Costimulatory molecule CD154 in systemic lupus erythematosus and rheumatoid arthritis. Therapeutic perspectives.

SLE is a systemic autoimmune disease characterized by B cell hyperactivity. Evidence from the last years has shown that B cells play a key role in the development of the immune response. The interaction of CD40 on B cells with its ligand CD154 on activated T cells provides a costimulatory signal that induces T dependent B cell proliferation and differentiation with subsequent antibody production. Moreover, CD154 can act as a cytokine, in addition to its main role to mediate the interactions between T and CD40+ target cells. This review focuses on the multiple roles of CD154 in systemic lupus erythematosus and rheumatoid arthritis and its involvement in the humoral immunity disregulation of patients with these diseases. It also takes in consideration the most recent therapeutic perspectives regarding the use of monoclonal antibodies against CD154, which might be a powerful tool in the treatment of these diseases in the future.

A soluble form of the human transferrin receptor is released by activated lymphocytes in vitro.

Soluble transferrin receptors (sTfR) were detected in culture supernatants of activated human peripheral blood mononuclear cells (PBMC) using a sandwich ELISA technique with two non-cross-reacting TfR MoAbs. Mitogenic stimulation of lymphoid cells induced both up-regulation of TfR surface density and release of sTfR to the medium. Peak levels of sTfR in culture supernatants occurred at day 4 after activation, 1 day later than maximum expression of TfR in the plasma membrane. Production of sTfR was independent of proliferation, as demonstrated by measuring sTfR release by PBMC, which had been irradiated with a dose of 20 Gy before activation. In addition to these in vitro experiments, we tested the sera of 85 patients with systemic lupus erythematosus (SLE), an autoimmune disease accompanied by in vivo activation of lymphocytes, for their sTfR levels. No correlation of these data was detectable to serum concentrations of the soluble alpha-chain of the IL-2 receptor, an unequivocal marker of lymphocyte activation. However, they correlated negatively to the haemoglobin content of the patients' erythrocytes, indicating that erythroid progenitors are the predominant source of sTfR in SLE patients' sera.

Enhancement of carcinoembryonic antigen (CEA) expression in colorectal tumors by neuraminidase.

Twelve colorectal carcinomas with transitional mucosa and 10 colorectal adenomas which previously displayed weak or no carcinoembryonic antigen (CEA) expression were selected to verify whether neuraminidase unmasks CEA carbohydrate epitopes and, consequently, enhances the CEA expression. Peroxidase-antiperoxidase (PAP) method was performed on routinely processed tissues, without and with neuraminidase pretreatment of the sections. Lysine, without and with neuraminidase pretreatment of the sections. Lysine, as a modifier of electrostatic charge at cell surface, instead of neuraminidase was used to clarify whether the enzyme yields a specific or non-specific influence on CEA expression. All colorectal tumors exhibited more CEA after neuraminidase pretreatment, while previous negative specimens developed CEA expression. The same effect was observed in some transitional mucosa sections. This has not occurred in normal mucosa, probably owing to a resistant sialylation. The enhancement effect of lysine, although more weakly and not entirely superimposed to that or neuraminidase, suggests non-specific mechanisms of enzyme action. The removal of the negative charge at cell surface, especially due to sialic acid, allows more anti-CEA antibodies to react. The neuraminidase pretreatment of the sections is a useful method to demonstrate the real incidence of CEA in the colorectal tumors.