Soluble HLA-G and HLA-A,-B,-C serum levels in patients with allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is characterized by Th2-polarized immune response. Soluble HLA (sHLA) molecules play an immunomodulatory activity. So far, however, no study investigated them in AR. OBJECTIVE: The aim of this study was to evaluate sHLA-G and sHLA-A,-B,-C serum levels in AR patients with pollen allergy and in a group of healthy controls. METHODS: Forty-nine AR patients were enrolled. A group of healthy nonallergic subjects was considered as control. sHLA-G and sHLA-A,-B,-C serum levels were determined by immunoenzymatic method. The study was conducted during the winter, such as outside the pollen season. RESULTS: Allergic patients had significantly higher levels of both sHLA-G (P < 0.0001) and sHLA-A,-B,-C (P = 0.011) molecules than normal controls. Moreover, there was a significant relationship between these two soluble molecules (r = 0.69) in allergic patients. CONCLUSION: The present study provides the first evidence that both sHLA-G and sHLA-A,-B,-C serum levels are significantly increased in AR patients with pollen allergy.

Relationship between soluble HLA-G and HLA-A,-B,-C serum levels, and interferon-gamma production after sublingual immunotherapy in patients with allergic rhinitis.

Allergic rhinitis (AR) is characterized by a T-helper (Th)-2 (Th2) polarized immune response. Soluble human leukocyte antigen (sHLA) molecules play an immunomodulatory role. Specific immunotherapy is the only causal treatment for AR and is able to shift the immune response to Th1 polarization. The aim of this study was to evaluate the relationship between sHLA-G and sHLA-A,-B,-C serum levels and interferon-gamma (IFN-gamma) production in AR patients with pollen allergy before and after a preseasonal course of sublingual immunotherapy (SLIT). A total of 40 AR patients with pollen allergy were enrolled and given a course of preseasonal SLIT for 3 months. Serum sHLA-G and sHLA-A,-B,-C levels were determined by enzyme-linked immunoabsorbent assay, and cell production of IFN-gamma was evaluated by enzyme-linked immunoabsorbent spot assay at baseline and 3 months after the end of the SLIT course. There was a significant relationship between sHLA-G serum level change and IFN-gamma increase as well as between sHLA-A,-B,-C level change and IFN-gamma increase after SLIT. The present study provides the first published evidence that the reduction of sHLA molecules serum levels and the increased IFN-gamma production after SLIT in AR patients with pollen allergy are significantly related phenomena.

Immunomodulatory effects of blood transfusions: the synergic role of soluble HLA Class I free heavy-chain molecules detectable in blood components.

BACKGROUND: Over the past decades, the weight of the published literature demonstrates that blood transfusions can induce clinically significant immunosuppression in recipients. Several studies showed significant improved clinical outcomes in the patients receiving leukoreduced transfusions, compared with control patients who received nonleukoreduced transfusions. Moreover, the immunosuppressive potential of blood products grows with the time of their storage and becomes highest in nonleukoreduced blood products stored for a long time. STUDY DESIGN AND METHODS: The interest was previously focused on the determination of immunomodulatory soluble molecules such as soluble HLA Class I (sHLA-I) and soluble Fas ligand (sFasL) in different blood components and on the evaluation of their immunomodulatory activities. On this basis, whether soluble beta2-microglobulin free HLA Class I heavy chains (sHLA-beta2fHC) could be detected and immunochemically characterized in different blood components was evaluated. Immunomodulatory activity of detectable sHLA-beta2fHC molecules was evaluated by apoptosis inducing capacity in interleukin-2-activated antigen-specific cytotoxic T lymphocytes (CTL). RESULTS: Double-determinant immunoenzymatic assay indicates that sHLA-beta2fHC levels in red blood cells stored for up to 30 days and in random-donor platelets are significantly (p < 0.001) higher than in other blood components, and the immunochemical characterization suggests that the major source of sHLA-beta2fHC molecules might be the residual white cells that undergo membrane damage during storage. Finally, allogeneic CD8+ CTL apoptosis induction confirmed biofunctionality of sHLA-beta2fHC molecules. CONCLUSION: These data are comparable with those previously reported dealing with contaminant soluble molecules in allogeneic and autologous blood components, suggesting that sHLA-beta2fHC molecules could contribute to the immunosuppressive effects of blood transfusions.

Transfer of maternal colostral leukocytes promotes development of the neonatal immune system Part II. Effects on neonatal lymphocytes.

It has been established that maternal leukocytes, conditioned by the mammary environment, cross the neonatal gut and circulate in the newborn calf. However, the impact of these cells on the development of neonatal immunity remains to be determined. This study examined the effects of maternal colostral leukocytes on development and maturation of neonatal adaptive immunity by examining the expression of surface markers on neonatal lymphocytes. At birth, neonatal calves were fed whole colostrum, or colostrum that had the maternal cells removed (cell-free colostrum), from their respective dams. Peripheral blood samples were collected at regular intervals over the first 4 weeks of life and lymphocytes were evaluated for surface expression of cellular markers. The results of these studies demonstrated that calves receiving whole colostrum had fewer CD11a positive lymphocytes in circulation during the first 2 weeks of life and this marker was expressed at a lower density than calves receiving cell-free colostrum. In addition, calves receiving whole colostrum also had a higher percentage of lymphocytes expressing the activation markers CD25 and CD26 by 7 days after birth. During the first week of life, lymphocytes from calves receiving whole colostrum had a higher density of MHC class I expression on their surfaces than cells from calves receiving cell-free colostrum. In general, these results indicate that transfer of maternal cells with colostrum allows for more rapid development of lymphocytes and maternal cells appeared to enhance their activation.

In vitro and in vivo immunotoxic and immunomodulatory effects of nonsupplemented and selenium-supplemented cigarette smoke condensate.

Cigarette smoke condensate has been evaluated for its in vitro and in vivo immunotoxic and immunomodulatory properties. It was found that cigarette smoke condensate used in vitro at concentration from 6.6 to 20 microg/ml exerted pronounced inhibitory effects upon cell surface antigen-presenting major histocompatibility complex class I (MHC-I) expression and immunoglobulin (Ig) synthesis. In vivo, i.p. administration of cigarette smoke condensate to C57BL/6 mice before challenging with ovalbumin (OVA) antigen, has led to a decrease of anti-OVA specific antibody response. This inhibition affected more Ig protein synthesis than membrane bound MHC-I expression. Supplementation with selenium (Se) significantly reduced the inhibitory effects both in vitro and in vivo.

In vitro immunosuppressive activity of soluble HLA class I and Fas ligand molecules: do they play a role in autologous blood transfusion?

BACKGROUND: The immunomodulatory effects of allogeneic blood transfusion may contribute to a poor prognosis in patients with cancer who are undergoing surgery, and clinical trials have been carried out to investigate whether these patients would benefit from autologous blood donation. As the immunomodulatory effects of allogeneic blood transfusion have been related to soluble molecules released from residual WBCs during storage, the in vitro immunomodulatory activity of soluble molecules detected in supernatants from stored autologous blood was evaluated. STUDY DESIGN AND METHODS: Blood was donated by four healthy volunteers. Packed WBC-reduced RBCs were obtained and stored for 30 days, and supernatants were collected. FFP and serum were also obtained. The concentration of soluble molecules was determined by immunoenzymatic assays. The in vitro immunomodulatory activity of undiluted blood component supernatant was assessed by antigen-specific cytotoxic T-cell activity and mixed lymphocyte reactions in autologous combinations and by apoptosis induction in Fas+ cells. RESULTS: The concentrations of soluble Fas-ligand and HLA class I molecules were higher in packed RBCs than in WBC-reduced RBCs, FFP, and serum. Undiluted supernatants of packed RBCs strongly inhibited functional assays and induced apoptosis in Fas+ cells. The immunomodulatory effects were correlated with the amount of soluble Fas ligand and HLA class I molecules. CONCLUSION: The results of the present study are comparable with those already reported in allogeneic blood components, and they indicate that undiluted supernatants of autologous blood components may exert immunosuppressive effects in vitro.

Diagnosis of hemochromatosis in family members of probands: a comparison of phenotyping and HFE genotyping.

PURPOSE: We wanted to compare phenotyping and HFE genotyping for diagnosis of hemochromatosis in 150 family members of 61 probands. METHODS: Phenotypes were defined by persistent transferrin saturation elevation, iron overload, or both; genotypes were defined by HFE mutation analysis. RESULTS: Twenty-five family members were C282Y homozygotes; 23 of these (92%) had a hemochromatosis phenotype. Twenty-three family members had HFE genotype C282Y/H63D; eight of these (35%) had a hemochromatosis phenotype. Six of 102 (6%) family members who inherited other HFE genotypes had a hemochromatosis phenotype. CONCLUSION: Phenotyping and genotyping are complementary in diagnosing hemochromatosis among family members of probands.