Evaluation of apoptosis related proteins in lymphocytes, monocytes and NK cells from patients with juvenile systemic lupus erythematosus

• Grant number: 12/22997-4
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2013
• End date: February 29, 2016
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Bernadete de Lourdes Liphaus
• Grantee: Bernadete de Lourdes Liphaus
• Host Institution: Instituto da Criança Professor Doutor Pedro de Alcantara (ICR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Cláudia Augusta Zago ; Claudia Goldenstein Schainberg ; Clovis Artur Almeida da Silva ; Magda Maria Sales Carneiro-Sampaio ; Patricia Palmeira Daenekas Jorge

Abstract

Systemic Lupus Erythematosus (SLE) is the prototype of systemic autoimmune diseases. The immune dysfunction observed in SLE involves not only T and B lymphocytes, but also elements of the innate immune system such as dendritic cells and complement proteins. The autoimmunity occurs when there is loss of immune tolerance, which is mediated by the depletion failure of autoreactive cells. The main mechanism responsible for the depletion of autoreactive cells is apoptosis or programmed cell death. The apoptosis can be initiated by two distinct pathways: the extrinsic pathway which begins with the aggregation of death receptors and the intrinsic pathway which begins with the release of mitochondrial factors. SLE patients have increased proportion of apoptotic peripheral lymphocytes, present changes in cellular expression and serum concentrations of apoptosis-related proteins, featuring a pro-apoptotic status.The present study aims to assess in patients with juvenile SLE; 1 - the expression of apoptosis-related proteins from the extrinsic, intrinsic and final common pathways in mononuclear cells, 2 - serum concentrations of these proteins, 3 - correlate the results with parameters of activity and disease damage and 4 - determine the concentrations of pro-and anti-inflammatory interleukins in mononuclear cell cultures with and without stimulus of cellular activation.The expressions, in the cytoplasm and in membrane, from the apoptosis-related proteins and the interleukin concentrations in cell cultures with and without stimulus of activation will be determined by flow cytometry. Serum levels of apoptosis-related proteins will be quantified by ELISA using commercial kits.Thus, this study will contribute to the knowledge of the correlation between cellular expression and serum levels of apoptosis-related proteins in different cell populations and subpopulations, and provide new perspectives regarding knowledge of the pathogenesis of Juvenile SLE. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LIPHAUS, B. L.; PALMEIRA, P.; LIMA, L.; SILVA, C. A.; GOLDENSTEIN-SCHAINBERG, C.; CARNEIRO-SAMPAIO, M.. SOLUBLE TAM (TYRO3, AXL, MER) RECEPTORS AND GAS6 LIGAND IN PATIENTS WITH JUVENILE SYSTEMIC LUPUS ERYTHEMATOSUS (JSLE). ANNALS OF THE RHEUMATIC DISEASES, v. 74, p. 1-pg., 2015-06-01. (12/22997-4, 08/58238-4)

LIPHAUS, BERNADETE L.; LIMA, LAILA; PALMEIRA, PATRICIA; SILVA, CLOVIS A.; GOLDENSTEIN-SCHAINBERG, CLAUDIA; CARNEIRO-SAMPAIO, MAGDA. Increased sMer, but not sAxl, sTyro3, and Gas6 relate with active disease in juvenile systemic lupus erythematosus. CLINICAL RHEUMATOLOGY, v. 39, n. 2, p. 6-pg., 2019-10-26. (12/22997-4, 08/58238-4)

LIPHAUS, BERNADETE L.; CARAMALHO, IRIS; RANGEL-SANTOS, ANDREIA; SILVA, CLOVIS A.; DEMENGEOT, JOCELYNE; SALLES CARNEIRO-SAMPAIO, MAGDA MARIA. LRBA deficiency: a new genetic cause of monogenic lupus. ANNALS OF THE RHEUMATIC DISEASES, v. 79, n. 3, p. 427-428, MAR 2020. (14/14880-5, 12/22997-4, 08/58238-4, 14/50489-9)

LIPHAUS, BERNADETE L.; LIMA, LAILA; PALMEIRA, PATRICIA; SILVA, CLOVIS A.; GOLDENSTEIN-SCHAINBERG, CLAUDIA; CARNEIRO-SAMPAIO, MAGDA. Increased sMer, but not sAxl, sTyro3, and Gas6 relate with active disease in juvenile systemic lupus erythematosus. CLINICAL RHEUMATOLOGY, OCT 2019. (12/22997-4, 08/58238-4)

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, MAGDA. Increased Soluble Cytoplasmic Bcl-2 Protein Serum Levels and Expression and Decreased Fas Expression in Lymphocytes and Monocytes in Juvenile Dermatomyositis. JOURNAL OF RHEUMATOLOGY, v. 45, n. 11, p. 1577-1580, NOV 1 2018. (08/58238-4, 12/22997-4)

LIPHAUS, B. L.; KISS, M. H. B.; SALLUM, A. E.; AIKAWA, N. E.; CARRASCO, S.; PALMEIRA, P.; LIMA, L.; SILVA, C. A.; GOLDENSTEIN-SCHAINBERG, C.; CARNEIRO-SAMPAIO, M.. UP-REGULATED SOLUBLE BCL-2: A UNIQUE PROFILE OF PATIENTS WITH JUVENILE DERMATOMYOSITIS (JDM). ANNALS OF THE RHEUMATIC DISEASES, v. 74, p. 2-pg., 2015-06-01. (12/22997-4)