Significance of anti-lymphocyte antibodies in systemic lupus erythematosus

Sera from patients with SLE frequently contain IgM and IgG antibodies with multiple specificities for lymphocyte surface determinants, including autologous antigens. The IgM antibodies are of relatively low binding avidity and exhibit broad reactivity with B and T lymphocytes from most individuals. IgG antibodies are reactive selectively with PBL from different individuals and appear to be more specific for B cell and a minor proportion of T cells. The molecular nature of the surface determinants involved and their relationship with known antigens and receptors remain largely undefined. Interest in anti-lymphocyte antibodies in SLE relates in part to data suggesting a causal role in the abnormal immune system function in this disorder. In this regard, possible mechanisms that are supported by indirect data include: a) antibody-mediated lymphocyte depletion in vivo, perhaps involving functional subsets specifically; b) antibody blockade of surface receptors operant in cell-cell and in cell-soluble antigen interactions. Certain data have raised the possibility that anti-lymphocyte antibodies represent serum markers for infection with virus as etiologic in SLE, but this question is controversial. Nevertheless, further investigation may yet reveal viral or genetically determined “SLE-specific” lymphocyte surface antigens. Clinically, anti-lymphocyte antibodies may have potential for mediating tissue injury in SLE, either directly or indirectly as circulating complexes in association with “shed” lymphocyte surface antigen. Direct evidence in support of such a role in the natural history of this disorder has not been forthcoming.     

抗核小体抗体测定在系统性红斑狼疮中的意义

目的检测系统性红斑狼疮（SEE）及其他结缔组织病患者的抗核小体抗体（AnuA）浓度，探讨核小体在SEE中的诊断及与疾病活动的意义。方法用酶联免疫吸附试验（ELISA）检测SEE患者及疾病对照组（包括原发性干燥综合征、多发性肌炎、系统性硬化、类风湿关节炎、混合性结缔组织病、强直性脊柱炎）中的AnuA，并记录SEE患者的各种临床表现及实验室指标，并分析其与AnuA的关系。结果（1）65例SEE患者中有59例AnuA阳性，阳性率为90％，在29例疾病对照组中仅有6．8％阳性，SEE中AnuA阳性率显著高于疾病对照组（P〈0．01）；AnuA在SEE患者的敏感性为90％，特异性为93．1％；阳性预测值和阴性预测值分别为96．7％、82．9％。（2）AnuA与抗dsDNA、Sm、U1RNP等抗体无相关性（P〉0．05）；与抗SSA、pANCA抗体有关（P〈0．05）；在抗dsDNA抗体与抗Sm抗体均阴性的SEE患者中AnuA阳性率为86％-90％。（3）AnuA阳性患者的脱发、皮疹、口腔溃疡、蛋白尿等临床表现发生率明显高于阴性患者（P〈0．05）；AnuA阳性患者的白细胞、血小板、C3降低的发生率明显高于阴性患者（P〈0．05）；且AnuA浓度与内生肌酐清除率（CCr）呈负相关（r=-0．377，P=0．037）。（4）AnuA阳性患者的红细胞沉降率（ESR）、C反应蛋白（CRP）升高的发生率高于阴性患者，差异有统计学意义（P〈0．05）；AnuA浓度高低与SEE疾病活动指数（SLEDAI）呈正相关（r=0．386，P=0．032）。结论AnuA可作为SEE的又一标记性抗体，且与疾病活动性相关。尤其对抗dsDNA、抗Sm等抗体阴性的患者意义较大。     

抗核小体抗体测定在系统性红斑狼疮诊断中的意义

目的　评价抗核小体抗体 (AnuA)对系统性红斑狼疮 (SLE)诊断的敏感性和特异性 ,并了解其与SLE活动性的关系及与其他自身抗体的关系。方法　用酶联免疫吸附 (ELISA)测定方法检测SLE患者、疾病对照组 (包括原发性干燥综合征、多发性肌炎、皮肌炎、系统性硬化症 )和正常对照组血清中的AnuA ,并记录SLE患者的各种临床表现及实验室指标 ,分析其与AnuA的关系。结果　 10 3例SLE患者中 6 9 9%血清AnuA阳性 ,6 6例疾病对照组仅 3 0 %阳性 ,30名正常对照组全部阴性 ;SLE组患者AnuA阳性率显著高于疾病对照组和正常对照组 (P <0 0 1) ,AnuA在SLE中检测的敏感性和特异性分别为 6 9 9%和 97 9%。AnuA阳性组的SLE患者肾损害、皮肤损害的发生率(6 1 1%、70 8% )明显高于AnuA阴性组 (2 9 0 %、32 3% ) (P <0 0 5 ) ;AnuA阳性组与AnuA阴性组相比 ,在年龄、性别、病程上差异无显著性 (P >0 0 5 )。AnuA滴度的高低与SLE患者的SLEDAI评分有明显相关性 (r=0 2 82 ,P <0 0 5 )。抗dsDNA抗体、抗Sm抗体、快速狼疮因子 (DNP)、抗组蛋白抗体 (AHA)阴性的SLE患者AnuA的阳性率分别为 6 5 6 %、6 8 0 %、6 3 9%、6 4 1%。结论　AnuA对SLE诊断的敏感性高、特异性强 ;它与SLE疾病活动性密切相关 ,对抗dsDNA抗体、Sm、DNP及AHA     

自身抗体联合检测在系统性红斑狼疮诊断中的意义

目的研究抗细胞膜DNA(cmDNA)抗体、抗核小体抗体(AnuA)、抗脱氧核糖核蛋白(DNP)抗体及抗双链DNA(dsDNA)抗体等特异性抗体在系统性红斑狼疮(SLE)诊断中的意义,并与抗核抗体(ANA)的敏感性和特异性进行比较。了解特异性自身抗体联合检测在SLE的诊断及临床应用中的意义。方法测定了125例SLE及118例疾病对照组(包括原发性干燥综合征、多发肌炎、系统性硬化症、未分化结缔组织病、类风湿关节炎、骨关节炎、强直性脊柱炎及银屑病关节炎)患者血清中的自身抗体。利用间接免疫荧光法测定抗cmDNA抗体和ANA,酶联免疫吸附试验(ELISA)测定AnuA、乳凝法检测抗DNP抗体、金标法测定抗dsDNA抗体。结果AnuA、抗cmDNA抗体、抗DNP抗体、抗dsDNA抗体和ANA在SLE患者中的阳性率分别为68%、38.4%、51.2%、49.6%和95.2%,均明显高于疾病对照组(3.4%、4.2%、1.7%、0.8%和25.4%),差异有统计学意义(P<0.001)。ANA与AnuA的敏感性显著高于其他三种抗体,差异有统计学意义(P<0.05);AnuA、抗cmDNA抗体、抗DNP抗体、抗dsDNA抗体和ANA的特异性分别为95.8%、96.6%、98.3%、99.2%和74.6%;AnuA在抗DNP抗体、抗dsDNA抗体阴性的SLE中的阳性率明显高于其他抗体(P<0.05);自身抗体的联合检测可提高SLE诊断的敏感性,但特异性无明显改变。结论抗cmDNA抗     

Toxoplasmosis and systemic lupus erythematosus.

The toxoplasma serological status of 50 patients with systemic lupus erythematosus (SLE) was compared with that of 50 healthy controls; high titres of toxoplasma antibody were significantly more common in the patients with SLE. These titres did not correlate with any of the routinely measured indices in SLE nor with the patients' prior treatment. A case history is used to illustrate the difficulty in diagnosing toxoplasmosis in the presence of SLE.     

Amyloidosis and systemic lupus erythematosus.

A patient with systemic lupus erythematosus who developed reactive amyloidosis associated with high levels of serum amyloid-A protein (SAA) is reported. The possible relevance of elevated SAA levels in the aetiology of amyloidosis is discussed.     

Ascites in systemic lupus erythematosus.

Peritoneal serositis is not a widely recognised aspect of systemic lupus erythematosus (SLE). Indeed, ascites in SLE is said to occur only when complicated by the nephrotic syndrome, congestive cardiac failure, or hepatic cirrhosis. We describe two patients who developed ascites that could be attributed to none of these complications.     

Fever in systemic lupus erythematosus.

The frequency, causes, clinical and laboratory features, and outcome of febrile episodes in 160 hospitalized patients with systemic lupus erythematosus were reviewed. Eighty-three febrile episodes were identified in 63 patients and were ascribed to active lupus erythematosus alone (60 per cent), infections (23 per cent) and miscellaneous causes (17 per cent). Bacteremia was present in nine of the 19 infectious episodes and resulted in a fatal outcome in a third of the patients. Leukocytosis, neutrophilia, shaking chills and normal levels of anti-DNA antibodies were associated with infection in febrile patients with lupus erythematosus.     

抗核小体抗体对系统性红斑狼疮的诊断价值及临床意义

目的评价抗核小体抗体(AnuA)对系统性红斑狼疮(SLE)诊断的敏感性和特异性。方法选取2004-01—2004-12天津市第一中心医院风湿免疫科住院患者及门诊健康体检者,用酶联免疫吸附法(ELISA)检测64例SLE患者、46例疾病对照组和30例正常对照组血清中的AnuA。结果64例SLE患者血清AnuA阳性率为73·44%,46例疾病对照组为13·04%,正常对照组全部为阴性;AnuA对SLE诊断的敏感性和特异性分别为73·44%、88·68%。AnuA在狼疮肾炎中的阳性率比在非狼疮肾炎中高(χ2=5·246,P=0·022)。在抗dsDNA抗体、抗Sm抗体、抗组蛋白抗体(AHA)阴性的SLE患者中AnuA阳性率分别为60·71%、69·57%、64·10%。结论AnuA在SLE血清中水平明显增高,AnuA测定在SLE诊断和治疗中有重要意义,特别对抗dsDNA抗体、抗Sm抗体、抗组蛋白抗体阴性的SLE的诊断有重要意义。     

ANA-negative systemic lupus erythematosus.

The presence of antinuclear antibodies (ANA) in serum is generally considered a decisive diagnostic sign of systemic lupus erythematosus (SLE). Ten patients with clinical signs of disease but persistent negative tests for ANA are examined in this study. Hair fall, Raynaud's phenomenon and recurrent oral ulcers were common in the ANA-negative group. ANA-negative SLE seems to be a subgroup of SLE that has not previously been given adequate attention.     

Significance of low molecular weight C1q in systemic lupus erythematosus.

The significance of high serum concentrations of low molecular weight C1q (LMW-C1q) in patients with systemic lupus erythematosus (SLE) was studied. Concentrations of LMW-C1q were increased in SLE, but not in rheumatoid arthritis or acute poststreptococcal glomerulonephritis. Concentrations of LMW-C1q in SLE serum samples correlated with titres of anti-dsDNA and were inversely related to concentrations of normal C1q and C3. Serial studies in six patients, who had rising anti-dsDNA titres and who developed a major exacerbation requiring admission to hospital, showed that LMW-C1q increased in parallel with anti-dsDNA, reaching peak values of more than 2000% of normal just before or at the time of clinical relapse and decreasing during convalescence. Most marked increases in LMW-C1q were noted in the three patients in whom C1q concentrations remained normal, whereas increases were less in the three patients who had strongly depressed concentrations of normal C1q. A study of C1q biosynthesis by macrophages cultured from patients with SLE and high serum concentrations of LMW-C1q did not show impaired secretion of normal C1q in favour of LMW-C1q, but indicated that serum concentrations of LMW-C1q may reflect the synthetic rate of C1q in vivo. The results show that increased serum concentrations of LMW-C1q may be helpful in diagnosing SLE and suggest that serial determination of LMW-C1q in serum may have predictive value in monitoring patients with SLE.     

三种自身抗体联合检测对狼疮疾病活动和狼疮肾炎的价值

目的探讨联合检测抗C1q抗体、抗核小体抗体(AnuA)和抗dsDNA抗体对狼疮活动和狼疮肾炎(LN)的价值。方法 90例系统性红斑狼疮(SLE)分为疾病活动和疾病稳定组、LN和非LN组, 酶联免疫吸附试验(ELISA)检测血清抗C1q抗体和AnuA水平,间接免疫荧光法比较三抗体单个和联合对疾病活动和LN的价值。结果抗C1q抗体、AnuA和抗dsDNA抗体阳性对疾病活动的敏感性分别为 71．4％、75．0％和66．1％,特异性分别为75．5％、70．6％和88．2％;抗dsDNA抗体阴性患者分别有36．7％抗 C1q抗体阳性和26．5％AnuA阳性。疾病活动组三抗体阳性率和抗体水平显著高于疾病稳定组;三抗体与 SLE疾病活动指数(SLEDAI)、血沉(ESR)、IgG、球蛋白水平显著正相关,与C3、C4及白蛋白水平显著负相关。LN组三抗体水平显著高于非LN组。结论三抗体都是狼疮疾病活动的指标,都与LN有关,联合检测可以提高疾病活动检出率。     

淋巴细胞减少及抗淋巴细胞抗体在系统性红斑狼疮中的分布及意义

目的 了解淋巴细胞减少、抗淋巴细胞抗体(ALA)在系统性红斑狼疮(SLE)中的分布及意义,并探讨ALA在淋巴细胞减少中的作用.方法 回顾性选取2003年2月至2008年2月住院的110例SLE患者作为研究对象.利用间接免疫荧光法测定上述患者的ALA.结果 ①淋巴细胞减少(＜1.5×109/L)的发生率为68.2%.淋巴细胞减少组与正常组在皮疹、浆膜炎、肾脏受累、神经系统异常、白细胞减少、抗核抗体(ANA)、抗双链DNA(dsDNA)抗体、红细胞沉降率(ESR)增快、IgG升高等方面的差异有统计学意义.淋巴细胞计数与SLE疾病活动指数(SLEDAI)评分的相关度好于白细胞计数.②ALA阻性率为46.4%,淋巴细胞减少组与健康组分别为61.3%与14.3%,两组差异具有统计学意义(P=0.000).ALA阳性组与阴性组在狼疮肾炎(LN)、神经精神性狼疮、白细胞计数、C3降低、ANA、抗dsDNA抗体、SLEDAI评分等方面差异有统计学意义.结论 淋巴细胞减少和疾病活动度显著相关.淋巴细胞减少和ALA相关,ALA可作为疾病活动的指标,并且和内脏损害及预后相关.     

Treatment of systemic lupus erythematosus.

Reports on a variety of therapies for systemic lupus erythematosus have been published over the past year. Most of these are single case reports or open studies. As reported last year in this journal, the potential uses of intravenous gamma globulin and plasmapheresis continue to be explored. The use of cyclophosphamide for nonrenal manifestations follows studies last year of its use for lupus nephritis. No major double-blind studies of therapy for lupus nephritis were published; however, the course of lupus patients receiving dialysis or grafts was the subject of three interesting studies. An interesting study on the ability of hydroxychloroquine to prevent disease exacerbations was also published. In summary, the reports of therapy over the past year represent variations on themes. The use of new agents will most likely be based on improvements in our understanding of the pathogenesis of systemic lupus erythematosus.     

Significance of anti-entactin antibodies in patients with systemic lupus erythematosus and related disorders.

OBJECTIVES--To further evaluate the association of anti-entactin antibodies with clinical manifestations in patients with systemic lupus erythematosus (SLE) and related disorders. METHODS--Sera were analysed for anti-entactin antibodies from 79 patients with SLE, 38 patients with rheumatoid arthritis, 20 patients with progressive systemic sclerosis and five with Behçet's syndrome. Sera from 150 healthy blood donors and 20 patients with pneumonia were analysed as controls. To study the association of anti-entactin antibodies with severity and activity in SLE, 30 patients were assigned into three groups with 10 patients in each: (1) with mild manifestations; (2) severe disease without renal involvement and (3) frank lupus nephritis. Two blood samples from each patient were analysed, one from the active and the other from the inactive phase of the disease. Additionally, serial sera from 12 patients with SLE were also analysed. RESULTS--Thirty one patients with SLE (39%) had IgG, IgM or both anti-entactin antibodies. Twenty three of these patients (29%) had biopsy verified glomerulonephritis and 12 (50%) were positive for anti-entactin antibodies. Of the remaining 56 patients without apparent renal involvement, 18 (36%) were positive for anti-entactin antibodies. (chi squared = 2.77, p > 0.05). With the exception of rheumatoid arthritis where six patients (24%) had IgM anti-entactin antibodies, the antibodies were present much less frequently in other diseases (two patients with systemic vasculitis whilst none of the patients with PSS or Behçet's syndrome). Only one patient with pneumonia and none of the 150 sera from healthy blood donors had anti-entactin antibodies. Among Group 1, three (30%) were positive for IgG or IgM anti-entactin antibodies. Six (60%) patients in group 2, and five patients (50%) in group 3 were positive for anti-entactin antibodies. However, the difference between the presence of anti-entactin antibodies between group 1 and 2 or between group 1 and 3 was not significant (p = 0.15 and 0.19 respectively). There was no significant correlation between the titres of anti-entactin antibodies and total serum concentration of IgG (r = 0.141, p > 0.10) and IgM. (r = 0.130, p > 0.10). Furthermore, no significant correlation was observed between SLE disease activity index (SLEDAI) scores and the titres of IgG (r = 0.067, p > 0.10) or IgM (r = -0.033, p > 0.10) anti-entactin antibodies. CONCLUSION--The study demonstrates that anti-entactin antibodies are present in a significant number of patients with SLE and tend to be more common in those with severe disease, with or without nephritis, than in patients with mild disease manifestations. There is no correlation between the titre of anti-entactin antibodies and severity or activity of SLE.     

Genetics of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which multiple genes appear to play important roles in pathogenesis. Hereditary deficiencies, both complete and partial, of several components of the complement system clearly predispose to lupus. HLA class II alleles appear to mediate specific autoantibodies, many of which are pathogenic. Modern molecular techniques are now providing insight into the specific major histocompatibility complex class II polymorphisms that are associated with different autoantibodies in SLE. Other genetic systems also may be important.     

Treatment of systemic lupus erythematosus.

The past year continued to see both major studies and interesting case reports slowly add suggestions, if not absolute knowledge, concerning the treatment of systemic lupus erythematosus. The Lupus Nephritis Collaborative Study Group published two papers, one of which concerned the lack of efficacy of plasmapheresis in treating severe lupus nephritis. A related paper documented the utility of initial serum creatinine in predicting renal failure in patients enrolled in both arms of the plasmapheresis study. Patients in the study received high-dose oral prednisone and low-dose oral cyclophosphamide. Whether this approach is superior to pulse intravenous cyclophosphamide is yet to be determined. Two other approaches to treatment were also reported: anti-CD4, based on success in case reports, merits further study; the modified androgen, 19-nortestosterone, was unfortunately not effective. Other case reports provide additional evidence for specific treatments in certain situations, such as the use of tetracycline pleurodesis for recurrent pleural effusions. Finally, reports of new side effects for old medicines and new ones are a reminder that the treatment can be part of the problem when a lupus patient develops complications.