[Clinical case of the month. Mild hemolytic disease of the newborn due to an anti-Wr(a) antibody]. / Maladie hémolytique néonatale modérê due à un anticorps anti-Wr(a).

A Caucasian woman, with a A+ CCD.ee K neg erythrocyte phenotype and no history of blood transfusion, delivered a first child who developed mild anemia. The direct antiglobulin test performed on the newborn red blood cells belonging to the A+ CCD.ee K neg group, was strongly positive for IgG. During the pregnancy and after the delivery, the woman had a negative irregular antibody screening test, using standard red blood cells. However, at birth, using a collection of thawed red blood cells with rare phenotypes (private antigens), the lab showed an antibody anti-Wr(a) in the maternal serum. The activity of the maternal antibody, with a titer of 16, was completely inhibited by dithiothreitol, indicating the nature IgM of the circulating antibody. The presence of the antigen Wr(a) on the surface of the newborn and its biological father red blood cells was confirmed. The concentration of IgG anti-Wr(a) on baby erythrocytes was demonstrated by the presence of the antibody anti-Wr(a) in the eluate. This case illustrates the difficulties to detect antibodies against private antigens on baby erythrocytes, responsible of hemolytic diseases of newborn. Indeed, standard red blood cell panels used for irregular antibodies screening test do not express generally those private antigens.

Blood, urine, and hair kinetic analysis following an acute lead intoxication.

A case of lead exposure resulting from the accidental ingestion of a lead-containing solution is reported. Because of clinical management rapidly performed through chelation therapy by 2,3-dimercaptopropane sulfonate sodium and meso-2,3-dimercaptosuccinic acid, blood lead levels of this 51-year-old patient were moderate (412.9 µg/L) and no clinical symptoms were observed. Numerous blood and urine samples were collected for kinetic analysis of lead elimination. However, we report the first case in which hair samples were analyzed to determine the excretion level of lead after acute intoxication.

Matrix Metalloproteinase-9 gene induction by a truncated oncogenic NF-kappaB2 protein involves the recruitment of MLL1 and MLL2 H3K4 histone methyltransferase complexes.

Constitutive nuclear factor (NF)-kappaB activation in haematological malignancies is caused in several cases by loss of function mutations within the coding sequence of NF-kappaB inhibitory molecules such as IkappaBalpha or p100. Hut-78, a truncated form of p100, constitutively generates p52 and contributes to the development of T-cell lymphomas but the molecular mechanism underlying this oncogenic potential remains unclear. We show here that MMP9 gene expression is induced through the alternative NF-kappaB-activating pathway in fibroblasts and also on Hut-78 or p52 overexpression in fibroblasts as well as in lymphoma cells. p52 is critical for Hut-78-mediated MMP9 gene induction as a Hut-78 mutant as well as other truncated NF-kappaB2 proteins that are not processed into p52 failed to induce the expression of this metalloproteinase. Conversely, MMP9 gene expression is impaired in p52-depleted HUT-78 cells. Interestingly, MLL1 and MLL2 H3K4 methyltransferase complexes are tethered by p52 on the MMP9 but not on the IkappaBalpha promoter, and the H3K4 trimethyltransferase activity recruited on the MMP9 promoter is impaired in p52-depleted HUT-78 cells. Moreover, MLL1 and MLL2 are associated with Hut-78 in a native chromatin-enriched extract. Thus, we identified a molecular mechanism by which the recruitment of a H3K4 histone methyltransferase complex on the promoter of a NF-kappaB-dependent gene induces its expression and potentially the invasive potential of lymphoma cells harbouring constitutive activity of the alternative NF-kappaB-activating pathway.