Serum immunoglobulins in patients with congenital coagulation defects and their relatives

Quantitative estimations of serum IgG, IgA and IgM were performed in 30 individuals with congenital coagulation defects and in 47 related persons.The majority of patients with hemophilia, congenital defects of the prothrombin complex and congenital afibrinogenemia showed a significant elevation in one or more immunoglobulins. By contrast, normal immunoglobulin concentrations were recorded in 3 persons with von Willebrand's disease, in 2 normal subjects with isolated factor VIII deficiency, and in 1 female patient with acquired deficiency of the liver-dependent clotting factors.In 11 out of 15 mothers of hemophiliacs immunoglobulin concentrations were significantly elevated. A high proportion of other relatives of these patients likewise showed significantly raised immunoglobulin concentrations. Follow-up tests on patients and their relatives over more than 1 year indicated that findings usually did not vary appreciably.On the basis of our study it is suggested that in patients with congenital coagulation defects elevated immunoglobulin concentrations are hereditary.

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Zusammenfassung Bei 30 Personen mit angeborenem Gerinnungsdefekt sowie bei 47 Blutsverwandten wurden IgG, IgA und IgM im Serum quantitativ bestimmt. Der überwiegende Teil der Patienten mit Hämophilie, kongenitalem Defekt im Prothrombinkomplex und kongenitaler Afibrinogenämie hatte eine signifikante Vermehrung eines oder mehrerer Immunglobuline. Normale Immunglobulinkonzentrationen fanden sich dagegen bei drei Personen mit v. Willebrand-Jürgens-Syndrom, bei zwei klinisch Gesunden mit isolierter Faktor VIII-Minderung und bei einer Patientin mit erworbener Verminderung der leberabhängigen Gerinnungsfaktoren.11 der 15 Mütter von Patienten mit Hämophilie oder Defekt im Prothrombinkomplex hatten signifikante Immunglobulinerhöhungen. Von den übrigen Verwandten dieser Patienten zeigte ein hoher Prozentsatz ebenfalls signifikant erhöhte Immunglobulinkozentrationen. Die Untersuchungsergebnisse wiesen in Verlaufskontrollen bis über 1 Jahr bei Patienten und Familienangehörigen in der Regel keine nennenswerten Schwankungen auf. Die Untersuchungen weisen darauf hin, daß bei Patienten mit kongenitalen Gerinnungsdefekten auch eine Erhöhung der Immunglobulinkonzentrationen hereditär ist.

     

The chemiluminescence response and bactericidal activity of polymorphonuclear neutrophils from newborns and their mothers.

Chemiluminescence (CL) was measured in the polymorphonuclear neutrophils (PMN) of 18 normal term infants, their mothers, and controls during phagocytosis of opsonized zymosan particles. Chemiluminescence was significantly lower in the PMN of newborns in comparison with the PMN of their mothers and of the controls. Depressed bactericidal activity was demonstrated in newborn PMN, in comparison with the activity of the PMN of their mothers and controls, when challenged with Escherichia coli at large bacteria-PMN ratios. Uptake of radio-labeled bacteria by PMN was identical in newborns, mothers, and controls, which indicates that reduced CL was not a result of impaired ingestion. Therefore, PMN of normal term infants have both depressed oxidative metabolic responsiveness as measured by CL and depressed bactericidal capacity.     

Stability and biological activity of epoietin beta in parenteral nutrition solutions

The aim of this in vitro study was to determine stability and biological activity of epoietin (Epo) beta in a parenteral nutrition solution over 24 h. Epo beta was added to the parenteral nutrition solution which was administered through intravenous tubing and a Posidyne Neo filter. Samples were collected after 0, 4, 12, and 24 h. The Epo concentrations were measured before and after filter passage by an ELISA assay. The Epo biological activity was determined in the UT7/Epo cell line. The Epo concentration in the parenteral nutrition solution remained stable for 24 h. However, 35% of the Epo was adsorbed by the filter. The samples collected induced proliferation of UT7/Epo cells. These results suggest that Epo can be administered in parenteral nutrition solutions, but the dosage would need to be increased when a filter is used.     

Physicochemical characterization and biological activity of intrinsic factor in cystic fibrosis

Absorption of crystalline labeled cobalamin is strongly decreased in cases of cystic fibrosis. In order to determine if this is due to an alteration or a lack of activation of intrinsic factor by proteases, the physicochemical properties and biological activity of intrinsic factor have been studied. Intrinsic factor was purified 800-fold from stimulated gastric juice of cystic fibrosis patients with a yield of 64.2%. Cystic fibrosis intrinsic factor had an estimated Mr of 57,000 in SDS-polyacrylamide gel electrophoresis. Its carbohydrate content resembled that of normal human intrinsic factor, except that the ratio fucose/sialic acid was higher (6.1 and 1.6, respectively) and that the content in N-acetylgalactosamine was decreased. The same alterations in carbohydrate composition were observed for Hc purified from cystic fibrosis saliva. Purified intrinsic factor from cystic fibrosis gastric juice was biologically active in vitro in the presence of ileal solubilized receptor as well as in vivo (Schilling test). The fate of iodinated cystic fibrosis intrinsic factor in guinea pig ileum studied by high-resolution radioautography was similar to that of normal intrinsic factor. In conclusion, despite modifications of the carbohydrate content of the molecule, the biological activity of intrinsic factor is not altered in cases of cystic fibrosis. The malassimilation of crystalline cobalamin observed in cystic fibrosis is due to a mechanism independent from intrinsic factor secretion.