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.- 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.
- The Current State of Knowledge on Baggio-Yoshinari Syndrome (Brazilian Lyme Disease-like Illness): Chronological Presentation of Historical and Scientific Events Observed over the Last 30 Years(2022) YOSHINARI, Natalino Hajime; BONOLDI, Virginia Lucia Nazario; BONIN, Serena; FALKINGHAM, Erica; TREVISAN, GiustoBaggio-Yoshinari Syndrome (BYS) is an emerging Brazilian tick-borne infectious disease that clinically mimics Lyme Disease (LD) present in the Northern Hemisphere. LD is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex and transmitted by Ixodid ticks of complex Ixodes rticinus. On the contrary, BYS is transmitted by hard Ixodid ticks of the genera Amblyomma, Rhipicephalus and Dermacentor. In 1992, the first cases of BYS were described in patients that developed EM rash, flu-like symptoms and arthritis after tick bite episodes. Since these findings, research in BYS has been developing for more than 30 years and shows that its epidemiological, clinical and laboratorial features are different from LD. Borrelia burgdorferi was never isolated in Brazil. In addition, specific serologic tests have shown little positivity. Furthermore, peripheral blood analysis of patients using electron microscopy exhibited structures resembling spirochete-like microorganisms or the latent forms of spirochetes (L form or cell wall deficient bacteria). For these reasons, Brazilian zoonosis was defined as an exotic and emerging Brazilian infectious disease, transmitted by ticks not belonging to the Ixodes ricinus complex, caused by latent spirochetes belonging to the B. burgdorferi sensu lato complex with atypical morphology. The Brazilian ecosystem, combined with its ticks and reservoir biodiversity, possibly contributed to the origin of this new zoonosis, which emerged as a result of the passage of B. burgdorferi through exotic vectors and reservoirs.
- 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.
- Brazilian borreliosis with special emphasis on humans and horses(2017) BASILE, Roberta Carualho; YOSHINARI, Natalino Hajime; MANTOVANI, Elenice; BONOLDI, Virginia Nazario; MACORIS, Delphim da Graca; QUEIROZ-NETO, Antonio deBorreliosis caused by Borrelia burgdorferi sensu lato is a cosmopolitan zoonosis studied worldwide; it is called Lyme disease in many countries of the Northern Hemisphere and Lyme-like or Baggio-Yoshinari Syndrome in Brazil. However, despite the increasing number of suspect cases, this disease is still neglected in Brazil by the medical and veterinary communities. Brazilian Lyme-like borreliosis likely involves capybaras as reservoirs and Amblyomma and Rhipicephalus ticks as vectors. Thus, domestic animals can serve as key carriers in pathogen dissemination. This zoonosis has been little studied in horses in Brazil. The first survey was performed in the state of Rio de Janeiro, and this Brazilian Borreliosis exhibits many differences from the disease widely described in the Northern Hemisphere. The etiological agent shows different morphological and genetic characteristics, the disease has a higher recurrence rate after treatment with antibiotics, and the pathogen stimulates intense symptoms such as a broader immune response in humans. Additionally, the Brazilian zoonosis is not transmitted by the Ixodes ricinus complex. With respect to clinical manifestations, Baggio-Yoshinari Syndrome has been reported to cause neurological, cardiac, ophthalmic, muscle, and joint alterations in humans. These symptoms can possibly occur in horses. Here, we present a current panel of studies involving the disease in humans and equines, particularly in Brazil. (C) 2016 Sociedade Brasileira de Microbiologia.
- Innate and Th1/Th17 adaptive immunity in acute and convalescent Brazilian borreliosis disease(2021) BONOLDI, Virginia Lucia Nazario; YOSHINARI, Natalino Hajime; ANIZ, Patricia Antonia Estima Abreu de; PEREIRA, Rosa Maria RodriguesIntroduction: Brazilian borreliosis (BB) disease is an infectious disease transmitted by ticks that mimics Lyme disease (LD) from the Northern Hemisphere. The BB clinical picture is characterized by a pathognomonic skin lesion (migratory erythema) and joint, neurological, cardiac and psychiatric symptoms. Innate and Th1/Th17 adaptive immunity seem to play an important role in the pathogenesis of Lyme disease. Objective: The aim of this study was to characterize the role of innate and Th1/Th17 adaptive immunity in BB patients with acute (<3 months) and convalescent (>3 months) disease. Methods: Fifty BB patients (28 with acute and 22 with convalescent disease) without treatment and 30 healthy subjects were evaluated. Levels of 20 cytokines or chemokines associated with innate and Th1/Th17 adaptive immunity were analyzed using Luminex (Millipore Corp., Billerica, MA). Results: Overall, BB patients had increased levels of IL-8 (6.29 vs 2.12 p = 0.002) and MIP-1 alpha/CCL3 (5.20 vs 2.06, p = 0.030), associated with innate immunity, and MIP3B/CCL19 (Th1; 297.86 vs 212.41, p = 0.031) and IL-17A (Th17; 3.11 vs 2.20, p = 0.037), associated with adaptive immunity, compared with the levels of healthy controls. When comparing acute BB vs. convalescent BB subjects vs. healthy controls, IL-1 beta, IL-8 and MIP-1 alpha/CCL3 (innate mediators) levels were highest in patients in the acute phase of disease (p < 0.05). TNF-alpha was associated with disseminated symptoms and with humoral reactivity against Borrelia burgdorferi. IL-10 was significantly correlated with IL-6 (r = 0.59, p = 0.003), IL-8 (r = 0.51, p <0.001), MIP-1 alpha/CCL3 (r= 0.42, p < 0.001) and MIP-3 beta/CCL19 (r= 0.40, p = 0.002) in all BB patients. Conclusions: This is the first study describing that innate and Th1/Th17 adaptive immunity play a crucial role in BB disease. Furthermore, innate mediators are particularly important in acute BB disease, and TNF-alpha is associated with evolution of BB symptoms. (C) 2021 Published by Elsevier Espana, S.L.U. on behalf of Sociedade Brasileira de Infectologia.
- AMPLIFICATION OF THE flgE GENE PROVIDES EVIDENCE FOR THE EXISTENCE OF A BRAZILIAN BORRELIOSIS(2012) MANTOVANI, Elenice; MARANGONI, Roberta G.; GAUDITANO, Giancarla; BONOLDI, Virgnia L. N.; YOSHINARI, Natalino H.Introduction: The symptoms of Brazilian borreliosis resemble the clinical manifestations of Lyme disease (LD). However, there are differences between the two in terms of epidemiological and laboratory findings. Primers usually employed to diagnose LD have failed to detect Borrelia strains in Brazil. Objective: We aimed to identify the Brazilian Borrelia using a conserved gene that synthesizes the flagellar hook (flgE) of Borrelia burgdorferi sensu lato. Method: Three patients presenting with erythema migrans and positive epidemiological histories were recruited for the study. Blood samples were collected, and the DNA was extracted by commercial kits. Results: The gene flgE was amplified from DNA of all selected patients. Upon sequencing, these positive samples revealed 99% homology to B. burgdorferi flgE. Conclusion: These results support the existence of borreliosis in Brazil. However, it is unclear whether this borreliosis is caused by a genetically modified B. burgdorferi sensu stricto or by a new species of Borrelia spp.