Objective. Recent findings demonstrated a reduced immunogenicity of the influenza A H1N1/2009 vaccine in juvenile rheumatic diseases. However, a point of concern is whether the vaccine could induce disease flares. The aim of this study was to assess the disease safety of and the possible influence of disease parameters and therapy on nonadjuvant influenza A H1N1 vaccine response of juvenile systemic lupus erythematosus (SLE) patients. Methods. One hundred eighteen juvenile SLE patients and 102 healthy controls of a comparable age were vaccinated. Seroprotection rate, seroconversion rate, and factor increase in geometric mean titer (GMT) were calculated and effective immune response was defined by the Food and Drug Administration and the European Committee for Proprietary Medicinal Products vaccine immunologic standards. Disease parameters, treatment, and adverse events were evaluated. Results. Age was comparable in juvenile SLE patients and controls (mean ؎ SD 16.0 ؎ 3.5 versus 15.9 ؎ 4.5 years; P ‫؍‬ 0.26). Three weeks after immunization, seroprotection rate (73.7% versus 95.1%; P < 0.001), seroconversion rate (63.6% versus 91.2%; P < 0.001), GMT (90.8 versus 273.3; P < 0.001), and factor increase in GMT (8.1 versus 19.9; P < 0.001) were significantly lower in juvenile SLE patients versus controls. Nonseroconversion was associated with a higher frequency of patients with a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score >8 (48.8% versus 24%; P ‫؍‬ 0.008) and a higher mean ؎ SD current glucocorticoid dosage (18 ؎ 21.4 versus 10.5 ؎ 12.5 mg/day; P ‫؍‬ 0.018). Multivariate logistic regression including a SLEDAI-2K score >8 revealed that only the SLEDAI-2K remained a significant factor for nonseroconversion (odds ratio 0.42, 95% confidence interval 0.18 -0.98; P ‫؍‬ 0.045). Disease parameters remained stable throughout the study and no severe vaccine adverse events were observed. Conclusion. The present study demonstrated adequate disease safety and is the first to discriminate that high disease activity impairs influenza A H1N1/2009 vaccine antibody production in juvenile SLE, in spite of an overall immune response within recommended levels.

The association of RASopathies [Noonan syndrome (NS) and Noonan-related syndromes] and autoimmune disorders has been reported sporadically. However, a concomitant evaluation of autoimmune diseases and an assessment of multiple autoantibodies in a large population of patients with molecularly confirmed RASopathy have not been performed. The clinical and laboratory features were analyzed in 42 RASopathy patients, the majority of whom had NS and five individuals had Noonan-related disorders. The following autoantibodies were measured: Anti-nuclear antibodies, anti-double stranded DNA, anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-RNP, anti-Scl-70, anti-Jo-1, anti-ribosomal P, IgG and IgM anticardiolipin (aCL), thyroid, anti-smooth muscle, anti-endomysial (AE), anti-liver cytosolic protein type 1 (LC1), anti-parietal cell (APC), anti-mitochondrial (AM) antibodies, anti-liver-kidney microsome type 1 antibodies (LKM-1), and lupus anticoagulant. Six patients (14%) fulfilled the clinical criteria for autoimmune diseases [systemic lupus erythematous, polyendocrinopathy (autoimmune thyroiditis and celiac disease), primary antiphospholipid syndrome (PAPS), autoimmune hepatitis, vitiligo, and autoimmune thyroiditis]. Autoimmune antibodies were observed in 52% of the patients. Remarkably, three (7%) of the patients had specific gastrointestinal and liver autoantibodies without clinical findings. Autoimmune diseases and autoantibodies were frequently present in patients with RASopathies. Until a final conclusion of the real incidence of autoimmunity in Rasopathy is drawn, the physicians should be alerted to the possibility of this association and the need for a fast diagnosis, proper referral to a specialist and ultimately, adequate treatment.

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-

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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.