RESUMO
The study of differentiation antigens of circulating mononuclear cells in 70 patients with primary immunodeficiency (PID) using monoclonal antibodies allowed us to define phenotypic profiles that are characteristic of the different described syndromes. In common variable immunodeficiency we found percentages of lymphocytes within normal ranges, and an altered CD4/CD8 ratio. In sex-linked agammaglobulinemia, absence of B lymphocytes with normal distribution of regulatory populations (CD4/CD8) were found. These results allow us to distinguish two clinically and infectologically similar conditions. In selective IgA deficiency, distribution of lymphocytic populations was normal. In immunodeficiency with hyper IgM, considered up to date as an abnormal maturation of B lymphocytes, we observed a deficiency in cellular immune response, and a phenotypic profile characterized by: decreased number of CD3 cells, inverted CD4/CD8 ratio, and increased CD38 population; this profile being similar to the one that we found in predominantly cellular immunodeficiency. In predominantly cell-mediated immunodeficiency and in those immunodeficiencies associated to other defects (such as: hyper IgE syndrome, Di George syndrome), the most important finding was a significative increase in CD38 population. Although it's not possible to consider on this basis that there is a defect at the thymic level of T-cells maturation, the high levels of circulating CD38 cells were a clear indication of altered cellular immune response in our series of patients. Patients with predominantly cell-mediated immunodeficiency showed the lowest levels of CD4 cells and the corresponding inversion of CD4/CD8 ratio. In Di George syndrome we found a markedly diminished CD8 population that differentiates this entity from the rest of the studied syndromes. In chronic mucocutaneous candidosis distribution of lymphocytic populations was normal, but a significative increase in the percentages of CD11b+ cells was observed. In patients with antibodies deficiency that received substitutive treatment with gammaglobulin we found no variations in lymphocytic populations distribution. In the group of patients with altered cellular immunity treated with thymic hormones, observed phenotypic changes (increase in T-cells population, trend to normalization in CD4/CD8 ratio, and decrease in CD38 population) were transient, and lasted only during the treatment period. We considered that describing these phenotypic profiles is a useful diagnosis tool when evaluating patients with PID, since these profiles are characteristic and very stable.
Assuntos
Síndromes de Imunodeficiência/imunologia , Leucócitos Mononucleares/imunologia , Adulto , Anticorpos Monoclonais , Antígenos CD/sangue , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Síndromes de Imunodeficiência/classificação , Síndromes de Imunodeficiência/diagnóstico , Contagem de Leucócitos , Masculino , Fenótipo , Receptores de Antígenos de Linfócitos B/análise , Formação de RosetaRESUMO
The following immunological studies were performed in circulating mononuclear cells of 17 patients with severe aplastic anemia (SAA): a) lymphocytic phenotypes; b) proliferative response to PHA; c) determination of interleukin 2 (IL2) production and d) expression of Tac CD25. Fifteen of the seventeen patients showed altered CD4/CD8 regulatory populations, expressed as a significantly diminished CD4/CD8 ratio (0.72 +/- 0.19, NV: 1.8 +/- 0.6) (Table 1). The proliferative response to PHA was normal in 80% of the cases; only 2 of the patients showed a diminished response to the mitogen (Fig. 1). IL2 production by PHA-stimulated mononuclear cells was significantly increased (56.6 +/- 9.8; NV: 11 +/- 7.69) (Fig. 1), and a deficient expression to CD25 antigen was also recorded (Table 2). In the other two patients, we observed a normal CD4/CD8 ratio (Table 1, patients 1 and 2) with absence of proliferative response to PHA and hypo-production of IL2 (Fig. 1). These results suggest that in these two cases the hematopoietic defect could be associated to a primary deficiency of cellular immunity. Our results support the current concept of diversity of pathogenetic mechanisms implicated in SAA, and suggest that there are groups of patients with variable degrees of immunological defect that can be delineated through laboratory assays. On the other hand, the altered distribution of regulatory populations mostly due to an absolute decrease of the CD4 subpopulation, associated to the hyperproduction of IL2 and deficient expression of the Tac antigen in most of our patients, suggest the existence of functional alterations.
Assuntos
Anemia Aplástica/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Anemia Aplástica/sangue , Relação CD4-CD8 , Criança , Pré-Escolar , Feminino , Hematopoese/imunologia , Humanos , MasculinoRESUMO
The following immunological studies were performed in circulating mononuclear cells of 17 patients with severe aplastic anemia (SAA): a) lymphocytic phenotypes; b) proliferative response to PHA; c) determination of interleukin 2 (IL2) production and d) expression of Tac CD25. Fifteen of the seventeen patients showed altered CD4/CD8 regulatory populations, expressed as a significantly diminished CD4/CD8 ratio (0.72 +/- 0.19, NV: 1.8 +/- 0.6) (Table 1). The proliferative response to PHA was normal in 80
of the cases; only 2 of the patients showed a diminished response to the mitogen (Fig. 1). IL2 production by PHA-stimulated mononuclear cells was significantly increased (56.6 +/- 9.8; NV: 11 +/- 7.69) (Fig. 1), and a deficient expression to CD25 antigen was also recorded (Table 2). In the other two patients, we observed a normal CD4/CD8 ratio (Table 1, patients 1 and 2) with absence of proliferative response to PHA and hypo-production of IL2 (Fig. 1). These results suggest that in these two cases the hematopoietic defect could be associated to a primary deficiency of cellular immunity. Our results support the current concept of diversity of pathogenetic mechanisms implicated in SAA, and suggest that there are groups of patients with variable degrees of immunological defect that can be delineated through laboratory assays. On the other hand, the altered distribution of regulatory populations mostly due to an absolute decrease of the CD4 subpopulation, associated to the hyperproduction of IL2 and deficient expression of the Tac antigen in most of our patients, suggest the existence of functional alterations.
RESUMO
In this report we present the leukocyte phenotypic analysis of 64 cases of primary immune deficiencies (PID). Functional studies related to lymphocyte activation (CD25 (Tac) antigen expression and response to exogenous IL2) as well as immunoregulatory pathways (spontaneous suppressor activities and suppression by soluble factors) were also considered taking immunodeficiency with hyper-IgM (IDHM) as model. The study of mononuclear cell populations with monoclonal antibodies allowed the characterization of defined phenotypes. In common variable immunodeficiency, B cells were present in normal percentages. In sex-linked agammaglobulinemia there was a lack of B lymphocytes and normal distribution of regulatory populations. These results point out the difference between these two entities despite their clinical and infective similarities. Excess of cells expressing CD38 antigen (NV: 4 +/- 2) were found in: predominantly cell mediated immunodeficiency (PCMI): 38 +/- 20; ataxia telangiectasia: 25 +/- 8, hyper-IgE syndrome: 24 +/- 13; Di George syndrome (DGS): 24 +/- 9, chronic mucocutaneous candidiasis: 15 +/- 7. The increased expression of this antigen was correlated with the presence of compromised cellular immunity. The DGS presented the lowest level of CD8 cells (6 +/- 5; NV: 21 +/- 7). In two patients with IDHM, the phenotypic profile was similar to that found in PCMI (low CD3 cells, low CD4/CD8 ratio and elevated CD38 cells). The depressed proliferative response to PHA demonstrates a cellular immune defect. In both patients we found a low expression of CD25 antigen in stimulated cells. Moreover, the addition of exogenous IL2 decreased the proliferative response to PHA in a dose-dependent fashion, suggesting that the cells expressing the CD25 antigen have suppressor capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Síndromes de Imunodeficiência/imunologia , Receptores de Interleucina-2/fisiologia , Linfócitos T/fisiologia , Humanos , Hipergamaglobulinemia/imunologia , Imunidade Celular , Imunoglobulina G/análise , Imunoglobulina M/análise , Interleucina-2/farmacologia , Ativação Linfocitária , Fenótipo , Linfócitos T/patologiaRESUMO
In this report we present the leukocyte phenotypic analysis of 64 cases of primary immune deficiencies (PID). Functional studies related to lymphocyte activation (CD25 (Tac) antigen expression and response to exogenous IL2) as well as immunoregulatory pathways (spontaneous suppressor activities and suppression by soluble factors) were also considered taking immunodeficiency with hyper-IgM (IDHM) as model. The study of mononuclear cell populations with monoclonal antibodies allowed the characterization of defined phenotypes. In common variable immunodeficiency, B cells were present in normal percentages. In sex-linked agammaglobulinemia there was a lack of B lymphocytes and normal distribution of regulatory populations. These results point out the difference between these two entities despite their clinical and infective similarities. Excess of cells expressing CD38 antigen (NV: 4 +/- 2) were found in: predominantly cell mediated immunodeficiency (PCMI): 38 +/- 20; ataxia telangiectasia: 25 +/- 8, hyper-IgE syndrome: 24 +/- 13; Di George syndrome (DGS): 24 +/- 9, chronic mucocutaneous candidiasis: 15 +/- 7. The increased expression of this antigen was correlated with the presence of compromised cellular immunity. The DGS presented the lowest level of CD8 cells (6 +/- 5; NV: 21 +/- 7). In two patients with IDHM, the phenotypic profile was similar to that found in PCMI (low CD3 cells, low CD4/CD8 ratio and elevated CD38 cells). The depressed proliferative response to PHA demonstrates a cellular immune defect. In both patients we found a low expression of CD25 antigen in stimulated cells. Moreover, the addition of exogenous IL2 decreased the proliferative response to PHA in a dose-dependent fashion, suggesting that the cells expressing the CD25 antigen have suppressor capacity.(ABSTRACT TRUNCATED AT 250 WORDS)