Comparison of autoantibody specificities between traditional and bead-based assays in a large, diverse collection of patients with systemic lupus erythematosus and family members.

OBJECTIVE: Replacement of standard immunofluorescence methods with bead-based assays for antinuclear antibody (ANA) testing is a new clinical option. The aim of this study was to evaluate a large, multiethnic cohort of patients with systemic lupus erythematosus (SLE), blood relatives, and unaffected control individuals for familial aggregation and subset clustering of autoantibodies by high-throughput serum screening technology and traditional methods. METHODS: Serum samples (1,540 SLE patients, 1,154 unaffected relatives, and 906 healthy, population-based controls) were analyzed for SLE autoantibodies using a bead-based assay, indirect immunofluorescence (IIF), and immunodiffusion. Autoantibody prevalence, sensitivity for disease detection, clustering of autoantibodies, and associations between newer methods and standard immunodiffusion results were evaluated. RESULTS: The frequencies of ANAs in the sera from African American, Hispanic, and European American patients with SLE were 89%, 73%, and 67%, respectively, by BioPlex 2200 bead-based assay and 94%, 84%, and 86%, respectively, by IIF. When comparing the serum prevalence of 60-kd Ro, La, Sm, nuclear RNP A, and ribosomal P autoantibodies across assays, the sensitivity of detection ranged from 0.92 to 0.83 and the specificity ranged from 0.90 to 0.79. Autoantibody cluster analysis showed associations of autoantibody specificities in 3 subsets: 1) 60 kd Ro, 52-kd Ro, and La, 2) spliceosomal proteins, and 3) double-stranded DNA (dsDNA), chromatin, and ribosomal P. Familial aggregation of Sm/RNP, ribosomal P, and 60-kd Ro in SLE patient sibling pairs was observed (P ≤ 0.004). Simplex-pedigree SLE patients had a greater prevalence of dsDNA (P = 0.0003) and chromatin (P = 0.005) autoantibodies compared to patients with a multiplex SLE pedigree. CONCLUSION: The frequencies of ANAs detected by a bead-based assay are lower than those detected by IIF in European American patients with SLE. These assays have strong positive predictive values across ethnic groups, provide useful information for clinical care, and provide unique insights into familial aggregation and autoantibody clustering.

Effects of autoimmune antibodies anti-lipoprotein lipase, anti-low density lipoprotein, and anti-oxidized low density lipoprotein on lipid metabolism and atherosclerosis in systemic lupus erythematosus.

INTRODUCTION: Premature development of atherosclerosis in systemic lupus erythematosus has been widely reported. Anti-lipoprotein lipase antibody may be one cause contributing to this disorder. OBJECTIVE: To assess the extent of coronary risk due to autoimmune antibodies in terms of carotid plaque in lupus patients. PATIENTS AND METHODS: We compared 114 documented lupus patients with 111 normal controls matched for sex and age. Anti-lipoprotein lipase (A-LPL), anti-oxidized low density lipoprotein (A-OXLDL), and anti-low density lipoprotein (A-LDL) were measured by enzme-linked immunoabsorbent assay. Low density lipoprotein-triglyceride (LDL-Trig) and high density lipoprotein-triglyceride (HDL-Trig) were also measured. Plaque was measured by bilateral carotid ultrasound. RESULTS: 45.6% of patients tested positive for A-LPL, and 34.4% for A-OXLDL. 44% of normal controls tested positive for A-LPL, and 20% for A-OXLDL. Risk increased sharply in subgroups with increased antibody levels. Patients with A-LPL and A-OXLDL > 0.40 (n = 12) showed coronary risk correlations of: A-LPL x LDL-Trig = 0.7008, P = 0.0111; bilateral ultrasound vs total cholesterol = 0.62205, P = 0.0308; LDL-Trig vs myocardial infarction (MI) = 0.76562, P = 0.0037; total triglycerides vs MI = 0.78191, P = 0.0027); LDL-Trig/LDL-cholesterol vs MI = 0.80493, P = 0.0016; A-OXLDL vs USBL = 0.71930, P = 0.0084. Correlations of SLEDAI with risk variables were highly significant only in subgroups of elevated antibody levels (SLEDAI x A-OXLDL = 0.70366, P = 0.0107). CONCLUSION: A-LPL initiates the development of LDL mutations, followed by antibody production, plaque formation and coronary risk in some SLE patients.

Efeitos de autoanticorpos antilipoproteína lipase, antilipoproteína de baixa densidade e antilipoproteína de baixa densidade oxidada sobre o metabolismo lipídico e aterosclerose no lúpus eritematoso sistêmico / Effects of autoimmune antibodies anti-lipoprotein lipase, anti-low density lipoprotein, and anti-oxidized low density lipoprotein on lipid metabolism and atherosclerosis in systemic lupus erythematosus

INTRODUÇÃO: O desenvolvimento prematuro de aterosclerose em lúpus eritematoso sistêmico tem sido amplamente divulgado. Anticorpo antilipoproteína lipase pode ser uma das causas que contribuem para esta doença. OBJETIVO: Avaliar o grau de risco coronariano devido a autoanticorpos em termos de placa carotídea em pacientes com lúpus. PACIENTES E MÉTODOS: Comparamos 114 pacientes com lúpus documentado e 111 controles normais pareados por sexo e idade. Antilipoproteína lipase (A-LPL), antilipoproteínas de baixa densidade oxidada (A-OXLDL), e antilipoproteínas de baixa densidade (A-LDL) foram medidos pelo teste imunoenzimático - ELISA. LDL-triglicéride (LDL-Trig) e HDL-Trig também foram dosados. A placa foi medida por ultrassom bilateral de carótida. RESULTADOS: 45,6 por cento dos pacientes foram positivos para A-LDL e 34,4 por cento para A-OXLDL; 44 por cento dos controles foram positivos para A-LDL e 20 por cento para A-OXLDL. O risco aumentou acentuadamente nos subgrupos com níveis elevados de anticorpos. Pacientes com A-LDL e A-OXLDL > 0,40 (n = 12) mostraram correlações de risco coronariano de: ALDL vs LDL-Trig = 0,7008, P = 0,0111; ultrassom bilateral vs colesterol = 0,62205, P = 0,0308; LDL-Trig vs infarto do miocárdio (IM) = 0,76562, P =0,0037; triglicerídeos totais vs IM = 0,78191, P = 0.0027); LDL-Trig/LDL-colesterol vs IM = 0,80493, P = 0,0016; A-OXLDL vs USBL = 0,71930, P = 0,0084. Correlações do SLEDAI com as variáveis de risco foram altamente significativas somente nos subgrupos com níveis elevados de anticorpos (SLEDAI x A-OXLDL = 0,70366, P = 0,0107). CONCLUSÃO: A-LPL inicia o desenvolvimento de mutações de LDL, seguido pela produção de anticorpos, formação da placa e do risco coronariano em alguns pacientes com lúpus erimatoso sistêmico (LES).

INTRODUCTION: Premature development of atherosclerosis in systemic lupus erythematosus has been widely reported. Anti-lipoprotein lipase antibody may be one cause contributing to this disorder. OBJECTIVE: To assess the extent of coronary risk due to autoimmune antibodies in terms of carotid plaque in lupus patients. PATIENTS AND METHODS: We compared 114 documented lupus patients with 111 normal controls matched for sex and age. Anti-lipoprotein lipase (A-LPL), anti-oxidized low density lipoprotein (A-OXLDL), and anti-low density lipoprotein (A-LDL) were measured by enzme-linked immunoabsorbent assay. Low density lipoprotein-triglyceride (LDL-Trig) and high density lipoprotein-triglyceride (HDL-Trig) were also measured. Plaque was measured by bilateral carotid ultrasound. RESULTS: 45.6 percent of patients tested positive for A-LPL, and 34.4 percent for A-OXLDL. 44 percent of normal controls tested positive for A-LPL, and 20 percent for A-OXLDL. Risk increased sharply in subgroups with increased antibody levels. Patients with A-LPL and A-OXLDL > 0.40 (n = 12) showed coronary risk correlations of: A-LPL x LDL-Trig = 0.7008, P = 0.0111; bilateral ultrasound vs total cholesterol = 0.62205, P = 0.0308; LDL-Trig vs myocardial infarction (MI) = 0.76562, P = 0.0037; total triglycerides vs MI = 0.78191, P = 0.0027); LDL-Trig/LDL-cholesterol vs MI = 0.80493, P = 0.0016; A-OXLDL vs USBL = 0.71930, P = 0.0084. Correlations of SLEDAI with risk variables were highly significant only in subgroups of elevated antibody levels (SLEDAI x A-OXLDL = 0.70366, P = 0.0107). CONCLUSION: A-LPL initiates the development of LDL mutations, followed by antibody production, plaque formation and coronary risk in some SLE patients.

Abnormal olfactory function demonstrated by manganese-enhanced MRI in mice with experimental neuropsychiatric lupus.

Mice with experimental neuropsychiatric lupus (NPSLE), induced by anti-ribosomal-P antibodies, developed depression-like behavior and a diminished sense of smell. Manganese-enhanced MRI (MEMRI) allows in vivo mapping of functional neuronal connections in the brain, including the olfactory tract. The aim of this study was to analyze and describe, via the MEMRI technique, the effect of the anti-ribosomal-P injection on the olfactory pathway. Twenty mice were intra-cerebra-ventricular injected to the right hemisphere: 10 with human anti-ribosomal-P antibodies and 10 with human IgG antibodies (control). Depression was addressed by forced swimming test and smell function was evaluated by smelling different concentrations of menthol. MEMRI was used to investigate the olfactory system in these mice. Passive transfer of anti-ribosomal-P to mice resulted in a depression-like behavior, accompanied with a significant deficit in olfactory function. MEMRI of these mice demonstrated significant reduction (P < 0.001) in normalized manganese enhancement ratios of olfactory structures, compared to control mice. We concluded that an impaired olfactory neuronal function in mice with experimental depression, mediated by passive transfer of human-anti-ribosomal-P, can be demonstrated by MEMRI.

Early targets of nuclear RNP humoral autoimmunity in human systemic lupus erythematosus.

OBJECTIVE: The U1 small nuclear RNPs are common targets of autoantibodies in lupus and other autoimmune diseases. However, the etiology and progression of autoimmune responses directed against these antigens are not well understood. The aim of this study was to use a unique collection of serial samples obtained from patients before and after the development of nuclear RNP (nRNP) antibodies to investigate early humoral events in the development of anti-nRNP autoimmunity. METHODS: Lupus patients with sera available from both before and after the development of nRNP antibody precipitin were identified from the Oklahoma Clinical Immunology Serum Repository. Antibodies in the serial samples were analyzed by enzyme-linked immunosorbent assay, Western blotting, solid-phase epitope mapping, and competition assays. RESULTS: The first-detected nRNP antibodies targeted 6 common initial epitopes in nRNP A, 2 in nRNP C, and 9 in nRNP 70K. The initial epitopes of nRNP A and nRNP C were significantly enriched for proline and shared up to 95% sequence homology. The initial nRNP 70K humoral epitopes differed from those of nRNP A and nRNP C. The initial antibodies to nRNP A and nRNP C were cross-reactive with the SmB'-derived peptide PPPGMRPP. Antibody binding against all 3 nRNP subunits diversified significantly over time. CONCLUSION: Autoantibodies to nRNP A and nRNP C initially targeted restricted, proline-rich motifs. Antibody binding subsequently spread to other epitopes. The similarity and cross-reactivity between the initial targets of nRNP and Sm autoantibodies identifies a likely commonality in cause and a focal point for intermolecular epitope spreading.

Anti-P ribosomal antibodies induce defect in smell capability in a model of CNS -SLE (depression).

UNLABELLED: Systemic lupus erythematosus (SLE) is an autoimmune disease associated with more than 100 different autoantibodies, some of which may be associated with specific neuropsychiatric (NPSLE) manifestations. Injection of anti-P ribosomal antibodies (anti-P) directly to the brain ventricles of mice induces depression manifested by increased immobility time in the forced swim test (FST). METHODS: Mice were injected intracerebroventricularily (ICV) with affinity-purified human anti-P antibodies or normal commercial IgG as control. Mice were examined for depression by the forced swimming test (FST) and for olfactory function by the smell threshold test. Treatments included the antidepressant drug fluoxetine or aroma therapy by exposure to lemon or cinnamon odor. RESULTS: Mice injected with anti-P developed depression-like behavior, which improved significantly upon treatment with fluoxetine. Depressed mice had a significant deficit in olfactory function which was not reversed by fluoxetine. Exposure of anti-P-injected mice to lemon odor was associated with some improvement of the immobility time, a measure of depression. CONCLUSIONS: ICV injection of anti-P induces both depression-like behavior and impaired olfactory function in mice. Fluoxetine and possibly lemon odor exposure improve depressive behavior in these mice.

A possible link between infection with burkholderia bacteria and systemic lupus erythematosus based on epitope mimicry.

We previously demonstrated that purified polyclonal and monoclonal anti-dsDNA antibodies bind a 15-mer peptide ASPVTARVLWKASHV in ELISA and Dot blot. This 15-mer peptide partial sequence ARVLWKASH shares similarity with burkholderia bacterial cytochrome B 561 partial sequence ARVLWRATH. In this study, we show that purified anti-dsDNA antibodies react with burkholderia fungorum bacterial cell lysates in Western blot. We used anti-dsDNA antibodies to make an anti-dsDNA antibodies affinity column and used this column to purify the burkholderia fungorum bacterial protein. Purified anti-dsDNA antibodies bind specifically to purified bacterial antigen and purified bacterial antigen blocked the anti-dsDNA antibodies binding to dsDNA antigen. Sera with anti-dsDNA antibodies bind specifically to purified bacterial antigen. We obtained protein partial sequence of RAGTDEGFG which is shared with burkholderia bacterial transcription regulator protein sequence. Sera with anti-dsDNA antibodies bind to RAGTDEGFG peptide better than control groups. These data support our hypothesis that the origin of anti-dsDNA antibodies in SLE may be associated with burkholderia bacterial infection.

Induction of autoimmune depression in mice by anti-ribosomal P antibodies via the limbic system.

OBJECTIVE: Autoantibodies against ribosomal P proteins are linked to the neuropsychiatric manifestations of systemic lupus erythematosus (SLE). The present study was undertaken to assess how the specific brain-binding autoantibody anti-ribosomal P can induce a depression-type psychiatric disorder in mice. METHODS: Mice were injected intracerebroventricularly with affinity-purified human anti-ribosomal P antibodies or IgG as control. Pharmacologic and immunologic treatments included the antidepressant drug fluoxetine, the antipsychotic drug haloperidol, and antiidiotypic antibodies. Behavior was assessed by the forced swimming test, motor deficits by rotarod, grip strength, and staircase tests, and cognitive deficits by T-maze alternation and passive avoidance tests. RESULTS: Anti-ribosomal P antibodies induced depression-like behavior in the mice (mean +/- SEM 147.3 +/- 19.2 seconds of immobility versus 75.2 +/- 12.1 seconds of immobility in IgG-injected control mice; P < 0.005). The anti-ribosomal P antibody-induced depression-like behavior was partially blocked by a specific antiidiotypic antibody and significantly blocked by long-term treatment with fluoxetine, but not by short- or long-term treatment with haloperidol. The depressive behavior was not associated with any motor or cognitive deficits. Anti-ribosomal P antibodies specifically stained neurons in the hippocampus, cingulate cortex, and the primary olfactory piriform cortex, compatible with the previously described binding to the membrane-bound P0 ribosomal protein. CONCLUSION: This is the first report of an experimental depression induced by a specific autoantibody. The results implicate olfactory and limbic areas in the pathogenesis of depression in general, and in central nervous system dysfunction in SLE in particular.

Fine specificity mapping of autoantigens targeted by anti-centromere autoantibodies.

Autoantibodies to centromeric proteins are commonly found in sera of limited scleroderma and other rheumatic disease patients. To better understand the inciting events and possible pathogenic mechanisms of these autoimmune responses, this study identified the common antigenic targets of CENP-A in scleroderma patient sera. Utilizing samples from 263 anti-centromere immunofluorescence positive patients, 93.5% were found to have anti-CENP-A reactivity and 95.4% had anti-CENP-B reactivity by ELISA. Very few patient samples exclusively targeted CENP-A (2.7%) or CENP-B (4.2%). Select patient sera were tested for reactivity with solid phase overlapping decapeptides of CENP-A. Four distinct epitopes of CENP-A were identified. Epitopes 2 and 3 were confirmed by additional testing of 263 patient sera by ELISA for reactivity with these sequences constructed as multiple antigenic peptides. Inhibition CENP-A Western blots also confirmed the specificity of these humoral peptide immune responses in a subset of patient sera. The first three arginine residues (aa 4-6) of CENP-A appear essential for antibody recognition, as replacing these arginines with glycine residues reduced antibody binding to the expressed CENP-A protein by an average of 93.2% (range 80-100%). In selected patients with serial samples spanning nearly a decade, humoral epitope binding patterns were quite stable and showed no epitope spreading over time. This epitope mapping study identifies key antigenic targets of the anti-centromere response and establishes that the majority of the responses depend on key amino-terminal residues.

A peptide DNA surrogate that binds and inhibits anti-dsDNA antibodies.

Autoantibodies to dsDNA are an important diagnostic marker and pathogenic factor for systemic lupus erythematosus (SLE). Although the anti-dsDNA antibodies present in SLE are indicative of an antigen-driven response, the antigen has not been conclusively identified. The specific SLE anti-dsDNA antibodies were obtained by affinity purification using a dsDNA-coupled Sepharose column. Using the anti-dsDNA antibodies to screen a phage peptide display library, we demonstrated that purified polyclonal anti-dsDNA antibodies and a monoclonal anti-dsDNA antibody specifically bind a 15 mer peptide ASPVTARVLWKASHV. This chemically synthesized peptide could be recognized by anti-dsDNA antibodies in ELISA and Dot blot. This 15 mer peptide can inhibit anti-dsDNA antibodies binding to dsDNA antigen in immunoassays and in the Crithidia luciliae assay while a control peptide did not inhibit anti-dsDNA antibodies. This study demonstrates the potential usefulness of the peptide DNA surrogate in diagnostic tests of SLE and in the investigation of the origin of anti-dsDNA antibodies. It may also be used in studies of the DNA-anti-DNA antibody interaction.

Humoral antigenic targets of the ribosomal P0 lupus autoantigen are not limited to the carboxyl region.

Autoantibodies binding the ribosomal P phosphoproteins are highly specific for systemic lupus erythematosus (SLE) and can be found in precipitating levels in approximately 15% of these patients. Anti-ribosomal P antibodies are directed against three proteins, and the primary autoimmune target of this response has been described as a common 22-amino acid sequence. Sera from 31 anti-ribosomal P immunodiffusion-positive SLE patients were tested for C-terminal P-peptide reactivity by ELISA. Sera from three patients (9.7%) were negative for the peptide ELISA, despite having anti-ribosomal P by immunodiffusion and Western blot. In addition, inhibition experiments showed that the common P-peptide response accounts for a variable amount of anti-ribosomal P0 reactivity (52-89% of the response dependent upon the patient serum). Based upon these findings, fine-specificity sequential humoral epitope mapping of ribosomal P0 was performed. Several common sequential antigenic targets were defined dispersed throughout the molecule. The most commonly targeted epitopes included RDMLLANKVPAAARA (amino acids 99-113, 11 of 12 patients reactive) and QALGITTKISRGT (amino acids 139-151, 9 of 12 patients reactive). This study confirms that the P22 ribosomal peptide is commonly targeted in SLE and accounts for a variable percentage of the anti-ribosomal P response. Additional anti-ribosomal P humoral epitopes are described.

Serological correlations with nephritis in systemic lupus erythematosus.

Autoantibodies have long been thought to participate in the pathogenesis of lupus nephritis. In this regard, antibodies to double stranded (ds)DNA and ribosomal P protein have been studied the most intensively. We now report a new specificity, antibodies to lipoprotein lipase (LPL) that is strongly associated with lupus nephritis and has a powerful synergistic effect with anti-ribosomal P antibodies in its association with nephritis. The recognition of anti-LPL antibodies and their synergy with anti-P antibodies are discussed in terms of the pathogenesis of lupus nephritis.

Production and characterization of a human monoclonal anti-idiotype to anti-ribosomal P antibodies.

Autoantibodies to ribosomal P protein (anti-P) are a specific hallmark of systemic lupus erythematous (SLE). Several authors found significant associations of anti-P antibodies with neuropsychiatric, hepatic, and renal disease. We now report the isolation by phage display of human anti-idiotype (Id) monoclonal antibody fragments as single-chain Fv fragment (scFv) against anti-P antibodies. The V gene repertoires were derived from the RNA obtained from the B cells of a SLE patient. Affinity-purified anti-P antibodies were used for the selection of bacterial clones producing anti-P-specific scFv antibody fragments and little reactivity with normal IgG and other IgG antibodies. The anti-Id antibody recognizes a public idiotope broadly cross-reactive with polyclonal anti-P antibodies and inhibited binding of anti-P to ribosomal P antigen in immunoassays and on Jurkat cells. The anti-Id scFv antibody fragment may have therapeutic implications in SLE. They may also be used as probes in the study of the structure of the idiotype.

Autoantibodies in mothers of children with neonatal liver disease.

OBJECTIVES: Neonatal lupus erythematosus (NLE) is associated with maternal anti-Ro/La autoantibodies. It is characterized by heart block and/or cutaneous skin lesions, and occasionally liver disease. This study was performed to determine whether idiopathic neonatal cholestasis (INC) represents NLE without its cardiac or cutaneous findings. METHODS: Sera were obtained for autoantibody analysis from mothers of children with INC (N = 11), biliary atresia (N = 25), other liver disease excluding viral hepatitis (liver disease control subjects, N = 14), and healthy children (normal control subjects [NC], N = 22). RESULTS: The characteristic serologic findings of NLE, high titer antibodies to Ro and/or La, were absent in mothers from all groups. An unexpected finding was the prevalence of autoantibodies in mothers of infants with liver disease of any type. The frequency of maternal antinuclear antibodies at > or = 1:120 dilution was greater than the estimated frequency in the general population (22% vs. 9%, P = 0.044). The frequency of maternal low titer autoantibodies to 52 kD Ro detected by ELISA was significantly greater than in the NC group (31% vs. 5%, P = 0.014). CONCLUSIONS: The majority of cases of INC do not represent NLE. The frequent presence of autoantibodies in mothers of infants in all neonatal liver disease groups raises the possibility that maternal serologic autoimmunity is associated with neonatal liver disease.

Correlations of anti-dsDNA and anti-ribosomal P autoantibodies with lupus nephritis.

Patients with systemic lupus erythematosus, with and without nephritis, were studied for their serological profiles. Patients were stratified into two groups defined by the presence or the absence of precipitating antibodies to ribosomal P proteins. It was found that 27 patients were positive for anti-P precipitins and the remaining 34 patients were studied for the presence of lesser amounts of anti-P antibodies by Western blot and ELISA tests. The nephritic patients were characterized most frequently by the presence of both autoantibodies to dsDNA and the ribosomal P proteins. In the group with anti-P precipitins, anti-dsDNA titers were much higher in the patients with nephritis than in those without nephritis. Thus, over a wide range of anti-ribosomal P antibody concentrations, the mutual occurrence of anti-P antibodies with anti-dsDNA antibodies was strongly associated with lupus nephritis.

Autoantibodies to lipoprotein lipase and dyslipidemia in systemic lupus erythematosus.

OBJECTIVE: To demonstrate the binding of bovine lipoprotein lipase (LPL) by IgG from sera obtained from patients with systemic lupus erythematosus (SLE) and other rheumatic diseases, and the relationship of anti-LPL to triglyceride levels in SLE. METHOD: Binding of LPL by IgG from sera obtained from patients with SLE and other rheumatic diseases was measured by an enzyme-linked immunosorbent assay technique. Lipid profiles for fasting blood samples obtained from SLE patients and control subjects were determined. RESULTS: Sera obtained from 105 patients with SLE were assessed for reactivity with LPL, and 49 (47%) of the results were positive. Sera obtained from patients with rheumatoid arthritis (RA) (n = 80), Sjögren's syndrome (n = 30), polymyositis and dermatomyositis (n = 30), and progressive systemic sclerosis (n = 31) were also studied, and 10 (13%), 3 (10%), 12 (40%), and 13 (42%), respectively, were positive for reactivity with LPL. It was determined that all affinity-purified anti-double-stranded DNA (dsDNA) antibodies and 4 of 5 monoclonal anti-dsDNA antibodies bound to LPL. The binding of IgG depleted of anti-dsDNA to LPL indicates a second anti-LPL activity in SLE. Measurements of fasting lipid levels in SLE patients with anti-LPL revealed a strong positive correlation of antibody levels and total serum triglycerides, apolipoprotein B, and apolipoprotein E concentrations. CONCLUSION: Antibodies to LPL occurred in 47% of SLE patients and in a similar percentage of patients with polymyositis or systemic sclerosis. The prevalence of these antibodies was less in patients with RA or Sjögren's syndrome. It is hypothesized that the elevated triglyceride levels in SLE patients are in part attributable to anti-LPL, and this lipid abnormality could contribute to the premature atherosclerosis known to be present in patients with SLE.