Antinuclear antibodies measured by enzyme immunoassay in patients with systemic lupus erythematosus: relation to disease activity

To evaluate the correlation between measurements of antinuclear antibodies serum levels by enzyme immunoassay (ANA-EIA), and the degree of systemic lupus erythematosus disease activity. To retest the performance of the test compared to measurement of antinuclear antibodies by immunofluorescence (ANA-IIF). Eighty-five sera from 71 patients with SLE were tested. Demographic, clinical, laboratory, and SLEDAI status were collected. The sera were tested for ANA-EIA and by ANA-IIF at 1:40 and 1:160 dilutions. Serum levels of ANA-EIA were compared to the overall SLEDAI score and to each of its components. A SLEDAI score of ≥6 was considered clinically significant. The sera of fifty-one healthy volunteers served as controls. Serum levels of ANA-EIA were significantly higher in patients with a SLEDAI score of ≥6 compared to the group of patients with a SLEDAI score of <6 (P = 0.004). High serum levels of ANA-EIA correlated significantly with elevated anti DS-DNA antibodies (P < 0.001), low C₃ or C₄ levels (P < 0.001), pyuria (P < 0.011), arthritis (P = 0.019), and new rash (P = 0.019). Levels of ANA-EIA were significantly higher in patients tested positive by IIF compared to those who tested negative. Higher serum levels of ANA-EIA correlated with clinically significant disease activity in patients with SLE. Higher serum levels of ANA-EIA also correlated with some single items of the SLEDAI. The results also reiterated the validity of ANA-EIA testing in patients with SLE. Further longitudinal studies are needed in order to test the hypothesis that serum ANA-EIA levels might reflect fluctuations in disease activity.     

Clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus patients

The aim of this study was to investigate the clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus (SLE) patients. IgG antinucleosome antibodies were detected by a qualitative enzyme immunoassay (immunodot) in the sera of SLE patients at onset of disease. The patients were divided into two groups according to the result of the antinucleosome antibodies test: positive (group A) and negative (group B). The two groups were also evaluated for clinical and biological parameters. Of 84 patients with SLE, 66 (78.6%) had antinucleosome antibodies. Among 21 patients negative for anti-double-stranded DNA (anti-dsDNA), 5 (23.8%) were antinucleosome positive. The most common initial features were haematological disorders (80.1%) and arthritis or arthralgias (79.8%). Renal disorders, observed in 59.5% of SLE patients, were more common in group A compared to group B (65 vs 38%) (p=0.04). The European Consensus Lupus Activity Measurement (ECLAM) mean score was higher in group A (6.42) than in group B (4.44) (p=0.002). Antinucleosome antibodies were positive in nearly one-fourth of SLE patients negative for anti-dsDNA. We found a correlation between antinucleosome antibodies, nephritis and SLE disease activity. Therefore, the determination of circulating antinucleosome antibodies could be a useful parameter for early diagnosis and follow-up of SLE patients.     

Significance of antibodies to cardiolipin in unselected patients with systemic lupus erythematosus: clinical and laboratory associations

In a multicentre study anticardiolipin antibodies of the IgG and IgM isotypes were measured by a solid phase enzyme immunoassay in 368 patients with systemic lupus erythematosus (SLE) who were not selected on the basis of features of antiphospholipid syndrome. Clinical and laboratory associations of increased levels of anticardiolipin antibodies were evaluated. IgG and IgM antibodies to cardiolipin were documented in 224 (60.9%) and 128 (34.8%) patients, respectively. Regarding the symptoms of antiphospholipid syndrome, elevated amounts of anticardiolipin IgG were significantly associated with spontaneous abortion (P<0.001), thrombocytopenia (P<0.01), livedo reticularis (P<0.01) and a positive direct Coombs test (P<0.05), but not with thrombosis or central nervous system diseases such as epilepsy and psychosis. IgM antibodies to cardiolipin were associated with a positive direct Coombs test (P<0.01), but with no other symptom of antiphospholipid syndrome. The predictive values of anticardiolipin antibody determinations in unselected SLE patients were poor for all features of antiphospholipid syndrome because of high proportions of false-positive and false-negative results. As for other manifestations of SLE, positive correlations between raised antibodies to double-stranded DNA and the occurrence of anticardiolipin antibodies of the IgG isotype were observed, and anticardiolipin IgM was negatively associated with nephritis.     

Anti-topoisomerase I antibodies in systemic lupus erythematosus as a marker of severe nephritis

The authors report nine patients with systemic lupus erythematosus associated with anti-topoisomerase I antibodies (ELISA test) without features of systemic sclerosis. These antibodies were correlated with the disease activity and might be a marker of the severity of the closely related to difusse proliferative glomerulonephritis.     

Enzyme-linked immunosorbent assays for antibodies to poly(A), poly dAT and histones: possibly useful tools for the evaluation of prognosis and disease activity in systemic lupus erythematosus

Summary In a prospective study 222 sera from 56 patients with systemic lupus erythematosus (SLE) were tested for antibodies to poly(A), poly dAT and histones using enzyme-linked immunosorbent assay (ELISA). Patients with active disease had significantly more often antibodies to poly(A), poly dAT and histones than patients with inactive disease. There was a positive correlation between the activity score of the disease and the levels of poly(A)-antibodies of IgG and IgM class, poly dAT-antibodies and antibodies to histones.Patients with SLE-nephritis had a higher level of poly dAT and IgG class poly(A) antibodies than patients without nephritis. Interestingly, patients with an SLE-nephritis had lower levels of IgM-poly(A)-antibodies than those without nephritis. Attempts to use the ELISAs in predicting the SLE exacerbations were unsuccessful. However, the assays can be used as parameters in the estimation of the disease activity.     

Anti-DNA antibodies of IgA class in patients with systemic lupus erythematosus

Summary Sera obtained from 53 patients with systemic lupus erythematosus (SLE) were investigated for the presence of immunoglobulin class-specific antibodies against native (ds)DNA and denatured (ss)DNA. The methods employed were the Crithidia luciliae test and an enzymelinked immunosorbent assay (ELISA), respectively. Anti-dsDNA antibodies of IgG class were seen in 42%, IgM-anti-dsDNA antibodies in 43%, and IgA-anti-dsDNA antibodies in 30% of the patients. There was an association between the presence of both IgG- and IgA anti-dsDNA antibodies and the activity of the disease. Patients with active nephritis also had anti-dsDNA antibodies of IgG and IgA class significantly more often than patients with inactive nephritis or without renal disease. IgG-anti-ssDNA antibodies were seen in 89%, IgM-anti-ssDNA antibodies in 51%, and IgA-anti-ssDNA antibodies in 66% of the patients. Patients with nephritis had low levels of antibodies to ssDNA of IgM class. We suggest that immunoglobulin class-specific anti-DNA antibodies should de determined in the diagnosis and monitoring of SLE.     

Endothelial cell-binding antibodies in patients with systemic lupus erythematosus

 The implications of endothelial cell-binding IgG antibodies (EC IgG) in systemic lupus erythematosus (SLE) was evaluated by determining level of EC IgG in sera from 112 SLE patients. The serum EC IgG level was determined by the cyto-ELISA method using human umbilical vein endothelial cells (HUVEC), human microvascular endothelial cells (HMVEC), and aortic endothelial cells (HAEC) as antigens. The levels of EC IgG were significantly higher among patients with SLE than among healthy control subjects (P < 0.001), and 68% (76/112) of SLE patients were shown to be EC IgG-positive. In patients with active lupus nephritis, the level of EC IgG was statistically and significantly elevated compared with those without lupus nephritis (P < 0.05). Negative correlations between EC IgG level and levels of CH50, C3, and lymphocyte count were revealed (P < 0.05, P < 0.005, and P < 0.05, respectively). When clinical course was evaluated, the levels of EC IgG correlated with disease activity. Definitive correlations in antibody levels between HUVEC and HMVEC, and between HUVEC and HAEC were revealed (both P < 0.0001). The results of this study revealed that the EC IgG in patients with SLE was involved in the onset of clinical manifestation, especially in patients with active lupus nephritis. Received: January 28, 2002 / Accepted: July 12, 2002 Acknowledgments This investigation was supported by grants from the Research Committee on Intractable Vasculitides, and the Ministry of Health and Welfare of Japan, from 1996 to 2000. Correspondence to:H. Bando     

Reversible dementia in systemic lupus erythematosus without antiphospholipid antibodies or cerebral infarction

Dementia is a very rare neurological manifestation of systemic lupus erythematosus (SLE) and has a deep link with antiphospholipid antibodies (APL) and cerebral infarction in its development. However, nonvascular dementia irrelevant to APL or cerebral infarction has not been reported in patients with SLE until now. We describe a case of reversible dementia in an SLE patient without APL or cerebral infarction which was successfully treated with corticosteroid and cyclophosphamide. There are two significant points in this case. One is that humoral factors other than APL might be involved in the development of dementia. Secondly, reversible dementia without APL or cerebral infarction may respond more favorably to immunosuppressive therapy.     

Antiphospholipid antibodies in children with systemic lupus erythematosus: a prospective study in northern India

Twenty-seven children with systemic lupus erythematosus (SLE) were tested for antiphospholipid antibodies (APLA), i.e. lupus anticoagulant and immunoglobulin (Ig)G or IgM anticardiolipin antibodies (ACLA), with beta-2 glycoprotein I as cofactor, in a single-centre, prospective study over 2 years. Eighteen patients (67%) tested positively for one or the other APLA during the course of the study. Twelve children (44%) tested positively for IgG ACLA and ten (37%) for IgM ACLA, whereas eight (30%) were positive for lupus anticoagulant. In two patients with thrombosis, IgG anticardiolipin positivity was seen to be variable. Unlike the results of most other reports in the literature, lupus anticoagulant positivity was not consistently associated with thrombosis. A majority of the children (83%) tested positively for ACLA during disease activity. Immunoglobulin G and IgM ACLA positivity did not correlate significantly with disease status. The results of this prospective study would indicate that, though frequently present, APLA may be unable to be predictive of disease behaviour in children with SLE.     

Antinucleosome antibodies in systemic lupus erythematosus patients: Relation to disease activity and lupus nephritis

Aim of the work

To evaluate the level of anti-nucleosome (anti-NCS) antibodies in systemic lupus erythematosus (SLE) patients and study their association with disease activity and lupus nephritis.

Anticardiolipin antibodies and lupus anticoagulant in patients treated with different methods of renal replacement therapy in comparison to patients with systemic lupus erythematosus

Summary Antiphospholipid antibodies were found to be associated with certain clinical manifestations such as recurrent venous thrombosis or arterial occlusions in a wide spectrum of immune disorders [6]. We analyzed the plasma concentration of two isotypes (IgG, IgM) of anticardiolipin antibodies (ACA) and lupus anticoagulant (LAC) activity in 84 patients with end-stage renal disease. They were receiving different types of renal replacement therapy and had a high frequency of thrombotic vascular complications. The prevalence of positive tests and the mean ACA concentration obtained in the plasma of renal patients were compared with those in patients with systemic lupus erythematosus (SLE) and in healthy controls. When analyzed as a whole group, renal patients maintained on dialysis (n=45: hemodialysis,n=20; peritoneal dialysis) or with a functioning kidney transplant (n=19) did not differ in mean ACA concentration and LAC activity (n=84, ACA: IgG 10±7 U/ml, IgM 2±1 U/ml, LAC ratio: 1.0±0.2) from healthy subjects (n=50, ACA: IgG 10±3, IgM 2±1 U/ml, LAC ratio: 1.0±0.1) but they had a higher incidence of raised IgG-ACA titers (renal replacement 14% vs. normal controls 4%,p<0.05). No significant correlation was found between thrombotic events and raised ACA or LAC activity in dialysis patients. In contrast, the proportion of SLE patients (n=51) with a raised concentration of ACA was significantly higher (IgG: 69%, IgM: 29%) than that among patients with renal replacement therapy (IgG: 14%, IgM: 4%) or normal controls (IgG: 4%, IgM: 2%,p<0.002). Moreover, recurrent manifestations of thrombosis in SLE were associated with very high IgG-ACA (n=11, IgG 117±91 U/ml) and LAC activity (LAC ratio: 2.4±0.7) in comparison to SLE patients without thrombotic events (n=40, ACA: IgG 23±13). The results of our investigations demonstrate that the pathogenetic role of these phospholipid antibodies in end-stage renal disease is far from established.     

Thymocytotoxic antibodies in patients with autoimmune hemolytic anemia systemic lupus erythematosus and lymphoproliferative diseases

Summary Cytotoxic antibodies against human thymocytes have been found in the sera from patients with AIHA (52%), active SLE (80%) or lymphoproliferative diseases (74%). Only 42% of thymocytotoxic sera were also reactive against mature T lymphocytes, whereas 70% of the sera containing antibodies against T lymphocytes were also thymocytotoxic. The thymocytotoxic antibodies could play a possible pathogenic role in the development of immunologic abnormalities in these diseases including autoantibody formation through loss of thymus dependent lymphocytes, as in the NZB animal model.Supported by grant from the Ministry of Education     

Association of IgA anti-dsDNA antibodies with vasculitis and disease activity in systemic lupus erythematosus

Previously it has been suggested that the presence of antibodies against dsDNA of the IgA class may define a subset of systemic lupus erythematosus (SLE) patients suffering from nephritis and arthritis. Therefore, these autoantibodies were measured in sera of 352 patients with SLE, 81 blood donors, and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgA anti-dsDNA antibodies were found in 19.9% of the sera from patients with SLE, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 36 laboratory parameters was calculated. IgA anti-dsDNA antibodies were found to be associated with parameters of disease activity such as elevated erythrocyte sedimentation rate and consumption of complement component C3, and the clinical parameters vasculitis, acral necrosis and erythema, but not with nephritis and arthritis. Therefore, IgA anti-dsDNA antibodies define a subset of SLE patients, and monitoring of IgA anti-dsDNA antibodies may be helpful as a prognostic parameter in patients with SLE. Received: 12 April 1998 / Accepted: 24 April 1998     

Clinical and serological correlates of antinucleosome antibodies in South Africans with systemic lupus erythematosus

Antinucleosome antibodies (AnuA) are increasingly recognized as an important biomarker in the diagnosis and subset stratification of patients with systemic lupus erythematosus (SLE). The aim of the study was to determine the sensitivity, specificity, and clinico-serological correlates of AnuA in black South Africans with SLE. We performed a cross-sectional study of 86 SLE patients attending a tertiary center and 87 control subjects. AnuA were tested using a second-generation enzyme-linked immunosorbent assay (ELISA). The sensitivity, specificity, positive predictive value, and negative predictive value of AnuA were 45.3, 94.3, 88.6, and 63.6%, respectively. The presence of AnuA were strongly associated with the co-presence of anti-dsDNA antibodies (OR = 3.4, p < 0.0005) and antihistone antibodies (OR = 15.7, p < 0.00001). Patients who were seropositive for AnuA were more likely to have skin involvement (discoid lupus and/or malar rash) and had higher SLE disease activity index (SLEDAI) scores and Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage scores (p < 0.05). IgG anticardiolipin antibody (aCL) levels showed a significant correlation with AnuA ratios (p < 0.01). Our findings provide further evidence that AnuA are a sensitive and specific diagnostic biomarker in SLE. Moreover, our finding that the presence of AnuA, but not anti-dsDNA antibodies, are associated with worse SLICC/ACR damage scores suggest that AnuA may have a role in predicting disease outcome. The correlation between IgG aCL and AnuA is a novel finding that merits further studies to determine possible common peptide specificities of the antibodies.     

Ocular manifestations in Egyptian systemic lupus erythematosus patients and their relation with disease activity and anti-phospholipid antibodies

Aim of the work

To identify the ocular manifestations in Egyptian SLE patients and its relation with disease activity and antiphospholipid (aPL) antibodies.

Thyroid disorders in Chinese patients with systemic lupus erythematosus

Summary To clarify the prevalence of thyroid disorders in Chinese patients with systemic lupus erythematosus (SLE), 45 SLE patients not receiving corticosteroid therapy for at least 6 months were selected over a period of 1 year. They were investigated by utilizing thyroid ultrasonography and by determinations of thyroid antibodies and thyroid function. Of these patients, 24 (53.3%) showed abnormal sonographic findings. Thyroid antibodies (microsomal and/or thyroglobulin) were detected in 21 patients (46.7%), but a low index of thyrotropinbinding inhibitory immunoglobulin (TBII) was found in only one euthyroid patient with a normal echogram. Ten patients (22.2%) had abnormal thyroid function. The mean disease duration was longer in patients with thyroid anomalies (p<0.05). Hashimoto's thyroiditis was found in four patients (8.8%), two of whom had hypothyroidism. We concluded that thyroid anomalies are frequently found in patients with SLE in the area of this study. The possibility of the coexistence of thyroid disorders in systemic lupus erythematosus should be carefully considered throught the course of patients' follow-up, especially in those with a long disease duration.     

Anti-nucleosome antibodies in systemic lupus erythematosus patients: Relation to anti-double stranded deoxyribonucleic acid and disease activity

Aim of the work

To measure the level of anti-nucleosome (anti-NCS) antibodies in systemic lupus erythematosus (SLE) patients and to evaluate their relation with anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies and SLE disease activity.

Human parvovirus B19 infection mimicking systemic lupus erythematosus

Abstract

Although several recent reports have discussed the similarities between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematosus (SLE), the relationship between these conditions has not been established owing to the small number of patients investigated. In 1998–1999, an outbreak of Erythema infectiosum occurred close to our hospital, enabling us to investigate the clinical, hematological, and serological findings, including serum complement and antinuclear antibodies (ANA), in 22 patients with acute HPV-B19 infection. The principal symptoms included rash (86.3%), edema (59%), arthralgia (45.4%) and fever (31.8%). Lymphadenopathy was seen in three of the 22 cases. The laboratory findings showed high incidences of leukopenia (50%), hypocomplementemia (95%), and ANA (64.7%). At the time of disease onset, patients with acute HPV-B19 infection presented with features which were similar to those of SLE. The possibility of HPV-B19 infection should therefore be considered in patients presenting with SLE-like features.     

Human parvovirus B19 infection mimicking systemic lupus erythematosus

Although several recent reports have discussed the similarities between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematosus (SLE), the relationship between these conditions has not been established owing to the small number of patients investigated. In 1998–1999, an outbreak of Erythema infectiosum occurred close to our hospital, enabling us to investigate the clinical, hematological, and serological findings, including serum complement and antinuclear antibodies (ANA), in 22 patients with acute HPV-B19 infection. The principal symptoms included rash (86.3%), edema (59%), arthralgia (45.4%) and fever (31.8%). Lymphadenopathy was seen in three of the 22 cases. The laboratory findings showed high incidences of leukopenia (50%), hypocomplementemia (95%), and ANA (64.7%). At the time of disease onset, patients with acute HPV-B19 infection presented with features which were similar to those of SLE. The possibility of HPV-B19 infection should therefore be considered in patients presenting with SLE-like features. Received: January 18, 2001 / Accepted: April 19, 2001     

Anti-Ro/SSA antibodies are associated with severe mitral valve regurgitation in patients with systemic lupus erythematosus

Objective: To assess whether anti-Ro/SSA antibodies are associated with cardiac valve disease in lupus.

Methods: A single-center, medical chart review was performed. Lupus patients were divided according to its anti-Ro/SSA status and subgroups were compared for valvular abnormalities and other characteristics. Dependence of anti-Ro/SSA reactivity to anti-Ro52/TRIM21 antibodies was also evaluated.

Results: Eighty-nine lupus patients were analyzed. The most common valvular abnormalities were tricuspid (60%), mitral (41%) and pulmonary (14%) regurgitation. Thirty-six patients were positive and 53 negative for anti-Ro/SSA antibodies. In patients positive to anti-Ro/SSA, a difference was noted for anti-dsDNA (67 versus 45%; p?=?0.04) and anti-La/SSB (19 versus 2%; p?=?0.004) antibodies. An association between anti-Ro/SSA antibodies and severe mitral regurgitation was observed; indeed, 4/15 patients with anti-Ro/SSA and mitral regurgitation had severe forms of valvulopathy as compared to only 1/22 patients with mitral regurgitation but negative to such antibody (27 versus 5%; p?=?0.02). Anti-Ro/SSA antibodies significantly elevated the risk of severe mitral regurgitation (OR?=?5). Anti-Ro52/TRIM21 levels (103?±?29 versus 42?±?43?U/mL; p?=?0.03) and anti-Ro52/TRIM21:?anti-Ro/SSA ratios (0.88?±?0.02 versus 0.35?±?0.37; p?=?0.03) were higher in patients with mitral valve regurgitation than in those with no valvulopathy.

Conclusion: Anti-Ro/SSA antibodies, mainly against Ro52/TRIM21 antigens, may be pathologically involved in lupus-associated mitral valve regurgitation.