Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity. Trial registration. www.clinicaltrials.gov, NCT01151644.

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-

SummaryThe aim of this study is to evaluate the humoral autoimmune response in the experimental model of systemic sclerosis (SSc) induced by human type V collagen (huCol V). New Zealand rabbits were immunized with huCol V in Freund's complete adjuvant (FCA) and boosted twice with 15 days intervals with huCol V in Freund's incomplete adjuvant. Control groups included animals injected only with FCA or bovine serum albumin. Bleeding was done at days 0, 30, 75 and 120. Tissue specimens were obtained for histopathological investigation. Serological analysis included detection of antibodies against huCol V and anti-topoisomerase I (AntiScl70) by enzyme-linked immunosorbent assay, antinuclear antibodies (ANA) by indirect immunofluorescence, and rheumatoid factor (RF) by a latex agglutination test. Target antigens were characterized by immunoblot. Histological analysis revealed extracellular matrix remodeling with fibrosis and vasculitis. Anti-Scl70 and ANA were detected as early as 30 days in all huCol V animals. The universal ANA staining pattern was Golgi-like. This serum reactivity was not abolished by previous absorption with huCol V. Characterization of the target antigen by immunoblot revealed two major protein fractions of 175 000 and 220 000 MW. Similarly to ANA, there was a gradual increase of reactivity throughout the immunization and also it was not abolished by preincubation of serum samples with huCol V. RF testing was negative in hyperimmune sera. Conclusion: The production of autoantibodies, including anti-Scl70, a serological marker for SSc associated with histopathological alterations, validates huCol V induced-experimental model and brings out its potential for understanding the pathophysiology of SSc.

Our data indicate differences of ANA antigenic specificity and complement consumption between EM and SLE. The high prevalence of generalized musculoskeletal complaints in EM justifies a multidisciplinary approach.

Proteinuria is a major feature of lupus nephritis (LN) and reflects podocyte injury. Analysis of podocyte biomarkers was performed attempting to identify if podocyte phenotype is distinct in pure membranous and proliferative LN. Expression of synaptopodin, Wilms tumor protein 1 (WT1), glomerular epithelial protein 1 (GLEPP1) and nephrin was evaluated in 52 LN biopsies by immunohistochemistry. Preserved synaptopodin expression was observed in only 10 (19.2%) of all biopsies while 42 (80.8%) had reduced expression. Both groups had comparable proteinuria at the time of biopsy (p = 0.22); however, in the mean follow-up of four years there was a tendency toward lower mean levels of proteinuria in patients with preserved synaptopodin staining (0.26±0.23 vs. 0.84±0.90 g/24 h, p = 0.05) compared with those with diminished expression. Thirty-nine (75%) biopsies were classified as proliferative and 13 (25%) as pure membranous. Comparison of podocyte biomarkers demonstrated a predominance of preserved staining of synaptopodin (69.2%), WT1 (69.2%), GLEPP1 (53.9%) and nephrin (60%) in the pure membranous group whereas only <10% of the proliferative showed preserved expression. Our data suggest that in proliferative forms there seems to occur structural podocyte damage, whereas in the pure membranous the predominant preserved pattern suggests a dysfunctional podocyte lesion that may account for the better long-term prognosis of proteinuria outcome.