Anti–lipoprotein lipase antibodies: A new player in the complex atherosclerotic process in systemic lupus erythematosus?

Abstract

Objective. The novel description of antibodies to lipoprotein lipase (anti-LPL) associated with dyslipoproteinemia prompted us to analyze the association of anti-LPL with clinical and serologic features in patients with systemic lupus erythematosus (SLE) and its link to markers of inflammation that are known to be involved in atherogenesis.Methods. Enzyme-linked immunosorbent assay was used to test for the presence of anti-LPL antibodies in 66 consecutive patients with SLE. Clinical and laboratory evaluation, including a fasting lipid profile, autoantibody screening, an assessment for markers of inflammation (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]), and the SLE Disease Activity Index (SLEDAI) were performed at the time of inclusion in the study. Exclusion criteria were any conditions that affect the lipid profile. SLE patients were categorized into 2 groups according to detection of these anti-LPL antibodies, as follows: anti-LPL؉ and anti-LPL؊.Results. Anti-LPL antibody IgG was detected in 25 SLE patients (37.8%). Triglyceride levels were significantly higher in the anti-LPL؉ group (112.4 ؎ 50.2 versus 89.9 ؎ 54.5 mg/dl in the anti-LPL؊ group; P ‫؍‬ 0.033), but no significant differences between the 2 groups were detected for total, high-density lipoprotein, and low-density lipoprotein cholesterol levels. A higher frequency of elevated CRP levels and ESRs was observed in the anti-LPL؉ group compared with the anti-LPL؊ group (44% and 17.1%, respectively [P ‫؍‬ 0.023] and 52% and 19.5%, respectively [P ‫؍‬ 0.013]). Moreover, SLE patients with anti-LPL antibodies also had significantly higher levels of CRP (11.1 ؎ 16.4 versus 2.4 ؎ 2.6 g/ml; P ‫؍‬ 0.036) and higher ESRs (33.4 ؎ 29.8 versus 16.5 ؎ 11.8 mm/hour; P ‫؍‬ 0.020). Anti-LPL titers had a significant positive correlation with the CRP level (r ‫؍‬ 0.56, P < 0.001), the ESR (r ‫؍‬ 0.55, P < 0.001), the SLEDAI score (r ‫؍‬ 0.45, P < 0.001), anti-double-stranded DNA (anti-dsDNA; r ‫؍‬ 0.52, P < 0.001), and anticardiolipin IgG antibodies (r ‫؍‬ 0.25, P ‫؍‬ 0.04), and a significant negative correlation was detected with total hemolytic complement activity (CH100) (r ‫؍‬ ؊0.34, P ‫؍‬ 0.005). Reinforcing these findings, multiple regression analysis also revealed a significant association of anti-LPL with the CRP level (P ‫؍‬ 0.025) and anti-dsDNA (P < 0.001). Importantly, a comparison of positive and negative anti-dsDNA sera revealed similar mean CRP levels (P ‫؍‬ 0.56) and ESRs (P ‫؍‬ 0.102), contrasting with the SLEDAI score (P ‫؍‬ 0.004) and CH100 (P ‫؍‬ 0.008).Conclusion. These data support the link between inflammation, immune response, and dyslipoproteinemia in SLE, introducing anti-LPL as a possible new player that may ultimately help in understanding the complex events of atherogenesis in this disease.Lipoprotein lipase (LPL) is a member of the lipase family, and LPL is known to hydrolyze triglyceride molecules found in lipoprotein particles (1,2). Physio-

Estudo longitudinal do anticorpo antilipoproteína lipase e sua relação com atividade de doença nos indivíduos com lúpus eritematoso sistêmico sem anticorpos anti-dsDNA

“…8,9 Out of this population, only 66 were included to perform a study previously published. 5 From this population and the inclusion criteria application of this present study (positivity of anti-LPL antibodies > 5), standard deviations and lack of anti-dsDNA antibody by two methods led us to five patients. All of them were clinically evaluated, completed a standardized form, had the medical records review, necessary data to complete SLEDAI, 10 and blood taking for laboratory tests.…”

“…Thus, in addition to anti-LPL association with hypertriglyceridemia already described, our previous results demonstrated a strong association with disease's activity, measured by SLEDAI score, by reduced complement levels, either by total hemolytic activity or by fractions in the same system (C3 and C4), as well as high sensitive CRP levels. 5 In those two patients with clinical activity of the disease, there was a trend to present normal or lower than normal complement levels during the severe disease's activity period. In one of those patients, there was an increment of total To corroborate such findings, anti-LPL antibodies were also associated with lupus nephritis, especially when concomitant with ribosomal anti-P antibodies.…”

“…5 A lipoproteína lipase (LPL) é uma enzima presente na superfície endotelial que tem como função a hidrólise de quilomícrons e triglicérides 6 e já foi demonstrada que a sua função reduzida está relacionada à hipertrigliceridemia. 7 disease activity index) = 16 e anti-LPL = 144UA.…”

“…8,9 Dessa população, apenas 66 foram incluídos para a realização de um trabalho anterior já publicado. 5 A partir dessa população e da aplicação dos critérios de inclusão do presente trabalho (positividade dos anticorpos anti-LPL > 5, os desvios-padrão e ausência de anticorpos anti-dsDNA) por dois métodos nos levaram a cinco pacientes. Todos eles foram analisados através de entrevista clínica e preenchimento de ficha padronizada do protocolo, revisão de prontuário, dados atividade clínica ou laboratorial e com SLEDAI persistentemente de zero, os anticorpos anti-LPL estavam presentes em altos títulos e sem variação significante dos seus valores.…”

“…5 Lipoprotein lipase (LPL) is an enzyme present in endothelial surface, which function is hydrolysis of chylomicrons and triglycerides, 6 and it has already been demonstrated that its reduced function is related to hypertriglyceridemia. 7 The purpose of this study were to verify anti-LPL antibody fluctuation over time in lupus patients and correlate this fluctuation to disease activity.…”