SOLANGE CARRASCO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject POSITIVE EFFECTS OF ANTI-MELANOCYTE STIMULATING HORMONE IN MURINE PRISTANE-INDUCED LUPUS(2013) PEIXOTO, T. V.; MELLO, S. B.; BOTTE, D. A.; CARRASCO, S.; VENDRAMINNI, M. B.; GOLDENSTEIN-SCHAINBERG, C.- Identification of Autoimmunity to Peptides of Collagen V alpha 1 Chain as Newly Biomarkers of Early Stage of Systemic Sclerosis(2021) VELOSA, Ana Paula Pereira; BRITO, Lais; QUEIROZ, Zelita Aparecida de Jesus; CARRASCO, Solange; MIRANDA, Jurandir Tomaz de; FARHAT, Cecilia; GOLDENSTEIN-SCHAINBERG, Claudia; PARRA, Edwin Roger; ANDRADE, Danieli Castro Oliveira de; SILVA, Pedro Leme; CAPELOZZI, Vera Luiza; TEODORO, Walcy RosoliaPatients with Systemic sclerosis (SSc) presents immune dysregulation, vasculopathy, and fibrosis of the skin and various internal organs. Pulmonary fibrosis leads to SSc-associated interstitial lung disease (ILD), which is the main cause of morbidity and mortality in SSc. Recently autoimmunity to type V collagen (Col V) has been characterized in idiopathic pulmonary fibrosis and show promise to be related to the development in SSc. Our aim was to evaluate autoimmunity to Col V alpha 1(V) and alpha 2(V) chains and to the antigenic peptides of these Col V chains in early-SSc sera employing lung tissue of SSc-ILD, as antigen source. We found that sera samples from patients with early-SSc were reactive to Col V (41.18%) and presented immunoreactivity for Col5A1(1.049) and Col5A1(1.439) peptides. The IgG isolated from early-SSc patients-anti-Col V positive sera (anti-ColV IgG) was adsorbed with alpha 1(V) chain (anti-ColV IgG/ads-alpha 1(V)) and alpha 2(V) chain (anti-ColV IgG/ads-alpha 2(V)) and biotinylated to evaluate the spectrum of reactivity in SSc-ILD patients lung biopsies by immunofluorescence. The SSc-ILD lung tissue samples immunostained with anti-ColV IgG showed increased green fluorescence in the vascular basement membrane, bronchiolar smooth muscle, and adventitial layer, contrasting with the tenue immunostaining in control lungs. Col V protein expression in these pulmonary compartments immunostained with early-SSc anti-ColV IgG was confirmed by immune colocalization assays with commercial anti-human Col V antibodies. In addition, SSc-ILD lung tissues immunostained with anti-ColV IgG/ads-alpha 1(V) (sample in which Col V alpha 1 chain-specific antibodies were removed) showed decreased green fluorescence compared to anti-ColV IgG and anti-ColV IgG/ads-alpha 2(V). Our data show that autoimmunity to Col V in early-SSc was related to peptides of the alpha 1(V) chain, suggesting that these antibodies could be biomarkers of SSc stages and potential target of immunotherapy with Col V immunogenic peptides.
- Post-Adipose-Derived Stem Cells (ADSC) Stimulated by Collagen Type V (Col V) Mitigate the Progression of Osteoarthritic Rabbit Articular Cartilage(2021) CRUZ, Isabele Camargo Brindo da; VELOSA, Ana Paula Pereira; CARRASCO, Solange; SANTOS FILHO, Antonio dos; MIRANDA, Jurandir Tomaz de; POMPEU, Eduardo; FERNANDES, Tiago Lazzaretti; BUENO, Daniela Franco; FANELLI, Camila; GOLDENSTEIN-SCHAINBERG, Claudia; FABRO, Alexandre Todorovic; FULLER, Ricardo; SILVA, Pedro Leme; CAPELOZZI, Vera Luiza; TEODORO, Walcy RosoliaCollagen is essential for cartilage adhesion and formation. In the present study, histology, immunofluorescence, morphometry, and qRT-PCR suggested that adipose-derived stem cells (ADSCs) stimulated by type V collagen (Col V) induce a significant increase of type II collagen (Col II) in the degenerative area of surgical-induced osteoarthritic rabbit articular cartilage (OA). In vitro, the effects of Col V on the proliferation and differentiation of ADSC were investigated. The expression of the cartilage-related genes Col2a1 and Acan was significantly upregulated and Pou5fl was downregulated post-ADSC/Col V treatment. Post-ADSC/Col V treatment, in vivo analyses revealed that rabbits showed typical signs of osteoarthritic articular cartilage regeneration by hematoxylin and eosin (H&E) and Safranin O/Fast Green staining. Immunohistochemical staining demonstrated that the volume of Col II fibers and the expression of Col II protein were significantly increased, and apoptosis Fas ligand positive significantly decreased post-ADSC/Col V treatment. In conclusion, the expression of Col II was higher in rabbits with surgical-induced osteoarthritic articular cartilage; hence, ADSC/Col V may be a promising therapeutic target for OA treatment.
conferenceObject HLA-B27 ANALYSIS BY FLOW CITOMETRY IN BRAZILIAN PATIENTS WITH ANKYLOSING SPONDYLITIS AND PSORIATIC ARTHRITIS(2013) GOLDENSTEIN-SCHAINBERG, C.; CARRASCO, S.; SAAD, C.; GONCALVES, C.; SAMPAIO-BARROS, P.; PARRA, E.- Collagen V alpha 1 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure(2022) MORAIS, Jymenez de; VELOSA, Ana Paula P.; ANDRADE, Priscila C.; FREDIANI, Denise; CARRASCO, Solange; QUEIROZ, Zelita A. de Jesus; MARTIN, Patricia; SAITO, Renata F.; ELIAS, Vitoria; GOLDENSTEIN-SCHAINBERG, Claudia; CHAMMAS, Roger; SAMPAIO-BARROS, Percival D.; CAPELOZZI, Vera L.; TEODORO, Walcy R.Cutaneous fibrosis is one of the main features of systemic sclerosis (SSc). Recent findings correlated abnormal collagen V (Col V) deposition in dermis with skin thickening and disease activity in SSc. Considering that Col V is an important regulator of collagen fibrillogenesis, understanding the role of Col V in the first two years of the skin fibrosis in SSc (early SSc) can help to determine new targets for future treatments. In this study, we analyzed the morphological, ultrastructural and molecular features of alpha 1(V) and alpha 2(V) chains and the expression of their coding genes COL5A1 and COL5A2 in collagen fibrillogenesis in early-SSc. Skin biopsies were obtained from seven consecutive treatment-naive patients with SSc-related fibrosis and four healthy controls. Our data showed increased alpha 1(V) and alpha 2(V) chain expression in the reticular dermis of early-SSc patients; however, immunofluorescence and ultrastructural immunogold staining determined a significant decreased expression of the alpha 1(V) chain along the dermoepidermal junction in the papillary dermis from early-SSc-patients in relation to the control (12.77 +/- 1.34 vs. 66.84 +/- 3.36; p < 0.0001). The immunoblot confirmed the decreased expression of the alpha 1(V) chain by the cutaneous fibroblasts of early-SSc, despite the increased COL5A1 and COL5A2 gene expression. In contrast, the alpha 2(V) chain was overexpressed in the small vessels (63.18 +/- 3.56 vs. 12.16 +/- 0.81; p < 0.0001) and capillaries (60.88 +/- 5.82 vs. 15.11 +/- 3.80; p < 0.0001) in the reticular dermis of early-SSc patients. Furthermore, COLVA2 siRNA in SSc cutaneous fibroblasts resulted in a decreased alpha 1(V) chain expression. These results highlight an intense decrease in the alpha 1(V) chain along the dermoepidermal junction, suggesting an altered molecular histoarchitecture in the SSc papillary dermis, with a possible decrease in the expression of the alpha 1(V)3 homotrimeric isoform, which could interfere with the thickening and cutaneous fibrosis related to SSc.
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.- CD4(+)CD69(+) T cells and CD4(+)CD25(+)FoxP3(+) Treg cells imbalance in peripheral blood, spleen and peritoneal lavage from pristane-induced systemic lupus erythematosus (SLE) mice(2019) PEIXOTO, Tatiana Vasconcelos; CARRASCO, Solange; BOTTE, Domingos Alexandre Ciccone; CATANOZI, Sergio; PARRA, Edwin Roger; LIMA, Thais Martins; UGRIUMOV, Natasha; SORIANO, Francisco Garcia; MELLO, Suzana Beatriz Verissimo de; RODRIGUES, Caio Manzano; GOLDENSTEIN-SCHAINBERG, ClaudiaBackground: Adaptive immune cells, including CD4(+)CD69(+) and CD4(+)CD25(+)FoxP3(+) regulatory T (Treg) cells, are important for maintaining immunological tolerance. In human systemic lupus erythematosus (SLE), CD4(+)CD25(+)FoxP3(+) Treg cells are reduced, whereas CD69 expression is increased, resulting in a homeostatic immune imbalance that may intensify autoreactive T cell activity. To analyze the mechanisms implicated in autotolerance failure, we evaluated CD4(+)CD69(+) and CD4(+)CD25(+)FoxP3(+) T cells and interleukin profiles in a pristane-induced SLE experimental model. Methods: For lupus induction, 26 female Balb/c mice received a single intraperitoneal 0.5 ml dose of pristane, and 16 mice received the same dose of saline. Blood and spleen samples were collected from euthanized mice 90 and 120 days after pristane or saline inoculation. Mononuclear cells from peripheral blood (PBMC), peritoneal lavage (PL) and splenocytes were obtained by erythrocyte lysis and cryopreserved for further evaluation by flow cytometry using the GuavaEasyCyte TM HT. After thawing, cells were washed and stained with monoclonal antibodies against CD3, CD4, CD8, CD25, CD28, CD69, FoxP3, CD14 and Ly6C (BD Pharmingen TM). Interleukins were quantified using Multiplex (R) MAP. The Mann-Whitney test and the Pearson coefficient were used for statistical analysis, and p < 0.05 considered significant. Results: Compared with the controls, SLE-induced animals presented increased numbers of CD4(+)CD69(+) T cells in the blood on T90 and T120 (p = 0.022 and p = 0.008) and in the spleen on T120 (p = 0.049), but there were decreased numbers in the PL (p = 0.049) on T120. The percentage of Treg was lower in blood (p < 0.005 and p < 0.012) on T90 and T120, in spleen (p = 0.043) on T120 and in PL (p = 0.001) on T90. Increased numbers of CD4+ CD69+ T cells in the PL were positively associated with high IL-2 (p = 0.486) and IFN-gamma (p = 0.017) levels, whereas reduced Treg cells in the blood were negatively correlated with TNF alpha levels (p = 0.043) and positively correlated with TGF beta 1 (p = 0.038). Conclusion: Increased numbers of CD4(+)CD69(+) T cells and reduced numbers of CD4(+)CD25(+)FoxP3(+) Treg cells with an altered interleukin profile suggests loss of autotolerance in pristane-induced lupus mice, which is similar to human lupus. Therefore, this model is useful in evaluating mechanisms of cellular activation, peripheral tolerance and homeostatic immune imbalance involved in human SLE.