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Background Bacterial, fungal, and viral infections often affect non-relapse mortality after allogeneic stem cell transplantation (allo SCT). Recovery from infections depends on a balanced integration between innate and adaptive immune responses. In this complex interplay, a key role is played by Toll-like receptors ( TLRs), which are sensors of pathogen-associated molecular patterns. To our knowledge, no previous study deals with both expression and function of all human TLRs together, in relation to infections in the setting of allo SCT. Methods We prospectively evaluated 9 TLRs by flow cytometry on T lymphocytes and monocytes of 35 patients in relation to infectious events from day +30 to day +120. Tumor necrois factor-alpha, interleukin-4, interferon-gamma, and monocyte chemoattractant protein-1 induction upon TLR activation was assessed by enzyme-linked immunosorbent assay on cell supernatants. Results In multivariate Cox regression analysis, levels of TLR-9 expression on T lymphocytes ( P = 0.01) and values of natural killer cells ( P = 0.01) correlated negatively with bacterial infections, whereas cytomegalovirus ( CMV) infection resulted as a positive predictor. We observed a trend for negative correlation between TLR-7 levels on T lymphocytes and fungal infections ( P = 0.07). Values of monocytes were negatively associated with CMV infection ( P = 0.03), whereas levels of TLR-5 on T lymphocytes were positive predictors ( P = 0.01). Age ( P = 0.03) and bacterial infections ( P = 0.006) negatively influenced overall survival. Monocyte values were positive predictors of survival ( P = 0.003). Conclusions Bacterial, fungal, and CMV infections were associated with a different expression of some TLRs on T lymphocytes. The protective role of TLR-7 and TLR-9 seemed dominant over other TLRs involved in recognizing fungi and bacteria. We also observed an atypical involvement of TLR-5 in CMV infection. The dominant and atypical role of some TLRs could depend on their pleiotropic functions and the changing inflammatory environment of transplanted patients. A specific TLR profile and an adequate count of monocytes could improve survival, promoting an effective control of infections, and balanced immune responses. If our findings will be confirmed by further studies, these immunological variables could be useful as parameters to predict susceptibility to infections. [ABSTRACT FROM AUTHOR]

The mouse monoclonal antibody (MoAb) IGMB17 (muIGMB17) is a high-affinity antibody- neutralizing human interferon (IFN)-γ and, accordingly, is a potential therapeutic agent for patients suffering from various diseases in which the cytokine is abnormally expressed. The clinical usefulness of mouse antibodies is limited, however, owing to their immunogenicity in humans. MuIGMB17 antibody was partially humanized by engrafting a small portion of mouse light chain (LC) in a human framework and by engineering its heavy chain (HC) in a chimeric version. The engineered IGMB17 (huIGMB17) was able to replicate a range of functional properties of the original muIGMB17, namely, specific binding to IFN-γ, inhibition of histocompatibility complex (HLA-DR) expression in response to IFN-γ induction, reversion of IFN-γ antiproliferative activity on sensitive cell lines. We have hypothesized that as huIGMB17 was able to block IFN-γ binding to its receptor as well as its murine counterpart, huIGMB17 could neutralize all cytokine activity, also in vivo . Indeed huIGMB17 was capable of interfering with delayed-type hypersensitivity reaction in humans, thus demonstrating its effectiveness in neutralizing IFN-γ-mediated reactions in vivo . [ABSTRACT FROM AUTHOR]

The addition of IFN-γ to cultures of peripheral blood mononuclear cells (PBMCs) obtained from asymptomatic HIV-infected patients increased cell proliferation in response to HIV envelope synthetic peptides (Env), influenza A virus (VIRUS), and allogeneic lymphocytes (ALLO) but not to phytohaemagglutinin (PHA) stimulation. F(Ab)2 fragments of IgG purified from the sera of HIV-seropositive patients specifically interfered with IFN-γ-induced cell proliferation in response to recall antigens. Neutralization of the lymphokine activity was found to be sustained by specific IFN-γ antibodies. Data obtained demonstrate that IFN-γ can restore the cell-mediated immunity of a number of asymptomatic HIV+ individuals in vitro, while IFN-γ antibodies present in sera of patients with AIDS interfere with the activity of the lymphokine. [ABSTRACT FROM AUTHOR]

We have designed and tested primers that amplify complete human kappa and lambda light chain genes, and human Fd fragments from gamma, mu and alpha heavy chain genes. These primers were tested for efficiency and specificity on monoclonal sources of human immunoglobulin RNA, obtained from human B-cell lines of known immunoglobulin gene expression. Analysis of the sequences derived from these B-cells confirms the specificity of the PCR primers and the extent of somatic mutation seen in different B-cell malignancies supports existing concepts for differing aetiologies in the tumours concerned. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Yellow Nail Syndrome Associated With Sleep Apnoea" in the September 2005 issue.

Focuses on megestrol treatment in patients with hepatocellular carcinoma. Improvement in survival in treated patients; Side effects of the treatment.