RESUMO
Intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) are effective in the treatment of patients with primary antibody deficiency disorders (PAD). The purpose of this study was to evaluate Streptococcus pneumoniae (Spn) antibody titres to 14 serotypes in patients receiving IVIG compared to SCIG and to correlate Spn antibody levels to clinical outcome. The doses of immunoglobulin (Ig)G/kg/month were similar in both IVIG and SCIG groups. In 11 patients treated with IVIG, Spn antibody titres were ≥ 1·3 µg/ml to 99·4 ± 2·1% of the 14 serotypes at peak IVIG but decreased to 66·9 ± 19·8% at trough IVIG. Loss of Spn titres ≥ 1·3 µg/ml was most frequent for Spn serotypes 1, 4, 9V and 23. This correlated with lower Spn antibody titres to these serotypes at peak IVIG compared to the other serotypes. In 13 patients treated with SCIG, Spn antibody titres were protective to 58·2 ± 23·3% of the serotypes 3-5 days after infusion, similar to trough IVIG. Similarly, the Spn serotypes with the least protective percentages were the same as the ones observed in trough IVIG. There were no annualized serious bacterial infections (aSBI) in either group. However, there were significantly decreased annualized other infections (aOI) in the SCIG group compared to the IVIG-treated group, 0·8 ± 0·7 versus 2·2 ± 1·2 infections/patient/year (P = 0·004). Breakthrough aOI did not correlate with protective or higher serum Spn antibody titres.
Assuntos
Anticorpos Antibacterianos/sangue , Imunoglobulinas Intravenosas/administração & dosagem , Síndromes de Imunodeficiência/terapia , Infecções Pneumocócicas/prevenção & controle , Polissacarídeos Bacterianos/imunologia , Streptococcus pneumoniae/imunologia , Administração Intravenosa , Adolescente , Criança , Feminino , Humanos , Imunoglobulina A/administração & dosagem , Imunoglobulina A/imunologia , Imunoglobulina G/administração & dosagem , Imunoglobulina G/imunologia , Imunoglobulina M/administração & dosagem , Imunoglobulina M/imunologia , Imunoglobulinas Intravenosas/imunologia , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/microbiologia , Injeções Subcutâneas , Masculino , Infecções Pneumocócicas/imunologiaRESUMO
Primary immunodeficiency diseases (PIDD) are associated with significant morbidity and mortality and result in a significant public health burden. This is in part due to the lack of appropriate diagnosis and treatment of these patients. It is critical that governments become aware of this problem and provide necessary resources to reduce this impact on health care systems. Leading physicians in their respective countries must be supported by their own governments in order to implement tools and provide education and thus improve the diagnosis and treatment of PIDD. The Latin American Society of Primary Immunodeficiencies (LASID) has initiated a large number of activities aimed at achieving these goals, including the establishment of a PIDD registry, development of educational programmes and guidelines, and the introduction of a PIDD fellowship programme. These initiatives are positively impacting the identification and appropriate treatment of patients with PIDD in Latin America. Nevertheless, much remains to be done to ensure that every person with PIDD receives proper therapy.
Assuntos
Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Congressos como Assunto , Humanos , América Latina , Sociedades MédicasRESUMO
Experts from six Latin American countries met to discuss critical issues and needs in the diagnosis and management of primary immunodeficiency diseases (PIDD). The diagnosis of PIDD is generally made following referral to an immunology centre located in a major city, but many paediatricians and general practitioners are not sufficiently trained to suspect PIDD in the first place. Access to laboratory testing is generally limited, and only some screening tests are typically covered by government health programmes. Specialised diagnostic tests are generally not reimbursed. Access to treatment varies by country reflecting differences in healthcare systems and reimbursement policies. An online PIDD Registry Programme for Latin America has been available since 2009, which will provide information about PIDD epidemiology in the region. Additional collaboration across countries appears feasible in at least two areas: a laboratory network to facilitate the diagnosis of PIDD, and educational programmes to improve PIDD awareness. In total, these collaborations should make it possible to advance the diagnosis and management of PIDD in Latin America.
Assuntos
Gerenciamento Clínico , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Alergia e Imunologia/educação , Conhecimentos, Atitudes e Prática em Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Imunoglobulinas Intravenosas/economia , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/economia , Cobertura do Seguro , Reembolso de Seguro de Saúde , América Latina , Sistema de RegistrosRESUMO
Early diagnosis and appropriate therapy are essential for the best prognosis and quality of life in patients with primary immunodeficiency diseases (PIDDs). Experts from several Latin American countries have been meeting on a regular basis as part of an ongoing effort to improve the diagnosis and treatment of PIDD in this region. Three programmes are in development that will expand education and training and improve access to testing facilities throughout Latin America. These programmes are: an educational outreach programme (The L-Project); an immunology fellowship programme; and the establishment of a laboratory network to expand access to testing facilities. This report provides the status of these programmes based on the most recent discussions and describes the next steps toward full implementation of these programmes.
Assuntos
Comitês Consultivos , Hispânico ou Latino , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/terapia , Sistema de Registros , Alergia e Imunologia/educação , Bolsas de Estudo , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/epidemiologia , Testes Imunológicos/normas , América Latina , Educação de Pacientes como Assunto , Guias de Prática Clínica como Assunto , Estados UnidosRESUMO
An alloreactive reaction similar to that occurring during GvHD can be generated in a mixed lymphocyte culture. The presence of both stimulator and responder cells in these cultures makes the identification and enumeration of alloreactive cells difficult and unreliable. We describe the use of PBMC sonicates as an alternative to the standard MLC method to stimulate an allogeneic reaction. Using combinations of autologous or allogeneic PBMC sonicates, we showed that the lymphocyte proliferative response to cell sonicates was comparable to the response using irradiated cells. The proliferative response was concentration dependent and reached maximum levels at day 6. Both irradiated cells and PBMC sonicates induced significantly lower responses when the stimulating cells were partially HLA-DR matched rather than completely mismatched. Alloreactive T cells stimulated with sonicates were enumerated by the flow cytometric detection of CD69 or CD25. In HLA-mismatched cultures, approximately 7% of CD3+ T cells were CD69+ or CD25+, suggesting alloreactivity. Although there was a significant correlation between the expression of these activation markers and lymphocyte proliferative responses, significant individual variations in the results of these two assays were observed. The results in this study demonstrate the potential of using PBMC sonicates instead of irradiated lymphocytes for the study and identification of alloreactive cells at the cellular and molecular level.
Assuntos
Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos T/análise , Leucócitos Mononucleares/imunologia , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos/métodos , Linfócitos T/imunologia , Humanos , Imunidade Celular/efeitos da radiação , Lectinas Tipo C , Sonicação , Linfócitos T/efeitos da radiação , Fatores de TempoRESUMO
OBJECTIVE: To determine whether children with recurrent respiratory infections who failed to respond to the conventional polysaccharide vaccine would respond to a pneumococcal conjugate vaccine. METHODS: Children referred to our clinic for recurrent respiratory infections who had no known primary or secondary immunodeficiencies were immunized with a 23-valent pneumococcal polysaccharide vaccine. IgG antibodies to pneumococcal serotypes 1, 3, 4, 6B, 9V, 14, 18C, 19F and 23F were determined by enzyme-linked immunosorbent assay before and 4 to 6 weeks after immunization. An adequate IgG antibody response to an individual serotype was arbitrarily defined as a postimmunization antibody titer > or =1.3 microg/ml or at least 4 times the preimmunization value. Immunization with an experimental CRM197-heptavalent pneumococcal conjugate vaccine was offered to patients without an adequate response to 4 or more vaccine serotypes (nonresponders). Post-conjugate immunization antibody concentrations were measured 4 to 6 weeks later. RESULTS: In nonresponder patients (n = 17) geometric mean post-conjugate immunization (C) serum antibody concentrations (microg/ml) compared with post-polysaccharide (PS) concentrations were: (serotype, C vs. PS) 4, 1.11 vs. 0.30 (P = 0.000227); 6B, 0.46 vs. 0.20 (P = 0.017267); 9V, 0.82 vs. 0.29 (P = 0.002163); 14, 1.88 vs. 0.27 (P = 0.000615); 18C, 0.98 vs. 0.32 (P = 0.021962); 19F, 1.24 vs. 0.34 (P = 0.002844); and 23F, 0.87 vs. 0.16 (P = 0.000194). In responder patients (n = 67), after 1 dose of the polysaccharide vaccine, geometric mean antibody concentrations were: 4, 1.05; 6B, 0.96; 9V, 1.55; 14, 1.65; 18C, 1.62; 19F, 1.30; and 23F, 1.02. CONCLUSIONS: Our results show that a pneumococcal conjugate vaccine is capable of inducing an IgG response in patients with recurrent infections who had failed to mount an adequate response to the polysaccharide vaccine. Conjugate vaccines may be of value in the management of children with recurrent pneumococcal respiratory infections.
Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/imunologia , Infecções Pneumocócicas/prevenção & controle , Infecções Respiratórias/prevenção & controle , Streptococcus pneumoniae/imunologia , Vacinas Conjugadas/imunologia , Adolescente , Vacinas Bacterianas/administração & dosagem , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Humanos , Esquemas de Imunização , Imunoglobulina G/sangue , Infecções Pneumocócicas/terapia , Polissacarídeos Bacterianos/imunologia , Recidiva , Infecções Respiratórias/terapia , Vacinas Conjugadas/administração & dosagemRESUMO
Patent infections with the lymphatic filariae, Wuchereria bancrofti and Brugia malayi, are associated with suppressed in vitro cellular responsiveness to filarial antigens. In studies of bancroftian filariasis in Haiti, a significant number of microfilaremic individuals can be characterized as "responders" to filarial antigens. Cells from 37/74 untreated microfilaremic subjects responded to B. pahangi antigen (stimulation ratio greater than 2) as detected by in vitro blastogenesis. A comparison of responders to nonresponders revealed a significant difference in mean B. pahangi reactivity (15,822 vs. 4,538 cpm, P less than 0.001), but no significant differences with respect to age, microfilaremia, PPD or PHA reactivity, or B. pahangi-specific antibody levels. Subtle differences may exist between these groups with respect to recognition of specific antigens on Western blots.
Assuntos
Antígenos de Helmintos/imunologia , Brugia/imunologia , Filariose Linfática/imunologia , Filariose/imunologia , Leucócitos Mononucleares/imunologia , Animais , Anticorpos Anti-Helmínticos/biossíntese , Haiti , Humanos , Imunidade Celular , Ativação Linfocitária , Microfilárias/imunologia , Wuchereria bancrofti/imunologiaRESUMO
SETTING: Immune response induced by BCG vaccination seems to reflect the development of T-cell immunity and monocyte activation. Participants were recruited from a large prospective study in infants from a suburb in Santiago, Chile. OBJECTIVE: To determine whether newborn BCG immunization changes the innate ability of cultured monocyte-macrophages to ingest and kill virulent mycobacteria in the absence of lymphocytes. DESIGN: The study population consisted of 15 three-month-old, tuberculin-positive infants immunized with BCG (Japanese) at birth, 13 randomly-selected, age-matched tuberculin-nonreactive infants in whom BCG immunization was postponed until one year of age, and five BCG-immunized, tuberculin-reactive adults. Adherent cells were cultured for 48 h. Monocyte-macrophage viability and number and viability of intracellular Mycobacterium tuberculosis bacilli were assessed after an additional 2 h and 4 and 7 days of incubation. RESULTS: There was no difference in the mean number of adherent cells present after 48 h among the three study groups. Adherent cells from BCG-immunized infants and adults had a significantly higher viability after 7 days in culture than adherent cells from non-immunized infants. The percentage of cells ingesting M. tuberculosis and the number of bacilli per cell after 2 h and 4 days was significantly higher in immunized infants and adults than in non-immunized infants. However, there was no evidence for increased killing of mycobacteria by cells from immunized infants and adults. CONCLUSION: These results suggest that BCG vaccination increases monocyte viability and the uptake of M. tuberculosis without enhancing the ability to kill ingested M. tuberculosis in the absence of lymphocytes.
Assuntos
Vacina BCG/administração & dosagem , Monócitos/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Tuberculose/prevenção & controle , Vacinação , Adulto , Fatores Etários , Análise de Variância , Células Cultivadas , Chile , Contagem de Colônia Microbiana , Humanos , Imunidade Celular/fisiologia , Lactente , Recém-Nascido , Mycobacterium tuberculosis/crescimento & desenvolvimento , Estudos Prospectivos , Valores de Referência , Linfócitos T/imunologia , Tuberculose/sangueRESUMO
Patent filarial infection has been correlated with a profound suppression of humoral and cellular responses to filarial antigens. In the present study, the filarial antigen-specific humoral and cellular reactivity of 30 Haitian subjects with patent Wuchereria bancrofti infection was monitored before and after treatment with diethylcarbamazine. Microfilarial density was reduced from a pre-treatment mean of 1778/ml to 9/ml, with residual microfilaraemias detectable in 10 subjects. Peripheral blood mononuclear cells from 18 of the 30 patients responded to an extract of Brugia pahangi before treatment, and this number increased to 25 after treatment. There was no significant change in the mean level of response to B. pahangi in patients who were responsive to filarial antigen before treatment; however, the mean responsiveness to B. pahangi of individuals who were classified as nonresponders before treatment was significantly increased following treatment. Cellular reactivity to purified protein derivative and geometric mean titres to soluble B. pahangi, measured by enzyme-linked immunosorbent assay, were unaffected by treatment. Similarly, most post-treatment sera did not recognize new B. pahangi bands on Western blots, compared to pre-treatment controls. These observations imply that the relationship between microfilariae and immunosuppression is complex.
Assuntos
Dietilcarbamazina/uso terapêutico , Filariose Linfática/imunologia , Filariose/imunologia , Adolescente , Adulto , Idoso , Animais , Anticorpos Anti-Helmínticos/biossíntese , Antígenos de Helmintos/imunologia , Brugia/imunologia , Criança , Filariose Linfática/tratamento farmacológico , Feminino , Humanos , Masculino , Microfilárias/isolamento & purificação , Pessoa de Meia-Idade , Wuchereria bancroftiRESUMO
IgG antibodies against pneumococcal polysaccharides are found predominantly within IgG subclass 2. We wished to evaluate retrospectively IgG subclasses and post-immunization pneumococcal antibody titers in children with recurrent respiratory infections. We examined total immunoglobulin levels and IgG subclasses, as well as pneumococcal antibody titers against serotypes 3, 7F, 9N, and 14 present 4-6 weeks after pneumococcal immunization in 56 children 2-18 years old. Titers > 200 ng Ab N/ml to any of the 4 serotypes tested were arbitrarily considered protective. Four patients did not have protective antibody levels against any of the 4 serotypes tested following vaccination. Of those, 3 had normal IgG subclass levels and 1 had an IgG2 subclass deficiency. Of 3 additional patients with IgG2 deficiency, 2 had protective antibody levels to only 1 serotype and 1 had protective antibody levels to 2 serotypes. Furthermore, in 2 patients with undetectable IgG2 at the time of immunization, the response was only transient. We conclude that patients with IgG2 deficiency may not develop protective antibody levels to all pneumococcal serotypes and that some may have deficient memory for IgG anti-pneumococcal polysaccharide antibodies.
Assuntos
Anticorpos Antibacterianos/análise , Vacinas Bacterianas/imunologia , Imunização , Imunoglobulina G/análise , Streptococcus pneumoniae/imunologia , Adolescente , Formação de Anticorpos , Criança , Pré-Escolar , Feminino , Humanos , Deficiência de IgG/imunologia , Lactente , Masculino , Vacinas Pneumocócicas , Estudos RetrospectivosRESUMO
The study objective was to determine the clinical value of positive antinuclear antibody (ANA) and ANA profile tests in children with autoimmune disorders. A retrospective chart review was carried out of all patients under 18 years of age with a positive ANA test (HEp-2 cell substrate, titre > or =1:40) and ANA profile (ELISA) referred to the paediatric rheumatology service at the authors' institution between 1992 and 1996. Of 245 children with a positive ANA test, 134 (55%) had an autoimmune disease, including juvenile rheumatoid arthritis (n = 49), systemic lupus erythematosus (SLE) (n = 40) and others (n = 45). The remaining 111 patients did not have identifiable autoimmune diseases. Patients with autoimmune disorders had significantly higher ANA titres of > or = 1:160 (chi2 = 16, P<0.0001). In addition, of the 245 patients with a positive ANA test, 86 had an ANA profile performed; this was positive in 32 and negative in 54. All 32 patients with a positive ANA profile (100%) had an autoimmune disorder, compared to 22 (41%) of 54 with a negative ANA profile who had autoimmune disorders. Of 22 SLE patients with a positive ANA profile, 16 (73%) had positive anti-dsDNA and 15 (68%) had positive anti-Sm and positive anti-RNP. A positive ANA profile correlated strongly with an ANA titre > or = 1:640 (chi2 = 5.7 , P<0.02). The study demonstrated that only 55% of children with a positive ANA test had a definitive diagnosis of autoimmune disorder. These children tend to have higher ANA titres of > or =1:160. However, a positive ANA profile was strongly correlated with an ANA titre > or =1:640 and highly indicative of an autoimmune disorder (100%). We suggest that in order to reduce cost, an ANA profile should not be performed on all patients with positive ANA, but reserved for those with an ANA titre of > or =1:640 and/or those with a high clinical index of suspicion for autoimmune disorder, especially SLE.
Assuntos
Anticorpos Antinucleares/análise , Doenças Autoimunes/imunologia , Artrite Juvenil/imunologia , Criança , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Doenças Musculoesqueléticas/imunologia , Estudos RetrospectivosRESUMO
This study examined the presence of a persistent state of low-grade inflammation in sickle cell anemia patients by measuring circulating sHLA-I heterodimers and C-reactive protein during the steady state and after recent crises. Thirty-nine pediatric sickle hemoglobinopathy patients were studied during the steady state and 11 patients were evaluated within 1 month of a painful crisis. A disease severity score was generated for each patient, and soluble HLA-I (sHLA-I) and C-reactive protein levels were determined. Soluble HLA-I was significantly elevated in 55% of the steady-state group and in 36% of the recent-crisis group. The percentage of patients with elevated sHLA-I differed in the various disease subgroups in the steady state: 46% of Hb SS patients, 70% of Hb SC patients, 75% of Hb S beta-thal patients, and 20% of Hb SSF patients. Steady-state and recent-crisis sHLA-I levels were not significantly different. C-reactive protein levels were elevated in 11% of steady-state patients and in 9% of recent-crisis patients. Soluble HLA-I levels did not correlate with C-reactive protein levels or disease severity score, age, hemoglobin, reticulocyte count, platelet count, or white cell count. These results show that the majority of sickle hemoglobinopathy patients have elevated sHLA-I levels during the steady state and after recent crisis, suggesting the presence of chronic inflammation during the steady state.
Assuntos
Anemia Falciforme/sangue , Antígenos de Histocompatibilidade Classe I/sangue , Anemia Falciforme/imunologia , Proteína C-Reativa/análise , Criança , Feminino , Humanos , Masculino , Índice de Gravidade de DoençaRESUMO
The aim of this study was to evaluate the effect of absorption with pneumococcal type 22F polysaccharide on antipneumococcal antibody titers in unimmunized Chilean pregnant women and on antibodies in their offspring at birth and 3, 6, and 12 months of age. Sera from 10 healthy pregnant women and from their offspring at birth and at 3, 6, and 12 months of age were studied. Immunoglobulin G antibodies against serotypes 1, 3, 4, 5, 6B, 9V, 14, 18, 19F, and 23F were measured by a standardized enzyme-linked immunosorbent assay method. All sera were absorbed with polysaccharide C, and aliquots of each serum were absorbed with polysaccharide 22F. Individual results were expressed in mug/ml based on the standard serum pool 89-SF. Absorption with polysaccharide 22F reduced antibody concentrations in all samples and to all 10 serotypes studied. Reduction was highest in maternal sera and in cord blood, but it was also present at 3, 6, and 12 months of age. The percent reduction ranged from 24% for serotype 14 to 50% for serotype 1 in maternal samples and from 20% for serotype 18C to 49% for serotype 4 in cord blood samples. The percentages of transplacental transmission were similar for nonabsorbed and absorbed maternal fetal pairs. Absorption with serotype 22F had a significant impact on antipneumococcal antibody concentrations in unimmunized pregnant women and in their offspring. Our results suggest that absorption with 22F polysaccharide needs to be performed in studies of transplacental transmission of antipneumococcal antibodies.
Assuntos
Anticorpos Antibacterianos/sangue , Sangue Fetal/imunologia , Imunoglobulina G/sangue , Polissacarídeos Bacterianos/imunologia , Streptococcus pneumoniae/imunologia , Absorção , Antígenos de Bactérias/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Materno-Adquirida , Lactente , Recém-Nascido , Gravidez , Streptococcus pneumoniae/classificaçãoRESUMO
Both nonspecific and antigen specific immunological alterations are associated with the presence of circulating microfilariae in Brugia pahangi infected jirds. T-cell growth factors are an essential element of an immune response; thus, modulation of the production or utilization of lymphokines by filarial antigens may be involved in these alterations. In the present study, the effect of soluble extracts of B. pahangi adult worms and microfilariae on the in vitro mitogen and antigen induced proliferative responsiveness of lymphocytes from uninfected and B. pahangi immunized jirds was investigated. Dose dependent suppression of lymphocyte proliferative responsiveness to the T-cell mitogen, concanavalin A ranged from 37% to 86% in the presence of adult or microfilarial (Mf) extracts, respectively. Similarly, a suppressive effect was observed when other mitogens were used to stimulate the lymphocytes. Mf extracts did not significantly suppress the proliferative response of lymph node cells from B. pahangi immunized jirds to parasite antigen. However, microfilarial fractions higher than 150 Kd, purified by gel filtration HPLC, consistently suppressed antigen as well as mitogen responses. Soluble extracts of B. pahangi females and Mf also suppressed mitogen induced lymphokine production by lymph node cells by 66% and 68% respectively. These findings suggest that a microfilarial-derived antigen may play a role in regulating immune reactivity in filarial infections. The absence of generalized nonspecific immunosuppression in filarial infections, however, suggests that the effect of microfilarial-derived antigens may be restricted to the microhabitat of the parasite.
Assuntos
Antígenos de Helmintos/imunologia , Brugia/imunologia , Ativação Linfocitária , Animais , Divisão Celular , Linhagem Celular , Concanavalina A/farmacologia , Feminino , Gerbillinae , Interleucina-2/biossíntese , Masculino , Microfilárias/imunologia , Peso Molecular , Solubilidade , Linfócitos T Citotóxicos/imunologiaRESUMO
Previous studies have demonstrated that the induction of immunoregulatory mechanisms in the spleens of Brugia pahangi-infected jirds is correlated with the onset of microfilaremia. This study investigated the relationship between production of a factor with IL-2-like activity and the regulation of T cell-mediated responses in jirds experimentally infected with B. pahangi. A factor present in culture supernatants of mitogen-stimulated jird lymphocytes supported the proliferation of murine CTLL cells and provided the basis for an IL-2 assay. Mitogen induced proliferative responses and IL-2 production of spleen cells but not lymph node cells from pre-patent and microfilaremic jirds were suppressed. Both B. pahangi Ag-induced proliferative responsiveness and IL-2 production of spleen cells from microfilaremic jirds were also suppressed relative to lymph node cells from the same animals or spleen cells from B. pahangi immunized or prepatent jirds. Depletion of histamine receptor-bearing cells restored the ability of spleen cells from microfilaremic jirds to produce significant levels of IL-2. In addition, in add-mixture experiments, spleen cells from microfilaremic jirds suppressed Ag-induced IL-2 production by cells from either B. pahangi- or KHL-immunized jirds. Exogenous IL-2 failed to reconstitute the suppressed Ag-induced proliferative response of spleen cells from microfilaremic jirds. This study demonstrates that the down-regulation of immune responses in B. pahangi infection is a cell-mediated event and is associated with an inability to produce IL-2.
Assuntos
Antígenos de Helmintos/imunologia , Filariose Linfática/imunologia , Filariose/imunologia , Interleucina-2/biossíntese , Ativação Linfocitária , Linfócitos T/imunologia , Animais , Brugia/imunologia , Gerbillinae , Interleucina-2/farmacologia , Cinética , Linfonodos/imunologia , Masculino , Microfilárias/imunologia , Baço/imunologiaRESUMO
Histamine is known to mediate potent immunosuppressive effects on lymphocyte function. In jirds infected with Brugia pahangi decreased mitogen and parasite antigen responsiveness are associated with the presence of histamine binding regulatory cells. The present study was thus designed to investigate the immunoregulatory role of histamine in experimental filariasis. Spleen cells from normal or B. pahangi infected jirds were incubated with BSA or histamine coupled Sepharose beads and the degree of cell-bead binding was quantitated. Cells from infected jirds demonstrated increased levels of histamine, but not BSA binding relative to normal cells, and this binding was blocked by soluble histamine or by the histamine receptor antagonist cimetidine. Cimetidine failed to restore the in vitro responsiveness of spleen cells from infected jirds to phytohemagglutinin or to a soluble extract of B. pahangi. Cimetidine did, however, reverse histamine-induced suppression of normal spleen cell responses to PHA. The present results suggest that histamine does not play a major role in the immunoregulatory alterations induced by B. pahangi infection.
Assuntos
Cimetidina/farmacologia , Filariose/imunologia , Tolerância Imunológica/efeitos dos fármacos , Animais , Antígenos de Helmintos/imunologia , Brugia , Adesão Celular/efeitos dos fármacos , Feminino , Gerbillinae , Histamina/imunologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Receptores Histamínicos/efeitos dos fármacos , BaçoRESUMO
We wished to determine whether pneumococcal polysaccharide antigens induce mRNA expression of CD40 ligand (CD40L) and Th1 or Th2 cytokines in unimmunized individuals in vitro and whether immunization with the 23-valent pneumococcal polysaccharide vaccine induces changes in CD40L and cytokine mRNA expression. Children with recurrent respiratory infections were studied before and 4 to 6 weeks after receiving the pneumococcal vaccine. One patient who failed to respond to the polysaccharide vaccine subsequently received a single dose of the experimental 7-valent pneumococcal conjugate vaccine. Unimmunized healthy adults were included as controls. Quantification of mRNA expression of CD40L, interleukin-4 (IL-4), IL-12p40, and gamma interferon (IFN-gamma) was performed by reverse transcription-PCR and enzyme-linked immunosorbent assay (ELISA)-PCR with resting and stimulated peripheral blood mononuclear cells. Serum immunoglobulin G (IgG) anti pneumococcal antibody levels were measured by ELISA. The results showed a significant increase in the expression of mRNAs for CD40L and IL-4, but not IL-12p40 or IFN-gamma, in stimulated cultures from unimmunized individuals. CD40L and IL-4 mRNA expression was significantly higher in postimmunization than in preimmunization samples stimulated with the individual pneumococcal serotypes. These results suggest that pneumococcal polysaccharide antigens specifically up-regulate CD40L expression and induce a Th2 response in vitro which parallels the increase in IgG antipneumococcal antibody levels in serum.
Assuntos
Ligante de CD40/genética , Vacinas Pneumocócicas/imunologia , Células Th2/imunologia , Adolescente , Ligante de CD40/imunologia , Criança , Pré-Escolar , Expressão Gênica/imunologia , Humanos , Imunoglobulina G/sangue , Interferon gama/genética , Interferon gama/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-4/genética , RNA Mensageiro/análise , Células Th1/imunologia , Regulação para Cima/imunologiaRESUMO
Iron deficiency induces thymus atrophy in laboratory animals and very likely in humans by unknown mechanisms. The atrophy is associated with impaired cell-mediated immunity. In this study, we tested the hypothesis that thymus atrophy is a result of increased apoptosis and reduced thymocyte proliferation. Thymocytes were obtained from twenty-seven control, twenty-seven pairfed, twenty-seven iron-deficient (ID) mice; twelve and fourteen ID mice that received the control diet (0.9 mmol/kg versus 0.09 mmol/kg for the ID diet) for 1 d (repletion, R1) and 3 d (R3), respectively. Cell cycle analysis and apoptosis were studied by flow cytometry using propidium iodide staining and terminal deoxyuridine nick end labeling of DNA breaks assay respectively. When mice were killed, haemoglobin, haematocrit, and liver iron stores of ID, R1, and R3 mice were 25-40 % of those of control and pairfed mice Absolute and relative thymus weights and thymocyte numbers were 19 to 68 % lower in ID, R1, and R3 than in control and pairfed groups We found no significant difference among groups in the percentage of cells undergoing apoptosis. A higher percentage of thymocytes from ID and R1 mice than those of control, pairfed, and R3 mice were in the resting phase of the normal cell cycle Conversely, a lower percentage of thymocytes from ID and R1 mice than those from control, pairfed, and R3 mice were in the DNA synthesis phase and late phase of DNA synthesis and onset of mitosis (G2-M) Indicators of iron status positively correlated (r 0.3 to 0.56) with the percentage of thymocytes in the G2-M phase Results suggest that reduced cell proliferation but not increased apoptosis is the cause of thymus atrophy associated with iron deficiency.
Assuntos
Anemia Ferropriva/patologia , Timo/patologia , Anemia Ferropriva/metabolismo , Animais , Apoptose , Atrofia/etiologia , Contagem de Células , Ciclo Celular , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Hematócrito , Hemoglobinas/análise , Marcação In Situ das Extremidades Cortadas , Ferro/análise , Fígado/química , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Atopic dermatitis is characterized by increased production of IgE and interleukin-4, immediate skin test reactivity to allergens, increased expression of CD23 on mononuclear cells, and decreased production of interferon-gamma. Soluble HLA-I molecule levels are elevated in conditions where T cells are activated such as viral infections, autoimmune diseases, and organ transplantation. OBJECTIVE: We wished to determine if sHLA-I heterodimers were also elevated in patients with atopic dermatitis and if sHLA-I elevations correlated with disease activity. METHODS: Fourteen children with atopic dermatitis resistant to conventional treatment were followed over an 8-week period during an ongoing trial of treatment with topical sodium cromoglycate. Extent of skin involvement, disease severity, absolute eosinophil counts, IgE and HLA-I levels were determined at the time of enrollment into the study. Additional sHLA-I levels were measured after 4 and 8 weeks of therapy. RESULTS: Mean sHLA-I levels were significantly elevated in atopic dermatitis patients, 2.07 +/- 1.14 versus 1.00 +/- 0.22 microg/mL in controls (P < .0001). Nine of 14 patients (64%) had elevated sHLA-I antigens. Soluble HLA-I levels did not correlate with the extent of disease, disease severity score, eosinophil count, or IgE levels. There was a remarkable consistency in sHLA-I levels at baseline and after 4 and 8 weeks of therapy, even with significant clinical improvement. CONCLUSION: We conclude that sHLA-I heterodimers are elevated in 64% of our patients with atopic dermatitis and that elevations persist after clinically effective therapy. This conclusion supports recommendations for prolonged preventative and treatment measures in this atopic disease.
Assuntos
Dermatite Atópica/sangue , Dermatite Atópica/imunologia , Antígenos de Histocompatibilidade Classe I/sangue , Criança , Pré-Escolar , Cromolina Sódica/uso terapêutico , Estudos Cross-Over , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Feminino , Antígenos HLA/sangue , Humanos , Lactente , Masculino , Índice de Gravidade de Doença , Pele/imunologia , SolubilidadeRESUMO
Hyper-IgM syndrome represents a diverse group of immunodeficiencies characterized by normal or high serum IgM concentrations with decreased or absent IgG, IgA, and IgE. The X-linked form of hyper-IgM syndrome is caused by mutations in the CD40 ligand gene, preventing its expression on activated T cells. The CD40 ligand--CD40 interaction is critical for effective isotype switching and for initiating antigen-specific Tf cell responses. In addition to recurrent pyogenic infections, patients with the CD40L defect also have opportunistic infections. An increased proportion of circulating gamma-delta T cells, shown to be important early during primary infections, has been demonstrated in numerous infectious diseases including toxoplasmosis. Here, we report a patient with hyper-IgM syndrome and CNS toxoplasmosis, who showed a marked increase in gamma-delta T cells in his peripheral blood and who has responded well to treatment of his toxoplasmosis and to high-dose immunoglobulin replacement therapy.