Clinical significance and correlation of antinuclear antibodies and anti-DNA antibodies.

The clinical significance and correlation of antinuclear antibodies (ANA) and anti-DNA antibodies was studied using 142 ANA positive sera from different patients having various diseases. High titers of ANA were found briefly in systemic lupus erythematosus and sometimes in scleroderma or mixed connective tissue disease. The peripheral pattern of ANA was seen exclusively in systemic lupus erythematosus and occasionally in mixed connective tissue disease. Anti-DNA antibodies could be found in systemic lupus erythematosus, discoid lupus erythematosus, scleroderma, chronic active hepatitis, but a high titer of anti-DNA (over 60 unit/ml) was present only in patients with systemic lupus erythematosus, especially those having lupus nephritis. There was little correlation between ANA and anti-DNA antibodies.     

Detection of antibodies after immune complex splitting in serum of patients with bullous pemphigoid and systemic lupus erythematosus

No free anti-basement membrane antibodies were found in the sera of four patients with bullous pemphigoid, and no free anti-DNA antibodies in the sera of two patients with systemic lupus erythematosus. The sera treated with 3 mol/l urea and by gel chromatography to separate these antibodies from any circulating complexes, and antibodies to basement membrane were detected by immunofluorescence and to DNA by the Farr technique. The appropriate antibodies were found in all the sera, indicating that failure to detect antibodies by routine procedures may be due to binding of the antibodies to soluble antigens forming complexes in the sera.     

Acquired haemophilia in a patient with systemic lupus erythematosus

INTRODUCTION: In patients with lupus, the most common acquired circulating anticoagulant is antiprothrombinase which is responsible for thrombosis. The presence of antibodies directed against factor VIII is rarely found in systemic lupus erythematosus. A case of acquired haemophilia in a patient with lupus is reported. CASE REPORT: A 30 year-old woman with systemic lupus erythematosus developed a right coxalgia and ecchymotic skin lesions which were prominent on the right arm and forearm. Laboratory values were as follows: positive antinuclear antibodies > 1: 2 560, anti-DNA antibodies (300 IU/ml), prolonged activated partial thromboplastin time, reduced factor VIII activity (1 p. 100) and the presence of antibodies against factor VIII. Magnetic nuclear resonance of the right hip confirmed the presence of an intramuscular hematoma. The patient was initially treated with intravenous pulse and oral corticosteroids, intravenous immunoglobulins and intravenous cyclophosphamide. Clinical and biological improvement was promptly obtained. DISCUSSION: In our patient with systemic lupus erythematosus, bleeding revealed acquired haemophilia with antibodies against factor VIII. It should be pointed out that the association between lupus and haemophilia is uncommon and that at present no standardized treatment can be recommended.     

Livedo reticularis in a patient with systemic lupus erythematosus and anticardiolipin antibodies

This report describes a case of livedo reticularis associated with increased titres of anticardiolipin antibodies (aCL) in a patient with systemic lupus erythematosus. A 38-year-old woman presented with fever, malaise, arthritis and livedo reticularis in a severe form. Antibodies to native DNA and an increased level of aCL were found. A significant positive correlation exists between livedo reticularis and elevated serum antiphospholipid activity in patients with systemic lupus erythematosus. aCL are shown to play a possible pathogenetic role in thrombotic events. This suggests that thrombosis is the underlying cause of livedo in these patients. A biopsy performed in a patient at the site where livedo was most marked showed no evidence of thrombi. It is postulated that the mechanism of livedo in lupus patients with aCL consists of both thrombosis and dysfunction in the regulation of the tone of the peripheral vascular bed.     

Cross-reactivity of murine monoclonal anti-DNA antibodies with human and murine skin: a possible pathogenetic role in skin lesions of lupus erythematosus

Anti-DNA autoantibodies are known to cross-react with a wide variety of substances including cell-surface molecules. Thus, we examined cross-reactivities of 20 murine monoclonal anti-DNA antibodies with normal human and mouse skin tissues. Hybridomas producing these monoclonal antibodies were established from non-immunized spleen cells from autoimmune MRL-lpr/lpr mice, a strain characterized by spontaneous development of SLE-like disorders including skin changes. They were selected based on their reactivity to DNA in a typical enzyme-linked immunosorbent assay, in which nine monoclonal antibodies were reactive with both double-stranded DNA and single-stranded DNA, whereas nine monoclonals were reactive only with single-stranded DNA. Even though only seven of them were observed to stain nuclei, most of the monoclonal antibodies revealed strong and distinct cross-reactivities to various components of the skin tissues including the epidermal basement membrane, keratinocytes at different locations of the epidermis, melanocytes, Langerhans cells, Thy-1+ dendritic cells in the case of murine skin, and mast cells. Our results suggest a possible role of so-called anti-DNA antibodies with high or low affinities to DNA in the pathogenesis of cutaneous lesions of lupus erythematosus.     

Humoral immunity in stage I mycosis fungoides: an increased incidence of lymphocytotoxic antibodies

Thirteen patients with stage I mycosis fungoides (MF) were studied for the presence of circulating autoantibodies including cold-reactive lymphocytotoxic antibodies (LCA), antinuc-lear antibodies and rheumatoid factor antibodies to common food antigens, bovine gamma globulin and casein; and immune complexes as measured by cryoglobulins and I¹²⁵ Clq binding. A significantly increased incidence (11/13) of LCA was found in the MF patients, and this may be related to the alterations in subpopulations of T cells seen in these patients. No significant increase in any other test was noted. There was no evidence of a diffuse hyperactivity of the humoral immune system as seen in systemic lupus erythematosus, which has a similar imbalance of T cell subpopulations.     

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.     

Clq binding activity in lupus erythematosus: correlation with the "lupus band test".

A 131I C1q binding assay was employed to estimate C1q binding activity (C1q BA), presumably due to the presence of circulating immune complexes, in lupus erythematosus sera. Thirteen of 16 sera from patients with systemic lupus erythematosus (SLE) had elevated C1q BA. Only 1 of 17 sera from patients with generalized discoid LE (GDLE) and none of 5 localized DLE patient's sera had elevated C1q BA. A correlation between a positive LE band test and the level of C1q BA was apparent. A positive LE band test tended to occur in patients with higher levels of C1q BA, whereas a negative LE band test tended to occur in patients with low levels of C1q BA.     

Disease activity in systemic lupus erythematosus

Serum samples and skin specimens from twenty patients with systemic lupus erythematosus were studied for antinuclear antibodies, C₃ and C₄ levels, circulating immune complexes, B and T lymphocytes and lupus hand test. The patients were divided into three categories: Group I, six patients with inactive disease; Group II, eleven patients with mildly active disease without renal involvement; Group III, three patients with severely active disease and renal involvement. In Groups II and III, high levels of antinuclear antibodies, low C₄ values, persistence of circulating immune complexes, reduction in T-lymphocyte number and positive lupus band test in uninvolved light exposed areas were usually associated with active lupus and tended to correlate with disease activity.     

Lupus erythematosus in small animals

In veterinary medicine, lupus erythematosus has been classically divided into systemic lupus erythematosus (SLE) and discoid (cutaneous) lupus erythematosus (DLE). These two subdivisions vary markedly in presenting clinical signs, laboratory evaluation, immunologic testing, aggressiveness of therapy and prognosis, and, therefore, will be discussed separately. Systemic LE has been reported in dogs,^1–15 cats,^16–19 and mice.⁸ Discoid LE has been reported in dogs.^20–23 SLE is a rare disease in dogs and has been estimated to affect approximately one of every 4000.²⁴ Epidemiologic studies have shown no increased risk of SLE in human contacts of SLE dogs or dogs with high-titer antinuclear antibody tests.^25,26 Human contacts and controls showed no difference in antinuclear, anti-DNA, anti-RNA, and anti-lymphocyte antibody titers, lymphocytotoxic activity, rheumatoid factors, or elevation of serum immunoglobulins.Prior to these studies, one unfortunate clinical brief erroneously implied a possible correlation between human and canine SLE based on DNA binding studies.²⁷     

Epidermolysis bullosa acquisita preceding the development of systemic lupus erythematosus

In most cases of epidermolysis bullosa acquisita that occur in patients with systemic lupus erythematosus, the diagnosis of systemic lupus erythematosus is made before the development of blistering. We observed three patients with well-documented epidermolysis bullosa acquisita that developed several years before the onset of systemic lupus erythematosus. One patient was producing anti-U1RNP autoantibodies at the time epidermolysis bullosa acquisita was diagnosed, and all five produced this antibody during the systemic lupus erythematosus phase of their illness. In addition, in all five cases of epidermolysis bullosa acquisita with systemic lupus erythematosus antibodies to double-stranded DNA ultimately developed, and severe systemic lupus erythematosus and lupus nephritis developed in four patients. Sera from 15 other patients with epidermolysis bullosa acquisita without overt systemic lupus erythematosus were analyzed for systemic lupus erythematosus-related autoantibodies. Four patients were found to have at least one such autoantibody. These findings further document an association between epidermolysis bullosa acquisita and systemic lupus erythematosus and suggest that patients with systemic lupus erythematosus who present with epidermolysis bullosa acquisita may represent a subset of lupus erythematosus that puts the patient at increased risk for the development of more severe systemic illness. Patients presenting with epidermolysis bullosa acquisita, especially those who are black or Hispanic, should be monitored for the development of potentially life-threatening systemic lupus erythematosus.     

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.     

Lupus erythematosus and reactive tests for syphilis: update.

Sera of patients with lupus erythematosus can produce false-positive reactions in most serologic tests for syphilis, including the FTA-ABS test. False-positive reactions in the FTA-ABS test can exhibit beaded, borderline or reactive patterns of fluorescence. Beaded fluorescence is commonly associated with anti-DNA antibody and other correlates of lupus activity. Borderline and reactive results are common in both systemic and discoid lupus erythematosus, and are usually not associated with increased clinical activity. TPI and MHA-TP tests appear helpful in detecting false-positive FTA-ABS results.     

Circulating immune complexes in lupus erythematosus, scleroderma and dermatomyositis.

Circulating immune complexes (CIC) were measured by three different methods in serum from 17 patients with systemic lupus erythematosus (SLE), 3 patients with "hydralazine-induced" SLE-like syndromes, 14 patients with discoid lupus (DLE), 8 patients with systemic sclerosis and 5 patients with dermatomyositis. Immune complexes were detected in 13 of the 17 patients with SLE. All patients with lupus nephritis and typical exanthema had circulating immune complexes. The concentration of immune complexes was inversely correlated to serum complements C4 and C3. All 3 patients with "hydralazine-induced" SLE-like syndromes had circulating immune complexes that disappeared after withdrawal of the drug. Immune complexes were detected in 3 of the 14 patients with DLE; all 3 patients with CIC had wide-spread DLE. In systemic sclerosis, CIC were detected in only 1 of the 8 patients. Four of the 5 patients with dermatomyositis demonstrated CIC in serum. No complement consumption was detected in dermatomyositis and the immune complexes may have been secondary to tissue destruction.     

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.     

病理性自身抗体在狼疮肾炎中的致病作用

狼疮肾炎是系统性红斑狼疮的主要并发症之一,具有较高的死亡率和病死率。主要特征是体内出现大量的病理性抗体,然而这些抗体究竟是怎样引起肾脏损害的,至今仍未清楚。本文就免疫沉积和抗dsDNA抗体穿透引起狼疮肾炎的发病机制作一下回顾性总结     

Pemphigus erythematosus--detection of anti-DNA antibodies

In an 80-year-old woman with pemphigus erythematosus, we demonstrated ANA as well as anti-DNA antibodies in the serum. This finding supports the argument that this skin disorder represents a combination of a disease of the pemphigus group with systemic lupus erythematosus.     

Evaluation of the Japanese-Chinese Herbal Medicine,Kampo, for the Treatment of Lupus Dermatoses in Autoimmune Prone MRL/Mp-lpr/lpr Mice

Kampo, a Japanese-Chinese traditional herbal medicine, has been used for the treatment of various diseases for about 3,000 years in China. Among herbal medicines, Sairei-to is well known for improving the symptoms of rheumatoid arthritis (RA) and other collagen diseases. However, its immunosuppressive effects on autoimmune cutaneous phenomena are not completely understood. We investigated the effects of Sairei-to on the development of lupus dermatoses in autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mice, an animal model which spontaneously develops skin lesions similar to those seen in human lupus erythematosus. Virgin female MRL/lpr mice at 1 month of age, which were treated orally with Sairei-to, had reduced amounts of IgG deposition at the dermoepidermal junction, titers of anti-DNA antibodies and rheumatoid factor, and lymphoproliferation. These results support the use of traditional herbal medicines in patients with human RA and systemic lupus erythematosus.     

Radioimmunological detection of soluble immune complexes in serum (author's transl)]

Immune complexes could be measured in sera with the use of plastfixed Clq and 125J-labeled anti-Ig-antibody. The sensitivity of the system is 0.1 microgram aggregated human IgG, the working range is between 0.1 and 10 micrograms per 0.5 ml. In 58% of the sera from patients with systemic lupus erythematosus was found an increase in the immune complex content.     

The Comparative Study of Anti-Double Stranded DNA Antibody Levels Measured by Radioimmunoassay and Enzyme-Linked Immunosorbent Assay in Systemic Lupus Erythematosus

Anti-double stranded (ds) DNA antibody is an autoantibody specific for systemic lupus erythematosus (SLE). For the measurement of this antibody, radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA) is widely used in Japan. We studied the correlation of anti-dsDNA levels in 158 sera from 53 SLE patients between RIA and ELISA. The correlation coefficient between anti-dsDNA antibody levels measured by RIA and ELISA was 0.736 (p<0.001). The concordance rate of sera with both ELISA/RIA-positive or both ELISA/RIA-negative results was 82.3% (130/158 sera). Twenty sera (12.7%) of 14 patients were ELISA-positive but RIA-positive, and 8 sera (5.0%) of 6 patients were ELISA-negative but RIA-positive. Our results suggest that both methods may be equally reliable for the detection of anti-dsDNA antibodies and that ELISA may be more sensitive than RIA. ELISA may be preferable because of its simplicity and convenience of the measurement procedure. The correlation coefficient between anti-ssDNA levels measured by ELISA and anti-dsDNA levels measured by RIA was 0.322 (p<0.01), and the correlation coefficient between anti-ssDNA and anti-dsDNA antibody levels measured by ELISA was slightly higher, 0.515 (p<0.001). These results may reflect the predominance of anti-DNA antibodies reactive with both ss and dsDNA in SLE sera. Since the clinical significance of anti-ssDNA antibodies remains unclear, further analysis of accumulated cases is required.