RESUMO
Recently we reported that monocyte phagocytosis and chemotaxis are impaired in X-linked agammaglobulinaemia (XLA) and common variable immunodeficiency (CVI) patients. Few data exist on the in vivo expression of receptors for the constant region of immunoglobulin (IgG) (Fc gammaR) and complement receptors (CR) in these patients. The objective of this study was to investigate the expression of Fc gammaR and CR on monocytes from XLA and CVI patients and compare it to that of healthy controls. Whole blood samples were obtained from 10 patients with XLA, 12 with CVI and 18 healthy controls. Monocyte phenotype was determined by flow cytometry with gating on CD14+ cells. Surface expression of Fc gammaRI (CD64), Fc gammaRII (CD32) and Fc gammaRIII (CD16), CR1 (CD35) and CR3 (CD11b and CD18) was measured by determination of the proportion of CD14+ cells positive for each receptor and by receptor density. Compared to controls, a significantly higher percentage of CD16 and CD35+ monocytes from XLA (P = 0.002 and P = 0.007, respectively) were observed. The relative fluorescence intensity (RFI) expression of Fc gammaRII (CD32) and Fc gammaRIII (CD16) were significantly lower on CVI monocytes compared to controls (P = 0.001 and P = 0.035, respectively). XLA patients, who have a reduction of Bruton's tyrosine kinase (Btk), showed normal or increased percentages of monocytes expressing Fc gamma and complement receptors. CVI patients, who have normal expression of Btk, showed reduced expression of CD16 and CD32 on monocytes. Inefficient chemotaxis and phagocytosis, reported previously in XLA patients, could be due to defects of cytoplasmatic transduction mechanisms.
Assuntos
Agamaglobulinemia/imunologia , Imunodeficiência de Variável Comum/imunologia , Monócitos/imunologia , Receptores de Complemento/sangue , Receptores de IgG/sangue , Adolescente , Adulto , Agamaglobulinemia/genética , Antígenos CD/sangue , Criança , Pré-Escolar , Feminino , Proteínas Ligadas por GPI , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Humanos , Imunofenotipagem , MasculinoRESUMO
The present study investigated the expression of the complement receptor type 1 (CR1) on the membrane of erythrocytes (CR1/E) of patients with systemic lupus erythematosus (SLE) by flow cytometry. We found a significant reduction in CR1/E numbers in SLE patients (n = 52), compared to controls (512 +/- 171 and 689 +/- 146, respectively, P = 0.0001). Reduction was more pronounced in active disease patients. The mean CR1/E number observed in patients with inactive disease was 546 +/- 163 CR1/E, while active SLE patients presented a mean of 385 +/- 133 CR1/E (P = 0.001). Patients with SLE with similar activity indexes tend to have similar CR1/E numbers, irrespective of disease severity. We also observed a trend to CR1/E reduction in severe nephritis patients. A small group of SLE patients with chronic renal failure and inactive disease showed CR1/E numbers nearly identical to controls (689 +/- 146 versus 686 +/- 123, respectively, P = 0.95). This was the only group of SLE patients with normal CR1/E numbers. These results confirm the CR1/E reduction in SLE patients as previously described, and also suggest that this reduction is related to disease activity and not to disease severity.
Assuntos
Eritrócitos/imunologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Receptores de Complemento/sangue , Adolescente , Adulto , Biomarcadores/sangue , População Negra , Doadores de Sangue , Brasil , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Pessoa de Meia-Idade , Nefrite/sangue , Nefrite/imunologia , Valores de Referência , Índice de Gravidade de Doença , População BrancaRESUMO
Complement receptor type 1 (CR1) is a membrane glycoprotein that acts as a receptor for the C3b, iC3b and C4b fragments of complement. In primates, one function of erythrocytes is to promote safe clearance of immunocomplexes (IC) from the circulation through CR1. Theoretically, in diseases characterized by high levels of circulating IC, an erythrocyte CR1 (CR1/E) deficiency may favor IC deposition in tissues or facilitate inappropriate activation of leukocytes in the circulation. Depression of the cell immune response occurs in paracoccidioidomycosis (PCM), especially in the more severe cases, and is frequently associated with high serum IC levels. In the present study we quantified the number of CR1/E in patients with the acute and chronic forms of PCM before and after treatment and correlated it with serum IC levels and CD4+ and CD8+ T cell concentration in the peripheral blood of these patients. Patients with PCM, particularly those with active disease and who had received treatment for shorter periods of time, had low numbers of CR1/E. In addition, an increase in serum IC concentration and a reduction in the CD4+/CD8+ T cell ratio were observed. After treatment there was a significant increase in mean CR1/E number and a reduction in serum IC levels. In patients with the chronic form of the disease the CD4+/CD8+ T cell ratio tended to increase after treatment and was associated with increased CR1/E levels. These results suggest that the reduction in CR1/E observed in patients is a phenomenon acquired with the disease and that CR1 could play a role in the pathogenesis of PCM.