Antiphospholipid antibodies: a disease marker in 25 patients with antinuclear antibody negative systemic lupus erythematosus (SLE). Comparison with a group of 91 patients with antinuclear antibody positive SLE

Twenty-five antinuclear antibody (ANA) negative patients with systemic lupus erythematosus (SLE) or lupus-like disease were compared to 91 ANA positive patients with SLE for clinical and biological symptoms. Cutaneous symptoms were infrequent in ANA negative patients (p less than 0.03). Thrombocytopenia (p less than 0.001), venous or arterial thrombosis (p less than 0.02) as well as cerebral infarction (p less than 0.001) were more frequent. Three types of antiphospholipid antibodies were determined by different methods; the VDRL, the lupus anticoagulant and an ELISA for IgG anticardiolipin antibody (aCL). The frequency of a positive VDRL test was significantly higher in the ANA negative group (p less than 0.05). Correlation studies suggest that the 3 methods are not redundant and detect overlapping but not identical antibodies. Of the 3 antiphospholipid antibody assays, only the IgG aCL test was significantly associated with thrombosis in the ANA negative group (p less than 0.02).     

Pathogenic role of antinuclear antibodies in lupus disease

The majority of anti-nuclear antibodies do not have a proven pathogenic role in systemic lupus erythematosus (SLE). The pathogenicity of native anti-DNA antibodies, suggested by clinical data, is difficult to confirm. It is linked to several factors: isotype and avidity of these antibodies, affinity for DNA, size of immune complexes. DNA, anti-DNA antibodies and cross-reactive anti-DNA idiotypes (16/6) have been isolated from human and NZB mouse glomeruli. Moreover, DNA has a particular affinity for the glomerular membrane due to its cross-reactivity with some constituents of this membrane. Anti-SSA (Ro) antibodies may play a role in some cases of nephropathy in SLE and participate in photosensitization. They are associated with neonatal lupus, with some cases of fetal death in black women and with the atrioventricular heart block. However, factors other than these antibodies are needed to induce such lesions. Anti-U1 RNP antibodies do not protect against kidney involvement in SLE; however, they can decrease suppressive function by penetrating into suppressor T cells. Anti-Sm antibodies may have particular immunoregulation properties. Some antinuclear antibodies may at least in part, be responsible for the lesions in SLE, in conjunction with other still-unknown factors.     

Adult Still's disease despite the presence of positive antinuclear antibodies

We report the case of a 60-year-old woman who had recently been examined for fever of unknown origin and who presented to our hospital with high fever and myalgia, weakness, sore throat, and rash. The patient had a markedly elevated serum ferritin concentration of 40,000 ng/mL and positive antinuclear antibodies (ANA) with a titer of 1/200. Despite the presence of positive ANA, the patient was diagnosed as having adult Still's disease (ASD). High-dose steroid therapy resulted in a remarkable clinical improvement. Such a severe case of systemic inflammatory response syndrome, masquerading as sepsis with a positive ANA test, has not been reported previously, at least not in the last 15 years.     

抗核抗体阳性肝硬化患者的临床特点

为了探讨抗核抗体 (ANA)阳性肝硬化患者的临床特点及环磷酰胺的治疗效果 ,检测 82例肝硬化患者血清ANA ,比较ANA阴性和阳性肝硬化患者的临床特点 ,观察环磷酰胺治疗ANA阳性肝硬化患者的疗效。结果与ANA阴性肝硬化患者比较 ,ANA阳性肝硬化患者女性多见 ,发病年龄较大 ,乙型肝炎病毒感染率低 ,Child -Pugh分级C级比例高 ;腹水、下肢浮肿症状较重 ;血清白蛋白水平低、球蛋白水平高 (P <0 0 5 )。ANA阳性肝硬化患者经环磷酰胺治疗后症状均好转 ,其中与对照组比较 ,腹水、下肢浮肿症状改善明显 (P <0 0 5 ) ;血清总蛋白、白蛋白水平增加 ,球蛋白水平下降 (P <0 0 5 ) ;部分患者ANA转阴 (P <0 0 5 )。说明ANA阳性肝硬化患者有其自身的临床特点 ,环磷酰胺治疗有效。     

Outcome of positive antinuclear antibodies in individuals without connective tissue disease

OBJECTIVE: To determine if individuals with high titer antinuclear antibodies (ANA) but without clinical evidence of connective tissue disease (CTD) subsequently develop CTD or experience a change in ANA positivity. METHODS: We included patients from an initial study database as well as those reviewed in an outpatient rheumatology clinic at the University of Alberta Hospital over the past 8 years. A telephone survey targeting signs and symptoms of CTD was conducted. Serum samples from consenting patients were then assayed for ANA, antibodies to extractable nuclear antigens (ENA), and anti-dsDNA by the Rheumatic Disease Unit at the University of Alberta Hospital. RESULTS: Sixty-two patients completed the telephone survey and 53 completed both the telephone survey and repeat serological blood investigations. Mean length of followup was 5.4 years, with an age range from 19 to 87 years. Forty-eight of 53 patients (91%) remained ANA positive on repeat testing, and 5 patients were also ENA positive. Three patients had been diagnosed with CTD since the previous study. The most common clinical features on telephone survey included joint pain (34 patients) followed by Raynaud's phenomenon (11 patients). CONCLUSION: Patients tended to remain ANA positive on repeat testing. Three out of 53 patients had developed CTD, reflecting the more sensitive but less specific nature of ANA testing. Another common condition associated with ANA positivity was hypothyroidism. Continued longterm followup with larger cohorts is needed.     

Cellular control of antinuclear antibody production. Anti-dsDNA and anti-Sm plaque forming cells in SLE patients and normal individuals

The in vitro response of lymphocytes to dsDNA, Sm, and Pokeweed Mitogen (PWM) and the role of monocytes in the control of this response were studied in 21 SLE and 14 healthy individuals. Specific hemolytic plaque assays were used to enumerate peripheral blood B lymphocytes secreting anti-dsDNA and anti-Sm antibodies. After 7 days in tissue culture without stimulation, anti-dsDNA or anti-Sm Plaque Forming Cells (PFC) were observed in 75% of SLE patients and 45% of normals. PWM, dsDNA, and Sm stimulation raised the levels of anti-dsDNA PFC in 25%, 37%, and 83% of SLE cultures respectively, and in all but one normal culture. PWM and dsDNA induced a decrease in anti-dsDNA PFC in 50% and 62% of SLE cultures. This suppressive effect was mainly exerted on spontaneous high producers of anti-dsDNA PFC. Monocyte depletion from cultures resulted in a decrease in PFC formation in all normals studied and in 7 SLE cultures. In 2 SLE cultures with no stimulation and one dsDNA stimulated culture, the number of anti-nuclear PFC increased after monocyte depletion. In cocultures of allogeneic, HLA-DR identical mononuclear cells, dsDNA pulsed SLE monocytes appeared more efficient than pulsed normal monocytes in helping to generate anti-dsDNA PFC. SLE lymphocytes responded less well than normals to dsDNA. These results suggest that: nuclear antigens may act as stimulators or suppressor of the specific autoimmune response, depending on the immune status of the SLE patient; and that abnormalities in both monocyte and lymphocyte responses lead to the excessive secretion of anti-dsDNA and anti-Sm antibodies by SLE B lymphocytes.     

In vivo antinuclear antibody of the skin: diagnostic significance and association with selective antinuclear antibodies.

Immunofluorescence microscopy of the skin has disclosed antibodies bound to epidermal cell nuclei in several connective tissue disorders. To establish the diagnostic potential of this phenomenon the results of immunofluorescence microscopy of biopsy specimens from 1651 subjects with various diseases and from 315 patients with systemic connective tissue disorders and related diseases were reviewed. It was found that the predictive value of the phenomenon for the presence of a systemic connective tissue disorder was, in general, 88%. Except for the homogeneous and thready patterns, which seldom appear, but are specific for SLE, in vivo antinuclear antibody (ANA) does not discriminate better between the various disorders than do serum antibodies. The presence of in vivo ANA in the skin was related to serum antibodies against non-histone nucleoproteins, but not to anti-dsDNA antibodies. Combined with the finding that antibodies against non-histone nucleoproteins can bind on the surface of human keratinocytes, this suggests that ANA of the skin occurs in vivo.     

Raynaud''s phenomenon and positive antinuclear antibodies in a malignancy.

Both Raynaud's phenomenon and the presence of antinuclear antibodies are uncommon features of malignant disease and the association of both with a malignancy extremely rare. The case is reported of a 78 year old woman who presented with Raynaud's phenomenon and positive antinuclear antibodies related to adenocarcinoma of unknown primary site.     

Anti-SS-A antibody and other antinuclear antibodies in systemic lupus erythematosus

Randomly selected sera from 88 patients with systemic lupus erythematosus (SLE) were studied for the frequency of antibodies to SS-A, SS-B, RANA, RNP, Sm, Sc-1, and dsDNA. Results were in agreement with previous reports except for an increased incidence of anti-SS-A antibody (33%). Nine of 14 patients with anti-SS-A antibody on whom serial studies were performed had fluctuating titers. Titer changes often correlated with disease activity and dsDNA antibody levels.     

Anti-dsDNA antibodies in sera of patients without systemic lupus erythematosus

133 sera of patients without systemic lupus erythematosus (SLE) have been analyzed by an ultramicro ELISA for antibodies to dsDNA. 14 sera (10.5%) had antibody concentrations greater than 120 mU/ml ("positive"). Additionally, 29 sera (21.5%) had antibodies within the range 60 . . . 120 mU/ml ("borderline"). Pathogenetic significance is discussed briefly.     

Antihistone antibodies in antinuclear antibody—positive juvenile Arthritis

The binding of antinuclear antibody—positive juvenile arthritis (JA) sera to bovine thymus histones H1, H2A, H2B, H3, and H4 was studied by an enzyme-linked immunosorbent assay. Seventy-five percent of the JA patients tested positive for at least 1 antibody specificity. Antihistone antibodies were predominantly IgM, while IgG antibodies were less common and were restricted to histones H1 or H3. In the group of patients with JA of pauciarticular onset, antihistone antibodies were significantly more elevated in patients with past or present uveitis than in patients without a history of uveitis. Anti-H1 antibodies in JA patients were found to react mostly with determinants located in the carboxylterminal domain of the H1 molecule. Sera were also reactive with human histone H1° or chicken histone H5, which are H1 variants found only in nondividing cells.     

Multiple antinuclear antibodies in mixed connective tissue disease: report of a patient with an unusual antibody profile

A patient with antibodies to RNP, n-DNA, Sm and PM-I is described. The first clinical manifestations of connective tissue disease appeared at age 10. A cystic pulmonary lesion, pericardial effusion and nephropathy appeared after 7 years of disease limited to skin and joints. Pulmonary, pericardial and renal disease all appeared to respond to corticosteroid therapy.     

The prevalence and significance of positive antinuclear antibodies in patients with fibromyalgia syndrome: 2-4 years' follow-up

The aim of this study was to ascertain whether fibromyalgia patients with positive ANA develop other features of connective tissue disease over 2-4 years' follow-up. Patients attending our clinic with a diagnosis of fibromyalgia were identified. All ANA-positive patients (n = 12) were recruited and matched for age and sex with 12 ANA-negative FMS patients. As further control groups, patients with a diagnosis of osteoarthritis (OA) were included. A screening questionnaire for possible features of connective tissue disease was sent to all participants. Patients who had three or more positive criteria were invited for further assessment. The ANA-positive rate was 12/137 (8.8%) in FMS and 20/225 (8.9%) in OA patients. All ANA positivity was at a low titre. Fourteen out of 20 (70%) FMS patients and 17/30 (56.7%) OA patients had three or more criteria (P = 0.34). No significant differences in the number of the positive criteria were found between those who were ANA positive or negative in both groups. On full assessment we found one patient who fulfilled the criteria for SLE from the ANA-positive FMS group and one in the ANA-negative group who fulfilled the criteria for primary Sj?gren's syndrome. Of the patients with OA, one who was ANA positive was diagnosed as having rheumatoid arthritis. The results from our study show that ANA (at least in low titre) is not a good predictor of the future development of connective tissue.     

Significance of anti–nuclear matrix antibodies in patients with in vivo speckled antinuclear antibody staining

Objective. Evidence suggests that patients with in vivo speckled antinuclear antibody (ANA) patterns have high titers of circulating ANA, specifically anti–U1 RNP antibody. A small percentage of patients with high titers of anti–U1 RNP antibody have anti–nuclear matrix antibodies, and some also demonstrate in vivo ANA. This study was designed to screen for the presence of antinuclear matrix antibodies in patients with in vivo ANA. Methods. Anti–nuclear matrix antibodies were detected by indirect immunofluorescence on HCI-extracted HEp-2 cell substrate, by enzyme-linked immunosorbent assay, and by immunoblot analysis. Results. All 10 patients with in vivo ANA were found to have anti–nuclear matrix antibody demonstrated using HCI-extracted HEp-2 cell substrate, and all exhibited antibody activity to a 36-kd protein from nuclear matrix antigen. Conclusion. These results suggest that anti–nuclear matrix antibodies are a major factor in the development of in vivo ANA.     

Reference sera for antinuclear antibodies. II. Further definition of antibody specificities in international antinuclear antibody reference sera by immunofluorescence and western blotting

Objective. To define the fine specificity of the 10 reference sera used for determination of antinuclear antibodies (ANA) and ANA subsets which are available from the Arthritis Foundation (AF) and from the Centers for Disease Control and Prevention (CDC). Methods. AF/CDC sera were assessed by experienced laboratory staff, using indirect immunofluorescence and Western blotting. Results. The original assignment of fluorescence patterns to 4 reference sera was confirmed, and the fluorescence intensities were determined using reference fluorescent beads. On Western blots, sera AF/CDC2 (anti—SS-B/La) and AF/CDC7 (anti—SS-A/Ro) did not detect Ro antigens, sera AF/CDC9 and AF/CDC10 appeared to be monospecific anti—Scl-70 and anti—Jo-1 sera, respectively, serum AF/CDC4 (anti—U1 small nuclear RNP) recognized the 70-kd band, and serum AF/CDC5 recognized the Sm antigen with its multiple bands. Semiquantitative analyses revealed that AF/CDC5, AF/CDC2, and AF/CDC10 were strongly reactive sera, whereas AF/CDC4 and AF/CDC9 were much weaker and should be used at lower dilutions on Western blots. Conclusion. The AF/CDC ANA reference sera, originally described as reference reagents for indirect immunofluorescence and double immunodiffusion techniques, are also useful for Western blotting. The data presented herein further support the use of these sera for reference purposes.     

Crossing of antinuclear antibodies and anti-leishmania antibodies

Visceral leishmaniasis or Kala-azar is an endemic parasitic infection in Mediterranean countries. We report an interesting case occurring in a 38-year-old woman suffering from systemic lupus erythematosus and secondary antiphospholipid syndrome. In our patient visceral leishmaniasis occurred during high dose-steroids treatment mimicking a flare of lupus. As the lupus resolved under immunosuppressive treatment, a reactivation of visceral leishmaniasis was observed and was confirmed by the successive serological tests which showed crossing of leishmania and antinuclear antibody titers. Our case shows that, faced with fever occurring in lupus patients in an endemic area, visceral leishmaniasis should be searched for before intensifying immunosuppressive treatments.     

永久性染发剂与抗核抗体阳性结缔组织病发病风险的临床研究

目的 探讨使用永久性染发剂与抗核抗体阳性结缔组织病(CTD)发病的风险.方法 采用病例对照研究,对440例CTD患者和性别、年龄相匹配的440名健康的患者家属或朋友进行比较分析.采用面对面的交谈,以调查问卷的方式记录研究对象的基本信息和染发信息(包括染发时间、染发频率、染发次数及与染发相关的过敏).记录病例组的现病史,包括疾病的诊断、病程、初发症状、各脏器受累情况及各项实验室检查.应用SPSS 17.0软件进行x2检验和Logistic回归分析.结果 使用永久性染发剂与CTD发病无明确因果关系[比值比(OR)=1.282,95％可信区间(CI)0.966～1.700,P=0.085 ];单独分析病例组中的系统性红斑狼疮(SLE)患者,使用永久性染发剂与SLE发病亦无明确因果关系(OR=1.092,95％CIO.795～1.500,P=0.587).结论 使用永久性染发剂无诱发抗核抗体阳性CTD的作用.