th1/Th2 balance of SLE patients with lupus nephritis

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease that is characterized by the production of multiple autoantibodies and immune complex formation. Lupus nephritis, which has various histological patterns and variable clinical outcomes, is one of the most important complications of SLE. Although this pathogenetic mechanism in each histologically different type of nephritis remains unclear, recent findings in murine lupus elucidate an essential role for the Th1 cytokine in the development of diffuse lupus nephritis (DLN), and Th2 cytokine in that of membranous lupus nephritis (MLN). These data support the hypothesis that individual Th1/Th2 balance is one of the critical determinants for histopathology of lupus nephritis. Therefore the value of Th1/Th2 ratio of the peripheral CD4+ T cells in SLE patients could be a useful index to predict histopathology of lupus nephritis.     

CD134 expression on CD4+ T cells is associated with nephritis and disease activity in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterized by a deviation of the immune system that involves T cell-dependent autoantibody production. The aim of this study was to investigate the role of co-stimulatory markers on T cells in this disease. Twenty-eight patients with SLE as defined by the American College of Rheumatology (ACR) criteria and 11 healthy controls were included into the study. Eleven patients had biopsy-proven lupus nephritis while 17 patients had no clinical evidence of lupus nephritis. Clinical disease activity was assessed according to the systemic lupus erythematosus disease index (SLEDAI). CD4+ T cell populations in the peripheral blood were analysed for the expression of co-stimulatory markers CD45RO, CD70, CD80, CD86, CD137, CD137L, CD134, CD152, CD154 and ICOS. SLE patients showed an increased frequency of peripheral CD4+ T cells expressing high levels of CD80, CD86 and CD134 compared to healthy controls (7.1 +/- 1.5% versus 1.7 +/- 0.9%; P < 0.005; 2.3 +/- 0.4% versus 1.0 +/- 0.2%; P = 0.008, 20.2 +/- 2.0% versus 10.6 +/- 1.9%; P < 0.005, respectively). Significantly higher levels of CD80 on CD4+ T cells were detected in SLE patients with lupus nephritis compared to patients without nephritis (11.9 +/- 3.3% versus 4.0 +/- 0.7%; P < 0.005). There was an increased presence of CD134+ CD4+ cells in SLE patients with lupus nephritis (27.5 +/- 4.0% versus 15.5 +/- 1.3%; P < 0.005). CD80 and CD134 expression was significantly correlated with SLEDAI (r = 0.42, P = 0.03; r = 0.56, P < 0.005). Co-stimulatory molecules on CD4+ T cells are associated with renal disease and disease activity in patients with systemic lupus erythematosus.     

系统性红斑狼疮患者血清IL-10的水平及临床意义

目的 观察系统性红斑狼疮(systemic lupus erythematosus,SLE)患者血清IL-10的表达与疾病活动的关系.方法 选取22例SLE患者及24名健康人作为对照,根据狼疮疾病活动指数(SLE disease activity index,SLEDAI)将SLE患者分为活动期组和非活动期组,检测血清抗dsDNA抗体,血清总补体溶血活性(CH50)及C反应蛋白(C reactive protein,CRP),酶联免疫吸附法(ELISA)检测血清IL-10表达.结果 与对照组[(18.11±6.97)ng/L]相比,IL-10在SLE活动期组[(78.54±5.62)ng/L,P＜0.01]及非活动期组[(30.36±10.98)ng/L,P＜0.05]均有所增高,活动期组增高更为明显(与非活动期组相比,P＜0.05).IL-10水平与SLEDAI呈正相关(SLE活动期,r=0.77,P＜0.01;SLE非活动期,r=0.84,P＜0.01),IL-10的水平与抗dsDNA抗体(r=0.71,P＜0.01)、CRP(r=0.63,P＜0.01)和CH50(r=-0.56,P＜0.05)均相关.结论 IL-10在SLE患者血清中表达升高,在疾病活动时更为明显,IL-10能反应疾病活动的程度,可以做为临床观察SLE疾病活动的指标之一.     

Elevated levels of soluble CD40 ligand (sCD40L) in serum of patients with systemic autoimmune diseases

The CD40–CD40L costimulatory pathway is involved in the evolution of many autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SS). Increased levels of sCD40L in the serum have been associated with disease activity in SLE. The aim of this study was to investigate the role of sCD40L in the development of lupus nephritis and examine its possible association with cryoglobulinemia in Sjögren's syndrome. We used a 2-site sandwich ELISA to measure the levels of sCD40L in sera, from 64 patients with SLE, RA and SS and 17 healthy blood donors. Biological specimens from the affected tissues such as urine from patients with lupus nephritis and saliva from patients with SS were also tested. In this regard, paired sera and first morning urine samples from 6 SLE patients (3 with active lupus nephritis and 3 with inactive lupus nephritis) were tested with the sCD40L ELISA protocol as well as paired sera and salivary samples from 5 patients with SS and cryoglobulinemia, 5 patients with SS and anti-Ro or anti-La autoantibodies and 5 age-matched healthy control donors. We also examined possible correlations of sCD40L levels with several laboratory and clinical parameters in SS and SLE. We found that sera from SLE and SS patients had significantly higher levels of sCD40L compared to sera from healthy control donors. No sCD40L was detected, in urine samples of patients with either active or inactive nephritis and in salivary samples from SS patients or normal subjects. Soluble CD40L is elevated in sera of SS and SLE patients but further investigation is needed to determine its possible role in SLE nephritis and Sjögren's syndrome.     

No evidence for an independent role of anti-heparan sulphate reactivity apart from anti-DNA in lupus nephritis.

The presence of anti-heparan sulphate (HS) reactivity in serum is closely related to the occurrence of nephritis in patients with systemic lupus erythematosus (SLE). Since patients with lupus nephritis in general also have high titres of anti-DNA antibodies, we wanted to clarify the relationship between anti-HS and anti-DNA reactivity in serum. Therefore, we studied longitudinally six patients with lupus nephritis who experienced 12 exacerbations of their disease, and five SLE patients without nephritis experiencing 10 periods of non-renal disease exacerbations. In addition, we tested single serum samples of another 24 patients obtained during a renal disease exacerbation and 22 sera of patients without nephritis. The sera of all patients were tested for anti-DNA (Farr assay) and anti-HS reactivity (ELISA). We confirmed that SLE patients during renal exacerbations have a significantly higher anti-HS reactivity than patients without nephritis (P < 0.003). In addition, patients with nephritis also had higher titres of anti-DNA antibodies during renal exacerbations than during non-renal exacerbations (P < 0.01). A correlation between anti-DNA and anti-HS reactivity was observed (r = 0.40, P < 0.02), which in itself explains the correlation between nephritis and anti-HS reactivity. Comparing sera from nephritis and non-nephritis patients matched for anti-DNA titre, we found no difference in anti-HS reactivity, and therefore must conclude that the anti-HS reactivity is a direct reflection of anti-DNA reactivity.     

Hepatitis B virus-related glomerulopathy in patients with systemic lupus erythematosus

The clinical data and renal pathologic information from three patients with systemic lupus erythematosus (SLE), active glomerular disease, and hepatitis B virus (HBV) antigenemia are presented. All three patients fulfilled the American Rheumatism Association criteria for the diagnosis of SLE. However, the renal pathologic results excluded the diagnosis of lupus nephritis. The common findings shared by these patients included the following: presence of hepatitis B surface antigen (HBsAg) in both serum and glomeruli and of glomerular hepatitis B core antigen (HBcAg), and the absence of polyclonal immunoglobulins, C1q and C4, deposition in renal tissue. These common features and the renal pathologic results indicated that the glomerulopathy was associated with HBV antigenemia. The cases described here may represent a subset of patients with SLE in whom expression of lupus nephritis was altered by the concomitant HBV-related glomerulonephritis.     

HLA class II antigens associated with lupus nephritis in Italian SLE patients

Human leukocyte antigen DR2 (HLA-DR2), namely the allelic variant HLA-DR15, have been associated with lupus nephritis (LN) in Caucasians. The study investigated the relationships between HLA class II alleles and lupus nephritis in Italian patients. Two hundred forty-four patients fulfilling the American Rheumatism Association criteria for systemic lupus erythematosus (SLE) were typed for HLA-DRB1*, -DQA1*, -DQB1*, and -DPB1* alleles by polymerase chain reaction-sequence-specific oligonucleotide and polymears chain reaction-single-strand polymorphism; 71 patients had renal damage assessed by renal biopsy. Glomerulonephritis was classified using WHO criteria. Significance was tested by X(2) on 2x2 tables. HLA-DQA1*0101 was strongly associated with LN (OR = 2.72 [1.43-5.19]; p = 0.002), whereas HLA-DRB1*1501 was only marginally associated (OR = 1.94 [0.88-4.26]; p = not significant). HLA-DQA1*0102 demonstrated a significant protective effect (OR = 0.31 [0.14-0.86]; p = 0.002). On analyzing the distribution of HLA-DRB1*1501 bearing haplotypes in our SLE patients we found that the HLA-DRB1*1501 greatly enhanced the risk of developing LN conferred by the DQA1*0101 allele (OR = 65.96 [9.35-1326.25]), whereas DQA1*0102 suppressed the nephritogenic effect of DRB1*1501. At renal biopsy, 80% of DRB1*15 positive patients were classified as having class IV LN with the remaining 20% having class III LN. The figures were 19% and 21%, respectively, among the HLA-DR15 negative patients. In the Italian population HLA-DQA and HLA-DR alleles interact in conferring susceptibility to or protection against lupus nephritis, the diffuse proliferative glomerulonephritis (i.e., the most severe form of nephritis) is associated with the HLA-DR15 bearing haplotypes.     

Pathogenic role of anti-C1q autoantibodies in the development of lupus nephritis--a hypothesis

A substantial proportion of patients with systemic lupus erythematosus (SLE) develop renal inflammatory disease, so-called lupus nephritis (LN). LN is a severe complication of SLE which is strongly associated with the presence of autoantibodies against C1q, the first component of the complement system, and other self-antigens (i.e. against DNA and nucleosomes) as well. In this review, the authors focus on anti-C1q autoantibodies and interpret the available data in order to explain how LN may develop and how anti-C1q autoantibodies contribute to its pathogenesis.     

Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes

The objective of this study was to investigate the prevalence and clinical significance of a spectrum of autoantibodies in systemic lupus erythematosus and incomplete lupus syndromes using a proteome microarray bearing 70 autoantigens. Microarrays containing candidate autoantigens or control proteins were printed on 16-section slides. These arrays were used to profile 93 serum samples from patients with systemic lupus erythematosus (SLE (n = 33), incomplete LE (ILE; n = 23), first-degree relatives (FDRs) of SLE patients (n = 20) and non-autoimmune controls (NC; n = 17). Data were analysed using the significance analysis of microarray (SAM) and clustering algorithms. Correlations with disease features were determined. Serum from ILE and SLE patients contained high levels of IgG autoantibodies to 50 autoantigens and IgM autoantibodies to 12 autoantigens. Elevated levels of at least one IgG autoantibody were detected in 26% of SLE and 19% of ILE samples; elevated IgM autoantibodies were present in 13% of SLE and 17% of ILE samples. IgG autoantibodies segregated into seven clusters including two specific for DNA and RNA autoantigens that were correlated with the number of lupus criteria. Three IgG autoantibody clusters specific for collagens, DNA and histones, were correlated with renal involvement. Of the four IgM autoantibody clusters, two were correlated negatively with the number of lupus criteria; none were correlated with renal disease. The IgG : IgM autoantibody ratios generally showed a stepwise increase in the groups following disease burden from NC to SLE. Insights derived from the expanded autoantibody profiling made possible with the antigen array suggest differences in autoreactivity in ILE and SLE. Determining whether the IgM aurotreactivity that predominates in ILE represents an early stage prior to IgG switching or is persistent and relatively protective will require further longitudinal studies.     

Anti-C1q autoantibodies specific against the globular domain of the C1qB-chain from patient with lupus nephritis inhibit C1q binding to IgG and CRP

Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus. Higher titers of serum anti-C1q autoantibodies correlate with disease activity in patients with lupus nephritis. Anti-C1q autoantibodies have been shown to bind neo-epitopes within the collagen region of human C1q. In a preliminary study, we recently reported that the anti-C1q autoantibodies could also recognize epitopes within the globular domain (gC1q) of the C1q molecule. Here, 38 sera from patients with renal biopsy-proven lupus nephritis were screened for the presence of anti-gC1q autoantibodies, using recombinant globular head regions of individual A (ghA), B (ghB) and C (ghC) chains of human C1q. We isolated anti-gC1q autoantibodies from three selected patients. Human C1q was pre-incubated with increasing concentrations of the isolated anti-ghA, anti-ghB or anti-ghC autoantibodies and its binding to different C1q target molecules such as IgG and CRP was then evaluated. Anti-ghB, but not anti-ghA and anti-ghC autoantibodies, markedly inhibited C1q interaction with IgG as well as CRP. These results appear to suggest that the anti-ghB autoantibodies may partially induce acquired functional C1q deficiency and thus may interfere with the biological function of C1q.     

系统性红斑狼疮患者血清脱氧核糖核酸酶活性检测的临床意义

检测系统性红斑狼疮(SLE)患者血清脱氧核糖核酸酶(DNase)的活性,探讨其在判断SLE疾病活动及狼疮肾炎(LN)中的临床意义.采集116例SLE患者、30例疾病对照者和30名健康体检者(对照组)的血清,用ELISA法定量检测血清DNase活性.结果表明:SLE患者血清DNase活性明显低于疾病对照组和健康对照组(P<0.01),且疾病活动期低于缓解期(P<0.01);DNase活性与SLE疾病活动程度呈负相关(P<0.01);狼疮肾炎组DNase活性低于SLE非狼疮肾炎组,两组比较有统计学意义(P<0.05).DNase活性下降可能是促进SLE及LN发生、发展的重要因素之一.血清DNase活性检测可用于判断SLE及其疾病活动程度的指标之一,同时也可作为判断LN的危险因素之一.     

Increased prevalence of transfusion-transmitted virus and cross-reactivity with immunodominant epitopes of the HRES-1/p28 endogenous retroviral autoantigen in patients with systemic lupus erythematosus

OBJECTIVE: Systemic lupus erythematosus (SLE) patients produce autoantibodies to HRES-1/p28, a human endogenous retrovirus-encoded nuclear protein. To identify cross-reactive viral antigens capable of triggering autoreactivity, HRES-1/p28 epitopes were mapped by SLE antibodies. METHODS: Forty-four peptides overlapping HRES-1/p28 and 13 viral peptides were synthesized on cellulose membrane and tested for recognition by antibodies from 16 HRES-1 Western blot seropositive SLE patients. Transfusion-transmitted virus (TTV) was detected by gene amplification in sera of 211 SLE patients, 78 healthy SLE family members, 199 unrelated healthy donors, and 91 rheumatoid arthritis (RA) patients. RESULTS: HRES-1/p28 residues 41-55, 121-135, and 156-170 were recognized by 12/16 (75.0%), 11/16 (68.8%), and 9/16 lupus sera (56.25%) and considered immunodominant. HRES-1/p28 residues 121-135 harbor cross-reactive epitope with retroviral peptides and the 70 K U1snRNP lupus autoantigen. HRES-1/p28 residues 41-55 and 156-170 exhibited the highest prevalence of cross-reactivity with TTV peptide ORF2a (14/16, 87%). Prevalence of TTV DNA was increased in lupus patients (120/211) with respect to healthy (66/199; P < 0.0001) or RA controls (23/91; P < 0.0001). TTV prevalence in healthy lupus relatives (40/78) was decreased with respect to lupus patients (80/121; P = 0.0184) and increased with respect to unrelated healthy donors (66/199; P = 0.0026). HRES-1/p28 Western blot reactivity was observed in 12/23 TTV PCR-negative donors and 43/58 TTV PCR-positive donors (P < 0.0281). CONCLUSIONS: Increased prevalence of TTV and molecular mimicry with HRES-1/p28 may contribute to generation of antinuclear antibodies and pathogenesis of SLE.