BERNADETE DE LOURDES LIPHAUS
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
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- Anti-C1q, anti-chromatin/nucleosome, and anti-dsDNA antibodies in juvenile systemic lupus erythematosus patients(2012) JESUS, Adriana Almeida de; CAMPOS, Lucia Maria Arruda; LIPHAUS, Bernadete Lourdes; CARNEIRO-SAMPAIO, Magda; MANGUEIRA, Cristovao Luis Pitangueira; ROSSETO, Eliane Aparecida; SILVA, Clovis Artur Almeida da; SCHEINBERG, MortonObjectives: To evaluate the presence of anti-C1q, anti-chromatin/nucleosome and anti-double stranded DNA (dsDNA) antibodies in juvenile systemic lupus erythematosus (JSLE) and controls. Methods: Sixty-seven JSLE and 34 healthy controls were analyzed for the presence of anti-C1q, anti-chromatin/nucleosome, and anti-dsDNA antibodies by ELISA. C1q levels were evaluated by radial immunodiffusion. Results: The mean current age was similar in JSLE patients and controls (14.6 +/- 3.86 vs. 13.6 +/- 2.93 years, P = 0.14). Higher frequencies of anti-C1q, anti-chromatin/nucleossome, and anti-dsDNA antibodies were observed in JSLE compared to controls (20% vs. 0%, P = 0.0037; 48% vs. 0%, P < 0.0001 and 69% vs. 3%, P < 0.0001, respectively). The median of anti-C1q, anti-chromatin/nucleossome, and anti-dsDNA antibodies were also significantly higher in JSLE patients than in controls [9.6 (5.5-127) vs. 7.5 (5-20) units, P = 0.0006; 18(1.9-212) vs. 3.2 (1.7-17) units, P < 0.0001; and 111 IU/mL (6-741) vs. 14(6-33) IU/mL; P < 0.0001, respectively]. The sensitivity for anti-C1q, anti-chromatin/nucleosome, and anti-dsDNA antibodies was 21% (CI: 11-33), 49% (CI: 36-62), and 70% (CI: 57-81). The specificity was 100% (CI: 88-100), 100% (88-100), and 97% (CI: 83-99), respectively. A positive correlation was found between anti-dsDNA levels and both anti-C1q (r = 0.51; CI: 0.29-0.68; P < 0.0001) and anti-chromatin/nucleosome antibodies (r = 0.87; CI: 0.79-0.92; P < 0.0001) levels. A negative correlation was observed between anti-C1q and C1q levels (r = -0.33; CI: -0.56-0.05; P = 0.018). The frequency of anti-dsDNA was higher in patients with SLEDAI-2K >= 1 (P = 0.0047) and no differences were observed in the frequencies of these three autoantibodies and nephritis (P > 0.05). Conclusion: Our study demonstrated an elevated specificity for lupus diagnosis involving the three autoantibodies, especially anti-C1q and anti-chromatin/nucleosome.
conferenceObject JUVENILE SYSTEMIC LUPUS ERYTHEMATOSUS (JSLE) AND JUVENILE DERMATOMYOSITIS (JDM) PATIENTS HAVE A DISTINCT PROFILE OF SOLUBLE APOPTOSIS MOLECULES(2012) LIPHAUS, B. L.; KISS, M. H. B.; CARRASCO, S.; SILVA, C. A.; GOLDENSTEIN-SCHAINBERG, C.- Organ-specific autoantibodies and autoimmune diseases in juvenile systemic lupus erythematosus and juvenile dermatomyositis patients(2012) AIKAWA, N. E.; JESUS, A. A.; LIPHAUS, B. L.; SILVA, C. A.; CARNEIRO-SAMPAIO, M.; VIANA, V. S. T.; SALLUM, A. M. E.Objectives To our knowledge, no study assessed simultaneously a variety of organ-specific autoantibodies and the prevalence of organ-specific autoimmune diseases in juvenile systemic lupus erythematosus (ISLE) and juvenile dermatomyositis (JDM). Therefore, the purpose of this study was to evaluate organ-specific autoantibodies and autoimmune diseases in JSLE and JDM patients. Methods Forty-one JSLE and 41 JDM patients were investigated for autoantibodies associated with autoimmune hepatitis, primary biliary cirrhosis, type I diabetes mellitus (TIDM, autoimmune thyroiditis (AT), autoimmune gastritis and coeliac disease (CD). Patients with positive antibodies were investigated for the respective organ-specific autoimmune diseases. Results Mean age at diagnosis was higher in ISLE compared to JDM patients (10.3 +/- 3.4 vs. 7.3 +/- 3.1 years, p=0.0001). The frequencies of organ-specific autoantibodies were similar in JSLE and JDM patients (p>0.05). Of note, a high prevalence of TIDM and AT autoantibodies was observed in both groups (20% vs. 15%, p=0.77 and 24% vs. 15%, p=0.41; respectively). Higher frequencies of ANA (93% vs. 59%, p=0.0006), anti-dsDNA (61% vs. 2%, p<0.0001), anti-Ro, anti-Sm, anti-RNP, anti-La and IgG-aCL were observed in JSLE (p<0.05). Organ-specific autoimmune diseases were evidenced only in ISLE patients (24% vs. 0%, p=0.13). Two ISLE patients had TIDM associated with Hashimoto thyroiditis and another had subclinical thyroiditis. Another JSLE patient had CD diagnosis based on iron deficiency anaemia, anti-endomysial antibody, duodenal biopsy compatible to CD and response to a gluten-free diet. Conclusions Organ-specific diseases were observed solely in ISLE patients and required specific therapy. The presence of these antibodies recommends the evaluation of organ-specific diseases and a rigorous follow-up.
- Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus(2012) LIPHAUS, Bernadete L.; JESUS, Adriana A.; SILVA, Clovis A.; COUTINHO, Antonio; CARNEIRO-SAMPAIO, MagdaOBJECTIVE: The aim of this study was to assess the IgE serum levels in juvenile systemic lupus erythematosus patients and to evaluate possible associations with clinical and laboratory features, disease activity and tissue damage. METHODS: The IgE serum concentrations in 69 consecutive juvenile systemic lupus erythematosus patients were determined by nephelometry. IgG, IgM and IgA concentrations were measured by immunoturbidimetry. All patients were negative for intestinal parasites. Statistical analysis methods included the Mann-Whitney, chi-square and Fisher's exact tests, as well as the Spearman rank correlation coefficient. RESULTS: Increased IgE concentrations above 100 IU/mL were observed in 31/69 (45%) juvenile systemic lupus erythematosus patients. The mean IgE concentration was 442.0 +/- 163.4 IU/ml (range 3.5- 9936.0 IU/ml). Fifteen of the 69 patients had atopic disease, nine patients had severe sepsis and 56 patients presented with nephritis. The mean IgE level in 54 juvenile systemic lupus erythematosus patients without atopic manifestations was 271.6 +/- 699.5 IU/ml, and only nine of the 31 (29%) patients with high IgE levels had atopic disease. The IgE levels did not statistically differ with respect to the presence of atopic disease, severe sepsis, nephritis, disease activity, or tissue damage. Interestingly, IgE concentrations were inversely correlated with C4 levels ( r = -0.25, p = 0.03) and with the SLICC/ACR-DI score (r = -0.34, p = 0.005). The IgE concentration was also found to be directly correlated with IgA levels (r = 0.52, p = 0.03). CONCLUSIONS: The present study demonstrated for the first time that juvenile systemic lupus erythematosus patients have increased IgE serum levels. This increase in IgE levels was not related to allergic or parasitic diseases. Our results are in line with the hypothesis that high IgE levels can be considered a marker of immune dysregulation.
- Low Gene Copy Number for C4, C4A and C4B Is a Strong Risk Factor for Developing Systemic Lupus Erythematosus in Childhood(2012) ANDRADE, Luis Eduardo C.; PEREIRA, Kaline M. C.; FARIA, Atila G. A.; LIPHAUS, Bernadete; JESUS, Adriana A.; SILVA, Clovis; CARNEIRO-SAMPAIO, MagdaBackground/Purpose: C4 is an important component of the Complement system and plays an essential role in the activation cascade of the classical Complement pathway. Complete C4 deficiency is among the strongest genetic risk factors for systemic lupus erythematosus (SLE). There are two C4 circulating isoforms (C4A and C4B) encoded by C4A and C4B genes, respectively, that differ by only five nucleotides. C4A protein is involved in the clearance of immune complex and apoptotic debris while C4B protein is relevant in the opsonization of microbes. C4A and C4B genes are located at a gene cassette within the MHC class III region and depict gene copy-number variation (CNV). The number of C4A copies may be related to the susceptibility to SLE. This study aimed to investigate the impact of the C4A and C4B gene CNV on juvenile SLE. Methods: We evaluated 90 children and 170 adults with SLE (meeting SLE ACR criteria) sequentially retrieved from the rheumatology outpatient clinic. Two hundred healthy individuals (HI) without evidence of auto-immune diseases were retrieved among blood bank donors. Peripheral blood leukocyte DNA was amplified by quantitative real-time PCR (qPCR) with primers for C4 gene and sequence specific TaqMan® probes for C4A (5FAM-ACCCCTGTCCAGTGTTAG-MGB 3) and C4B (5FAM-ACCTCTCTCCAGTGATAC-MGB 3). Gene copy number (GCN) was determined by the delta-delta cycle threshold (DDCT) method. Results: Children with SLE had lower GCN of total C4 (mean total C4=3.1; 95% CI=2.8–3.4), C4A (mean C4A=1.7; 95% CI=1.5–1.9) and C4B (mean C4B=1.5; 95% CI=1.3–1.6) than HI (C4=4.3 with 95% CI=4.1–4.5, p<0.001; C4A =2.3 with 95% CI=2.2–2.5, p<0.001; C4B=2.0 with 95% CI=1.8–2.1; p<0.001). The frequency of SLE children with total C4 low GCN (<4 copies) was significantly higher than in HI (SLE=59% versus HI=28%; OR=3.68; 95% CI=2.19–6.20; p<0.001). The same was observed for C4A low GCN (2