EVANDRO ARARIGBOIA RIVITTI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Dermatologia, Faculdade de Medicina - Docente
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Update on fogo selvagem, an endemic form of pemphigus foliaceus(2015) AOKI, Valeria; RIVITTI, Evandro A.; DIAZ, Luis A.Pemphigus are organ-specific autoimmune diseases, where autoantibodies (mainly immunoglobulin [Ig]G) directed against epidermal targets (glycoproteins of the desmosomal core) are detected. Endemic pemphigus foliaceus or fogo selvagem (FS) is one of the variants of pemphigus foliaceus pemphigus foliaceus that shares the same clinical and immunopathological features of the classic non-endemic pemphigus foliaceus form, including pathogenic IgG (mainly IgG4) autoantibodies directed against the ectodomain of desmoglein 1 (Dsg1), that lead to acantholysis. Pathogenesis of FS is complex, involving genetic, environmental and immunological factors. Human leukocyte antigen (HLA)-DRB1 alleles DRB1*0404, *1402, *1406 or *0102 have been previously identified as risk factors for FS (relative risk, >14). Individuals exposed to hematophagous insects are more susceptible to develop the disease. Non-pathogenic anti-Dsg1 antibodies of the IgG1 subclass, directed against the extracellular 5 domain of Dsg1, are detected in patients in the preclinical stage of the disease, and also in healthy controls living in endemic areas. In counterpart, patients with FS show pathogenic anti-Dsg1 IgG4 autoantibodies that bind the pathogenic extracellular 1 and 2 domains of Dsg1, emphasizing the intramolecular epitope-spreading hypothesis. A possible explanation for the development of the autoimmune process would be antigenic mimicry, initiated by environmental stimuli in those genetically predisposed individuals. Characterization of the pathogenesis of FS will allow the development of specific therapeutic targets, and the elucidation of other autoimmune processes.
- IgG Autoantibody Response against Keratinocyte Cadherins in Endemic Pemphigus Foliaceus (Fogo Selvagem)(2012) FLORES, Gustavo; CULTON, Donna A.; PRISAYANH, Phillip; QAQISH, Bahjat F.; JAMES, Kirk; MALDONADO, Mike; AOKI, Valeria; HANS-FILHO, Gunter; RIVITTI, Evandro A.; DIAZ, Luis A.It is well established that autoantibodies against desmoglein 3 and desmoglein 1 (Dsg1) are relevant in the pathogenesis of pemphigus vulgaris and pemphigus foliaceus, including its endemic form fogo selvagem (FS). Isolated reports have shown that in certain patients with these diseases, autoantibodies against other desmosomal cadherins and E-cadherin may also be present. The goal of this investigation was to determine whether FS patients and normal individuals living in endemic areas possess autoantibodies against other desmosomal cadherins and E-cadherin. By testing a large number of FS and endemic control sera by ELISA, we found a consistent and specific autoantibody response against Dsg1 and other keratinocyte cadherins in these individuals, which is quite different from healthy individuals from the United States (US controls). Overall, the highest correlations among the autoantibody responses tested were in the endemic controls, followed by FS patients, and lowest in the US controls. These findings suggest that multiple, perhaps cross-reactive, keratinocyte cadherins are recognized by FS patients and endemic controls.
- An Insight into the Sialotranscriptome of Triatoma matogrossensis, a Kissing Bug Associated with Fogo Selvagem in South America(2012) ASSUMPCAO, Teresa C. F.; EATON, Donald P.; PHAM, Van M.; FRANCISCHETTI, Ivo M. B.; AOKI, Valeria; HANS-FILHO, Gunter; RIVITTI, Evandro A.; VALENZUELA, Jesus G.; DIAZ, Luis A.; RIBEIRO, Jose M. C.Triatoma matogrossensis is a Hemiptera that belongs to the oliveirai complex, a vector of Chagas' disease that feeds on vertebrate blood in all life stages. Hematophagous insects' salivary glands (SGs) produce potent pharmacologic compounds that counteract host hemostasis, including anticlotting, antiplatelet, and vasodilatory molecules. Exposure to T. matogrossensis was also found to be a risk factor associated with the endemic form of the autoimmune skin disease pemphigus foliaceus, which is described in the same regions where Chagas' disease is observed in Brazil. To obtain a further insight into the salivary biochemical and pharmacologic diversity of this kissing bug and to identify possible allergens that might be associated with this autoimmune disease, a cDNA library from its SGs was randomly sequenced. We present the analysis of a set of 2,230 (SG) cDNA sequences, 1,182 of which coded for proteins of a putative secretory nature.
- Profile of Trypanosoma cruzi Reactivity in a Population at High Risk for Endemic Pemphigus Foliaceus (Fogo Selvagem)(2012) SOUSA JR., Joaquim X.; DIAZ, Luis A.; EATON, Donald P.; HANS-FILHO, Guenter; FREITAS, Elder Lanzani de; DELGADO, Livia; ICHIMURA, Ligia Maria F.; CRISTALDI, Flavia; ORLANDI, Renata; KESPER JR., Norival; UMEZAWA, Eufrosina S.; RIVITTI, Evandro A.; AOKI, ValeriaFogo Selvagem (FS) is an autoimmune bullous disease with pathogenic IgG autoantibodies recognizing desmoglein 1 (Dsg1), a desmosomal glycoprotein. In certain settlements of Brazil, a high prevalence of FS (3%) is reported, suggesting environmental factors as triggers of the autoimmune response. Healthy individuals from endemic areas recognize nonpathogenic epitopes of Dsg1, and exposure to hematophagous insects is a risk factor for FS. Fogo selvagem and Chagas disease share some geographic sites, and anti-Dsg1 has been detected in Chagas patients. Indeterminate Chagas disease was identified in a Brazilian Amerindian population of high risk for FS. In counterpart, none of the FS patients living in the same geographic region showed reactivity against Trypanosoma cruzi. The profile of anti-Dsg1 antibodies showed positive results in 15 of 40 FS sera and in 33 of 150 sera from healthy individuals from endemic FS sites, and no cross-reactivity between Chagas disease and FS was observed.
- IgE, IgM, and IgG4 Anti-Desmoglein 1 Autoantibody Profile in Endemic Pemphigus Foliaceus (Fogo Selvagem)(2011) QIAN, Ye; PRISAYANH, Phillip; ANDRACA, Eugenio; QAQISH, Bahjat F.; AOKI, Valeria; HANS-FILHIO, Gunter; RIVITTI, Evandro A.; DIAZ, Luis A.
- A Lutzomyia longipalpis Salivary Protein Induces Cross-Reactive Antibodies to Pemphigus Autoantigen Desmoglein 1(2020) DIAZ, Luis A.; PRISAYANH, Phillip; QAQISH, Bahjat; TEMPLE, Brenda R.; AOKI, Valeria; HANS-FILHO, Gunter; RIVITTI, Evandro A.; FRIEDMAN, Horacio; KARETNICK, Morgan; HERBERT, Samantha M.; VALENZUELA, Jesus G.Fogo selvagem (FS) is a blistering skin disease caused by pathogenic IgG4 autoantibodies to desmoglein 1 (DSG1). Preclinical FS and leishmaniasis are endemic to certain regions of Brazil and exhibit nonpathogenic anti-DSG1 antibodies. Recurring bites from Lutzomyia longipalpis, the sand fly vector of leishmaniasis, immunize individuals with L. longipalpis salivary antigens LJM17 and LJM11. We measured the antibody responses to LJM17, LJM11, and DSG1 in normal settlers and patients with FS from an endemic focus of FS and nonendemic control populations. We also immunized mice with these antigens and assessed the IgG response. Healthy individuals and patients with FS from endemic areas had significantly higher values of IgG4 anti-LJM17 antibodies than nonendemic controls (P < 0.001 for both). The levels of IgG anti-DSG1 and IgG4 anti-LJM17 and anti-LJM11 antibodies correlated positively in normal settlers and patients with FS. Mice immunized with recombinant LJM17 produced IgG1 antibodies (human IgG4 homolog) that strongly cross-reacted with recombinant DSG1; these IgG1 antibodies were inhibited by LJM17, LJM11, and DSG1 in a dose-dependent manner. However, they did not bind human or mouse epidermis by indirect immunofluorescence. Lastly, we identified short-sequence homologies of surface-exposed residues within the human DSG1 ectodomain and LJM17. Inoculation by LJM17 from L. longipalpis-elicited DSG1-cross-reactive IgG4 antibodies may lead to FS in genetically predisposed individuals.
- IgE Anti-LJM11 Sand Fly Salivary Antigen May Herald the Onset of Fogo Selvagem in Endemic Brazilian Regions(2015) QIAN, Ye; JEONG, Joseph S.; ABDELADHIM, Maha; VALENZUELA, Jesus G.; AOKI, Valeria; HANS-FILHIO, Gunter; RIVITTI, Evandro A.; DIAZ, Luis A.
conferenceObject Adult atopic dermatitis: Evaluation of TH17 and TH22 cytokines in peripheral blood mononuclear cells induced by staphylococcal enterotoxins A and B(2012) ORFALI, Raquel Lean; RIVITTI, Evandro; SATO, Maria Notomi; TAKAOKA, Roberto; AOKI, ValeriaObjective: Evaluation of interleukins (IL) 17, 22, and 23 induced by Staphylococcus aureus enterotoxin stimulation in peripheral blood mononuclear cells (PBMC) of adults with atopic dermatitis. Background: Atopic dermatitis (AD) is a chronic, inflammatory disease with a high prevalence and complex etiopathogenesis.S aureusis present in 80% to 100% of AD patients, and secretes exotoxins that might relate to its pathogenesis. TH17 has been described as playing a major role in inflammatory diseases with a close relationship to bacterial pathogens, as well as TH22 in modulating the immunopathogenesis of some skin diseases. Methods: Thirty-eight AD patients (mean age, 28.55), 19 female and 19 male, and 40 healthy controls (mean age, 34.1), 21 females and 19 males (without personal or family history of atopy and negative prick-test) were selected. Hanifin and Rajka’s criteria were used to diagnose AD. Disease severity was established according to EASI (Eczema Area and Severity Index). IL-17, IL-22, and IL-23 production from PBMC after staphylococcal enterotoxins A (SEA) and B (SEB), and phytohemaglutinin (PHA) stimuli and IL-22 serum levels were measured by ELISA. Results: In AD patients, there was increased IL-22 levels in sera as well as in vitro secretion by PBMC after SEA and SEB stimuli, when compared to healthy controls. No correlation between IL-22 levels and EASI was observed (P ≤ .05). Conclusion: These findings suggest an involvement of TH22 subtype in the pathogenesis of adults with AD, especially because of its link to S aureus enterotoxins.- Overlapping IgG4 Responses to Self- and Environmental Antigens in Endemic Pemphigus Foliaceus(2016) QIAN, Ye; JEONG, Joseph S.; YE, Jian; DANG, Bim; ABDELADHIM, Maha; AOKI, Valeria; HANS-FILHIO, Gunter; RIVITTI, Evandro A.; VALENZUELA, Jesus G.; DIAZ, Luis A.The etiology of human autoimmune diseases in general remains largely unknown, although the genetic and environmental interplay may be relevant. This applies to the autoimmune diseases of the skin such as the pemphigus phenotypes and others. In this group, there is an endemic form of pemphigus foliaceus (also known as fogo selvagem [FS]) in which the pathogenic IgG4 autoantibody response to the self-antigen desmoglein 1 (Dsg1) cross-reacts with the LJM11 sand fly salivary gland Ag. In this investigation, we dissected the IgG4 autoantibody repertoires used by FS patients in response to endogenous self-Dsg1 and exogenous LJM11 sand fly Ag. Based on analyses of the genetic clonal signatures of these Abs, our results indicate that there is a significant overlap between these two responses, as all identified IgG4 mAbs cross-react to both Dsg1 and LJM11 Ags. Germline H-and L-chain V gene Abs generated according to mutated cross-reactive mAbs preserved their reactivity to both Ags. Our findings suggest that both Dsg1 autoantigen and LJM11 environmental Ag could be the initial antigenic stimulants for the IgG4 autoimmune responses in FS. These results support our hypothesis that LJM11 Ag plays a substantial role in triggering the IgG4 autoantibody development in FS and provide new insights on how noninfectious environmental Ag(s) may drive the generation of autoantibodies in IgG4-related autoimmune diseases.
- Atopic dermatitis: correlation between non-damaged skin barrier function and disease activity(2012) ADDOR, Flavia A. S.; TAKAOKA, Roberto; RIVITTI, Evandro A.; AOKI, ValeriaBackground Atopic dermatitis (AD) is a chronic dermatosis, predominant in childhood, characterized by pruritus and eczematous-type lesions with xerosis as the prominent clinical sign. Objectives To analyze the correlation between biophysical measurements of skin barrier function and other assessment criteria of clinical severity according to Rajka and Langelands criteria. Methods Biophysical measurements [transepidermal water loss (TEWL) and corneometry] were obtained from 120 patients with the diagnosis of AD. Serum levels of IgE were also evaluated. Results A significant correlation between corneometry, TEWL, and clinical severity of AD was found. Data showed an inverse correlation between corneometry, TEWL, and AD severity, and a significant difference (P < 0.001) between mean of corneometry and TEWL and AD severity (mild, moderate, and severe). As for IgE levels, corneometry had significant negative correlation, in contrast with TEWL, which showed a significant positive correlation (P < 0.001). Conclusion Biophysical measurements of skin barrier in non-lesional skin of AD may work as an evaluation factor for AD severity.