Clinical immunology and immunopathology最新文献

To investigate the molecular mechanism of glandular parenchyma destruction in Sjögren's syndrome (SS), Bcl-2, Bax, Bcl-X, and Bak expression were studied. SS (n= 18) and control salivary glands (n= 6) were examined by immunohistochemistry. Apoptosis was assessed byin situDNA nick end labeling. Infiltrating mononuclear cells in the SS salivary gland showed elevated Bcl-2. These mononuclear cells expressed increased Bax but did not undergo apoptosis. Both SS and control salivary gland ductal epithelial cells expressed Bcl-2, Bax, and Bcl-X. SS, but not normal, salivary gland acinar cells expressed Bax and underwent apoptosis. These results suggest that elevated Bax expression in SS salivary gland acinar cells may play an important role in the apoptotic pathway. In contrast, Bcl-2 expression in SS infiltrating mononuclear cells and ductal cells may contribute to their survival.

The gastrointestinal form of Chagas disease is characterized by lumenal enlargement and wall thickening of the esophagus and/or colon. Very little is known about the involvement of the immune system in the development of the gastrointestinal form of the disease. In this paper we describe our initial observations on the phenotypic analysis of peripheral blood mononuclear cells from patients with the gastrointestinal form of Chagas disease. A significant decrease in the absolute number of CD3⁺T cells as well as in CD19⁺B lymphocytes was observed. However, the most striking observation was an inversion of the CD4/CD8 ratio, contrasting with results from cardiac chagasic patients in whom the ratio is normal. A decrease of the percentage of CD4⁺CD28⁺cells and an increase in the expression of HLA–DR both on CD4⁺and on CD8⁺cells suggest that although these T cells express activation markers their function may be altered by the lack of CD28 expression.

Serum biomarkers, such as neopterin, β₂-microglobulin (B2M), and soluble interleukin-2 receptors (sIL-2R), are elevated in viral infections, including HIV-1 infection, and in inflammatory conditions, autoimmune disease, and malignancies. For many of these conditions, serum levels correlate with disease activity. Application of these biomarkers in adolescents is limited by a lack of information on the range and determinants of variability (age, sex, race) for serum levels of these important molecules in this age group. To address this question, we analyzed serum samples from a well-characterized heterogeneous population of 111 healthy adolescents. White children had significantly higher serum levels of sIL-2R and IgM and lower levels of IgG (P≤ 0.001) than black children. Boys had higher sIL-2R and B2M levels (P< 0.005) and lower IgM levels (P< 0.05) than girls. No significant age effect on B2M or neopterin level was observed over the age range of 12–19 years included in this analysis. However, stratification by race showed that serum sIL-2R level was significantly associated with age among whites, but not among blacks. Values of these biomarkers in this population are compared with age-stratified values in the previously analyzed 20- to 69-year-old population from whose households the adolescent subjects were recruited.

The etiology and pathogenesis of amyloid A (AA) amyloidosis that may occur as an occasional complication of chronic inflammatory and infectious diseases are poorly understood. The preamyloid phase of experimentally induced AA amyloidosis can be greatly shortened in recipient animals by intravenous or intraperitoneal transfer of amyloid enhancing factor (AEF) when there is a concomitant inflammatory episode. AEF is an operational term applied to poorly characterized tissue extracts and increased AEF activity that precedes amyloid deposition. We now report that AA is rapidly formed in mice following oral administration of an AEF preparation that does not contain AA peptides. This finding indicates that a transmissible agent present in diet may be a contributory factor in amyloid fibril formation.

The progression ofCoxiella burnetiiinfection to acute or chronic Q fever has been attributed to biological characteristics of the bacterium and to the host immune response. We measured whether serum levels of total and specific subclasses IgA1 and IgA2 could be correlated with the course of disease in acute and chronic Q fever infections, and with the occurrence of endocarditis. In patients with chronic infection, total IgA2 levels were significantly increased. Q-fever-specific IgA1 antibodies were detectable in both acute and chronic infections, but only patients with endocarditis had IgA2 antibodies toC. burnetiiphase II antigens. These findings indicate that the measurement of IgA subclasses may be a useful aid in the serological diagnosis of Q fever. Our results reinforce the idea that immunologically mediated host factors are important in the pathogenesis of Q fever and in the disease outcome of this infection.

Anti-thyroid autoimmune responses have been examined in fetal lambs, the immune systems of which had matured in the absence of exposure to thyroid-specific antigens. The lymphocytic infiltrate in self-thyroid tissue reintroduced into autoimmune lambs showed well-differentiated B and T cell domains. However, T cells from these fetuses were not sensitized against ovine thyroglobulin nor did serum antibodies appear against ovine thyroglobulin or thyroid peroxidase. In the light of these observations, it is inferred that the primary abnormality in the immune systems of fetuses deprived of exposure to thyroid autoantigens is likely to be a failure of the development of a normal T cell subpopulation responsible for down-regulation of autoreactivity. It is also concluded that overt autoimmunity develops only when these fetuses are challenged with thyroid tissue and that B cells may undertake an antigen-presentation role in its induction.

Chronic graft-versus-host disease (GvHD) in mice is a model resembling glomerulonephritis in human systemic lupus erythematosus. In the present study congenic mouse strains were used to investigate the pathogenetic role of (1) donor T cell subset chimerism and (2) donor thymocytes in this model. In GvHD employing minor lymphocyte-stimulating-1 (Mls-1)-compatible donors and recipients, full-blown immune complex glomerulonephritis was associated with a low-donor CD8⁺T cell chimerism. Injection of lymphocytes from Mls-1-negative donors (Mls-1^b) into Mls-1-positive recipients (Mls-1^a) induces a type of GvHD characterized by rapid self-limitation accompanied by the immediate inhibition of donor T cell chimerism and the absence of glomerulonephritis. However, omission of thymocytes from the donor inoculate does result in glomerular depositions containing immunoglobulins. These results suggest that donor CD8⁺T cell chimerism is associated with attenuation of immune complex glomerulonephritis, whereas Mls-1-incompatible donor T cell precursors prevent the disease.

Celiac disease (CD) and dermatitis herpetiformis (DH) are gluten-sensitive diseases with different clinical features that can initiate similar intestinal changes. The flat-destructive stage corresponds to severe lesions involving activated T-cells. However, other inflammatory cells such as eosinophils are also abundant. The mechanisms for the intestinal recruitment of eosinophils in patients with CD and DH remain unknown. Eosinophil recruitment and activation are inducedin vitroby three main cytokines: interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte–macrophage colony-stimulating factor (GM-CSF). In this study, IL-3, IL-5, and GM-CSF were detected by immunohistochemistry in all patients with CD and DH but not in the control group. By ultrastructural immunogold staining, these three cytokines had the same subcellular localization in the granule matrix of eosinophils. This result suggests that eosinophils may be involved in the immune response at the flat-destructive stage of both CD and DH.

Wiskott–Aldrich syndrome (WAS) is an X-linked primary immunodeficiency that is usually associated with thrombocytopenia and eczema. The very variable phenotype of WAS results from defects in the WAS protein (WASP), the function of which is not well understood. In many cases causative mutations have now been identified in theWASgene. Attempts have been made to correlate the nature of the mutations with the severity of the disease. In this study we investigated mutations in 13 patients with WAS and analyzed the expression of WASP in patient blood samples by immunoblot analysis. We found that despite extensive variation in the nature of the mutations in patients with severe WAS symptoms, none express the protein. However, in 1 patient with a mild clinical phenotype WASP expression was detected. Such an analysis could be used as an initial screening procedure for the diagnosis of WAS prior to genotypic analysis.