Roberto R. Kretschmer

Defective Monocyte Chemotaxis in Children with Down's Syndrome

Summary: Under-agarose random migration, chemokinesis and chemotaxis of monocytes from 36 patients with Downs syndrome were compared to those of monocytes from 42 healthy, age-matched control children. Random migration of monocytes from patients with Downs syndrome was comparable to that of controls. In contrast, chemotaxis of monocytes from patients with Downs syndrome was significantly increased (P <0.001) when compared to that of controls, even though chemokinesis was significantly increased (P <0.001). Age, sex, and physical development of patients with Downs syndrome or of control children included in this study had no apparent effect upon monocyte mobility.

Enhancement of antigen-induced leukocyte histamine release by a mononuclear cell-derived factor

Supernatant fluids of phytohemagglutinin-stimulated mononuclear cells from ragweed-sensitive patients significantly enhanced the release of histamine from antigen-triggered leukocytes of ragweed-sensitive as well as control individuals. Supernatants of mononuclear cells from control individuals did not reveal this enhancing effect, nor was it found with the use of supernatants of unstimulated mononuclear cells of ragweed-sensitive patients or culture media with PHA alone. Supernatant fluids of phytohemagglutinin-stimulated mononuclear cells of patients sensitive to trees and grass also revealed this enhancing effect. The factor(s) responsible for the enhancement of antigen-induced histamine is heat labile and has a molecular weight of less than 10,000 daltons. The mechanism and site of action of the enhancing factor could involve initiating and/or modulating steps of the leukocyte histamine release reaction. This factor, presumably a lymphokine or a monokine, may constitute a regulating link between cell-mediated immunity and histamine-mediated hypersensitivity reactions in allergic patients.

Protective Value of Gamma Globulin Preparations against Group B Streptococcal Infections in Chick Embryos and Mice

Summary: The protective value of pooled human gamma globulin (GG) and a group B streptococcal immune globulin (GBSIG) was studied in a chick embryo and a murine model of group B streptococcal (GBS) infection. Chick embryos were protected by the IV administration of 0.4 to 0.8 mg of GG from three manufacturers against IV challenge with type Ia GBS. Two of three GG preparations at doses of 0.4 to 1.65 mg protected chick embryos against type III, but 1.65 mg of all three preparations failed to protect against GBS types Ib and II. Mice were protected from lethal IP challenges with types Ia and Ib by the prior IM inoculation of three and two of the three GG preparations at doses of 0.5 to 1.0 mg, respectively. Administration IM of 1 mg of GG failed to protect mice against types II and III.The IV administration of 0.2 mg of GBSIG protected chick embryos against IV inoculation with GBS types Ia, Ib, II, and III. Administration IM of 0.5 mg of GBSIG protected mice against IP challenges with types Ia, Ib, and II, but not with type III. The IP administration of 0.25 mg of GBSIG simultaneously with type III GBS protected mice, whereas GG was not protective. GBSIG should undergo clinical trials for the prevention of GBS infections and their recurrences and as a possible adjunct to antibiotic and supportive therapy of severe GBS infections.Speculation: Some human sera contain antibody which protects animals against infection with group B streptococcus. If passive immunization with human gamma globulin or group B streptococcal immune globulin is effective in animal models, it may be potentially useful in preventing neonatal group B streptococcal infections, and clinical trials would be indicated.

Heavy chain disease, rheumatoid arthritis and cryoglobulinemia

Abstract Acase of double paraproteinemia—gamma-HCD protein and type-L IgG cryoglobulin—is described in a 30 year old patient with rheumatoid arthritis. Clinical and histopathological features of gamma-HCD were observed along with those of cryoglobulinemia and rheumatoid arthritis. The small size of the gamma HCD-protein (2.0 S) and the coexistence of a serum monoclonal cryoglobulin associated with the presence of type-L-light chains in the urine, constitute unusual findings. It is suggested that the association of HCD, rheumatoid arthritis and cryoglobulinemia may well be more than a coincidence.

Quantitative nitrobluetetrazolium reduction by normal newborn monocytes.

The phagocytosis-induced metabolic burst of human newborn monocytes, as evaluated by their capacity to reduce NBT, was comparable to that of adult monocytes. The NBT reduction assay constitutes a simple method of ascertaining the functional capacity of human monocytes.

822 PASSIVE IMMUNIZATION AGAINST GROUP B STREPTOCOCCI WITH HUMAN GAMMA GLOBULIN IN THE CHICK EMBRYO

Clinical and experimental observations have indicated that lack of type-specific antibody is a predisposing factor in the susceptibility of newborn infants to group B beta hemolytic streptococcal (GBBHS) disease. In a study limited to GBBHS type Ia, we showed that IM or IV pooled human gamma globulin (HGG) protects 21-day-old mice from a lethal challenge (J. Infect. Dis., Nov. 1977). We now report HGG protection studies with types Ia, II and III using a chick embryo model. 0.1 ml. of different dilutions of 16% HGG was injected IV into 12-day-old chick embryos simultaneous to the IV challenge with a lethal inoculum of GBBHS. Protection was established if at least 75% of the chick embryos survived the bacterial challenge. HGG protected chick embryos from a lethal challenge of GBBHS-Ia at a dilution as low as 1:20, which is approximately equivalent to an IM injection of 0.2 ml/kg of pooled HGG in the human newborn. In contrast, undiluted HGG failed to protect chick embryos challenged with lethal doses of GBBHS types II and III. The results in mice and chick embryos suggest that passive immunization in newborn infants with HGG is feasible against GBBHS type Ia, but will not provide immunity to GBBHS strains II and III. Since some human sera protect chick embryos against challenge with type II and III strains, future studies should evaluate hyperimmune HGG.

Murine resistance to type III group B streptococci

SummaryWe examined the role of serum, complement and the reticuloendothelial system in mouse resistance to type III group B streptococci (GBS). Normal serum obtained from 21 day-old mice failed to protect chick embryos against a lethal intravenous (IV) inoculation of GBS-III-SS620/50. Mice that were decomplemented using cobra venom factor remained resistant to intraperitoneal (IP) inoculation of 106 colony-forming units (CFU) of GBS-III-SS620/50, GBS-III-Bell and GBS-III-Minnesota. In contrast, mice prepared with IP oleic acid were killed with 104 CFU of GBS-III-SS620/50 IP. However, when mice were injected IV with oleic acid, they remained resistant to IP inoculation of GBS-III-SS620/50. These results suggest that peritoneal macrophages play a role in murine defense against IP infection with GBS-III-SS620/50.ZusammenfassungWir untersuchten die Bedeutung von Serum, Complement und des retikuloendothelialen Systems für die Resistenz von Mäusen gegenüber Streptokokken der Gruppe B, Typ III (GBS). Normales Serum von 21 Tagen alten Mäusen schützte Hühnerembryonen nicht gegen die letale intravenöse (IV) Inokulation von GBS-III-SS620/50. Mäuse blieben nach Dekomplementierung durch einen Kobra Giftfaktor resistent gegenüber der intraperitonealen (IP) Inokulation von 106 Keimen (CFU) von GBS-III-SS620/50, GBS-III-Bell und GBS-III-Minnesota. Hingegen wurden Mäuse nach Vorbehandlung mit intraperitoneal injizierter Oleinsäure durch 104 Keime von GBS-III-SS620/50 IP getötet. Wenn Mäuse Oleinsäure IV erhielten, dann blieben sie gegenüber der IP Inokulation von GBS-III-SS620/50 resistent. Diese ERgebnisse lassen annehmen, daß die peritonealen Makrophagen bei Mäusen für die Abwehr von IP Infektionen mit GBS-III-SS620/50 eine Rolle spielen.

Thymosin-induced leukocyte histamine release reaction in an infant with DiGeorge syndrome

Abstract A limited number of T-cell responses but no change in clinical condition were recorded in a patient with complete DiGeorge syndrome treated with thymosin for a 59-day period. A striking rise in IgE was observed, probably reflecting the appearance of reaginic antibodies to some constituent of thymosin. Although no local or systemic anaphylactic reactions were observed, the patients serum caused a significant increase in histamine release from normal leukocytes in the presence of thymosin. Thus, allergic reactions to thymosin may complicate therapy of thymic deficiency diseases.

681 THYMOSIN TREATMENT OF DI GEORGE SYNDROME

A 2½-month-old infant with complete DiGeorge syndrome was treated with bovine thymosin fraction V. Initial evaluation revealed normal numbers of blood lymphocytes, 29% EAC rosettes, 41% sIg lymphocytes and no T-rosettes. T-rosettes rose to 15% upon in vitro incubation with thymosin. There was no in vitro response to PHA, PWM, SLO, candida or allogeneic cells, and delayed skin reactivity to SKSD, candida and DNCB was absent. IgG, A, M and E were 175 mg%, 15 mg%, 40 mg% and 10 Iu/ml respectively. He received 10 mg/day of thymosin for 21 days, followed by 20 mg/day for an additional 17 days, and weekly injections of the same dose thereafter. During therapy the lymphocyte count did not change, but T-rosettes rose to 26% while EAC rosettes and sIg lymphocytes decreased to 14% and 10% respectively. Lymphocytes remained unreactive in vitro to PHA, PWM, candida and allogeneic cells, but reacted to SLO (S.I.=42). Delayed skin reactions remained negative. IgG, A and M were 120 mg%, 20 mg% and 62 mg% at 4 months of age, while IgE rose to 255 Iu/ml. No specific antibodies were detected. He died of sepsis at 4½ months of age. In the postmortem no thymus or parathyroids could be found, and the lymphoid tissue revealed depleted T-dependent areas with poorly developed germinal centers. Similar partial reconstitution of T-cell functions, presumably resulting from the maturation of null-cells, have been observed in other immunodeficiencies treated with thymic extracts.

458 LEUCOCYTE LOCOMOTION IN PATIENTS WITH TURNER'S SYNDROME

Leucocyte locomotion abnormalities have been found in chromosomopathies such as Downs, Cri-du-chat and Edwards syndromes, in all of which a variable increase in susceptibility to infections has been described as well. We evaluated the peripheral blood leucocyte (polymorphonuclear (PMN) and monocyte (MP)) locomotion (random mobility, chemokinesis and chemotaxis) in 13 infection-free patients with Turners syndrome and compared it to that of 10 age-matched healthy girls. Leucocytes were obtained by density gradient centrifugation and the three locomotion varieties were assayed using double-filtered Boyden chambers and zymosan activated serum as attractant. Random mobility, chemokinesis and chemotaxis of MP from patients with Turners syndrome were comparable to those of controls. So were random mobility and chemokinesis of PMN. Chemotaxis of PMN from patients with Turners syndrome was significantly (p <; 0.002) diminished (57 ± 19 PMN/hpf, mean ± SEM) when compared to controls (93 ± 56 PMN/hpf). These results suggest an intrinsic PMN chemotactic defect in patients with Turners syndrome that does not translate into an increase in the susceptibility to infections.