Histo-blood group antigens as allo- and autoantigens

The science of blood groups has made giant steps forward during the last decade. Blood-group typing of red blood cells (RBCs) is performed on more than 15 million samples per year in Europe, today much less often for forensic reasons than for clinical purposes such as transfusion and organ transplantation. Specific monoclonal antibodies are used with interpretation on the basis of RBC agglutination patterns, and mass genotyping may well be on its way to becoming a routine procedure. The discovery that most blood group systems, whose antigens are by definition found on RBCs, are also expressed in multiple other tissues has sparked the interest of transplantation medicine in immunohematology beyond the HLA system. The one and only "histo-blood group" (HBG) system that is routinely considered in transplantation medicine is ABO, because ABO antigen-incompatible donor/recipient constellations are preferably avoided. However, other HBG systems may also play a role, thus far underestimated. This paper is an up-to-date analysis of the importance of HBG systems in the alloimmunity of transplantation and autoimmune events, such as hemolytic anemia.

Dietary supplementation with the tribomechanically activated zeolite clinoptilolite in immunodeficiency: effects on the immune system

Natural zeolites are crystalline aluminosilicates with unique adsorption, cation-exchange, and catalytic properties that have multiple uses in industry and agriculture. TMAZ, a natural zeolite clinoptilolite with enhanced physicochemical properties, is the basis of the dietary supplements Megamin and Lycopenomin, which have demonstrated antioxidant activity in humans. The aim of this prospective, open, and controlled parallel-group study was to investigate the effects of supplementation with TMAZ on the cellular immune system in patients undergoing treatment for immunodeficiency disorder. A total of 61 patients were administered daily TMAZ doses of 1.2 g (Lycopenomin) and 3.6 g (Megamin) for 6 to 8 weeks, during which the patients' primary medical therapy was continued unchanged. Blood and lymphocyte counts were performed at baseline and at the end of the study. Blood count parameters were not relevantly affected in either of the two treatment groups. Megamin administration resulted in significantly increased CD4+, CD19+, and HLA-DR+ lymphocyte counts and a significantly decreased CD56+ cell count. Lycopenomin was associated with an increased CD3+ cell count and a decreased CD56+ lymphocyte count. No adverse reactions to the treatments were observed.

T cells infiltrate the liver and kill hepatocytes in HLA-B(∗)57:01-associated floxacillin-induced liver injury.

Drug-induced liver injury is a major safety issue. It can cause severe disease and is a common cause of the withdrawal of drugs from the pharmaceutical market. Recent studies have identified the HLA-B(∗)57:01 allele as a risk factor for floxacillin (FLUX)-induced liver injury and have suggested a role for cytotoxic CD8(+) T cells in the pathomechanism of liver injury caused by FLUX. This study aimed to confirm the importance of FLUX-reacting cytotoxic lymphocytes in the pathomechanism of liver injury and to dissect the involved mechanisms of cytotoxicity. IHC staining of a liver biopsy from a patient with FLUX-induced liver injury revealed periportal inflammation and the infiltration of cytotoxic CD3(+) CD8(+) lymphocytes into the liver. The infiltration of cytotoxic lymphocytes into the liver of a patient with FLUX-induced liver injury demonstrates the importance of FLUX-reacting T cells in the underlying pathomechanism. Cytotoxicity of FLUX-reacting T cells from 10 HLA-B(∗)57:01(+) healthy donors toward autologous target cells and HLA-B(∗)57:01-transduced hepatocytes was analyzed in vitro. Cytotoxicity of FLUX-reacting T cells was concentration dependent and required concentrations in the range of peak serum levels after FLUX administration. Killing of target cells was mediated by different cytotoxic mechanisms. Our findings emphasize the role of the adaptive immune system and especially of activated drug-reacting T cells in human leukocyte antigen-associated, drug-induced liver injury.