HansD. Ochs

Immune response after splenectomy.

The immune response to intravenously administered bacteriophage phiX 174 and subcutaneously administered tridecavalent pneumococcal polysaccharide vaccine was studied in 31 patients with anatomical or functional asplenia. Antibody responses to primary immunisation with phiX 174 were significantly decreased while clearance was normal. Secondary responses were quantitatively normal; however, production of antibody did not switch from IgM to IgG as seen in controls. All groups of asplenic patients accept those patients with Hodgkins disease demonstrated significant seroconversions in response to pneumococcal polysaccharide antigens. One patient with Hodgkins disease, treated with local irradiation only, demonstrated normal responses to pneumococcal capsular antigens. 10 of the 12 capsular antigens for which antibody was measured stimulated threefold increases in antibody in the 26 asplenic patients without Hodgkins disease, which is similar to that observed in controls. Since the majority of cases of overwhelming postsplenectomy infection are caused by Streptococcus pneumoniae, all patients with either anatomical or functional asplenia should receive pneumococcal polysaccharide vaccine.

A Point Mutation in gp91-phox of Cytochrome b558 of the Human NADPH Oxidase Leading to Defective Translocation of the Cytosolic Proteins p47-phox and p67-phox

The superoxide-forming NADPH oxidase of human phagocytes is composed of membrane-bound and cytosolic proteins which, upon cell activation, assemble on the plasma membrane to form the active enzyme. Patients suffering from chronic granulomatous disease (CGD) are defective in one of the following components: p47-phox and p67-phox, residing in the cytosol of resting phagocytes, and gp91-phox and p22-phox, constituting the membrane-bound cytochrome b558. In an X-linked CGD patient we identified a novel missense mutation predicting an Asp-->Gly substitution at residue 500 of gp91-phox, associated with normal amounts of nonfunctional cytochrome b558 in the patients neutrophils. In PMA-stimulated neutrophils and in a cell-free translocation assay with neutrophil membranes and cytosol, the association of the cytosolic proteins p47-phox and p67-phox with the membrane fraction of the patient was strongly disturbed. Furthermore, a synthetic peptide mimicking domain 491-504 of gp91-phox inhibited NADPH oxidase activity in the cell-free assay (IC50 about 10 microM), and the translocation of p47-phox and p67-phox in the cell-free translocation assay. We conclude that residue 500 of gp91-phox resides in a region critical for stable binding of p47-phox and p67-phox.

The Pharmacokinetics of Total Igg, Igg Subclasses, and Type Specific Antibodies in Immunodeficient Patients

The advent of immunoglobulin concentrates suitable for intravenous administration has greatly improved the clinical management of patients with a primary immunodeficiency syndrome. However, proper treatment requires understanding of the pharmacokinetics of the infused IgG and its components. We review here the work that has been conducted in this area. In particular, two studies have shown that these concentrates have adequate catabolic properties with regards to total IgG, IgG subclasses, and specific antibodies. We conclude that careful evaluation of the pharmacokinetics of a given IgG preparation is necessary in order to determine an appropriate treatment regimen.

HLA typing of cultured amniotic cells for the prenatal diagnosis of complement C4 deficiency.

It has recently been reported that HLA typing can be used for the prenatal diagnosis of the HLA‐linked monogenetic disease, congenital adrenal hyperplasia (21‐hydroxylase deficiency type). We describe here the use of HLA typing of cultured amniotic cells for the prenatal diagnosis of another HLA‐linked disease, complement C4 deficiency. Although C4 is actually coded for by genes at two very closely linked loci, mapping near the HLA‐B locus, absolute C4 deficiency behaves genetically like a monogenetic autosomal recessive disease linked to HLA. The HLA typing results for amniotic cells from a pregnancy at risk for C4 deficiency predicted that the fetus would share only one HLA haplotype with the affected child and would therefore be a clinically normal heterozygous carrier of the C4 deficiency alleles with half‐normal levels of C4 activity. These predictions were confirmed after delivery.