NATALINO HAJIME YOSHINARI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
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 CORRELATION BETWEEN SHORTER DISEASE DURATION IN SYSTEMIC SCLEROSIS (SSC) AND ANTI-COLLAGEN TYPE V(2014) UGOLINI, M.; MANTOVANI, E.; DINIS, V.; BONOLDI, V.; RIBEIRO, A.; YOSHINARI, N.; ANDRADE, D.- Survival, Causes of Death, and Prognostic Factors in Systemic Sclerosis: Analysis of 947 Brazilian Patients(2012) SAMPAIO-BARROS, Percival D.; BORTOLUZZO, Adriana B.; MARANGONI, Roberta G.; ROCHA, Luiza F.; RIO, Ana Paula T. Del; SAMARA, Adil M.; YOSHINARI, Natalino H.; MARQUES-NETO, Joao FranciscoObjective. To analyze survival, prognostic factors, and causes of death in a large cohort of patients with systemic sclerosis (SSc). Methods. From 1991 to 2010, 947 patients with SSc were treated at 2 referral university centers in Brazil. Causes of death were considered SSc-related and non-SSc-related. Multiple logistic regression analysis was used to identify prognostic factors. Survival at 5 and 10 years was estimated using the Kaplan-Meier method. Results. One hundred sixty-eight patients died during the followup. Among the 110 deaths considered related to SSc, there was predominance of lung (48.1%) and heart (24.5%) involvement. Most of the 58 deaths not related to SSc were caused by infection, cardiovascular or cerebrovascular disease, and cancer. Male sex, modified Rodnan skin score (mRSS) > 20, osteoarticular involvement, lung involvement, and renal crisis were the main prognostic factors associated to death. Overall survival rate was 90% for 5 years and 84% for 10 years. Patients presented worse prognosis if they had diffuse SSc (85% vs 92% at 5 yrs, respectively, and 77% vs 87% at 10 yrs, compared to limited SSc), male sex (77% vs 90% at 5 yrs and 64% vs 86% at 10 yrs, compared to female sex), and mRSS > 20 (83% vs 90% at 5 yrs and 66% vs 86% at 10 yrs, compared to mRSS <20). Conclusion. Survival was worse in male patients with diffuse SSc, and lung and heart involvement represented the main causes of death in this South American series of patients with SSc. (First Release Aug 15 2012; J Rheumatol 2012;39:1971-8; doi:10.3899/jrheum.111582)
- Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis(2019) SOBANSKI, Vincent; GIOVANNELLI, Jonathan; ALLANORE, Yannick; RIEMEKASTEN, Gabriela; AIRO, Paolo; VETTORI, Serena; COZZI, Franco; DISTLER, Oliver; MATUCCI-CERINIC, Marco; DENTON, Christopher; LAUNAY, David; HACHULLA, Eric; CERINIC, Marco Matucci; GUIDUCCI, Serena; WALKER, Ulrich; KYBURZ, Diego; LAPADULA, Giovanni; IANNONE, Florenzo; DISTLER, Oliver; MAURER, Britta; JORDAN, Suzana; BECVAR, Radim; SIERAKOWSKY, Stanislaw; BIELECKA, Otylia Kowal; CUTOLO, Maurizio; SULLI, Alberto; VALENTINI, Gabriele; CUOMO, Giovanna; VETTORI, Serena; SIEGERT, Elise; REDNIC, Simona; NICOARA, Ileana; KAHAN, Andre; ALLANORE, Yannick; VLACHOYIANNOPOULOS, Panayiotis; MONTECUCCO, Carlo; CAPORALI, Roberto; STORK, Jiri; INANC, Murat; CARREIRA, Patricia E.; NOVAK, Srdan; CZIRJAK, Laszlo; VARJU, Cecilia; CHIZZOLINI, Carlo; KUCHARZ, Eugene J.; KOTULSKA, Anna; KOPEC-MEDREK, Magdalena; WIDUCHOWSKA, Malgorzata; COZZI, Franco; ROZMAN, Blaz; MALLIA, Carmel; COLEIRO, Bernard; GABRIELLI, Armando; FARGE, Dominique; WU, Chen; MARJANOVIC, Zora; FAIVRE, Helene; HIJ, Darin; DHAMADI, Roza; AIRO, Paolo; HESSELSTRAND, Roger; WOLLHEIM, Frank; WUTTGE, Dirk M.; ANDREASSON, Kristofer; MARTINOVIC, Duska; BALBIR-GURMAN, Alexandra; BRAUN-MOSCOVICI, Yolanda; TROTTA, Francesco; MONACO, Andrea Lo; HUNZELMANN, Nicolas; PELLERITO, Raffaele; BAMBARA, Lisa Maria; CARAMASCHI, Paola; MOROVIC-VERGLES, Jadranka; BLACK, Carol; DENTON, Christopher; DAMJANOV, Nemanja; HENES, Joerg; SANTAMARIA, Vera Ortiz; HEITMANN, Stefan; KRASOWSKA, Dorota; SEIDEL, Matthias; HASLER, Paul; BURKHARDT, Harald; HIMSEL, Andrea; BAJOCCHI, Gianluigi; NUOVA, Arcispedale Santa Maria; SALVADOR, Maria Joao; SILVA, Jose Antonio Pereira Da; STAMENKOVIC, Bojana; STANKOVIC, Aleksandra; SELMI, Carlo Francesco; SANTIS, Maria De; MARASINI, Bianca; TIKLY, Mohammed; ANANIEVA, Lidia P.; DENISOV, Lev N.; MUELLER-LADNER, Ulf; FRERIX, Marc; TARNER, Ingo; SCORZA, Raffaella; PUPPO, Francesco; ENGELHART, Merete; STRAUSS, Gitte; NIELSEN, Henrik; DAMGAARD, Kirsten; SZUCS, Gabriella; SZAMOSI, Szilvia; MENDOZA, Antonio Zea; PUENTE, Carlos de la; GIRALDO, Walter Alberto Sifuentes; MIDTVEDT, Oyvind; REISETER, Silje; GAREN, Torhild; HACHULLA, Eric; LAUNAY, David; VALESINI, Guido; RICCIERI, Valeria; IONESCU, Ruxandra Maria; OPRIS, Daniela; GROSEANU, Laura; WIGLEY, Fredrick M.; CORNATEANU, Roxana Sfrent; IONITESCU, Razvan; GHERGHE, Ana Maria; SOARE, Alina; GORGA, Marilena; BOJINCA, Mihai; MIHAI, Carina; MILICESCU, Mihaela; SUNDERKOETTER, Cord; KUHN, Annegret; SANDORFI, Nora; SCHETT, Georg; DISTLER, Joerg H. W.; BEYER, Christian; MERONI, Pierluigi; INGEGNOLI, Francesca; MOUTHON, Luc; KEYSER, Filip De; SMITH, Vanessa; CANTATORE, Francesco Paolo; CORRADO, Ada; ULLMAN, Susanne; IVERSEN, Line; MUEHLEN, Carlos Alberto von; BOHN, Jussara Marilu; LONZETTI, Lilian Scussel; POZZI, Maria Rosa; EYERICH, Kilian; HEIN, Ruediger; KNOTT, Elisabeth; WILAND, Piotr; SZMYRKA-KACZMAREK, Magdalena; SOKOLIK, Renata; MORGIEL, Ewa; MADEJ, Marta; HOUSSIAU, Frederic A.; ALEGRE-SANCHO, Juan Jose; KRUMMEL-LORENZ, Brigitte; SAAR, Petra; ARINGER, Martin; GUENTHER, Claudia; WESTHOVENS, Rene; LANGHE, Ellen de; LENAERTS, Jan; ANIC, Branimir; BARESIC, Marko; MAYER, Miroslav; UPRUS, Maria; OTSA, Kati; YAVUZ, Sule; GRANEL, Brigitte; RADOMINSKI, Sebastiao Cezar; MUELLER, Carolina de Souza; AZEVEDO, Valderilio Feijo; JIMENEZ, Sergio; BUSQUETS, Joanna; AGACHI, Svetlana; GROPPA, Liliana; CHIABURU, Lealea; RUSSU, Eugen; POPA, Sergei; ZENONE, Thierry; PILECKYTE, Margarita; STEBBINGS, Simon; HIGHTON, John; MATHIEU, Alessandro; VACCA, Alessandra; SAMPAIO-BARROS, Percival D.; YOSHINARI, Natalino H.; MARANGONI, Roberta G.; MARTIN, Patricia; FUOCCO, Luiza; STAMP, Lisa; CHAPMAN, Peter; O'DONNELL, John; SOLANKI, Kamal; DOUBE, Alan; VEALE, Douglas; O'ROURKE, Marie; LOYO, Esthela; LI, Mengtao; MOHAMED, Walid Ahmed Abdel Atty; ROSATO, Edoardo; AMOROSO, Antonio; GIGANTE, Antonietta; OKSEL, Fahrettin; YARGUCU, Figen; TANASEANU, Cristina-Mihaela; POPESCU, Monica; DUMITRASCU, Alina; TIGLEA, Isabela; FOTI, Rosario; CHIRIEAC, Rodica; ANCUTA, Codrina; FURST, Daniel E.; VILLIGER, Peter; ADLER, Sabine; LAAR, Jacob van; KAYSER, Cristiane; EDUARDO, Andrade Luis C.; FATHI, Nihal; HASSANIEN, Manal; LEFEBVRE, Paloma Garcia de la Pena; RUBIO, Silvia Rodriguez; EXPOSITO, Marta Valero; SIBILIA, Jean; CHATELUS, Emmanuel; GOTTENBERG, Jacques Eric; CHIFFLOT, Helene; LITINSKY, Ira; EMERY, Paul; BUCH, Maya; GALDO, Francesco Del; VENALIS, Algirdas; BUTRIMIENE, Irena; VENALIS, Paulius; RUGIENE, Rita; KARPEC, Diana; SAKETKOO, Lesley Ann; LASKY, Joseph A.; KERZBERG, Eduardo; MONTOYA, Fabiana; COSENTINO, Vanesa; LIMONTA, Massimiliano; BRUCATO, Antonio Luca; LUPI, Elide; ROSNER, Itzhak; ROZENBAUM, Michael; SLOBODIN, Gleb; BOULMAN, Nina; RIMAR, Doron; COUTO, Maura; SPERTINI, Francois; RIBI, Camillo; BUSS, Guillaume; KAHL, Sarah; HSU, Vivien M.; CHEN, Fei; MCCLOSKEY, Deborah; MALVEAUX, Halina; PASQUALI, Jean Louis; MARTIN, Thierry; GORSE, Audrey; GUFFROY, Aurelien; POINDRON, VincentObjective Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. Methods A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty-four clinical and serologic variables were used for clustering. Results Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. Conclusion Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis.
- First report of mild Brazilian spotted fever associated to arthritis(2014) BONOLDI, Virginia Lucia Nazario; MARANGONI, Roberta Gongalves; GAUDITANO, Giancarla; MORAES-FILHO, Jonas; LABRUNA, Marcelo Bahia; YOSHINARI, Natalino HajimeWe describe the first Brazilian case of mild Rickettsiosis, complicated by knee monoarthritis, in young adult bitten by a tick on his left leg in Camburi zone, located in Sao Sebastiao municipality, southern coastal region of the State of Sao Paulo, in the Atlantic rainforest region, Brazil. The patient developed inoculation eschar at the tick bite site associated with enlarged lymph nodes in the left groin, fever, polyarthralgia, headache and macular rash. Twenty days after tick bite episode, he displayed monoarthritis in his right knee. The diagnosis of mild Rickettsiosis was established by sequential immunological analysis in serum and synovial fluid, using the indirect immunofluorescence (IF) assay for antibodies reactive with Rickettsia parkeri and Rickettsia rickettsii. The mild Rickettsiosis is an emerging zoonosis, that must be investigated by physicians, including rheumatologists, in patients that present macular rash, fever and eventually arthritis, after visiting the southern coastal Atlantic rainforest region in Brazil.
conferenceObject DYNAMIC COLLAGEN V REMODELING IS RELATED TO SKIN THICKENING IN SSc(2012) MARTIN, P.; TEODORO, W. R.; VELOSA, A. P.; CARRASCO, S.; MORAIS, J. de; CHRISTMANN, R. B.; PARRAS, E. R.; CAPELOZZI, V. L.; YOSHINARI, N. H.Background. Normal physiological properties of skin, one of the primary organs affected in SSc, depends on collagen Types I (COL I), III (COLIII) and V (COLV) assembly forming heterotypic fibres. COLV regulates fibril diameter and loss of this function could result in tissue fibrosis. In this way, our aim was to evaluate the histological and molecular profiles of COLI, COLIII and COLV in SSc skin and its correlation with skin thickening and disease activity. Methods. Skin biopsies of 18 patients (5 at early and 13 at late disease stage) and 10 healthy controls were studied. Assessment of skin thickening was performed using the modified Rodnan skin score (MRSS) and disease activity was calculated by Valentini Disease Activity Index. Quantification of COLI, COLIII and COLV was evaluated by histomorphometry in dermis and quantitative RT–PCR in dermal fibroblast culture. Results. A higher expression of abnormal COLV was observed in dermis of patients with early disease when compared with control group and late disease. The COLIII content was also higher in early SSc when compared with healthy controls and late SSc. On the other hand, the amount of COLI was higher in late disease when compared with control and early SSc. A positive correlation between COLV and MRSS (r = 0.42, P = 0.04) as well as disease activity (r = 0.45, P = 0.03) was observed, but there was no correlation between COLI and COLIII expression and these parameters. COLV α-1 and COLV α-2, as well as COLI α-1 and COLIII α-1 mRNA expression were higher in SSc when compared with control group. Conclusion. We found increased COLIII and COLV deposition in early SSc and increased COLI expression in late SSc indicating that collagen remodelling in SSc is a dynamic process. The fact that abnormal COLV expression decreases in later disease stages could explain why skin thickening sometimes improves spontaneously with time. Besides, COLV is correlated to MRSS and disease activity. These findings include COLV as an important regulator of cutaneous thickness in SSc and may add this protein as a new target for future treatments.conferenceObject ASSOCIATION WITH OTHER AUTOIMMUNE DISEASES IS FREQUENT IN A COHORT OF 901 BRAZILIAN PATIENTS WITH SSc(2012) SAMPAIO-BARROS, P.; MARANGONI, R.; ROCHA, L.; RIO, A. P. Del; YOSHINARI, N.; MARQUES-NETO, J. F.- Anti-collagen type v: a marker of early systemic sclerosis?(2019) UGOLINI-LOPES, Michelle R.; MANTOVANI, Elenice; BONOLDI, Virginia Lucia N.; RIBEIRO, Ana Cristina de Medeiros; BONFA, Eloisa; YOSHINARI, Natalino; ANDRADE, DanieliObjective: To evaluate the frequency of anti-collagen type V in humans with early systemic sclerosis (SSc) compared to defined SSc patients and healthy controls, since collagen type V was shown to be overexpressed in early SSc patients' skin and there is no data concerning the presence of this antibody in early stages of human SSc. Experimental studies showed that animal models immunized with collagen type V developed a disease similar to human systemic sclerosis (SSc), with antibodies production, mainly in early stages post-immunization. Methods: Eighty-one female SSc patients were included and divided into two groups: early-SSc (18 patients-EULAR Preliminary Criteria) and defined-SSc (63 patients-ACR Criteria 1980). The control group consisted of 19 healthy women age-matched to Early-SSc group. Anti-collagen type V was performed by ELISA. Data was analyzed by appropriate tests. Results: The prevalence of anti-collagen type V in early-SSc, defined-SSc and control groups was respectively 33, 17 and 5% (p = 0.07). SSc patients with anti-collagen type V had shorter disease duration compared to those without this antibody (8.8 +/- 5.1 vs. 14.7 +/- 8.9, p = 0.006). Likewise, early-SSc patients with anti-collagen V also had a shorter disease duration than patients negative for this antibody (4.6 +/- 2.2 vs. 9.7 +/- 5.2, p = 0.04). No association with clinical subsets or scleroderma antibodies specificities was observed (p > 0.05). Conclusion: The production of anti-collagen type V in SSc seems to be an early event independent of other antibodies specificities. Further studies are necessary to determine if the underlying mechanism for this chronology involves a primary immune response to abnormal expression of collagen type V.
- Cross-cultural adaptation and validation of the Brazilian version of the Scleroderma Health Assessment Questionnaire (SHAQ)(2014) ROCHA, Luiza F.; MARANGONI, Roberta G.; SAMPAIO-BARROS, Percival D.; LEVY-NETO, Mauricio; YOSHINARI, Natalino H.; BONFA, Eloisa; STEEN, Virginia; KOWALSKI, Sergio C.The Scleroderma Health Assessment Questionnaire (SHAQ) is a feasible multisystem specific tool that has been extensively used as an additional assessment for systemic sclerosis (SSc). The aim of this study is to cross-culturally adapt and validate the Brazilian version of the SHAQ. Construct validity was assessed based on the correlations between SHAQ and both the Medical Outcomes Survey Short Form 36 version 2 (SF-36v2 (TM)) and the Health Assessment Questionnaire Disability Index (HAQ-DI). The correlation between the SHAQ and disease severity was assessed by Spearman's correlation coefficient. The reproducibility of the SHAQ was evaluated by the intraclass correlation coefficient (ICC). Among the 151 consecutive outpatients evaluated, 59 % had limited SSc subtype. The overall disease severity visual analog scale (VAS) of the SHAQ was statistically significantly correlated to HAQ-DI, pain VAS, and the SF-36v2 (TM) physical component summary score (r = 0.595, r = 0.612, and r = -0.582, respectively; p < 0.001). Further analysis of all SF-36v2 (TM) components revealed statistically significant correlations between overall disease severity VAS and bodily pain (r = -0.621, p < 0.001), vitality (r = -0.544, p < 0.001), physical function (r = -0.510, p < 0.001), and role limitation-physical dimensions (r = -0.505, p < 0.001). Moreover, digestive, pulmonary, and overall disease severity VASs were statistically significantly correlated to the number of organs involved (r = 0.178, p = 0.029; r = 0.214, p = 0.008; r = 0.282, p < 0.001). We also demonstrated high reproducibility for SHAQ (ICC = 0.757, 95 % confidence interval = 0.636-0.842). The Brazilian version of the SHAQ demonstrated both construct and discriminant validities as well as good reproducibility.
- Chronic lymphomonocytic meningoencephalitis, oligoarthritis and erythema nodosum: report of Baggio-Yoshinari syndrome of long and relapsing evolution(2014) ROSA NETO, Nilton Sal Les; GAUDITANO, Giancarla; YOSHINARI, Natalino HajirneThe Brazilian human borreliosis, also known as Baggio-Yoshinari Syndrome (BYS), is a tick-borne disease but whose ticks do not pertain to the Ixodes ricinus complex. It is caused by Borrelia burgdorferi sensu lato microorganisms and resembles clinical and laboratory features of Lyme disease (LD). BYS is also distinguished from LD by its prolonged clinical evolution, with relapsing episodes and autoimmune dysfunction. We describe the case of a young female who, over one year, progressively presented with oligoarthritis, cognitive impairment, menigoencephalitis and erythema nodosum. Diagnosis was established by means of the clinical history and a positive serology to Borrelia burgdorferi sensu strictu. The patient received Ceftriaxone 2 g IV/day during 30 days, followed by 2 months of doxicycline 100 mg bid. Symptoms remitted and the Borrelia serology tests returned to normality. BYS is a new disease described only in Brazil, which has a raising frequency and deserves the attention from the country's medical board because of clinical, epidemiological and laboratory differences from LD. Despite the fact that it is a hard-to-diagnose zoonosis, it is important to pursuit an early diagnosis because the symptoms respond well to antibiotics or it might be resistant to treatment and may evolve to a chronic phase with both articular and neurological sequelae.
conferenceObject COLLAGEN V-INDUCED NASAL TOLERANCE PROMOTES DECREASE IN TOPO I PROTEIN SYNTHESIS AND PULMONARY FIBROSIS OF SSc MODEL(2012) VELOSA, A. P.; TEODORO, W. R.; CALLADO, M. R.; FILHO, A. S.; FERNEZLIAN, S. M.; KATAYAMA, M. L.; PARRA, E. R.; CAPELOZZI, V. L.; YOSHINARI, N. H.Background. Autoantibodies against topo I (anti-Scl-70) are found to be associated with increased mortality and correlate with the extent of pulmonary fibrosis in SSc. To evaluate anti-Scl-70 antibodies and topo I expression in lung and to correlate with pulmonary fibrosis in experimental SSc after collagen V (COL V)-induced nasal tolerance. Methods. Female New Zealand rabbits (n = 12) were immunized with 1 mg/ml of COL V in Freund's adjuvant (IM). After 150 days, six immunized animals were tolerated by nasal administration of type COL V (25 μg/day) (IM-TOL), daily during 60 days. Anti-Scl-70 antibodies were evaluated by ELISA. Immunohistochemistry, histomorphometry and RT–PCR evaluated pulmonary topo I expression, types I, III and V collagen and TGF-β expression in pulmonary parenchyma. Results. A significant decrease in topo I expression by pulmonary endothelial cells was found comparing IM-TOL vs IM [29.86 (10.48) vs 76.11 (20.91), P = 0.019]. No difference was found for the anti-Scl-70 frequency after tolerance. Type V collagen content around the small vessels [0.371 (0.118) vs 0.874 (0.282), P < 0.001] and bronchioles [0.294 (0.139) vs 0.646 (0.172), P < 0.001], beyond mRNA expression to types I [0.10 (0.07) vs 1.0 (0.528), P = 0,002] and V [1.12 (0.42) vs 4.74 (2.25), P = 0,009] collagen decreased in IM-TOL, when compared with IM TGF-β expression decreased in endothelial [10.77 (4.3) vs 43.5 (5.7), P < 0,0001] and smooth muscle cells [9.93 (3.77) vs 53.68 (4.06), P < 0,0001] from pulmonary vessels, epithelial cells [6.03 (1.47) vs 13.65 (1.39), P < 0,0001] and interstitial fibroblasts [11.55 (1.88) vs 20.13 (1.60), P < 0,0001] in IM-TOL compared with IM. Conclusions. The results showed that a direct link between nasal type V collagen tolerance and a decline in topo I expression may reduce pulmonary fibrosis, suggesting that strategies aimed at preventing the increase of the type V collagen synthesis, or the local responses to increased topo I expression, may have a greater impact in SSc.