ABSTRACT
BACKGROUND: Anticardiolipin antibodies (aCL) have been found to be elevated in patients with coronary artery disease (CAD) and have been associated with an adverse outcome owing to their prothrombotic activity. The aim of this study was to investigate the effect of aspirin treatment on aCL levels in patients with chronic CAD. MATERIALS AND METHODS: Forty patients with chronic CAD scheduled for elective coronary artery bypass graft surgery (CABG) and 40 healthy controls participated in the study. Patients were treated with 300 mg of aspirin once daily (o.d.) for the first 12 days and placebo for the following 12 days before CABG in a double-blind, cross-over trial. Immunoglobulin (Ig) G-, IgM-, IgA-aCL and C-reactive protein (CRP) levels were measured in the controls and at the end of each treatment period in the patients with CAD. RESULTS: The IgA- and IgG-aCL levels were greater in patients with CAD than in the controls. Compared with the placebo, IgA, IgG subtypes and CRP levels were reduced after aspirin treatment (P = 0.001, P = 0.02, P = 0.04, respectively). The percentage reduction of IgA- and IgG-aCL was related to the percentage reduction of CRP after aspirin (P < 0.05). CONCLUSION: Aspirin treatment with 300 mg o.d. reduced the serum levels of IgA and IgG subtypes in patients with chronic CAD in parallel to a reduction in CRP. These findings offer an additional pathophysiological mechanism of the beneficial effects of aspirin in patients with chronic CAD.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antibodies, Anticardiolipin/drug effects , Aspirin/therapeutic use , Coronary Artery Disease/drug therapy , Antibodies, Anticardiolipin/blood , Case-Control Studies , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Middle AgedABSTRACT
OBJECTIVE: To determine the prevalence and clinical correlates of anti-phospholipid antibodies (aPL), including anti-cardiolipin antibodies (aCL), lupus anti-coagulant (LA), anti-beta2-glycoprotein 1 (abeta2GP1), and anti-prothrombin (aPT) antibodies, in Black South African patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study of 100 SLE patients in whom clinical characteristics, including features of the anti-phospholipid syndrome (APS), disease activity, and damage were documented, and sera tested for aCL, abeta2GP, and aPT of all isotypes, and LA. RESULTS: Positive aCL, abeta2GPI, aPT, and LA were found in 53, 84, 20, and 2 patients, respectively. Immunoglobulin (Ig)A aCL and IgG abeta2GPI were the commonest aCL (49.1%) and abeta2GPI (47%) isotypes, respectively. IgA abeta2GPI were associated with both a history of thrombosis alone (p<0.05) and a history of any clinical feature, thrombosis, and/or spontaneous abortion of the APS (p<0.05); IgA aCL were associated with a history of any clinical APS event (p<0.05); and abeta2GPI of any isotype were associated with a history of arthritis (p<0.001). CONCLUSION: Our findings provide further evidence that screening for abeta2GPI and IgA aCL isotypes may improve the risk assessment for APS in SLE patients of African extraction. Further prospective studies are warranted to determine the clinical utility of these tests and to elucidate the genetic basis for the increased IgA aPL response in SLE patients of African extraction.
Subject(s)
Antibodies, Antiphospholipid/blood , Lupus Erythematosus, Systemic/immunology , Antibodies, Antinuclear/blood , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/immunology , Female , Humans , Immunoglobulin A/blood , Immunoglobulin M/blood , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/epidemiology , Prevalence , Prothrombin/immunology , South AfricaABSTRACT
The objectives of this study were to estimate the prevalence of IgA anticardiolipin antibodies (aCL) and anti-beta(2)-glycoprotein 1 antibodies (abeta(2)-GP1) in a large number of patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (PAPS) and to examine possible associations between the clinical manifestations of the APS and the levels of IgA aCL and abeta(2)-GP1. We also assessed the operative characteristics of IgA aCL and abeta(2)-GP1. We retrospectively studied 130 patients with SLE and 35 patients with PAPS. In all patients we measured IgG, IgM, and IgA aCL and abeta(2)-GP1 and recorded any of the clinical manifestations of the APS. IgA aCL were positive in 8.5% of patients with SLE and in 40% of patients with PAPS. Positive IgA abeta(2)-GP1 were found in 17.7% of patients with SLE and in 25.7% of patients with PAPS. IgA aCL were associated with a history of venous thrombosis, thrombocytopenia, and recurrent fetal loss. In contrast, we could not establish significant associations between IgA abeta(2)-GP1 and any of the clinical manifestations of the APS. Measurement of the IgA in addition to IgG and IgM aCL hardly changed the operative characteristics of aCL testing, while measurement of the IgA in addition to IgG and IgM abeta(2)-GP1 increased sensitivity but with a greater loss in specificity. IgA aCL is significantly associated with more than one of the clinical manifestations of the APS in contrast to the IgA abeta(2)-GP1. Routine measurement of the IgA isotype of both aCL and abeta(2)-GP1 does not improve the operative characteristics of aCL and abeta(2)-GP1 and therefore is not recommended at present.
Subject(s)
Antibodies, Anticardiolipin/blood , Antiphospholipid Syndrome/immunology , Autoantibodies/blood , Glycoproteins/immunology , Immunoglobulin A/analysis , Lupus Erythematosus, Systemic/immunology , Adult , Aged , Aged, 80 and over , Enzyme-Linked Immunosorbent Assay , Ethnicity , Female , Humans , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , beta 2-Glycoprotein IABSTRACT
OBJECTIVES: To investigate IgG, IgM, and IgA, antiphospholipid antibodies (aPL), against cardiolipin (aCL), beta(2)-glycoprotein I (anti-beta(2)GPI), and prothrombin (anti-PT), in black South African patients with infectious disease. Unlike patients with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS), raised levels of aPL in infectious diseases are not usually associated with thrombotic complications. PATIENTS AND METHODS: Serum samples from 272 patients with a variety of infectious diseases (100 HIV positive, 112 leprosy, 25 syphilis, 25 malaria, and 10 HCV patients) were studied and compared with autoantibody levels in 100 normal controls. All three aPL were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. RESULTS: Raised levels of all three aPL were found in all patient groups studied: aCL in 7%, anti-beta(2)GPI in 6%, and aPT in 43% of 100 HIV patients, in 29%, 89%, and 21% of 112 patients with leprosy, in 8%, 8%, and 28% of 25 patients with syphilis, in 12%, 8%, and 28% of 25 patients with malaria, and in 20%, 30%, and 30% of 10 HCV patients studied, respectively. CONCLUSIONS: The prevalence of aCL and anti-beta(2)GPI in black South African HIV positive patients, or those with syphilis, malaria, or hepatitis C virus is lower than reported for mixed race or white populations. aPT were the most prevalent aPL detected in these patient groups, except in patients with leprosy, for whom anti-beta(2)GPI was the most prevalent, and where the spectrum of aPL was similar to that seen in patients with SLE and APS.
Subject(s)
Autoantibodies/blood , Communicable Diseases/ethnology , Communicable Diseases/immunology , Glycoproteins/immunology , Prothrombin/immunology , Adult , Aged , Antibodies, Anticardiolipin/blood , Antibodies, Antiphospholipid/blood , Antiphospholipid Syndrome/immunology , Black People , Case-Control Studies , Female , HIV Infections/immunology , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Leprosy/immunology , Malaria/immunology , Male , Middle Aged , Prevalence , South Africa , Syphilis/immunology , beta 2-Glycoprotein IABSTRACT
OBJECTIVES: To investigate IgG, IgM, and IgA, antiphospholipid antibodies (aPL), against cardiolipin (aCL), beta(2)-glycoprotein I (anti-beta(2)GPI), and prothrombin (anti-PT), in black South African patients with infectious disease. Unlike patients with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS), raised levels of aPL in infectious diseases are not usually associated with thrombotic complications. PATIENTS AND METHODS: Serum samples from 272 patients with a variety of infectious diseases (100 HIV positive, 112 leprosy, 25 syphilis, 25 malaria, and 10 HCV patients) were studied and compared with autoantibody levels in 100 normal controls. All three aPL were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. RESULTS: Raised levels of all three aPL were found in all patient groups studied: aCL in 7%, anti-beta(2)GPI in 6%, and aPT in 43% of 100 HIV patients, in 29%, 89%, and 21% of 112 patients with leprosy, in 8%, 8%, and 28% of 25 patients with syphilis, in 12%, 8%, and 28% of 25 patients with malaria, and in 20%, 30%, and 30% of 10 HCV patients studied, respectively. CONCLUSIONS: The prevalence of aCL and anti-beta(2)GPI in black South African HIV positive patients, or those with syphilis, malaria, or hepatitis C virus is lower than reported for mixed race or white populations. aPT were the most prevalent aPL detected in these patient groups, except in patients with leprosy, for whom anti-beta(2)GPI was the most prevalent, and where the spectrum of aPL was similar to that seen in patients with SLE and APS.
Subject(s)
Male , Female , Humans , Adult , Middle Aged , Aged , Antibodies, Anticardiolipin , Antibodies, Antiphospholipid , Autoantibodies , Communicable Diseases , Case-Control Studies , Glycoproteins , Leprosy , Immunoglobulin A , Immunoglobulin G , Immunoglobulin M , HIV Infections , Malaria , Prevalence , Prothrombin , Syphilis , Antiphospholipid Syndrome , South AfricaABSTRACT
OBJECTIVES: To determine the immunoglobulin G (IgG) subclass distribution of anticardiolipin (aCL) and anti-beta(2)-glycoprotein 1 (beta(2)-GP1) antibodies (abeta(2)-GP1), and to examine possible associations between the different abeta(2)-GP1 and aCL subclasses and the main clinical manifestations of the antiphospholipid syndrome (APS). METHODS: We studied 130 patients with systemic lupus erythematosus and 35 patients with primary APS. We used enzyme-linked immunosorbent assays to measure IgG aCL and abeta(2)-GP1 and to determine the IgG subclass distribution of these two autoantibodies. RESULTS: When the number of patients positive for each subclass was examined, IgG(3) and IgG(2) aCL were more frequent (63.5 and 54.1% of patients were positive for the two subclasses, respectively), while for abeta(2)-GP1 IgG(2) was the most prevalent subclass (81.8% of patients were positive). IgG(2) aCL was significantly associated with arterial thrombosis (P=0.023) and fetal loss (P=0.013), and IgG(3) aCL was significantly associated with arterial thrombosis (P=0.0003) and fetal loss (P=0.045). IgG(2) abeta(2)-GP1 was associated with venous thrombosis (P=0.012) and IgG(3) abeta(2)-GP1 was associated with venous thrombosis (P=0.036) and fetal loss (P=0.024). CONCLUSIONS: The IgG(2) predominance of abeta(2)-GP1 suggests that the antibody response against beta(2)-GP1 may be T-cell-independent. As IgG(2) and IgG(3) differ in their effector functions, their association with the same clinical manifestations (i.e. thrombosis and fetal loss) suggests that more than one mechanism may be involved in the pathogenesis of thrombosis and fetal loss in APS.
Subject(s)
Antibodies, Anticardiolipin/classification , Antiphospholipid Syndrome/immunology , Glycoproteins/immunology , Immunoglobulin G/classification , Lupus Erythematosus, Systemic/immunology , Antibodies, Anticardiolipin/analysis , Antiphospholipid Syndrome/pathology , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G/analysis , Lupus Erythematosus, Systemic/pathology , Reference Values , Retrospective Studies , beta 2-Glycoprotein IABSTRACT
OBJECTIVE: To investigate whether anticardiolipin (aCL) and anti-beta(2)-glycoprotein I (anti-beta(2)GPI) antibodies are associated with lupus nephritis (group II patients), and whether there are differences in the prevalence of these two autoantibodies between group II patients and patients with non-nephritis SLE (group I) and primary antiphospholipid syndrome (PAPS) patients (group III). METHODS: IgG and IgM aCL were measured in 31 patients and anti-beta(2)GPI in 30 patients with systemic lupus erythematosus (SLE) nephritis and 25 without SLE nephritis and in 36 PAPS patients by validated enzyme immunoassays. Relationships of anti-double-stranded DNA (anti-dsDNA) antibodies and antibodies to the collagenous region of C1q (anti-C1q) with SLE nephritis were also examined. RESULTS: The prevalence and levels were higher for aCL, but not for anti-beta(2)GPI, antibodies in group II than in group I patients. Absolute values of aCL and anti-beta(2)GPI in all three patient groups correlated with each other. The prevalences of aCL, anti-dsDNA and anti-C1q antibodies were significantly higher in group II than in group I and group III patients. CONCLUSION: The observations in this paper suggest that raised levels of aCL antibodies are associated with lupus nephritis. We were not able to demonstrate an association between anti-beta(2)GPI antibodies and kidney disease either in patients with lupus or in patients with primary antiphospholipid syndrome. In SLE, we demonstrated that the presence of anticardiolipin antibodies in conjunction with elevated levels of anti-dsDNA and anti-C1q antibodies is highly specific for glomerulonephritis in patients with lupus.
Subject(s)
Anticoagulants/immunology , Autoantibodies/blood , Cardiolipins/immunology , Glycoproteins/immunology , Lupus Nephritis/blood , Lupus Nephritis/immunology , Adult , Aged , DNA/immunology , Female , Humans , Male , Middle Aged , Prevalence , beta 2-Glycoprotein IABSTRACT
OBJECTIVE: To assess the phospholipid specificity and immunoglobulin isotype of antiphospholipid (aPL) antibodies in patients with acute parvovirus B19 infection. METHODS: Specificity of aPL and isotype distribution in the negatively charged phospholipids, cardiolipin and phosphatidyl serine, and in the neutral phospholipid, phosphatidyl ethanolamine, were measured in the sera of patients with acute parvovirus B19 infections (n = 12), in those with other acute viral infections (n = 10), and in those with syphilis (n = 15) by enzyme-linked immunosorbent assays. The dependence of anticardiolipin (aCL) binding on the presence of beta 2-glycoprotein I (beta 2-GPI) as a binding cofactor was assessed in these same groups, and was compared with sera from systemic lupus erythematosus (SLE) patients (n = 11) with raised aCL antibody reactivity. RESULTS: Antibodies against any of the 3 phospholipids were found in all 3 groups of patients with infections (B19 in 11 of 12 patients, other viral infections in 8 of 10 patients, and syphilis in 14 of 15 patients). B19 patients' sera contained predominantly IgG antibodies against the negatively charged phospholipids, cardiolipin and phosphatidyl serine, and differed in their specificity and isotype distribution from those found in the other 2 patient groups. B19-associated aCL increased their binding to antigen in the presence of beta 2-GPI as a binding cofactor, similar to aCL found in SLE patients, but unlike antibodies from patients with other viral infections or from those with syphilis. CONCLUSION: The results show the remarkable similarity in specificity of aPL antibodies between B19-infected patients and SLE patients, and raise the question of whether parvovirus infection may be a trigger for the development of aPL antibodies in autoimmune diseases.
Subject(s)
Antibodies, Antiphospholipid/immunology , Antibody Specificity , Lupus Erythematosus, Systemic/immunology , Parvoviridae Infections/immunology , Parvovirus B19, Human/isolation & purification , Antibodies, Anticardiolipin/immunology , Autoantibodies , Binding Sites, Antibody/immunology , Glycoproteins/immunology , Humans , Immunoglobulin Isotypes , beta 2-Glycoprotein IABSTRACT
OBJECTIVE: To investigate the origins of antiphospholipid antibodies associated with thrombosis and other disorders that are found in patients with systemic lupus erythematosus and primary antiphospholipid syndrome (APS). METHODS: Characterization, idiotypic study, and nucleotide sequencing of a human monoclonal antiphospholipid antibody generated from a patient with primary APS. Identification of the germline genes from which the antibody is derived. RESULTS: A human monoclonal antibody, BH1, was generated. This antibody has ligand-binding properties that closely resemble those of the serum antiphospholipid antibodies found in our patient and in other individuals with APS: it recognizes negatively charged phospholipids, and has lupus anticoagulant activity; it does not bind to neutral phospholipids, or to single-stranded or double-stranded DNA. The relevance of BH1 to the patient's serum antibodies is supported by our idiotypic studies. BH1 is encoded by a new germline VH gene, and by a lambda light chain gene that displays > 99% homology with the V lambda III.1 germline gene. CONCLUSION: Serum antiphospholipid antibodies associated with thrombosis may be encoded by either germline or only slightly mutated variable-region genes.
Subject(s)
Antibodies, Antiphospholipid/immunology , Antibodies, Monoclonal/immunology , Amino Acid Sequence , Animals , Antibodies, Antiphospholipid/genetics , Antibodies, Monoclonal/genetics , Antibody Specificity , Antiphospholipid Syndrome/genetics , Antiphospholipid Syndrome/immunology , Base Sequence , DNA/immunology , Enzyme-Linked Immunosorbent Assay , Gene Expression/immunology , Genes, Immunoglobulin/genetics , Genes, Immunoglobulin/immunology , Germ-Line Mutation/immunology , Humans , Immunoglobulin Idiotypes/immunology , Mice , Molecular Sequence Data , Phospholipids/immunology , Phospholipids/metabolism , Protein Binding/physiologyABSTRACT
The cause of thrombosis in the antiphospholipid syndrome (APS) is unknown. There have been reports of abnormalities in the antigenic levels or activity of endothelium-derived haemostatic factors, such as tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1); however the data from these studies are conflicting. We studied plasma from nine patients with APS; seven of them had a history of thrombosis, and three had systemic lupus erythematosus (SLE). We also studied nine matched control patients who had SLE without APS, and 14 healthy individuals. We measured t-PA, von Willebrand factor (vWF), anticardiolipin antibody (ACA) and anti-endothelial cell antibody (AECA) levels by enzyme-linked immunoassay (ELISA), PAI-1 activity by a parabolic-rate chromogenic assay, and lupus anticoagulant (LA) activity by a standard mixing test. For t-PA and PAI-1, measurements were made on morning and evening plasma samples. The two groups of patients did not differ significantly with respect to age, sex, plasma lipids or anti-inflammatory drugs. Most APS patients (7/9) but none of the controls were taking warfarin. Between the APS and the control patients no significant differences were detected in t-PA, PAI-1, vWF or AECA levels. When APS patients were considered alone, vWF levels correlated positively with IgG ACA levels (r = 0.81, P < 0.01) and negatively with platelet count (r = -0.68, P < 0.05). There was no correlation between levels of ACA or LA activity and t-PA, PAI-1 or AECA. Compared with healthy volunteers, the diurnal variation of t-PA and PAI-1 was blunted in the two patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Antibodies, Antiphospholipid/blood , Antiphospholipid Syndrome/blood , Autoantibodies/blood , Plasminogen Activator Inhibitor 1/blood , Tissue Plasminogen Activator/blood , von Willebrand Factor/analysis , Adult , Antiphospholipid Syndrome/immunology , Biomarkers/blood , Female , Humans , Male , Middle Aged , Periodicity , Statistics as TopicSubject(s)
Factor V/genetics , Mutation , Thrombophlebitis/genetics , Antibodies, Antiphospholipid/analysis , Contraceptives, Oral/adverse effects , Female , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/immunology , Risk Factors , Thrombophlebitis/chemically induced , Thrombophlebitis/etiologyABSTRACT
The class and subclass distribution of an antibody response may give insight into the stimulating mechanism and likely effector functions. IgA, IgG and IgM anticardiolipin antibodies (aCL) were quantified in a consecutive series of 200 samples sent to an autoimmune serology laboratory to determine the relationships between aCL responses of each of these antibody classes and, in particular, whether there was any utility in the measurement of IgA aCL. Positive results for one of the three aCL isotypes were found in 105 samples (53%), and in 41 samples IgA aCL was detected (21%). However, amongst these unselected samples, little additional information was obtained by measurement of IgA aCL, which was found in conjunction with IgM or IgG aCL in all but five samples, and in these the isolated elevation of IgA aCL was only slight, and showed no disease specificity. The levels of each of the four IgG subclasses of aCL were measured in a subgroup of serum samples from 28 patients with autoimmune disease and from 29 patients with syphilis. Amongst the SLE patients IgG1 and IgG3 aCL were the predominant IgG subclasses, consistent with an antigen-driven, T cell-dependent antibody response. However, a subgroup of eight of the autoimmune subjects had predominant elevation of IgG2 aCL, possibly implying a role for T cell-independent antibody production to cardiolipin. Amongst the syphilis patients IgG1 and IgG3 aCL were also the predominant subclasses of aCL but IgG4 aCL were also detected in the majority of subjects, consistent with prolonged antigenic stimulation.
Subject(s)
Antibodies, Anticardiolipin/analysis , Immunoglobulin G/classification , Immunoglobulins/classification , Immunoglobulins/immunology , Lupus Erythematosus, Systemic/immunology , Antibodies, Anticardiolipin/blood , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin Isotypes/analysis , Immunoglobulin M/immunology , Longitudinal Studies , Lupus Erythematosus, Systemic/blood , Syphilis/immunologyABSTRACT
Anticardiolipin antibody (ACA) levels were determined in 17 Asian female SLE patients with autoimmune haemolytic anaemia (AIHA) and 29 Asian female SLE inpatients without AIHA (control patients). Both IgG and IgM isotypes were measured by ELISA. Elevated IgM APA titres (greater than 5 SD of normal health controls) were seen in 11 (64.7%) of 17 AIHA patients and six (20.7%) of 29 control patients (P less than 0.01). There was no significant difference in IgG ACA titres between the two groups. Thrombocytopenia was present in 11 (64.7%) of the AIHA patients and nine (31%) of the control patients (P less than 0.05). None of the control SLE patients with thrombocytopenia had raised IgM ACA levels and only one had an elevated IgG ACA titre. Autoimmune haemolytic anaemia occurring in the context of SLE frequently associated with the concomitant presence of thrombocytopenia (Evan's syndrome) and with the presence of ACA.
Subject(s)
Anemia, Hemolytic, Autoimmune/immunology , Autoantibodies/metabolism , Cardiolipins/immunology , Lupus Erythematosus, Systemic/immunology , Thrombocytopenia/immunology , Anemia, Hemolytic, Autoimmune/etiology , Chi-Square Distribution , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Lupus Erythematosus, Systemic/complications , Prospective Studies , Thrombocytopenia/etiologyABSTRACT
A monoclonal IgG anti-human IgG, 1B12, was used in a radio-ligand-binding assay to quantify IgG on erythrocytes of patients and normals. The assay detected a range of 10-700 IgG molecules. Good correlation was achieved between the number of molecules and the strength of agglutination in antiglobulin tests performed in capillary tubes. The assay was capable of detecting subagglutinating immune bound IgG on erythrocytes from patients with systemic lupus erythematosus (SLE).
Subject(s)
Erythrocytes/immunology , Immunoglobulin G/blood , Lupus Erythematosus, Systemic/immunology , Radioligand Assay , Antibodies, Anti-Idiotypic/immunology , Antibodies, Anticardiolipin/immunology , Antibodies, Monoclonal/immunology , Complement C3/analysis , Complement C4/analysis , Humans , Indicators and Reagents , Lupus Erythematosus, Systemic/bloodABSTRACT
Two-dimensional echocardiographic studies were prospectively performed in 93 patients with systemic lupus erythematosus (SLE) to discover the incidence and spectrum of cardiac abnormalities and to relate these findings to the presence of high levels of anticardiolipin antibodies. Assessment of the intracardiac anatomy was also performed in an additional 12 patients who had increased anticardiolipin antibody levels but did not have SLE. Fifty patients (54%) with SLE had cardiac abnormalities, and 43 patients (46%) had normal hearts. Three categories of cardiac abnormalities were identified--valvular lesions, ranging from vegetations to valvular thickening, were found in 28%, pericardial effusion or thickening was found in 20%, and regional or global left ventricular dysfunction was found in 5%. High levels of anticardiolipin antibodies were detected in 50 patients (54%) with SLE. Of those, only 11 (22%) had an entirely normal heart, whereas the remaining 39 (78%) had at least one cardiac abnormality (valvular lesions in 20, pericardial effusion in 15, and myocardial dysfunction in five patients). In patients with SLE, the presence of abnormal intracardiac anatomy was strongly associated with increased levels of anticardiolipin antibodies (p less than 0.0001). The overall sensitivity and specificity of high levels of anticardiolipin antibodies in the prediction of cardiac abnormalities was 78% and 74%, respectively, with a positive predictive accuracy of 78% and a negative predictive accuracy of 74%. Eight of the 12 patients (67%) who had increased anticardiolipin antibodies but whose disease did not fulfill the American Rheumatism Association classification criteria for SLE had cardiac abnormalities similar to those in patients with SLE compared with only four (33%) who had normal hearts (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Antibodies/analysis , Cardiolipins/immunology , Heart/physiopathology , Lupus Erythematosus, Systemic/physiopathology , Echocardiography , Echocardiography, Doppler , Follow-Up Studies , Heart Diseases/complications , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/immunology , Prospective StudiesABSTRACT
The binding specificities were investigated of anti-phospholipid antibodies derived from sera from 55 patients with SLE and related diseases, and from 33 patients with syphilis. Antibodies from both these groups of patients bind strongly to cardiolipin in solid-phase immunoassays, but only antiphospholipid antibodies from patients with autoimmune diseases are associated with thrombotic complications and recurrent spontaneous abortions. IgG anti-phospholipid antibodies from both groups of patients cross-reacted with a range of negatively charged phospholipids, but binding to neutral phospholipids was largely restricted to sera from patients with syphilis. A monoclonal IgM lambda anti-cardiolipin antibody, derived from a patient with autoimmunity, was used to inhibit binding of anti-phospholipid antibodies to cardiolipin and to phosphatidic acid. This antibody inhibited the binding of autoimmune sera to cardiolipin more strongly than sera from syphilis patients, but the converse pattern of inhibition of binding to phosphatidic acid was observed. The VDRL titre correlated with anti-phospholipid antibody activity in sera from syphilis patients, but not from those with autoimmunity. Lupus anti-coagulant activity correlated weakly with IgG antibody levels to each of the negatively charged phospholipids among the patients with autoimmunity. Lupus anticoagulant activity did not correlate uniquely with any anti-phospholipid antibody specificity. These results provide further documentation of the great heterogeneity of anti-phospholipid antibodies associated with autoimmune disease and syphilis.
Subject(s)
Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Lupus Erythematosus, Systemic/immunology , Phospholipids/immunology , Syphilis/immunology , Antibody Specificity , Female , Humans , MaleABSTRACT
In order to assess lactoferrin (LF), stored in specific granules of neutrophils, as a marker of inflammation, LF was measured in plasma and serum samples of patients with active rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In active RA, the median plasma LF level (800 ng/ml) was significantly higher than in normal individuals (220 ng/ml) (P less than 0.00001) and patients with active SLE (235 ng/ml) (P less than 0.00001). Median plasma elastase-proteinase inhibitor complex (EPIC) and C-reactive protein (CRP) levels were also significantly higher in patients with RA than in normal individuals (P less than 0.00001) and active SLE (P less than 0.00001 for both EPIC and CRP). Elevations of LF, EPIC and CRP in RA were independent of rheumatoid factor titres. Plasma lactoferrin in RA correlated significantly with EPIC (Rs = 0.7, P less than 0.0001), CRP (Rx = 0.72, P less than 0.0001) and absolute neutrophil counts (Rs = 0.483, P less than 0.02), but surprisingly not with the Ritchie index, with which CRP showed a weak but significant correlation (Rs = 0.27, P less than 0.05 greater than 0.025). Thus plasma LF and EPIC are markers of inflammation in RA and their levels may reflect release of mediators of inflammation into the joint space and periarticular tissue.
Subject(s)
Arthritis, Rheumatoid/blood , Lactoferrin/blood , Lactoglobulins/blood , Lupus Erythematosus, Systemic/blood , Neutrophils/enzymology , Pancreatic Elastase/metabolism , Adolescent , Adult , Arthritis, Rheumatoid/enzymology , Arthritis, Rheumatoid/pathology , Blood Sedimentation , C-Reactive Protein/analysis , Female , Humans , Leukocyte Count , Lupus Erythematosus, Systemic/enzymology , Lupus Erythematosus, Systemic/pathology , Male , Middle Aged , Pancreatic Elastase/antagonists & inhibitorsABSTRACT
PURPOSE: We recently noticed the occurrence of both livedo and elevated anticardiolipin antibody levels in a small number of patients with lupus. The purpose of our study was two-fold: (1) to investigate whether anticardiolipin antibodies were more common in lupus patients with livedo than in those without; and (2) to determine if the features of Sneddon's syndrome (livedo and cerebrovascular disease) also were found in patients with lupus. PATIENTS AND METHODS: In this case-control study of lupus patients without significant renal impairment, 29 patients with livedo reticularis (cases) were compared clinically and immunologically with 29 patients without livedo (controls). RESULTS: Both groups shared many disease characteristics and were similar in age and sex. However, they differed markedly in other respects. Elevated anticardiolipin antibody levels were significantly more common in the cases. Indeed, 81% of all cases from our study sample had elevated anticardiolipin levels. A history of thrombosis and thrombocytopenia--clinical associates of the anticardiolipin antibody--was also significantly more common in cases than in controls. The relative odds of livedo reticularis were 23-fold greater in those with elevated anticardiolipin levels than in those without these antibodies. The estimated proportion of livedo-positive patients with elevated anticardiolipin antibodies in a general lupus population without significant renal impairment was 0.77. CONCLUSION: The association between livedo reticularis and cerebrovascular disease, originally described by Sneddon in otherwise healthy individuals, also applies to lupus patients. The presence of elevated anticardiolipin antibody levels in 10 of 11 such patients suggests that the anticardiolipin antibody may be of pathogenetic importance in the manifestations of Sneddon's syndrome in lupus and also possibly in the idiopathic form of this disease.