Abstract Background Anti-desmoglein (Dsg)1 is produced in pemphigus foliaceus (PF), affecting exclusively the skin. Pemphigus vulgaris (PV) shows the production of anti-Dsg3 in the mucosal form, and anti-Dsg1 and 3 in the mucocutaneous form. Anti-Dsg3 autoantibodies have been rarely reported in PF. Objectives To determine the factors associated with the production and pathogenicity of anti-Dsg3 in PF. Methods Comparative analytical study of three patients groups: 16 PF-anti-Dsg3+, and 42 PF-anti-Dsg3(-) and 22 PV treatment-naïve cases. Serum was used in the anti-Dsg1 and 3 ELISA, and in immunoblotting (IB) with human epidermis extract. The expression of Dsg1 and 3 in paraffin sections was analyzed by immunohistochemistry (IHC). HLA-DRB1 alleles were compiled from a database. Results In the PF-anti-Dsg3+ group: age range similar to that of the PV group (p > 0.9999); predominance of the generalized form of PF (p = 0.002); anti-Dsg3 titers lower than those of PV (p < 0.0001); IB confirmed Dsg3 identification in one (8.33%) of 12 patients; IHC showed exclusive cytoplasmic internalization of Dsg1; HLA-DRB1 alleles of susceptibility to PF, with the absence of alleles associated with PV, in the five typed patients. Study limitations Most of the patients in the PF-anti-Dsg3+ group were undergoing treatment. Conclusion The presence of anti-Dsg3 antibodies in PF was related to older age (comparable to that of PV) and the generalized form of PF. The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to the low serum anti-Dsg3 titers, the lack of Dsg3 internalization as detected by IHC, and the absence of PV-associated HLA-DRB1 alleles. Antidesmoglein Anti desmoglein Dsg 1 (Dsg) , (PF) skin (PV antiDsg3 antiDsg anti anti-Dsg antiDsg1 AntiDsg3 AntiDsg Anti-Dsg groups PFantiDsg3+, PFantiDsg3 PFantiDsg Dsg3+, 4 PF-anti-Dsg3(- 2 treatmentnaïve treatment naïve cases ELISA (IB extract IHC. . (IHC) HLADRB1 HLADRB HLA DRB1 DRB HLA-DRB database PFantiDsg3+ Dsg3+ PF-anti-Dsg3 p 0.9999 09999 0 9999 0.9999) 0.002 0002 002 0.002) 0.0001 00001 0001 0.0001) 8.33% 833 8 33 (8.33% comparable nonpathogenicity non PVassociated (Dsg (PF PF-anti-Dsg3( (IHC PF-anti-Dsg 0.999 0999 999 0.00 000 00 0.000 0000 8.33 83 (8.33 0.99 099 99 0.0 8.3 (8.3 0.9 09 9 0. 8. (8. (8 (

Abstract Background Dexamethasone-cyclophosphamide pulse (DCP) and dexamethasone pulse (DP) have been successfully used to treat pemphigus, but DCP/DP outcomes comparing pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are scarce. Objective To compare DCP/DP outcomes in a Brazilian cohort of PV and PF patients according to demographic and clinical data. Methods Retrospective analytical cohort study, reviewing medical charts of PV and PF patients (for DCP/DP Phases I‒IV consult Pasricha et al.16‒18). Results 37 PV and 41 PF patients non responsive to usual treatments were included similarly for DCP or DP therapy. Disease duration was longer among PF before DCP/DP prescription (p < 0.001); PF required a higher number of monthly pulses to acquire remission in Phase I (median 10 and 6 pulses, respectively; p = 0.005). DCP/DP outcomes were similar in both groups: remission in 37.8% of PV and 34.1% of PF after completed DCP/DP cycles following a median of 13 months (1-56 months follow-up); failure occurred in 13.5% of PV and 14.6% of PF in Phase I; relapse in 13.5% of PV and 12.2% of PF, and dropout in 27% of PV and 24.4% of PF in Phases II to IV. Mild side effects were documented. Study limitations The severity of PV and PF disease was not assessed by score indexes. Conclusions PV and PF patients presented similar DCP/DP outcomes. DCP/DP should be initiated earlier in PF patients due to the longer duration of their disease in order to decrease the number of pulses and the duration of Phase I to acquire remission. Dexamethasonecyclophosphamide Dexamethasone cyclophosphamide (DCP (DP DCPDP (PV (PF scarce data study IIV IV al.16‒18. al1618 al al.16‒18 . 16 18 al.16‒18) 3 4 therapy 0.001 0001 0 001 0.001) 1 respectively 0.005. 0005 0.005 005 0.005) groups 378 8 37.8 341 34 34.1 156 56 (1-5 followup follow up follow-up) 135 5 13.5 146 14 14.6 122 12 2 12.2 27 244 24 24.4 documented indexes al161 al.16‒1 0.00 000 00 37. 34. 15 (1- follow-up 13. 14. 12. 24. al16 al.16‒ 0.0 (1 al1 al.16 0. ( al.1 al.

CONTEXTO E OBJETIVO:A deficiência na imunidade celular localizada parece contribuir para a patogênese e progressão das neoplasias intraepiteliais cervicais (NIC), no entanto, ainda não está totalmente esclarecido o mecanismo molecular fundamental nesse processo de progressão. A identificação de novos marcadores moleculares de prognóstico e diagnóstico das NIC em estágios precoces pode ajudar a diminuir a quantidade de casos de NIC. Várias novas moléculas com função imunorregulatória foram descobertas nos últimos anos, inclusive o antígeno leucocitário humano G (HLA-G), que, através de interação com os receptores, tem importantes funções tolerogênicas. Diversas linhas de evidência sugerem que as células T-ajudantes produtoras de interleucina-17 (IL-17, células Th17), podem desempenhar um papel na imunidade antitumoral. Porém, recentes relatos implicaram as células Th17 e suas citocinas tanto em processos pro- quanto anti-tumorigênicos. O objetivo do estudo foi avaliar o papel do HLA-G e Th17 na imunopatogênese das NIC I.TIPO DE ESTUDO E LOCAL:Estudo transversal analítico com grupo controle em 58 espécimes cervicais dos arquivos de um hospital universitário público com assistência prestada no nível terciário.MÉTODOS:Avaliamos a expressão de HLA-G e IL-17 por imunoistoquímica no microambiente cervical, associando esses achados com as características clínico-patológicas.RESULTADOS:Houve tendência aumentada da expressão de HLA-G e IL-17 em espécimes que apresentaram NIC I, sugerindo que essas moléculas têm contribuição na progressão cervical.CONCLUSÃO:Estes resultados sugerem que a expressão do HLA-G e da IL-17 pode ser um marcador precoce para avaliar a progressão das lesões cervicais.

CONTEXT AND OBJECTIVE:Impaired local cell immunity seems to contribute towards the pathogenesis and progression of cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and diagnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregulatory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G), which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17)-producing cells (Th17 cells) may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I.DESIGN AND SETTING:Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care.METHODS:We examined HLA-G and IL-17 expression in the cervical microenvironment by means of immunohistochemistry, and correlated these findings with clinical and pathological features.RESULTS:There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression.CONCLUSION:These findings suggest that HLA-G and IL-17 expression may be an early marker for assessing the progression of cervical lesions.

OBJETIVO: Verificar se pacientes com glaucoma primário de ângulo aberto portadores de haplotipos HLA de classe I (HLA - A9-B12; -A2-B40; e -A1-B8) associados a essa doença poderiam ter progressão maior do que pacientes que não apresentassem esses haplotipos. Método: Avaliação anatômica e funcional de 25 pacientes (6 dos quais com um dos haplotipos associados a glaucoma), seguidos no Ambulatório de Glaucoma do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), por dez anos depois da tipificação de seus antígenos HLA, para comparação com as condições anteriores. RESULTADOS: Houve aumento maior da relação escavação/disco em pacientes com haplotipos HLA associados com predisposição para glaucoma primário de ângulo aberto, no entanto não foram encontradas diferenças significantes entre esses e outros pacientes com glaucoma na progressão do dano fisiológico e nem na perda de fibras nervosas da retina. CONCLUSÃO: Os resultados indicam a associação de haplotipos HLA de classe I com maior taxa de progressão das alterações anatômicas da cabeça nervo óptico em pacientes com glaucoma.

PURPOSE: To verify if patients with primary open-angle glaucoma with HLA class I haplotypes (A9-B12, A2-B40, A1-B8) associated with this disease may have a greater rate of progression than patients who do not present these haplotypes. METHODS: Anatomical and functional glaucoma evaluation (cup-to-disc ratio and visual field) of 25 patients (six of them with one of the haplotypes associated with glaucoma) followed at the Glaucoma Outpatient Clinic of the University Hospital, Ribeirão Preto School of Medicine, São Paulo University (HCFMRP-USP) for ten years after typing of their HLA antigens in order to compare with their previous condition. RESULTS: A greater increase of the cup-to-disc ratio was observed in patients with HLA haplotypes associated with primary open-angle glaucoma predisposition. However, no significant differences in functional damage progression or in retinal nerve fibers loss were detected between them and other patients with glaucoma. CONCLUSION: The present results indicate an association of class I HLA haplotypes with progression of anatomic alterations of the optic nerve head in glaucomatous patients.

Gliomas are the most common tumors in the central nervous system, the average survival time of patients with glioblastoma multiforme being about 1 year from diagnosis, in spite of harsh therapy. Aiming to study the transcriptional profiles displayed by glioma cells undergoing cisplatin treatment, gene expression analysis was performed by the cDNA microarray method. Cell survival and apoptosis induction following treatment were also evaluated. Drug concentrations of 12.5 to 300 μM caused a pronounced reduction in cell survival rates five days after treatment, whereas concentrations higher than 25 μM were effective in reducing the survival rates to ~1%. However, the maximum apoptosis frequency was 20.4% for 25 μM cisplatin in cells analyzed at 72 h, indicating that apoptosis is not the only kind of cell death induced by cisplatin. An analysis of gene expression revealed 67 significantly (FDR < 0.05) modulated genes: 29 of which down- and 38 up-regulated. These genes belong to several classes (metabolism, protein localization, cell proliferation, apoptosis, adhesion, stress response, cell cycle and DNA repair) that may represent several affected cell processes under the influence of cisplatin treatment. The expression pattern of three genes (RHOA, LIMK2 and TIMP2) was confirmed by the real time PCR method.

Studies carried out in various populations have reported an association between some HLA specificities and susceptibility to tuberculosis. We investigated the class I and class II HLA profile in Brazilian patients of various ethnic backgrounds who had AIDS and tuberculosis. Twenty-two adult patients with AIDS and tuberculosis (Group I), 103 patients with AIDS without tuberculosis (Group II) and 423 healthy individuals not infected with HIV (Group III) were evaluated. Diagnosis of HIV infection was made by ELISA, confirmed by a gelatin particle agglutination test. Diagnosis of tuberculosis was made based on clinical/radiological presentation and direct bacilloscopy or clinical specimen cultures. Class I antigens were typed by microlymphotoxicity. Class II alleles were characterized by the polymerase chain reaction (PCR). Differences in frequency of HLA specificities between groups were found in the following antigens/alleles: Group I x Group II: HLA-A31 - p=0.026; HLA-B41 - p= 0.037; HLA-DRB1*10 - p=0.037; HLA-DQB1*5 - p=0.009. Group I x Group III (control): HLA-A31 - p = 0.000008; odds ratio (OR)=31.75; HLA-B41 - p=0.003; HLA-DQB1*5 - p=0.02. HLA-A31 and HLA-B41 antigens and the HLA-DRB1*10 and HLA-DQB1*05 alleles were over-represented in patients with AIDS and tuberculosis (Group I), suggesting that these HLA molecules are associated with susceptibility to tuberculosis in Brazilian patients with AIDS.

CONTEXTO E OBJETIVO: Diabetes mellitus é uma síndrome clínica que freqüentemente leva ao desenvolvimento de complicações crônicas, e também, alta susceptibilidade a infecções, provavelmente devido a um defeito na defesa imunológica, que pode ser relacionada ao controle metabólico da doença. Neste estudo, propomos avaliar o efeito do controle metabólico no comportamento imunocelular de pacientes diabéticos tipo 1 e 2 através da proliferação in vitro de células mononucleares de sangue periférico (PBMC) em pacientes com controle metabólico inadequado e adequado. TIPO DE ESTUDO E LOCAL: Estudo experimental e laboratorial, realizado em hospital universitário. MÉTODOS: Estudamos 11 diabéticos do tipo 1 e 13 do tipo 2 além de 21 controles saudáveis, divididos em dois grupos (11/10), pareados para sexo e idade aos diabéticos tipo 1 e 2. Usamos culturas de PBMCs estimuladas com concanavalina (Con-A) para medir a incorporação de ³H-timidina após 72 horas de cultura de células. As culturas foram realizadas no primeiro dia de internação para os pacientes em controle metabólico inadequado, e repetidas após o controle metabólico adequado. RESULTADOS: O índice de estimulação das culturas estimuladas com Con-A nos diabéticos tipo 1 foi significantemente maior que na cultura de indivíduos saudáveis e diabéticos tipo 2, independentemente do controle metabólico. Além disso, foi observada uma correlação negativa entre o índice de proliferação e o índice de massa corporal e níveis de proteína-C. CONCLUSÃO: O aumento na capacidade de proliferação de linfócitos de diabéticos tipo 1 não é causado por hiperglicemia e/ou insulinopenia relacionada a controle inadequado.

CONTEXT AND OBJECTIVE: Diabetes mellitus is a clinical syndrome that frequently leads to the development of chronic complications and high susceptibility to infections. It is probably due to defective immunological defense, which may be related to metabolic control of the disease. The aim of this study was to evaluate the effect of metabolic control on immune-cell behavior in type 1 and type 2 diabetic patients. For this, the in vitro proliferation of peripheral blood mononuclear cells (PBMC) was analyzed in patients with inadequate and adequate metabolic control. DESIGN AND SETTING: Experimental/laboratory study at a university hospital. METHODS: Eleven type 1 and thirteen type 2 diabetic patients were studied, together with 21 healthy individuals divided in two groups (11/10), who were matched by sex and age with those diabetic patients. PBMC cultures stimulated with concanavalin-A (Con-A) were used to measure ³H-thymidine incorporation after 72 hours of cell culturing. For patients with inadequate metabolic control, culturing was performed on the first day of patient hospitalization and again after intensive treatment to achieve adequate control. RESULTS: The proliferation index for Con-A-stimulated cultures from type 1 diabetic patients was significantly greater than that for cultures from healthy individuals and type 2 diabetic patients, independent of metabolic control. A negative correlation between the proliferation cell index and body mass index and serum C-reactive protein levels was also observed. CONCLUSION: The increase in the proliferation capacity of type 1 diabetic T lymphocytes was probably not caused by hyperglycemia and/or insulinopenia related to inadequate metabolic control.

O diabetes mellitus do tipo 1 tem sido considerado uma doença auto-imune órgão-específica, decorrente da destruição seletiva das células betapancreáticas. Apresenta patogenia complexa, envolvendo a participação de vários fatores, dentre esses a susceptibilidade imunogenética com forte associação aos genes de histocompatibilidade (HLA), eventos ambientais e resposta auto-imune com presença de auto-anticorpos e/ou linfócitos auto-reativos, culminando em anormalidades metabólicas. Neste estudo, a revisão da literatura descreve os mecanismos pelos quais determinados fatores conferem susceptibilidade para o seu desencadeamento e, adicionalmente, as inovações na predição dessa desordem que, certamente, contribuirão para a assistência de enfermagem aos pacientes portadores do diabetes tipo 1.

Type 1 diabetes mellitus has been considered an organ-specific autoimmune disease derived from the selective destruction of pancreatic beta cells. It presents a complex pathogenesis, involving the participation of several factors, including the immunogenetic susceptibility with strong association to histocompatibility genes (HLA), environmental events and autoimmune response with the presence of autoantibodies and/or autoreactive lymphocytes, culminating in metabolic abnormalities. In this study, the literature review describes mechanisms through which some factors cause susceptibility to its appearance and, additionally, prediction innovations regarding this disorder, which will certainly contribute to nursing care for patients with type 1 diabetes.

La Diabetes Mellitus tipo 1 ha sido considerada una enfermedad autoinmune órgano-específica debido a la destrucción selectiva de las células beta pancreáticas. Presenta una patogenia compleja, involucrando la participación de varios factores, entre esos la susceptibilidad inmunogenética con fuerte asociación a los genes de histocompatibilidad (HLA), eventos ambientales y respuesta autoinmune con presencia de auto-anticuerpos y/o linfocitos auto-reactivos, culminando en anormalidades metabólicas. En este estudio, la revisión de la literatura describe los mecanismos por los cuales determinados factores resultan en susceptibilidad para su desarrollo y, adicionalmente, las innovaciones en la predicción de ese desorden que, por cierto, van a contribuir para la atención de enfermería a los pacientes portadores de la diabetes tipo 1.

Type 1 diabetes mellitus has been considered an organ-specific autoimmune disease derived from the selective destruction of pancreatic beta cells. It presents a complex pathogenesis, involving the participation of several factors, including the immunogenetic susceptibility with strong association to histocompatibility genes (HLA), environmental events and autoimmune response with the presence of autoantibodies and/or autoreactive lymphocytes, culminating in metabolic abnormalities. In this study, the literature review describes mechanisms through which some factors cause susceptibility to its appearance and, additionally, prediction innovations regarding this disorder, which will certainly contribute to nursing care for patients with type 1 diabetes.

La Diabetes Mellitus tipo 1 ha sido considerada una enfermedad autoinmune órgano-específica debido a la destrucción selectiva de las células beta pancreáticas. Presenta una patogenia compleja, involucrando la participación de varios factores, entre esos la susceptibilidad inmunogenética con fuerte asociación a los genes de histocompatibilidad (HLA), eventos ambientales y respuesta autoinmune con presencia de auto-anticuerpos y/o linfocitos auto-reactivos, culminando en anormalidades metabólicas. En este estudio, la revisión de la literatura describe los mecanismos por los cuales determinados factores resultan en susceptibilidad para su desarrollo y, adicionalmente, las innovaciones en la predicción de ese desorden que, por cierto, van a contribuir para la atención de enfermería a los pacientes portadores de la diabetes tipo 1.

O diabetes mellitus do tipo 1 tem sido considerado uma doença auto-imune órgão-específica, decorrente da destruição seletiva das células betapancreáticas. Apresenta patogenia complexa, envolvendo a participação de vários fatores, dentre esses a susceptibilidade imunogenética com forte associação aos genes de histocompatibilidade (HLA), eventos ambientais e resposta auto-imune com presença de auto-anticorpos e/ou linfócitos auto-reativos, culminando em anormalidades metabólicas. Neste estudo, a revisão da literatura descreve os mecanismos pelos quais determinados fatores conferem susceptibilidade para o seu desencadeamento e, adicionalmente, as inovações na predição dessa desordem que, certamente, contribuirão para a assistência de enfermagem aos pacientes portadores do diabetes tipo 1.

Este estudo relata a mortalidade por doenças infecto-parasitárias em Teresina, nos últimos trinta anos do século XX. Os resultados mostraram que as mortes por doenças infecto-parasitárias diminuíram em coeficientes e em anos potenciais de vida perdidos, e foram superadas pelas mortes relacionadas aos aparelhos circulatório e respiratório, causas externas e neoplasias, entre 1980 e 1990. Em 2000, a faixa etária mais acometida entre as mortes por doenças infecto-parasitárias foi a de cinqüenta anos e mais, e em especial nos homens. As causas de morte mais freqüentes foram as septicemias, as enterites, a tuberculose, a aids e a leishmaniose, e entre as doenças infecciosas que se encontram em outros grupos de causas, vale ressaltar as pneumonias. Durante o período analisado, três doenças emergentes apareceram no quadro das doenças infecciosas em Teresina: a aids, a dengue e a cólera, enquanto as permanecentes, como a tuberculose e a leishmaniose, voltaram a ter relevância no quadro de morbi-mortalidade. Nesse mesmo período, em Teresina, o impacto das doenças emergentes e o peso das permanecentes, junto com as transformações socioeconômicas, demográficas e ambientais, experimentadas pelo município, fizeram com que as doenças infecto-parasitárias voltassem a ter importância para o século XXI.

This study evaluated mortality due to infectious and parasitic diseases in the city of Teresina in the last 30 years of the 20th century. Infectious and parasitic disease mortality rates decreased in terms of potential years of life lost and were surpassed by mortality due to cardiocirculatory/respiratory diseases and cancer and external causes, between 1980 and 1990. In 2000, infectious/parasitic disorders affected mostly individuals with fifty years of age and older, especially men. The most frequent causes of death were: septicemia, dysentery, tuberculosis, AIDS, and leishmaniosis, and the role of pneumonia should be emphasized among the infectious diseases included in other disease classification groups. During the research, three emerging infectious diseases were observed in Teresina: AIDS, dengue and cholera, whereas other diseases, such as tuberculosis and leishmaniosis recovered their relevance in terms of morbidity-mortality. In Teresina, the impact of emerging diseases and the burden of persevering diseases, along with the socio-economic, demographic and environmental transformations that the city has gone through in the past three decades, have made infectious and parasitic disorders become a problem to be solved in the 21st century.

Este estudo relata a mortalidade por doenças infecto-parasitárias em Teresina, nos últimos trinta anos do século XX. Os resultados mostraram que as mortes por doenças infecto-parasitárias diminuíram em coeficientes e em anos potenciais de vida perdidos, e foram superadas pelas mortes relacionadas aos aparelhos circulatório e respiratório, causas externas e neoplasias, entre 1980 e 1990. Em 2000, a faixa etária mais acometida entre as mortes por doenças infecto-parasitárias foi a de cinqüenta anos e mais, e em especial nos homens. As causas de morte mais freqüentes foram as septicemias, as enterites, a tuberculose, a aids e a leishmaniose, e entre as doenças infecciosas que se encontram em outros grupos de causas, vale ressaltar as pneumonias. Durante o período analisado, três doenças emergentes apareceram no quadro das doenças infecciosas em Teresina: a aids, a dengue e a cólera, enquanto as permanecentes, como a tuberculose e a leishmaniose, voltaram a ter relevância no quadro de morbi-mortalidade. Nesse mesmo período, em Teresina, o impacto das doenças emergentes e o peso das permanecentes, junto com as transformações socioeconômicas, demográficas e ambientais, experimentadas pelo município, fizeram com que as doenças infecto-parasitárias voltassem a ter importância para o século XXI.

This study evaluated mortality due to infectious and parasitic diseases in the city of Teresina in the last 30 years of the 20th century. Infectious and parasitic disease mortality rates decreased in terms of potential years of life lost and were surpassed by mortality due to cardiocirculatory/respiratory diseases and cancer and external causes, between 1980 and 1990. In 2000, infectious/parasitic disorders affected mostly individuals with fifty years of age and older, especially men. The most frequent causes of death were: septicemia, dysentery, tuberculosis, AIDS, and leishmaniosis, and the role of pneumonia should be emphasized among the infectious diseases included in other disease classification groups. During the research, three emerging infectious diseases were observed in Teresina: AIDS, dengue and cholera, whereas other diseases, such as tuberculosis and leishmaniosis recovered their relevance in terms of morbidity-mortality. In Teresina, the impact of emerging diseases and the burden of persevering diseases, along with the socio-economic, demographic and environmental transformations that the city has gone through in the past three decades, have made infectious and parasitic disorders become a problem to be solved in the 21st century.

Although cellular immunity is essential for the elimination of human papillomavirus (HPV), the mechanisms involved are still poorly understood. We summarize the main mechanisms involved in cellular immune response to infections caused by HPV. Immunotherapies for HPV-related cancers require the disruption of T-cell response control mechanisms, associated with the stimulation of the Th1 cytokine response.