RESUMO
Background: Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement. Methods: Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3-CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels. Results: Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = -0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls. Conclusion: This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell-based.
Assuntos
Dermatomiosite , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Anticorpos Antinucleares , Apoptose , Proteína X Associada a bcl-2 , Caspase 3 , Dermatomiosite/complicações , Células Matadoras Naturais , Receptores Tipo I de Fatores de Necrose TumoralRESUMO
Invasive meningococcal disease persists as a fulminant disorder worldwide. Although cases caused by Neisseria meningitidis serogroup X (MenX) occur infrequently, outbreaks have been reported in countries in Africa in recent decades. We report 2 cases of MenX invasive meningococcal disease in São Paulo, Brazil, in 2021 and 2022, during the COVID-19 pandemic.
Assuntos
COVID-19 , Meningite Meningocócica , Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis , Brasil/epidemiologia , Humanos , Meningite Meningocócica/epidemiologia , Infecções Meningocócicas/epidemiologia , PandemiasRESUMO
From February 26, 2020 to March 11, 2021, coronavirus disease 2019 (COVID-19) pandemic resulted in 11,439,558 cases and 277,102 deaths in Brazil. Among them, 2,195,130 cases and 63,965 deaths occurred in Sao Paulo State, Southeast Brazil. The recent emergence and rise of new variants of SARS-CoV-2 is of concern because of their higher transmissibility and possible association with more severe disease. Cases of SARS-CoV-2 reinfections have been described since December 2020 in Brazil. This report describes two cases of COVID-19 reinfection, that occurred five and six months after the first infection, during the second wave of the pandemic in Sao Paulo State. Both patients presented mild symptoms in the two COVID-19 episodes and different lineages of SARS-CoV-2 were identified: B.1.1.33 and B.1.1.28 lineages in case 1 and B1.1.128 and P. 2 lineages in case 2.
Assuntos
COVID-19 , SARS-CoV-2 , Brasil/epidemiologia , Humanos , Pandemias , ReinfecçãoAssuntos
DNA Circular/genética , Púrpura Trombocitopênica Idiopática/genética , Receptores de Antígenos de Linfócitos T/genética , Adolescente , Criança , Pré-Escolar , DNA Circular/imunologia , Feminino , Humanos , Masculino , Púrpura Trombocitopênica Idiopática/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Timo/imunologia , Timo/metabolismoRESUMO
From February 26, 2020 to March 11, 2021, coronavirus disease 2019 (COVID-19) pandemic resulted in 11,439,558 cases and 277,102 deaths in Brazil. Among them, 2,195,130 cases and 63,965 deaths occurred in Sao Paulo State, Southeast Brazil. The recent emergence and rise of new variants of SARS-CoV-2 is of concern because of their higher transmissibility and possible association with more severe disease. Cases of SARS-CoV-2 reinfections have been described since December 2020 in Brazil. This report describes two cases of COVID-19 reinfection, that occurred five and six months after the first infection, during the second wave of the pandemic in Sao Paulo State. Both patients presented mild symptoms in the two COVID-19 episodes and different lineages of SARS-CoV-2 were identified: B.1.1.33 and B.1.1.28 lineages in case 1 and B1.1.128 and P. 2 lineages in case 2.
Assuntos
Relatório de Pesquisa , Reinfecção , SARS-CoV-2RESUMO
INTRODUCTION/OBJECTIVES: Tyro3, Axl, and Mer (TAM) receptors and ligands mediate apoptotic bodies engulfment which alteration has been related with juvenile systemic lupus erythematosus (JSLE) pathogenesis. Thus, the aim was to determine their soluble levels. METHODS: Serum sTyro3, sAxl, sMer, and Gas6 levels were measured using ELISA in 67 JSLE patients, 12 juvenile idiopathic arthritis (JIA) inflammatory and 20 healthy controls and related with SLEDAI-2K score, anti-dsDNA antibody, ESR, CRP, C3, C4 levels, and nephritis. RESULTS: JSLE patients with active disease (SLEDAI-2K> 4) had significantly increased sMer levels compared with healthy controls (median 8.4 vs. 6.0 ng/mL, p = 0.009) and inactive disease patients (5.2 ng/mL, p = 0.0003). sMer levels correlated with SLEDAI-2K (r = 0.44; p = 0.0004) and ESR (r = 0.24; p = 0.04), while sAxl correlated with SLEDAI-2K (r = 0.33; p = 0.008) and C4 levels (r = - 0.24; p = 0.04). JSLE patients taking glucocorticoid had increased sAxl and sMer levels. Moreover, sAxl correlated with sMer and sTyro3 levels. Patients with nephritis and those with focal or diffuse proliferative glomerulonephritis had these protein levels similar to healthy controls and patients without renal involvement. sTyro3 levels of JSLE patients taking glucocorticoid were decreased, and correlated with Gas6 and sAxl, while Gas6 levels correlated with age upon enrollment. JIA controls had protein levels similar to healthy controls and JSLE patients. CONCLUSIONS: This study reinforces that sMer is increased in active JSLE patients, yet sMer and sAxl correlates with disease activity parameters, and their alterations are disease-specific. However, further studies are needed to determine exact roles of sTyro3 and Gas6 in disease pathogenesis. Key Points ⢠sMer and sAxl serum levels are related with active disease in JSLE patients ⢠sMer correlated with SLEDAI-2K score in JSLE ⢠sTyro3, sAxl, sMer and Gas6 levels did not related with nephritis in JSLE patients ⢠sTyro3 and Gas6 exact roles in JSLE are not established and further studies are needed.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/sangue , Lúpus Eritematoso Sistêmico/sangue , Proteínas Proto-Oncogênicas/sangue , Receptores Proteína Tirosina Quinases/sangue , c-Mer Tirosina Quinase/sangue , Estudos de Casos e Controles , Humanos , Receptor Tirosina Quinase AxlRESUMO
OBJECTIVE: To evaluate soluble Fas antigen (sFas), sFas ligand (sFasL), soluble tumor necrosis factor-related apoptosis-inducing ligand, and soluble cytoplasmic Bcl-2 protein (sBcl-2) serum levels, Fas and Bcl-2 expressions in T and B lymphocytes and monocytes and relations with erythrocyte sedimentation rate, C-reactive protein (CRP), Childhood Myositis Assessment Scale, and manual muscle testing in juvenile dermatomyositis (JDM). METHODS: Serum levels were determined by ELISA and peripheral cell expressions by flow cytometry for patients with JDM or juvenile idiopathic arthritis (JIA), and healthy controls. RESULTS: Patients with JDM had increased sBcl-2, which correlated with CRP. Expression of Bcl-2 was increased and expression of Fas was decreased in CD3+, CD4+, and CD8+ T lymphocytes compared with JIA and/or healthy controls. CONCLUSION: Patients with JDM presented a unique apoptosis-related proteins profile, which may contribute to disease development.
Assuntos
Dermatomiosite/metabolismo , Proteína Ligante Fas/sangue , Linfócitos/metabolismo , Monócitos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Receptor fas/sangue , Adolescente , Artrite Juvenil/metabolismo , Sedimentação Sanguínea , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Adulto JovemRESUMO
Registros de casos de leishmaniose tegumentar na cidade de São Paulo, em parques e seusentornos, desde a década de 1970, e o início da expansão da área de transmissão da leishmaniosevisceral, no final dos anos de 1990, levaram o Centro de Controle de Zoonoses do município deSão Paulo (atualmente Divisão de Vigilância de Zoonoses) a desenvolver coletas sistematizadasde flebotomíneos em 12 áreas florestais da cidade, representadas por dez parques: Alfredo Volpi,Anhanguera, Cantareira (Núcleo Pedra Grande), do Carmo, Ecológico Tietê, Fundação ParqueZoológico, Guarapiranga, Jaraguá, Previdência e Tenente Siqueira Campos (Trianon), e em doisfragmentos de matas residuais: do Instituto Butantan e da Secretaria da Agricultura do Estado deSão Paulo. As coletas foram realizadas com armadilhas automáticas luminosas tipos New Jersey(NJ) e Center of Disease Control (CDC), entre 1981 e 2001. Flebotomíneos foram encontradosem 10/12 áreas amostradas. Nos parques Guarapiranga e Siqueira Campos (Trianon) as coletasforam negativas. No total das demais áreas, coletou-se 2.638 espécimes de flebotomíneos (79%fêmeas e 21% machos) de 23 espécies, pertencentes a 11 gêneros Brumptomyia...
Reports of cutaneous leishmaniasis cases in areas in and near urban parks in the city of São Paulosince the 1970s, and the spread of visceral leishmaniasis since the end of the 1990s led the Centrode Controle de Zoonoses (currently the Divisão de Vigilância de Zoonoses) of the municipalityof São Paulo to undertake systematic collections of phlebotomine sand flies in 12 forested areas,represented by 10 parks: Alfredo Volpi, Anhanguera, Cantareira (Núcleo Pedra Grande), do Carmo,Ecológico Tietê, Fundação Parque Zoológico, Guarapiranga, Jaraguá, Previdência and TenenteSiqueira Campos (Trianon), and two fragments of residual forest: of the Instituto Butantan andof the Secretariat of Agriculture of the state of São Paulo. The collections were carried out usingautomatic light traps, New Jersey (NJ) and Center of Disease Control (CDC) types, between1981 and 2001. In the Guarapiranga and Tenente Siqueira Campos (Trianon) parks the collectionswere negative. In the all other areas 2,638 sand flies (79% female and 21% male) of 23 species,belonging to 11 genera, were captured: Brumptomyia (5), Evandromyia (1), Expapillata (1),Lutzomyia (1), Martinsmyia (1), Migonemyia (1), Nyssomyia (3), Pintomyia (3), Psathyromyia(3), Psychodopygus (3) and Sciopemyia (1), and also four taxa identified only at the genus level.The Cantareira park presented the greatest species richness (15 species + 1 Brumptomyia sp.).Pintomyia fischeri was collected at all the above...
Assuntos
Doença , MeningiteRESUMO
The aims of this study were to assess serum Fas, FasL, TRAIL, and Bcl-2 levels in patients with juvenile-onset systemic lupus erythematosus (JSLE) and to evaluate their relations with disease activity parameters and nephritis. Forty-eight JSLE patients, 33 juvenile idiopathic arthritis (JIA, inflammatory controls) patients and 40 healthy controls were enrolled. sFas, sFasL, sTRAIL, and sBcl-2 serum levels were measured by ELISA. Disease activity parameters included SLEDAI score, ESR, anti-dsDNA antibodies, C3, and C4 levels. Thirty-five JSLE patients had nephritis and 32 patients were classified as having active disease (SLEDAI ≥4). Statistical analysis methods included Mann-Whitney test and Spearman's rank test. JSLE patients had significantly increased sFas serum levels compared with healthy controls (median 177.6 vs. 117.5 pg/mL; p = 0.0001), higher sTRAIL (median 484.6 vs 270.8 pg/mL; p = 0.02), and reduced sFasL (median 0.05 vs 0.3 ng/mL; p = 0.0002). The same results were observed for JSLE patients with active disease and for patients with nephritis. Additionally, sFas levels in JSLE patients directly correlated with SLEDAI score (r = 0.40; p = 0.009), and sTRAIL levels were increased in JSLE patients with neuropsychiatric disease compared with those without this involvement (median 667.9 vs. 216.2 pg/mL; p = 0.03). Otherwise, sBcl-2 levels of JSLE patients were similar to healthy controls. JIA patients had sFas, sFasL, sTRAIL, and sBcl-2 serum levels similar to JSLE patients and to healthy controls. In summary, this study characterized in JSLE a distinct profile from adult SLE that comprises increased sFas, sTRAIL, and reduced sFasL, notably in patients with active disease and with nephritis.
Assuntos
Proteína Ligante Fas/sangue , Lúpus Eritematoso Sistêmico/sangue , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Receptor fas/sangue , Adolescente , Criança , Feminino , Humanos , Nefrite Lúpica/sangue , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Adulto JovemRESUMO
The aim of the present study was to assess the prevalence of Haemophilus influenzae type b (Hib) nasopharyngeal (NP) colonisation among healthy children where Hib vaccination using a 3p+0 dosing schedule has been routinely administered for 10 years with sustained coverage (> 90%). NP swabs were collected from 2,558 children who had received the Hib vaccine, of whom 1,379 were 12-< 24 months (m) old and 1,179 were 48-< 60 m old. Hi strains were identified by molecular methods. Hi carriage prevalence was 45.1% (1,153/2,558) and the prevalence in the 12-< 24 m and 48-< 60 m age groups were 37.5% (517/1,379) and 53.9% (636/1,179), respectively. Hib was identified in 0.6% (16/2,558) of all children in the study, being 0.8% (11/1,379) and 0.4% (5/1,179) among the 12-< 24 m and 48-< 60 m age groups, respectively. The nonencapsulate Hi colonisation was 43% (n = 1,099) and was significantly more frequent at 48-< 60 m of age (51.6%, n = 608) compared with that at 12-< 24 m of age (35.6%, n = 491). The overall resistance rates to ampicillin and chloramphenicol were 16.5% and 3.7%, respectively; the co-resistance was detected in 2.6%. Our findings showed that the Hib carrier rate in healthy children under five years was very low after 10 years of the introduction of the Hib vaccine.
Assuntos
Portador Sadio/imunologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/uso terapêutico , Haemophilus influenzae tipo b/imunologia , Nasofaringe/microbiologia , Resistência a Ampicilina/imunologia , Cápsulas Bacterianas/imunologia , Brasil/epidemiologia , Portador Sadio/microbiologia , Pré-Escolar , Resistência ao Cloranfenicol/imunologia , Estudos Transversais , Infecções por Haemophilus/epidemiologia , Haemophilus influenzae tipo b/classificação , Humanos , Esquemas de Imunização , Lactente , Vacinação em Massa , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Prevalência , Inquéritos e QuestionáriosRESUMO
A indoleamina 2,3-dioxigenase (IDO) é uma enzima responsável por catabolizar o aminoácido triptofano. Sua presença no ambiente uterino placentário está relacionada à tolerância imunológica ao semi-aloenxerto, pois impede a proliferação de células imunológicas maternas, seja pela falta do aminoácido, ou pela ação de alguns catabólitos oriundos da quebra do triptofano, como o ácido quinolínico, que é tóxico principalmente para os linfócitos T. Pouco se conhece sob a influência de substâncias (hormônios e citocinas) presentes na interface materno fetal e a expressão dessa enzima. Por esta razão, formulou-se a hipótese de que hormônios e interleucinas presentes na região uteroplacentária poderiam exercer algum efeito na expressão da IDO. Células oriundas da interface materno fetal de ratas Wistar foram mantidas em cultivo, onde receberam suplementação com estradiol e interferon-γ. A expressão da enzima foi avaliada pela técnica de citometria de fluxo nos períodos de 4, 24 e 48 horas e confirmação da presença proteica por imuno-histoquímica. Os resultados mostraram um aumento na expressão de IDO após a adição de estrógeno (9,03±0,81/11,25±0,25) e interferon-γ (9,03±0,81/20,43±0,60). O efeito do interferon-γ já era esperado como relatado na literatura, contudo, a elevação da expressão da IDO pela adição do estrógeno constitui nova informação sobre possíveis mecanismos envolvidos na ativação da enzima. O melhor esclarecimento desses achados poderia contribuir para uma melhor compreensão da participação dessa enzima na tolerância materno-fetal e para uma futura modulação terapêutica da mesma...
The indoleamine 2,3-dioxygenase (IDO) is an enzyme responsible for catabolizing the tryptophan. Its presence in the placental uterine environment is related to immunological tolerance to the semi-allograft because it prevents proliferation of maternal immune cells, either by the lack of this amino acid or by the action of its catabolites, such as the quinolinic acid, which is particularly toxic for T lymphocytes. Little is known regarding the influence of hormones and cytokines on the expression of IDO in the maternal fetal interface. Therefore, the hypothesis that some hormones and interleukins present in uteroplacental region could have an effect on the expression of IDO on cultured cells was tested. Cells derived from the fetal maternal interface from Wistar rats were kept in culture and supplemented with estradiol and interferon-γ. Expression of the enzyme was assessed by flow cytometry at periods of 4, 24 and 48 hours and confirmation of the presence of protein by immunohistochemistry. The results showed an increasing of IDO expression after the addition of estrogen (9.03±0.81 to 11.25±0.25) and interferon-γ (9.03±0.81 to 20.43±0.60). The effect of interferon-γ was expected as reported in the literature, however, elevated IDO expression by estrogen represents new information on possible mechanisms involved in the enzyme activation. These findings could provide a better understanding of IDO contribution on maternal-fetal tolerance and may collaborate to future therapeutic modulation of this enzyme...
Assuntos
Animais , Feminino , Gravidez , Cobaias , Estrogênios , Interferon gama , Ratos Wistar/embriologia , Citometria de Fluxo/veterinária , Ensaios Enzimáticos Clínicos/veterinária , Imuno-Histoquímica/veterinária , PlacentaRESUMO
The aim of the present study was to assess the prevalence of Haemophilus influenzaetype b (Hib) nasopharyngeal (NP) colonisation among healthy children where Hib vaccination using a 3p+0 dosing schedule has been routinely administered for 10 years with sustained coverage (> 90%). NP swabs were collected from 2,558 children who had received the Hib vaccine, of whom 1,379 were 12-< 24 months (m) old and 1,179 were 48-< 60 m old. Hi strains were identified by molecular methods. Hi carriage prevalence was 45.1% (1,153/2,558) and the prevalence in the 12-< 24 m and 48-< 60 m age groups were 37.5% (517/1,379) and 53.9% (636/1,179), respectively. Hib was identified in 0.6% (16/2,558) of all children in the study, being 0.8% (11/1,379) and 0.4% (5/1,179) among the 12-< 24 m and 48-< 60 m age groups, respectively. The nonencapsulate Hi colonisation was 43% (n = 1,099) and was significantly more frequent at 48-< 60 m of age (51.6%, n = 608) compared with that at 12-< 24 m of age (35.6%, n = 491). The overall resistance rates to ampicillin and chloramphenicol were 16.5% and 3.7%, respectively; the co-resistance was detected in 2.6%. Our findings showed that the Hib carrier rate in healthy children under five years was very low after 10 years of the introduction of the Hib vaccine.
Assuntos
Humanos , Lactente , Pré-Escolar , Portador Sadio/imunologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/uso terapêutico , Haemophilus influenzae tipo b/imunologia , Nasofaringe/microbiologia , Resistência a Ampicilina/imunologia , Cápsulas Bacterianas/imunologia , Brasil/epidemiologia , Portador Sadio/microbiologia , Resistência ao Cloranfenicol/imunologia , Estudos Transversais , Infecções por Haemophilus/epidemiologia , Haemophilus influenzae tipo b/classificação , Esquemas de Imunização , Vacinação em Massa , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Prevalência , Inquéritos e QuestionáriosRESUMO
A indoleamina 2,3-dioxigenase (IDO) é uma enzima responsável por catabolizar o aminoácido triptofano. Sua presença no ambiente uterino placentário está relacionada à tolerância imunológica ao semi-aloenxerto, pois impede a proliferação de células imunológicas maternas, seja pela falta do aminoácido, ou pela ação de alguns catabólitos oriundos da quebra do triptofano, como o ácido quinolínico, que é tóxico principalmente para os linfócitos T. Pouco se conhece sob a influência de substâncias (hormônios e citocinas) presentes na interface materno fetal e a expressão dessa enzima. Por esta razão, formulou-se a hipótese de que hormônios e interleucinas presentes na região uteroplacentária poderiam exercer algum efeito na expressão da IDO. Células oriundas da interface materno fetal de ratas Wistar foram mantidas em cultivo, onde receberam suplementação com estradiol e interferon-γ. A expressão da enzima foi avaliada pela técnica de citometria de fluxo nos períodos de 4, 24 e 48 horas e confirmação da presença proteica por imuno-histoquímica. Os resultados mostraram um aumento na expressão de IDO após a adição de estrógeno (9,03±0,81/11,25±0,25) e interferon-γ (9,03±0,81/20,43±0,60). O efeito do interferon-γ já era esperado como relatado na literatura, contudo, a elevação da expressão da IDO pela adição do estrógeno constitui nova informação sobre possíveis mecanismos envolvidos na ativação da enzima. O melhor esclarecimento desses achados poderia contribuir para uma melhor compreensão da participação dessa enzima na tolerância materno-fetal e para uma futura modulação terapêutica da mesma.(AU)
The indoleamine 2,3-dioxygenase (IDO) is an enzyme responsible for catabolizing the tryptophan. Its presence in the placental uterine environment is related to immunological tolerance to the semi-allograft because it prevents proliferation of maternal immune cells, either by the lack of this amino acid or by the action of its catabolites, such as the quinolinic acid, which is particularly toxic for T lymphocytes. Little is known regarding the influence of hormones and cytokines on the expression of IDO in the maternal fetal interface. Therefore, the hypothesis that some hormones and interleukins present in uteroplacental region could have an effect on the expression of IDO on cultured cells was tested. Cells derived from the fetal maternal interface from Wistar rats were kept in culture and supplemented with estradiol and interferon-γ. Expression of the enzyme was assessed by flow cytometry at periods of 4, 24 and 48 hours and confirmation of the presence of protein by immunohistochemistry. The results showed an increasing of IDO expression after the addition of estrogen (9.03±0.81 to 11.25±0.25) and interferon-γ (9.03±0.81 to 20.43±0.60). The effect of interferon-γ was expected as reported in the literature, however, elevated IDO expression by estrogen represents new information on possible mechanisms involved in the enzyme activation. These findings could provide a better understanding of IDO contribution on maternal-fetal tolerance and may collaborate to future therapeutic modulation of this enzyme.(AU)
Assuntos
Animais , Feminino , Gravidez , Cobaias , Indolamina-Pirrol 2,3,-Dioxigenase , Estrogênios , Interferon gama , Ratos Wistar/embriologia , Citometria de Fluxo/veterinária , Imuno-Histoquímica/veterinária , Ensaios Enzimáticos Clínicos/veterinária , PlacentaRESUMO
OBJECTIVE: To perform a molecular characterization of the C1q, C2 and C4 genes in patients with juvenile systemic lupus erythematosus. METHODS: Patient 1 (P1) had undetectable C1q, patient 2 (P2) and patient 3 (P3) had decreased C2 and patient 4 (P4) had decreased C4 levels. All exons and non-coding regions of the C1q and C2 genes were sequenced. Mononuclear cells were cultured and stimulated with interferon gamma to evaluate C1q, C2 and C4 mRNA expression by quantitative real-time polymerase chain reaction. RESULTS: C1q sequencing revealed heterozygous silent mutations in the A (c.276 A>G Gly) and C (c.126 C>T Pro) chains, as well as a homozygous single-base change in the 3' non-coding region of the B chain (c*78 A>G). C1qA mRNA expression without interferon was decreased compared with that of healthy controls (p<0.05) and was decreased after stimulation compared with that of non-treated cells. C1qB mRNA expression was decreased compared with that of controls and did not change with stimulation. C1qC mRNA expression was increased compared with that of controls and was even higher after stimulation. P2 and P3 had Type I C2 deficiency (heterozygous 28 bp deletion at exon 6). The C2 mRNA expression in P3 was 23 times lower compared with that of controls and did not change after stimulation. The C4B mRNA expression of P4 was decreased compared with that of controls and increased after stimulation. CONCLUSIONS: Silent mutations and single-base changes in the 3' non-coding regions may modify mRNA transcription and C1q production. Type I C2 deficiency should be evaluated in JSLE patients with decreased C2 serum levels. Further studies are needed to clarify the role of decreased C4B mRNA expression in JSLE pathogenesis.