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
5 resultados
Resultados de Busca
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- Molecular characterization of the complement C1q, C2 and C4 genes in Brazilian patients with juvenile systemic lupus erythematosus(2015) LIPHAUS, Bernadete L.; UMETSU, Natalia; JESUS, Adriana A.; BANDO, Silvia Y.; SILVA, Clovis A.; CARNEIRO-SAMPAIO, MagdaOBJECTIVE: To perform a molecular characterization of the C1q, C2 and C4 genes in patients with juvenile systemic lupus erythematosus. METHODS: Patient 1 (P1) had undetectable C1q, patient 2 (P2) and patient 3 (P3) had decreased C2 and patient 4 (P4) had decreased C4 levels. All exons and non-coding regions of the C1q and C2 genes were sequenced. Mononuclear cells were cultured and stimulated with interferon gamma to evaluate C1q, C2 and C4 mRNA expression by quantitative real-time polymerase chain reaction. RESULTS: C1q sequencing revealed heterozygous silent mutations in the A (c.276 A>G Gly) and C (c.126 C>T Pro) chains, as well as a homozygous single-base change in the 39 non-coding region of the B chain (c*78 A>G). C1qA mRNA expression without interferon was decreased compared with that of healthy controls (p<0.05) and was decreased after stimulation compared with that of non-treated cells. C1qB mRNA expression was decreased compared with that of controls and did not change with stimulation. C1qC mRNA expression was increased compared with that of controls and was even higher after stimulation. P2 and P3 had Type I C2 deficiency (heterozygous 28 bp deletion at exon 6). The C2 mRNA expression in P3 was 23 times lower compared with that of controls and did not change after stimulation. The C4B mRNA expression of P4 was decreased compared with that of controls and increased after stimulation. CONCLUSIONS: Silent mutations and single-base changes in the 3' non-coding regions may modify mRNA transcription and C1q production. Type I C2 deficiency should be evaluated in JSLE patients with decreased C2 serum levels. Further studies are needed to clarify the role of decreased C4B mRNA expression in JSLE pathogenesis.
- 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.
- Complement and antibody primary immunodeficiency in juvenile systemic lupus erythematosus patients(2011) JESUS, A. A.; LIPHAUS, B. L.; SILVA, C. A.; BANDO, S. Y.; ANDRADE, L. E. C.; COUTINHO, A.; CARNEIRO-SAMPAIO, M.Objective: To evaluate the frequency of primary immunodeficiencies (PID) in juvenile systemic lupus erythematosus (JSLE) patients. Methods: Some 72 JSLE patients were analyzed for levels of immunoglobulin classes and IgG subclasses and early components of the classical complement pathway. Determination of C4 gene copy number (GCN) and detection of type I C2 deficiency (D) were also performed. Results: PID was identified in 16 patients (22%): C2D in three, C4D in three, C1qD in two, IgG2D (<20 mg/dl) in four, IgAD (<7 mg/dl) in three, and IgMD (<35 mg/dl) in three; one of these patients presented IgA, C2 and C4D. Two patients had low C4 GCN and two had type I C2D. Demographic data, family history of autoimmune disease and PID, JSLE clinical findings, occurrence of infections, disease activity and therapies were similar in patients with and without PID (p > 0.05). Remarkably, the median of Systemic Lupus International Collaborating Clinics/ACR-damage index (SLICC/ACR-DI) was significantly higher in JSLE patients with PID compared with patients without these abnormalities (p = 0.0033), likewise the high frequency of SLICC/ACR-DI > 1 (p = 0.023). Conclusions: A high frequency of PID was observed in JSLE patients, suggesting that these defects may contribute to lupus development. Our findings indicate that these two groups of PID should be investigated in severe pediatric lupus. Lupus (2011) 20, 1275-1284.
- 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.