Antidouble-stranded DNA isotypes in lupus erythematosus patients with prevalent cutaneous presentation

BACKGROUND: Antidouble-stranded DNA antibodies (anti-dsDNA Ab), in particular of the IgG isotype, are usually considered a marker of systemic lupus erythematosus and often correlate with the disease activity. OBJECTIVES: To determine IgG, IgA and IgM anti-dsDNA Ab in a group of 330 patients with lupus erythematosus and prevalent cutaneous lesions. METHODS: The titre of anti-dsDNA Ab was determined by enzyme-linked immunosorbent assay, and disease activity was assessed by means of the systemic lupus activity measure. RESULTS: One hundred and six patients had anti-dsDNA Ab. Thirty-nine patients had antibodies of all three isotypes of immunoglobulins, 17 had IgG + IgM, five IgG + IgA, and two IgA + IgM. Forty-three patients had a single isotype of anti-dsDNA Ab. Patients with systemic disease and higher disease activity had antibodies of all three isotypes of immunoglobulins or of IgG isotype. Remarkably, anti-dsDNA Ab of the IgA isotype, alone or associated with IgM, marked dermatological patients with low disease activity, but often with disquieting clinical and/or laboratory alterations. CONCLUSIONS: These results indicate a correlation between disease activity and both frequency and isotype of anti-dsDNA Ab.     

High titers of antibodies to single-stranded DNA in linear scleroderma

Seven patients with severe linear scleroderma were initially found to have antibodies to double-stranded DNA (dsDNA) in higher titers, using the Farr technique. These patients, however, lacked the systemic involvement normally accompanying such antibodies. A detailed investigation of their sera using Crithidia luciliae assay and single-stranded DNA (ssDNA) labeled with iodine 131 disclosed high titers of antibodies to ssDNA and absent dsDNA antibodies. The ssDNA antibody titer was considerably higher than the mean for unselected patients with systemic lupus erythematosus. It is possible that these antibodies define a subgroup of patients with linear scleroderma who have more severe and extensive involvement of skin and underlying tissues.     

Bullous eruption of SLE—a case report and investigation of the relationship of anti-basement-membrane-zone antibodies to blistering

We describe the clinical and immunopathological findings in a patient with a bullous eruption and systemic lupus erythematosus (SLE). The bullous eruption preceded a dramatic flare of the SLE with a rise in anticardiolipin antibodies and life-threatening cardiac vasculitis. The clinical and histological findings were similar to those described in the classic bullous eruption of SLE but, unlike previous cases, IgG anti-basement-membrane-zone (anti-BMZ) antibodies were detected on the epidermal as well as the dermal side of the split in chemically separated human skin. We screened the sera of another eight patients with SLE and 10 patients with chronic cutaneous lupus erythematosus (CCLE) without evidence of systemic involvement for the presence of anti-BMZ antibodies and demonstrated that these were present in a low titre in a further two SLE patients neither of whom had a history of blistering. Once more there was binding to both sides of the split. We conclude that although there may be low titres of antibodies to several BMZ antigens in patients with SLE, these are not always associated with blistering and their role in the initiation or perpetuation of cutaneous disease is uncertain.     

Elevated levels of antibodies to polyuridylic acid detected and quantitated in systemic scleroderma patients by solid phase radioimmunoassay

A solid support radioimmunoassay has been developed to detect immunoglobulin specific circulating antibodies to polyuridylic acid (Pol U), single-stranded RNA (ss RNA), and single-stranded DNA (ss DNA) in scleroderma and other connective tissue diseases. The assay system uses flex-vinyl microtiter plates on which bovine methyl albumin, the respective polynucleotide, a 1:80 dilution of patient serum, and tritiated high affinity anti-IgG, -IgA, or -IgM are layered. The individual wells containing the sandwich assay are then counted for the presence of labeled immunoglobulins and the results are reported in microgram/ml. Of the 30 scleroderma patients tested, only patients with diffuse systemic scleroderma had antibody levels reactive to Poly U > 4.0 microgram/ml and to ss RNA < 3.0 microgram/ml. Patients with linear scleroderma or morphea had antibody levels to Poly U < 3.0 microgram/ml and very little antibody to ss DNA or ss RNA in their sera. Partial cross reactivity to Poly U was found only in SLE patients with high levels of Ab to ss DNA. Insignificant levels of Poly U antibody were found in patients with other connective tissue diseases and in normal controls. High levels of serum antibody in patients which reacted with Poly U suggest active diffuse systemic scleroderma.     

Papulonodular mucinosis indicating systemic lupus erythematosus

We describe an 18‐year‐old girl with systemic lupus erythematosus (SLE) who had cutaneous papulonodular mucinosis (PNM) as the first sign of SLE. She presented with multiple flesh‐coloured papules on the face, abdomen and limbs. Histological examination of a biopsy taken from a papule showed diffuse deposition of mucin throughout the dermis, and direct immunofluorescence of lesional skin showed a dermoepidermal junction band composed of IgG, IgM and C3, consistent with PNM. Investigations showed that that the patient had leucopenia, positive antinuclear and anti‐double‐stranded DNA antibodies and lupus nephritis. PMN can be an unusual clinical presentation of SLE.     

抗核抗体阴性、IgE升高的系统性红斑狼疮1例

报告1例抗核抗体阴性IgE升高的重症系统性红斑狼疮,在整个病程中5次抗核抗体阴性,血清IgE水平高于正常,颅CT示脑梗塞,肾脏穿刺免疫荧光见IgG,IgM,IgAＣ３呈团块状沉积。     

Prevalence and characteristics of anti-single-stranded DNA antibodies in localized scleroderma. Comparison with systemic lupus erythematosus

Prevalence, levels, and immunoglobulin classes of anti-single-stranded DNA antibodies were determined by an enzyme-linked immunosorbent assay in 52 patients with localized scleroderma (33 with morphea, four with generalized morphea, and 15 with linear scleroderma), in 60 healthy controls, and, for comparison, in 31 patients with systemic lupus erythematosus. Localized scleroderma revealed a significant prevalence of anti-single-stranded DNA antibodies, mainly characterized by high levels and IgM and IgA isotypes. Comparison of antibody characteristics in different clinical forms of localized scleroderma showed some significant differences (levels and immunoglobulin isotypes). Comparison with systemic lupus erythematosus showed that frequency, high levels, and IgG isotype of anti-single-stranded DNA antibodies significantly prevailed in systemic lupus erythematosus, while the IgM isotype significantly prevailed in localized scleroderma. However, generalized morphea and linear scleroderma did not significantly differ from systemic lupus erythematosus as regards antibody frequency and prevalence of high antibody levels.     

Prognostic Implications of Cutaneous Immunoglobulin Deposits In Systemic Lupus Erythematosus

The class of immunoglobulin (Ig) deposited at the dermal-epidermal junction (DEI) of the skin in patients With systemic lupus erythematosus (SLE) has been proposed to have prognostic implications. The authors studied disease activity in 51 SLE patients with a positive lupus band. Patients with cutaneous IgM deposits had significantly more severe disease than those with only IgG or with mixed immunoglobulin deposits. While their data suggest an association between IgM depostis, severe disease and a poor prognosis, they urge caution in utilizing Ig deposits as a prognostic indicator.     

免疫金银染色检测IgM和IgG型抗核抗体及其组分的比较

经制备金标羊抗人ＩｇＭ，以免疫金银染色检测系统性红斑狼疮和类风湿关节炎等病患者２５９份、正常人４０份血清的ＩｇＭ型抗核抗体、抗染色体抗体及抗双链ＤＮＡ抗体，并与ＩｇＧ型相应抗体对照，比较它们的敏感性、特异性及临床意义。     

Conversion of Antinuclear Antibody Specificity as a Marker of Deterioration of Cutaneous Lupus Erythematosus into Lupus Nephritis

A 34-year-old male systemic lupus erythematosus patient (SLE) with cutaneous vasculitis developed renal failure after switching anti-nuclear antibody (ANA) specificity. He developed cutaneous lupus erythematosus with homogeneous and speckled type ANA and a high titer of anti-DNA antibody without renal involvement at 21 years of age. After developing lupus nephritis at the age of 27, the original ANA disappeared gradually. Two years later, a discrete speckled type ANA titer elevated abruptly to as high as 1:640 with low complementemia and without DNA antibody. Within five years, he suffered renal failure. This case of SLE suggests a direct correlation with ANA pattern and organ involvement.     

Antibodies to UV DNA and photosensitivity

Antibodies to ultraviolet light denatured DNA (UV DNA) have been measured in the sera of patients with systemic lupus erythematosus, discoid lupus erythematosus, and light sensitive skin lesions. Antibodies were found in significant levels in the patients with SLE but not in the other groups. It appears that although UV denaturation of dermal DNA occurs in vivo this is not sufficient to induce antibodies to UV DNA in patients with a normal DNA repair mechanism. This may not be the case in patients with SLE in whom a break in tolerance to Native (N-) DNA has already occurred and where antibody to N-DNA will cross react with UV DNA.     

Comparison of IgG subclass autoantibodies in patients with systemic lupus erythematosus and subacute cutaneous lupus erythematosus

Circulating antinuclear antibodies and in vivo bound immunoglobulins at the dermal-epidermal junction are frequently seen in patients with lupus erythematosus. The present study was designed to examine the distribution of the IgG subclasses of in vivo skin bound IgG and circulating antinuclear antibodies (ANA) in patients with systemic lupus erythematosus (SLE) or subacute cutaneous lupus erythematosus (SCLE). Immunofluorescence studies on skin biopsies showed IgG1 to be the predominant IgG subclass in SCLE patients, present in 20 of 21 (95%) of the specimens. IgG2 was present in 4 patients (19%), IgG3 in 1 (5%), and IgG4 in 7 (33%). The frequencies of IgG2, IgG3, and IgG4 skin staining were significantly higher in the seven SLE patients who were studied: IgG1 in 7/7 (100%), IgG2 in 7/7 (100%) and IgG4 in 6/7 (86%). Immunoblot analysis for the IgG subclasses was performed on serum of 29 patients with SCLE who had antibodies to SSA/Ro antigen. Twenty-seven (93%) of these patients were positive for IgG1 anti-SSA/Ro antibody, while the frequencies for IgG2, IgG3, and IgG4 anti-SSA/Ro were very low. These studies indicate that there is a difference in the IgG subclass antibody response in patients with SLE and SCLE. The presence of more than one subclass antibody may be indicative of systemic disease.     

Immunohistological studies, with anti-connective tissue and anti-immunoglobulin antisera, of the skin in lupus erythematosus and scleroderma

Skin lesions from six patients with systemic lupus erythematosus, five patients with discoid lupus erythematosus, twelve patients with systemic sclerosis, five patients with localized morphoea and twenty controls were examined by immunohistological techniques using fluorescein-labelled antihuman IgG, anti-human C3 and anti-human renal glomerulus antisera. The major immunohistological changes in systemic sclerosis and in localized morphoea consisted of foci of intercollagenous staining for connective tissue antigens in the reticular layer of the dermis. It is suggested that these findings indicate collagen neogenesis. In lupus erythematosus the major changes occur in the dermo-epidermal junction and consist of deposits of IgG and C3 and thickening and disruption of the membrane as demonstrated by the use of heterologous sera containing antibasement membrane antibodies. Immunohistological techniques are useful in the diagnostic differentiation between scleroderma and lupus erythematosus.     

A reappraisal of the relationship between subepidermal immunoglobulin deposits and DNA antibodies in systemic lupus erythematosus: a study using the Crithidia luciliae immunofluorescence anti-DNA assay.

The relationship between normal skin subepidermal Ig deposits (subepi. Ig) and disease activity in systemic lupus erythematosus (SLE) is controversial. For this reason we have compared certain qualitative and semiquantitative aspects of subepi. Ig in skin biopsies from uninvolved flexor forearm skin to an objective measure of disease severity in SLE, i.e., serum antibodies to double stranded DNA (anti-dsDNA) as determined by the Crithidia luciliae indirect immunofluorescence assay. We have found that both the number of subepi. Ig classes present and the subepi. Ig fluorescence intensity correlate positively with the presence and amount of circulating anti-dsDNA. The group of patients with subepi. IgM alone had anti-dsDNA no more frequently than the group without subepi. Ig; whereas, the group who concurrently had subepi. IgG, IgA, and IgM frequently had high titers of anti-dsDNA. There were some exceptions to these findings in individual patients, however. These findings illustrate the importance of carefully defining the immunofluorescence findings in SLE normal skin.     

Bullous systemic lupus erythematosus

A 19-year-old woman with a 6 month history of systemic lupus erythematosus (SLE) developed a widespread urticated, erythematous eruption associated with tense, fluid-filled blisters, erosions and crusting. Biopsy showed subepidermal blistering with a prominent neutrophilic infiltrate. Direct immunofluorescence showed markedly positive granular IgG deposition with weak IgM, IgA and C3 at the dermoepidermal junction. No circulating antibodies were detected on indirect immunofluorescence. A diagnosis of bullous systemic erythematosus was made. Treatment with prednisone was ineffective. Subsequent treatment with dapsone led to rapid sustained remission of skin symptoms. Bullous SLE is a rare manifestation of SLE. We review the recent literature and discuss the distinctive features of this condition and contrast them with cutaneous SLE with blisters and the subepidermal blistering disorders.     

Autoantibodies to the heat-shock protein hsp73 in localized scleroderma

We determined the presence of antibodies to the heat-shock protein hsp73 (anti-hsp73) in 57 serum samples from patients with localized scleroderma using an enzyme-linked immunosorbent assay (ELISA). In addition, 30 samples from healthy individuals, 30 from patients systemic lupus erythematosus (SLE) and 32 from patients with systemic sclerosis were assessed. IgG and/or IgM anti-hsp73 antibodies were detected in 33% (19/57) of the patients with localized scleroderma. Among the three subtypes of localized scleroderma, generalized morphoea showed the highest incidence of anti-hsp73 antibodies (40%, 6/15). IgG and/or IgM anti-hsp73 antibodies were also detected in 9/30 samples (30%) from patients with SLE and in 13/32 samples (41%) from patients with systemic sclerosis, while the samples from the healthy controls were all negative for anti-hsp73. By immunoblotting, specific binding of antibodies to hsp73 was confirmed with representative serum samples that were positive for anti-hsp73 in the ELISA. Our findings indicate that the presence of anti-hsp73 is an additional immunological abnormality in localized scleroderma.     

系统性红斑狼疮血清干扰素诱导蛋白10的检测及其意义

目的:检测系统性红斑狼疮(SLE)患者血清干扰素诱导蛋白10(IP-10)水平,并探讨其临床意义.方法:采用ELISA法检测58例SLE患者及40名正常对照者血清IP-10,比较分析其与SLE病情活动指数(SLEDAI)、肾损害、抗dsDNA、补体C3和白细胞计数的相关性.结果:SLE患者血清IP-10水平明显高于正常对照组(P＜0.01),并且活动期高于静止期(P＜0.01),肾损组高于无肾损组.血清IP-10水平与SLEDAI(P＜0.01)、抗dsDNA抗体滴度对数值呈正相关(P＜0.05),与C3(P＜0.01)、白细胞计数(P＜0.05)呈负相关.结论:检测血清IP-10水平有可能作为狼疮活动的敏感指标之一.     

梅毒、红斑狼疮和皮肌炎患者抗磷脂抗体检测

目的：探讨抗磷脂抗体与梅毒、系统性红斑狼疮(SLE)和皮肌炎(DM)的关系。方法：应用酶联免疫吸附试验检测16例梅毒患者、32例SLE患者和11例皮肌炎患者血清中的抗磷脂抗体。结果：①梅毒患者抗磷脂抗体的吸光度（A值)[lgG型抗磷脂酰胆碱抗体(aPC)除外]和IgM型阳性率[抗磷脂酸抗体(aPA)除外]与正常人相比显著升高，IgG型抗磷脂抗体阳性率只有抗心磷脂抗体(aCL)和抗磷脂酸抗体(aPA)，与正常人相比显著升高；②SLE患者抗磷脂抗体的A值和阳性率[IgG型抗磷脂酰乙醇胺抗体(aPE)和IgM型抗磷脂酰肌醇抗体(aPI)除外1与正常人相比显著升高；③DM患者抗磷脂抗体的A值[IgG型抗磷脂酰乙醇胺抗体(aPE)除外1与正常人相比显著升高。④梅毒和SLE患者总阳性率与正常人相比显著升高。结论：自身免疫性疾病患者的抗磷脂抗体与感染时有所不同；抗磷脂抗体虽然存在于多种自身免疫性疾病中，但以SLE的阳性率最高。     

SLE疾病活动性与补体及免疫球蛋白水平相关性的探讨

目的 :　探讨SLE患者治疗过程中疾病活动性与血清补体及免疫球蛋白水平的相关性。方法 :以SLAM评估 2 0 4例患者疾病活动性 ,并对其中 2 6例初诊患者行 15个月的追踪观察。速率散射比浊法测定血清C3、C4 、IgG、IgA、IgM水平。结果 :　高度活动组患者C3、C4 、IgG水平与非活动组及中度活动组均有显著差异 (P <0 .0 5 ) ,但中度活动组与非活动组间所有指标均无显著差异 (P >0 .0 5 )。高度活动组患者治疗初期SLAM分值与C3、C4 、IgG水平相关 ,但随疾病活动性下降到一定程度后便失去相关性。结论 :不能单凭C3、C4 、IgG水平变化判断SLE疾病活动性或调整用药。IgA、IgM水平与疾病活动性未见相关     

SLE患者血清弓形体抗体的检测

目的　了解SLE患者血清弓形体IgG抗体的阳性率。 方法　以酶联免疫吸附试验 (ELISA)检测 72例SLE患者血清标本 ,同时以 5 8例健康人血清为对照。结果　SLE患者血清抗弓形体IgG抗体阳性率为 15 .3 %,对照组为3 .45 %,两组比较差异有显著性 (P <0 .0 5 )。结论　SLE患者有继发弓形体病的高度危险。