Follicular bronchiolitis as phenotype associated with CD25 deficiency.

Regulatory T cells [Tregs ; CD4(+) CD25(+) forkhead box protein 3 (FoxP3(+) )] are subsets of T cells involved in the maintenance of peripheral self-tolerance by actively suppressing the activation and expansion of autoreactive T cells. Signalling through the interleukin-2 receptor (IL-2R) contributes to T cell tolerance by controlling three important aspects of regulatory T cell (Treg ) biology. CD25 is the α-chain of the IL-2R that, in concert with the ß-chain and γ-chain, constitutes the complete IL-2R. CD25 contributes only to IL-2 binding affinity but not to the recruitment of signalling molecules. However, its importance in the development of a normal immune response is emphasized by the finding that a truncation mutant of CD25 results in an immunodeficiency in humans characterized by an increased susceptibility to viral, bacterial and fungal infections. In 1997, Sharfe et al. described an infant with severe bacterial, viral and fungal infections. Counts of autologous T lymphocytes were moderately low, T cells displayed a weak proliferative response to mitogens in vitro and the patient displayed no rejection of an allogeneic skin graft. However, unlike children with severe combined immunodeficiency (SCID), besides not having circulating T cells, the patient also developed peripheral lymphocytic proliferation and autoimmune primary biliary cirrhosis. We present the first female Argentine patient with mutation in CD25 associated with chronic and severe inflammatory lung disease (follicular bronchiolitis with lymphocyte hyperplasia), eczema and infections. She has no expression of CD25 on CD4(+) T cells and an extremely low amount of Tregs . The molecular study confirmed homozygous missense mutation in the alpha subunit of the IL-2 receptor (CD25αR) (c. 122 a > c; p. Y41S).

[Kawasaki disease. Immunological evaluation of 26 cases]. / Enfermedad de Kawasaki. Evaluación inmunológica de 26 casos.

Kawasaki disease (KD) is an acute febrile vasculitis of childhood, characterized by multiple clinical and biochemical features of inflammation with special involvement of the heart. The activation of lymphocytes and monocytes/macrophages and their secreted soluble products, cytokines, play a central role in the pathogenesis of the disease. In this study we performed immunologic studies in 26 patients with KD. No constant pattern of serum levels of IgG, IgA, IgM, C3 and C4 fractions of complement measured by Nephelometry and neither autoantibodies, FAN and ANCA performed by indirect immunofluorescence were found in 22 patients in the acute stage. Variable percentages of CD3, CD4, CD8, CD20, CD56 and DR in peripheral mononuclear cells specifically stained and analysed by flow cytometry were seen among 25 patients in the acute stage. CD25 was elevated in 17/25 cases. Serum levels of TNF alpha performed by ELISA in 12 patients in acute stage were low. Intracellular cytokines such as TNF alpha, IL1 beta, IL2 and IFN gamma were measured in peripheral mononuclear cells of 15 patients in acute stage, in 5th and 30th days after gammaglobulin treatment, utilizing specific staining and analysis by flow cytometry showing no sole characteristic profile. In 2 patients there was an elevated percentage of TNF alpha and IL1 beta in monocytes during the convalescent stage; both had coronary sequelae. More research on this question is needed. In conclusion, immunologic studies showed an heterogeneous profile and no laboratory finding was registered in the acute stage that could be used as predictive factor of cardiovascular involvement.

Enfermedad de Kawasaki. Evaluación inmunológica de 26 casos. / [Kawasaki disease. Immunological evaluation of 26 cases]

Kawasaki disease (KD) is an acute febrile vasculitis of childhood, characterized by multiple clinical and biochemical features of inflammation with special involvement of the heart. The activation of lymphocytes and monocytes/macrophages and their secreted soluble products, cytokines, play a central role in the pathogenesis of the disease. In this study we performed immunologic studies in 26 patients with KD. No constant pattern of serum levels of IgG, IgA, IgM, C3 and C4 fractions of complement measured by Nephelometry and neither autoantibodies, FAN and ANCA performed by indirect immunofluorescence were found in 22 patients in the acute stage. Variable percentages of CD3, CD4, CD8, CD20, CD56 and DR in peripheral mononuclear cells specifically stained and analysed by flow cytometry were seen among 25 patients in the acute stage. CD25 was elevated in 17/25 cases. Serum levels of TNF alpha performed by ELISA in 12 patients in acute stage were low. Intracellular cytokines such as TNF alpha, IL1 beta, IL2 and IFN gamma were measured in peripheral mononuclear cells of 15 patients in acute stage, in 5th and 30th days after gammaglobulin treatment, utilizing specific staining and analysis by flow cytometry showing no sole characteristic profile. In 2 patients there was an elevated percentage of TNF alpha and IL1 beta in monocytes during the convalescent stage; both had coronary sequelae. More research on this question is needed. In conclusion, immunologic studies showed an heterogeneous profile and no laboratory finding was registered in the acute stage that could be used as predictive factor of cardiovascular involvement.

[Lymphocytic, phenotypic and functional studies in primary immunodeficiencies]. / Estudios linfocitarios, fenotípicos y funcionales en inmunodeficiencias primarias.

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)

Estudios linfocitarios, fenotípicos y funcionales en inmunodeficiencias primarias. / [Lymphocytic, phenotypic and functional studies in primary immunodeficiencies]

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)