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
16 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 16
- Latent and Overt Polyautoimmunity in Children and Adolescents With Immune Thrombocytopenia(2020) KAMIOKA, Priscila E.; LIPHAUS, Bernadete L.; BEATRICE, Julia M.; MATSUMOTO, Lucy C.; REIS, Joyce M. A.; LIMA, Laila; CARNEIRO-SAMPAIO, Magda M. S.; CARNEIRO, Jorge D. A.Autoantibodies are biomarkers for autoimmune disease diagnosis, monitoring, and prediction. Therefore, this study established the frequency of latent and overt polyautoimmunity in children and adolescents with >6 months of diagnosis of immune thrombocytopenia (ITP). Forty-seven patients with chronic or persistent disease had non-organ-specific and organ-specific autoantibodies assessed. Frequency of latent polyautoimmunity was 36.2%, and, of overt polyautoimmunity, it was 4.3%. Of ITP patients with latent polyautoimmunity, 52.9% were positive for antinuclear antibody (ANA), 47.1% for autoantibodies other than ANA, and 64.7% for multiple autoantibodies. In addition, patients with latent polyautoimmunity and those positive for ANA were significantly older at disease onset. Both ITP patients positive and negative for autoantibodies reported family members with autoimmune diseases. The autoantibodies observed were as follows: ANA, anti-dsDNA, anti-SSA/Ro, IgM aCL, anti-GAD, anti-IA2, anti-IAA, anti-TG, anti-TPO, anti-LKM1, and SMA. Of ITP patients with overt polyautoimmunity, 1 was diagnosed with type 1 diabetes mellitus and the other with thyroiditis. In conclusion, children and adolescents with ITP present high frequency of latent and overt polyautoimmunity even for autoantibodies other than ANA. Therefore, ANA and other non-organ-specific and organ-specific autoantibodies should be considered for assessment during ITP patients' follow-up.
- Inflammasome polymorphisms in juvenile systemic lupus erythematosus(2015) PONTILLO, Alessandra; REIS, Edione C.; LIPHAUS, Bernadete L.; SILVA, Clovis A.; CARNEIRO-SAMPAIO, MagdaInflammasome is the cytoplasmic complex responsible for pro-IL1 cleavage and secretion of IL-1. Recently our group reported the first association between polymorphisms in the inflammasome receptor NLRP1 and adult-onset systemic lupus erythematosus (SLE) di per se and especially in SLE-associated renal disease, suggesting the involvement of NLRP1-inflammasome in the immune dysregulation characteristic of SLE patients. Considering that juvenile-onset SLE (JSLE) is more severe than adult SLE, and that the genetic background plays a major role in the early development of autoimmune diseases, we analysed selected polymorphisms in inflammasome genes (NLRP1, NLRP3, CARD8, IL1B, TNFAIP3) of children and adolescents with JSLE (n=90) and in healthy controls (n=144). A single polymorphism in IL1B, and not NLRP1, gene resulted in association with JSLE, suggesting that IL-1 is involved in the pathogenesis of SLE, but different genes could play specific role in adult- or early-onset disease.
- 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.
- Increased Soluble Cytoplasmic Bcl-2 Protein Serum Levels and Expression and Decreased Fas Expression in Lymphocytes and Monocytes in Juvenile Dermatomyositis(2018) LIPHAUS, Bernadete L.; SALLUM, Adriana E. M.; AIKAWA, Nadia E.; KISS, Maria Helena B.; CARRASCO, Solange; PALMEIRA, Patricia; LIMA, Laila; SILVA, Clovis A.; GOLDENSTEIN-SCHAINBERG, Claudia; CARNEIRO-SAMPAIO, MagdaObjective. To evaluate soluble Fas antigen (sFas), sFas ligand (sFasL), soluble tumor necrosis factor-related apoptosis-inducing ligand, and soluble cytoplasmic Bcl-2 protein (sBcl-2) serum levels, Fas and Bcl-2 expressions in T and B lymphocytes and monocytes and relations with erythrocyte sedimentation rate, C-reactive protein (CRP), Childhood Myositis Assessment Scale, and manual muscle testing in juvenile dermatomyositis (JDM). Methods. Serum levels were determined by ELISA and peripheral cell expressions by flow cytometry for patients with JDM or juvenile idiopathic arthritis (JIA), and healthy controls. Results. Patients with JDM had increased sBcl-2, which correlated with CRP. Expression of Bcl-2 was increased and expression of Fas was decreased in CD3+, CD4+, and CD8+ T lymphocytes compared with JIA and/or healthy controls. Conclusion. Patients with JDM presented a unique apoptosis-related proteins profile, which may contribute to disease development.
- LRBA deficiency: a new genetic cause of monogenic lupus(2020) LIPHAUS, Bernadete L.; CARAMALHO, Iris; RANGEL-SANTOS, Andreia; SILVA, Clovis A.; DEMENGEOT, Jocelyne; CARNEIRO-SAMPAIO, Magda Maria Salles
- Reduced expressions of Fas and Bcl-2 proteins in CD14+monocytes and normal CD14 soluble levels in juvenile systemic lupus erythematosus(2013) LIPHAUS, B. L.; KISS, M. H. B.; CARRASCO, S.; GOLDENSTEIN-SCHAINBERG, C.In order to evaluate Fas and Bcl-2 expressions in CD14+ monocytes, to measure soluble CD14 serum levels and to analyze the relationships with lupus nephritis and disease activity, we enrolled 41 patients with juvenile systemic lupus erythematosus (JSLE) and 27 healthy volunteers. Disease activity was determined by SLEDAI score. Peripheral monocytes were stained for CD14, Fas and Bcl-2 molecules, and cellular expressions were determined by flow cytometry. Soluble CD14 levels were measured by a quantitative ELISA kit. JSLE patients, those with active disease and those with nephritis, presented significantly reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes compared with healthy controls. Significant inverse correlations between percentages of CD14+Fas+ cells, SLEDAI score and anti-dsDNA antibodies were observed. JSLE patients had soluble CD14 levels similar to controls, although sCD14 levels positively correlated with ESR, but not with SLEDAI score. JSLE patients with nephritis also presented sCD14 levels similar to controls. In conclusion, the reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes from JSLE patients depict that monocyte apoptotic mechanisms may be important in lupus 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.
- Low C4, C4A and C4B gene copy numbers are stronger risk factors for juvenile-onset than for adult-onset systemic lupus erythematosus(2016) PEREIRA, Kaline M. C.; FARIA, Atila G. A.; LIPHAUS, Bernadete L.; JESUS, Adriana A.; SILVA, Clovis A.; CARNEIRO-SAMPAIO, Magda; ANDRADE, Luis E. C.Objective. Complete deficiency of Complement C4 component is a strong genetic risk factor for SLE. C4 is encoded by two different genes, C4A and C4B, which show considerable gene copy number (GCN) variation. This study investigates the association of total C4, C4A and C4B GCN with JSLE. Methods. Ninety JSLE patients, 170 adult-onset SLE (aSLE) patients and 200 healthy individuals were evaluated for C4A and C4B GCN by quantitative real-time PCR. Results. JSLE patients had lower GCN for C4A (mean = 1.7; 95% CI: 1.5, 1.9) and C4B (mean = 1.5; 95% CI: 1.3, 1.6) compared with healthy individuals (mean C4A = 2.3; 95% CI: 2.2, 2.5, P< 0.001; C4B = 2.0; 95% CI: 1.8, 2.1; P< 0.001) or with aSLE patients (mean C4A = 1.9; 95% CI: 1.8, 2.1, P = 0.006; mean C4B = 1.8; 95% CI: 1.7, 1.9, P< 0.001). Low total C4 GCN (< 4 copies) was more frequent in JSLE than in healthy individuals (59% vs 28%; P< 0.001). The same was observed for low C4A (<= 1 copy) (52% vs 18%; P< 0.001) and for low C4B (60% vs 31%; P< 0.001). JSLE had a stronger association with low total C4 (OR = 3.68, 95% CI: 2.19, 6.20), C4A (OR = 4.98, 95% CI: 2.88, 8.62) and C4B (OR = 3.26; 95% CI: 1.95, 5.47) than aSLE (C4 OR= 2.03; 95% CI: 1.32, 3.13; C4A OR= 2.36; 95% CI: 1.46, 3.81; C4B OR= 1.13; 95% CI: 0.73, 1.74). In addition, pericarditis in JSLE patients was associated with low C4 (OR= 4.13; 95% CI: 1.02, 16.68; P = 0.047) and low C4A (OR = 5.54; 95% CI: 1.37, 22.32; P = 0.016). Conclusion. Low total C4, C4A and C4B GCN were associated with a stronger risk for developing JSLE than aSLE. Additionally, low total C4 and C4A GCN are risk factors for pericarditis in JSLE.
- Low T-cell receptor excision circles (TREC) in children and adolescents with immune thrombocytopenia(2021) SANTANA-SANTOS, Denis; LIPHAUS, Bernadete L.; BEATRICE, Julia M.; CARNEIRO, Jorge D. A.; CARNEIRO-SAMPAIO, Magda M. S.; RANGEL-SANTOS, Andreia
- Increased serum sFas, sTRAIL, and reduced sFasL in juvenile-onset systemic lupus erythematosus(2017) LIPHAUS, Bernadete L.; KISS, Maria Helena B.; CARRASCO, Solange; PALMEIRA, Patricia; GOLDENSTEIN-SCHAINBERG, Claudia; CARNEIRO-SAMPAIO, MagdaThe aims of this study were to assess serum Fas, FasL, TRAIL, and Bcl-2 levels in patients with juvenile-onset systemic lupus erythematosus (JSLE) and to evaluate their relations with disease activity parameters and nephritis. Forty-eight JSLE patients, 33 juvenile idiopathic arthritis (JIA, inflammatory controls) patients and 40 healthy controls were enrolled. sFas, sFasL, sTRAIL, and sBcl-2 serum levels were measured by ELISA. Disease activity parameters included SLEDAI score, ESR, anti-dsDNA antibodies, C3, and C4 levels. Thirty-five JSLE patients had nephritis and 32 patients were classified as having active disease (SLEDAI ae4). Statistical analysis methods included Mann-Whitney test and Spearman's rank test. JSLE patients had significantly increased sFas serum levels compared with healthy controls (median 177.6 vs. 117.5 pg/mL; p = 0.0001), higher sTRAIL (median 484.6 vs 270.8 pg/mL; p = 0.02), and reduced sFasL (median 0.05 vs 0.3 ng/mL; p = 0.0002). The same results were observed for JSLE patients with active disease and for patients with nephritis. Additionally, sFas levels in JSLE patients directly correlated with SLEDAI score (r = 0.40; p = 0.009), and sTRAIL levels were increased in JSLE patients with neuropsychiatric disease compared with those without this involvement (median 667.9 vs. 216.2 pg/mL; p = 0.03). Otherwise, sBcl-2 levels of JSLE patients were similar to healthy controls. JIA patients had sFas, sFasL, sTRAIL, and sBcl-2 serum levels similar to JSLE patients and to healthy controls. In summary, this study characterized in JSLE a distinct profile from adult SLE that comprises increased sFas, sTRAIL, and reduced sFasL, notably in patients with active disease and with nephritis.