RESUMO
Turner syndrome (TS) is one of the most common sexual chromosome abnormalities and is clearly associated with an increased risk of autoimmune diseases, particularly thyroid disease and coeliac disease (CD). Single-nucleotide polymorphism analyses have been shown to provide correlative evidence that specific genes are associated with autoimmune disease. Our aim was to study the functional polymorphic variants of PTPN22 and ZFAT in relation to thyroid disease and those of MYO9B in relation to CD. A cross-sectional comparative analysis was performed on Mexican mestizo patients with TS and age-matched healthy females. Our data showed that PTPN22 C1858T (considered a risk variant) is not associated with TS (X2 = 3.50, p = .61, and OR = 0.33 [95% CI = 0.10-1.10]). Also, ZFAT was not associated with TS (X2 = 1.2, p = .28, and OR = 1.22 [95% CI = 0.84-1.79]). However, for the first time, rs2305767 MYO9B was revealed to have a strong association with TS (X2 = 58.6, p = .0001, and OR = 10.44 [95% C = 5.51-19.80]), supporting a high level of predisposition to CD among TS patients. This report addresses additional data regarding the polymorphic variants associated with autoimmune disease, one of the most common complications in TS.
Assuntos
Doenças Autoimunes/etiologia , Doenças Autoimunes/genética , Miosinas/genética , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 2/genética , Fatores de Transcrição/genética , Síndrome de Turner/complicações , Síndrome de Turner/genética , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etnologia , Feminino , Humanos , México/epidemiologia , México/etnologia , Síndrome de Turner/epidemiologia , Síndrome de Turner/etnologiaRESUMO
BACKGROUND: Postmenopausal women present weight gain and intensification of obesity, especially visceral adipose tissue (VAT) increases in postmenopausal women. But it is still not clear whether abdominal fat increases during this stage independently of body weight. OBJECTIVE: compare the VAT and lipid profile between postmenopausal and premenopausal Mexican women. METHODS: A case control study in postmenopausal women matched for BMI with premenopausal women. Anthropometric and laboratory measurements as well as body composition analysis were performed. RESULTS: VAT was increased in postmenopausal women in contrast with premenopausal women (114.8 ± 39.5 vs 97.3 ± 29.0, p<0.05). Compared with premenopausal women, postmenopausal women showed higher total cholesterol (231 .6 ± 56.1 vs 206.8 ± 29.5 p <0.05), and LDL-cholesterol levels (145.9 ± 48.3 vs 121.7 ± 34.1, p < 0.05), whereas H DL-cholesterol remained unchanged. CONCLUSION: The results of the present study have demonstrated that Mexican postmenopausal women had a significant increment in visceral adipose tissue and in other metabolic risk factors, independent of the body mass index.
Assuntos
Gordura Intra-Abdominal , Lipídeos/sangue , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND AND AIMS: Common variable immunodeficiency (CVID) is a primary antibody deficiency characterised by decreased antibody production and low or normal B-cell numbers. To elucidate the clinical and immunological heterogeneity of CVID, we studied 16 patients diagnosed with CVID. METHODS: We analysed B, T and NK cell populations. We also assessed CD27 expression to define B-cell subsets and examined the expression of molecules important in B-cell proliferation and differentiation, such as the transmembrane activator and CALM interactor (TACI), inducible costimulator (ICOS), CD154 and CD40. RESULTS: We observed reduced B and T-cell numbers in CVID patients; this reduction was more pronounced in adults. While one group of patients (group I) showed a significant reduction in CD27+ memory B-cells, another group (group II) of patients exhibited numbers of CD27+ memory B-cells similar to the healthy donor. The frequency of B-cells and T-cells expressing CD40 and ICOS, respectively, was significantly lower in all CVID patients compared with healthy donors. Finally, a correlation between the frequency of CD27+ memory B-cells and clinical features was observed in CVID patients. CONCLUSION: These results suggest that in some patients, the combined defects in both T and B-cells may account for CVID. Additionally, patients in group I exhibited an increased frequency of pneumonia and chronic diarrhoea.
Assuntos
Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Imunodeficiência de Variável Comum/imunologia , Células Matadoras Naturais/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Antígenos CD40 , Ligante de CD40/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Memória Imunológica , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Masculino , México , Pessoa de Meia-Idade , Proteína Transmembrana Ativadora e Interagente do CAML/genética , Proteína Transmembrana Ativadora e Interagente do CAML/metabolismo , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To study the association of HLA-B27 with IgG antibodies to different enterobacterial HSP60s in patients with ankylosing spondylitis (AS). METHODS: IgG antibodies to 60 kDa enterobacterial HSPs were determined by ELISA in paired samples of sera and synovial fluid from 21 HLA-B27+ ankylosing spondylitis (AS) patients; and in sera from 32 HLA-B27+ AS patients, 35 HLA-B27+ healthy relatives of AS patients, and 60 HLA-B27- healthy individuals with no family members with AS. RESULTS: HLA-B27+ patients and healthy individuals showed significantly higher IgG antibody levels to recombinant enterobacterial HSP60s than HLA-B27- healthy controls. The levels of anti-HSP60Sf and anti-HSP60Ec antibodies correlated with disease activity and anti-HSP60Ec antibodies with male gender. No association between enterobacterial HSP60 antibody levels and disease duration was observed. All groups had lower levels of IgG antibodies to rHSP60 from Streptococcus pyogenes (rHSP60 Spy). In paired samples of sera and synovial fluid from B27+ patients, IgG antibodies to enterobacterial HSP60s were detected, but in significantly higher levels in sera than in synovial fluid. The anti-rHSPSpy IgG response in these samples was lower and similar in the three groups. CONCLUSIONS: A correlation was found between HLA-B27 and the response to recombinat enterobacterial HSP60s. This response could be associated with disease activitir and gender in some proteins and the presence eof IgG antibodies to these proteins in synovial fluid could be associated with the inflammatory process and initiation of AS.
Assuntos
Chaperonina 60/imunologia , Infecções por Enterobacteriaceae/imunologia , Antígeno HLA-B27/imunologia , Espondilite Anquilosante/imunologia , Líquido Sinovial/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Chaperonina 60/biossíntese , Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/complicações , Feminino , Antígeno HLA-B27/genética , Humanos , Indígenas Norte-Americanos/genética , Masculino , México , Pessoa de Meia-Idade , Proteínas Recombinantes/imunologia , Espondilite Anquilosante/sangue , Espondilite Anquilosante/microbiologia , Líquido Sinovial/microbiologia , Adulto JovemRESUMO
Between June 2003 and November 2004, we collected mobilized peripheral blood units from 29 patients with non-Hodgkin's lymphoma and multiple myeloma for autologous peripheral blood stem cell transplantation. They received granulocyte colony-stimulating factor (G-CSF) (16 micro g/kg/day) for a total of 5 days. Immediately before and 3 h after the fourth and fifth dose of G-CSF, we performed flow cytometry analysis to quantify: T cells (CD3+CD4+, CD3+CD8+), B cells (CD19+), NK cells (CD3-CD16+CD56+), NKT cells (CD3+CD16+CD56+), type 1 dendritic cells (DC1) (lin-HLA-DR+CD11c+), type 2 dendritic cells (DC2) (lin-HLA-DR+CD123+), regulatory T cells (Tregs) (CD4+CD25+), and activated T cells (CD3+HLA-DR+). All cell subsets were mobilized after G-CSF treatment with the exception of B, NK, and NKT lymphocytes. The median number of Treg cells before and after G-CSF was statistically different (29+/-14.9x10(6)/l vs 70.1+/-46.1x10(6)/l, P<0.02). DCs were mobilized significantly with a 5.9-fold increase in DC2 (15.1+/-30.3x10(6)/l vs 89.8+/-81.0x10(6)/l, P<0.02) and a 2.6-fold increase for DC1 (41+/-42.5x10(6)/l vs 109.5+/-58.0x10(6)/l, P<0.04). Patients received a mean of 3.1+/-1.2x10(7)/kg NK cells, 1.3+/-0.9x10(7)/kg NKT cells, 0.41+/-0.29x10(7)/kg DC1, 0.2+/-0.22x10(7)/kg DC2, and 1.8+/-1.9x10(7)/kg Tregs. In conclusion, intermediate doses of G-CSF induce mobilization of different lymphocyte subsets, with the exception of B, NK, and NKT cells. The mobilization of certain suppressive populations (DC2 and Treg) could be in theory deleterious, at least in patients with cancer.
Assuntos
Células Dendríticas , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Linfócitos , Linfoma não Hodgkin , Mieloma Múltiplo , Adulto , Idoso , Antígenos de Diferenciação/metabolismo , Fracionamento Celular/métodos , Células Dendríticas/patologia , Feminino , Filgrastim , Humanos , Linfócitos/patologia , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Proteínas Recombinantes , Transplante AutólogoRESUMO
We prospectively conducted a quantitative and phenotypic analysis of T, B, natural killer (NK), NKT, type 1 and 2 dendritic cells (DC), and regulatory T cells, before and after mobilization with intermediate doses of granulocyte colony-stimulating factor (G-CSF) (16 microg/kg per day). Between November, 2003, and December, 2004, we collected stem cells from 25 HLA identical sibling donors for allogeneic hematopoietic stem cell transplantation. Before mobilization and 3 h after the fourth and fifth doses of G-CSF, blood samples were taken for blood counts and flow cytometry. The median number of regulatory T cells before and after G-CSF was statistically different (69 +/- 41 x 10(6)/L versus 161 +/- 159 x 10(6)/L, p < 0.01). We observed a 1.7-fold increase in NK and NKT cells (p < 0.009 and p < 0.02, respectively). DC were mobilized with a 11.5-fold increase in type 2 (p < 0.004) and a 8.5-fold increase in type 1 DC (p < 0.003). The patients received a mean of: 2.2 x 10(7)/kg +/- 1.4 x 10(7)/kg of NK cells, 0.95 x 10(7)/kg +/- 0.81 x 107/kg of NKT cells, 0.43 x 107/kg +/- 0.53 x 10(7)/kg of type 1 DC, 0.3 v 10(7)/kg +/- 0.45 x 10(7)/kg of type 2 DC and 1.4 x 10(7)/kg +/- 1.2 x 10(7)/kg of regulatory T cells. Using intermediate doses of G-CSF, we have demonstrated the mobilization of different lymphocyte subsets, in particular regulatory T cells and DC, which can be expanded later and used in the treatment of cancer and autoimmune diseases.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Transplante de Células/métodos , Células Dendríticas/imunologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Ativação Linfocitária , Linfócitos/imunologia , Receptores de Interleucina-2/análise , Células-Tronco/citologia , Adulto , Antígenos CD/análise , Remoção de Componentes Sanguíneos/métodos , Feminino , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , IrmãosRESUMO
BACKGROUND: Klebsiella pneumoniae is a major cause of neonatal sepsis and nosocomial infections in Mexico. Antibiotic therapy is the first choice for treatment but the increase in multiple resistance strains has forced scientists to look for alternative treatments, such as immunotherapy. In this work, we propose that porins could be a common antigen among four different capsular serotypes of Klebsiella pneumoniae for the production of immune sera with opsonizing capacity. METHODS: The 35 and 36 kDa porins from four different serotypes of the bacteria were isolated by the Nikaido method followed by purification in Sephacryl column chromatography. The 36 kDa of serotype K8 was further purified by electroelution. The 35 and 36 kDa porins were used to obtain rabbit polyclonal antibodies (PolyAb) to the four serotypes and the 36 kDa from K8 for the production of monoclonal antibodies (MoAb). Antigenic reactivity of PolyAb and MoAb were analyzed by ELISA and WB and their opsonizing capacity for human PMN was measured by chemiluminescence (CL) using capsulated and non-capsulated bacteria. RESULTS: Porins from the four strains showe electrophoretic homology and cross reaction by ELISA and WB. CL assays indicated that PolyAb opsonized heterologous strains and that MoAb perform this in the absence of capsule. CONCLUSIONS: K.pneumoniae 35 and 36 kDa porins are common antigens for the four serotypes studied and induce opsonizing antibodies.
Assuntos
Anticorpos Antibacterianos/biossíntese , Antígenos de Bactérias/imunologia , Klebsiella pneumoniae/imunologia , Porinas/imunologia , Opsinas de Bastonetes/imunologia , Animais , Humanos , CoelhosRESUMO
BACKGROUND: Psoriasis is a chronic disease of the skin that appears to be of autoimmune nature. It has a strong association with throat streptococcal infections, as well as with stressful events. Although many groups consider psoriasis to be a T-cell-mediated autoimmune disease, autoantibodies could also play a role in the development of this process. METHODS: In this work, we looked for autoantibodies to psoriatic skin in 21 psoriatic patients and four healthy donors (controls). The immunoperoxidase technique was used to look for autoantibodies in autologous sera in skin sections obtained from lesions or from healthy areas of the same patient, before and after immunoadsorption with a Streptococcus pyogenes extract. The skin biopsies were also analyzed with a pool of sera from mice immunized with the streptococcal extract. RESULTS: We found that all psoriatic patients had autoantibodies to antigens present in keratinocytes, whereas healthy subjects did not. These antibodies did not recognize epitopes on healthy skin from the same psoriatic patients or controls. Immunoadsorption of autologous sera removed the reactivity to antigens in skin lesions in all cases. Mouse anti-streptococcal sera recognized epidermal antigens present in lesional psoriatic skin, but not in healthy skin from psoriatic patients or controls. Deposits of immunoglobulin G (IgG) were not detected in the lesions. CONCLUSIONS: It seems that autoantibodies, although they do not appear to participate in the pathogenesis of psoriasis, are an important feature, and that skin antigens, which appear in lesional immature keratinocytes, cross-react with S. pyogenes and contribute to the autoimmune process in psoriasis.
Assuntos
Antígenos de Bactérias/imunologia , Autoanticorpos/análise , Autoantígenos/imunologia , Psoríase/imunologia , Pele/imunologia , Streptococcus pyogenes/imunologia , Adulto , Idoso , Animais , Reações Cruzadas , Feminino , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Faringe/microbiologia , Psoríase/diagnóstico , Psoríase/patologia , Pele/química , Pele/citologia , Infecções Estreptocócicas/patologia , Streptococcus pyogenes/isolamento & purificaçãoRESUMO
In the search for the pathogenic consequences of the molecular mimicry between the Klebsiella pneumoniae nitrogenase and the HLA-B27 antigen, sera from individuals belonging to 16 kindreds with juvenile-onset ankylosing spondylitis cases, were analyzed for antibodies against nitrogenase-positive and -negative K. pneumoniae whole bacterial extracts. An initial screening for nitrogenase producing K. pneumoniae strains was performed in 31 clinical isolates. The best nitrogenase producing strain was selected as well as a non producing one for immunoblot analysis using sera from 82 subjects, 55 HLA-B27 positive, of which 26 had some clinical manifestations. Even though electrophoretic patterns were different in both strains, there was no distinctive differential recognition of the 30-40 kDa proteins where the nitrogenase subcomponent which shares the sequence QTDRED with the HLA-B27 molecule is located. On the other hand, strong recognition of a protein of 60 kDa (p60Kp) was detected in 75% of HLA-B27 positive tested subjects independently of their clinical status. Studies on the nature of this protein and its participation in the pathogenesis of ankylosing spondylitis are now in progress.
Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Proteínas de Bactérias/imunologia , Klebsiella pneumoniae/imunologia , Mimetismo Molecular , Nitrogenase/imunologia , Espondilite Anquilosante/imunologia , Especificidade de Anticorpos , Doenças Autoimunes/genética , Reações Cruzadas , Antígeno HLA-B27/análise , Antígeno HLA-B27/genética , Humanos , Klebsiella pneumoniae/enzimologia , Espondilite Anquilosante/genéticaRESUMO
The mechanisms of immune response generation and regulation at the intestinal level are not well known, mainly due to the lack of suitable and reproducible methods to measure local immune responses. The Cunningham direct and indirect hemolytic plaque assay for the quantification of antibody producing cells against Salmonella in Peyer's patches of mice orally infected with Salmonella typhimurium was used. After infection IgM and IgG producing cells were determined on days 6, 9, 12 and 19. Specific antibody producing cells appeared after bacterial invasion of Peyer's patches, nine days after infection. At this time, there were more antibody producing cells in the distal part of the intestine, which correlated with a higher infection of these Peyer's patches as detected by bacterial culture. After day nine, the number of plaque forming cells was similar in both parts of the intestine. The peak of response was on day 12 and diminished on day 19. The number of IgM and IgG producing cells was similar in all days analyzed. Histological analysis of Peyer's patches of infected mice showed inflammation with disorganization and tumefaction.