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The serum levels of soluble HLA class I antigens (sHLA-A, -B, -C and sHLA-G) were determined in 40 HCV genotype 1-infected patients before ( T ), after 3, 6, and 12 months ( T , T , and T ) of pegylated-IFN-α plus ribavirin therapy and 6 months ( T ) after the end of treatment. Twenty patients were sustained virological responders (SVR), and 20 were non-responders (NR). sHLA-A, -B, -C levels at T were significantly higher in both SVR (mean 10.48 μg/ml) and NR (mean 11.87 μg/ml) patients as compared to healthy controls (mean 0.34 μg/ml, p < 0.0001) and HIV-infected subjects (mean 1.22 μg/ml, p < 0.0001). sHLA-G levels at T were significantly higher in SVR (mean 24.78 ng/ml) and NR (mean 24.93 ng/ml) patients as compared to healthy controls (mean 10.34 ng/ml, p = 0.015 and p = 0.014, respectively) but were lower as compared to HIV-infected subjects (mean 48.00 ng/ml, p < 0.0001). The levels of sHLA-A, -B, -C and sHLA-G significantly decreased in SVR from T to T (mean 1.64 and 1.43 ng/ml, respectively, p < 0.0001) and correlated with HCV-RNA, AST, ALT, γGT, and ALP levels. The determination of soluble HLA class I levels could be proposed as a surrogate marker to discriminate SVR and NR HCV-infected patients during PEG-IFN-α plus ribavirin therapy. [ABSTRACT FROM AUTHOR]

Background It has been reported that soluble HLA-G serum levels are increased in patients with pollen-induced allergic rhinitis and decrease after immunotherapy. However, no functional study has been conducted so far. The aim of this study was to evaluate the membrane expression and secretion of HLA-G molecules in peripheral blood mononuclear cells from allergic rhinitis patients after in vitro incubation with the causal allergen. Methods and results Twenty-two allergic rhinitis patients and ten healthy subjects were enrolled. Membrane HLA-G expression was determined by flow cytometry and soluble HLA-G in culture supernatant was determined by immunoenzymatic assay. HLA-G expression was detected in CD4+ (T-helper-2) cells and monocytes after in vitro stimulation with the causal allergen but not with non specific stimuli and non causal allergens. Accordingly, the release of soluble HLA-G in culture supernatant occurred only after the stimulation with the causal allergen. Collectively, these results were confirmed by Western blot analysis. Conclusions The present study provides the first in vitro evidence that in allergic patients HLA-G expression and secretion is specifically induced by the causal allergen. These data may add new insights into the pathogenetic mechanisms underlying allergic inflammation and allergen specific immunotherapy. [ABSTRACT FROM AUTHOR]

Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen-specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes-macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is characterized by T helper 2 polarized immune response. The soluble HLA-G (sHLA-G) molecule has an immunomodulatory activity. However, so far, no study has investigated this activity in perennial AR (PAR). Objective: The aim of this study was to evaluate serum sHLA-G levels in PAR patients and in a group of healthy controls. Methods: Twenty-five PAR patients were enrolled. A group of 50 healthy non-allergic subjects was considered as control. sHLA-G serum levels were determined by immunoenzymatic method. Results:Allergic patients had significantly higher levels of the sHLA-G (p < 0.001) molecule than normal controls. Moreover, there was a very strong correlation between sHLA-G and symptom severity and drug use (r = 0.85 and 0.793, respectively). Conclusion: The present study provides first evidence that serum sHLA-G levels are significantly increased in PAR patients. Moreover, sHLA-G might be considered as a biomarker for assessing clinical severity. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: We have previously reported that the serum levels of soluble human leukocyte antigen (HLA)–A, -B, -C, and -G antigens are elevated in human immunodeficiency virus (HIV)–infected subjects and decrease after antiretroviral therapy. In this study, we measured soluble HLA-G serum levels in patients with acquired immune deficiency syndrome (AIDS) affected by different AIDS-defining conditions before and during antiretroviral therapy and correlated them with virologic and immunologic parameters of response to treatment. Soluble HLA-G levels were significantly higher in AIDS patients before treatment as compared with healthy controls and significantly decreased after 36 months of therapy. The decrease of soluble HLA-G correlated with the decrease of plasma HIV-RNA level and CD8+ T-lymphocytes number and with the increase of CD4+ T-lymphocytes number. Soluble HLA-G levels were significantly higher in patients with opportunistic infections and Kaposi''s sarcoma compared with patients with the wasting syndrome. These data suggest that infections and neoplasms may trigger the shedding of soluble HLA-G molecules, and confirm that the level of soluble HLA-G in serum might represent a surrogate marker to monitor virologic response and immune reconstitution in HIV-positive individuals. [Copyright &y& Elsevier]

Abstract: We have reported that serum level of soluble HLA-A, -B, -C (sHLA-A,-B,-C) antigens is elevated in HIV-infected subjects and decreases after antiretroviral therapy (HAART). In this study, we measured the levels of soluble HLA-G (sHLA-G) antigens in a cohort of HIV-infected patients before and during HAART. sHLA-G and sHLA-A, -B, -C levels were significantly elevated in HIV-infected subjects as compared with controls before antiretroviral treatment and significantly decreased after 36 months of HAART. sHLA-G levels were correlated with sHLA-A, -B, -C levels, the decrease of plasma HIV-RNA level, the increase of CD4+ T-lymphocyte number and the decrease of CD8+ T-lymphocyte number. These results suggest that the measurement of sHLA-G and sHLA-A, -B, -C antigen serum levels might represent a useful surrogate marker to monitor virological response and immune reconstitution in HIV-positive subjects undergoing HAART treatment. [Copyright &y& Elsevier]

Abstract: Background: Allergic rhinitis (AR) is characterized by a Th2 polarized immune response and soluble HLA (sHLA) molecules play an immunomodulatory role in this response. Previously, it has been reported that these molecules are increased in sera of patients with pollen-induced allergic rhinitis studied outside the pollen season. To date, however, no study has investigated there in AR patients during the pollen season. Objective: The aim of this study was to evaluate serum sHLA-G and sHLA-A, -B, -C levels in both AR patients and healthy controls. Methods: 60 symptomatic allergic patients were enrolled. A group of 50 healthy subjects was included as a control. Serum sHLA-G and sHLA-A, -B, -C levels were determined by an immunoenzymatic method. Allergy severity was assessed by VAS for symptoms and drug use. Results: Allergic patients had significantly higher levels of both sHLA-G (p <0.001) and sHLA-A, -B, -C (p =0.001) than normal controls. In addition, there was a very strong correlation between sHLA-G levels and clinical severity. Conclusion: The present study confirms evidence that serum sHLA-G and sHLA-A, -B, -C molecules are significantly increased in patients with pollen-induced AR also during the pollen season. Moreover, sHLA-G might be considered as a biomarker for assessing clinical severity. [Copyright &y& Elsevier]

Abstract: Allergic rhinitis (AR) is characterized by Th2 polarized immune response. Soluble HLA (sHLA) molecules play an immunomodulatory activity. Specific immunotherapy is the only causal treatment for AR. So far no study investigated the effect of sublingual immunotherapy (SLIT) on sHLA molecules. The aim of the study was to evaluate sHLA-G and sHLA-A,-B,-C serum levels in AR patients with pollen allergy before and after a pre-seasonal course of SLIT. Forty AR patients with pollen allergy were enrolled and they assumed a pre-seasonal SLIT course for 3 months. Serum sHLA-G and sHLA-A,-B,-C and IFN-γ and IL-4 levels were determined by ELISA method at baseline and 3 months after the end of the SLIT course. Symptoms severity was assessed by a Visual Analogue Scale. Both sHLA-G and sHLA-A,-B,-C levels significantly diminished (p <0.0001 for both) after SLIT. Moreover, there was a highly significant relationship between the serum levels of these two soluble molecules (r =0.84). Significant relationship between symptoms evaluated by VAS and change of sHLA molecules was also evidenced (r =0.60 and 0.63). Serum cytokines were not affected by SLIT. Therefore, this preliminary study provides the first evidence that both sHLA-G and sHLA-A,-B,-C levels are significantly reduced by SLIT in AR patients with pollen allergy. Therefore, the clinical implication of this study is that these soluble molecules might be interpreted as biomarker of response to SLIT. [Copyright &y& Elsevier]

Summary: 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-γ (IFN-γ) 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-γ 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-γ increase as well as between sHLA-A,-B,-C level change and IFN-γ increase after SLIT. The present study provides the first published evidence that the reduction of sHLA molecules serum levels and the increased IFN-γ production after SLIT in AR patients with pollen allergy are significantly related phenomena. [Copyright &y& Elsevier]