Gamma-globulin Preparations Research Articles

Protective value of gamma globulin preparations against group B streptococcal infections in chick embryos and mice.

The protective value of pooled human gamma globulin (GG) and a group B streptococcal immune globulin (GBSIG) was studiedf 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.

In vivo behaviour of gamma globulin preparations.

Metabolic properties of standard gamma globulin (St-GG) and of several gamma globulin (GG) preparations for intravenous use were analyzed in radioactive tracer studies. The in vivo behaviour of St-GG was investigated in 16 probands and found to be comparable to that of normal IgG. The kinetics of the resorption of St-GG from intramuscular deposits, its elimination from the intravascular compartment and from the body were studied in 2 probands. Metabolic properties of GG preparations for intravenous use were compared with those of St-GG in 3-4 probands after simultaneous injection of 125I- and 131I-labelled tracer doses. Important differences in the half-times of intravascular survival, in the rates of catabolism and in the distribution in the body were noticed for most of the preparations for intravenous use except for an improved acid-treated (pH 4) GG, the in vivo behaviour of which was similar to that of St-GG.

IgG subclasses in human gamma-globulin preparations for intravenous use and their reactivity with staphylococcus protein A.

In two of four non-enzymatically treated gamma-globulin preparations C Immunoglobulin Schura, Immunoglobulin SRK), the distribution of IgG subclasses was found to be close to that of normal human serum. In two other preparations (sulphonated and beta-propiolactone-treated) IgG3 was not detectable by means of appropriate antiserum. The IgG residual portion of plasmin-treated gamma-globulin was enriched in IgG2, while IgG3 was absent. In affinity chromatography on protein A Sepharose, IgG3 in the unbound and IgG1, IgG2 and IgG4 in the bound fractions were found in Immunoglobulins Schura and SRK. In the sulphonated preparation no IgG was found in the unbound fraction, while IgG1, IgG2 and IgG4 were eluted from the bound fraction. In beta-propiolactone-treated gamma-globulin IgG1, IgG2 and IgG4 were present in both fractions. The testing of reactivity of IgG subclasses with Staphylococcus protein A can supply important information about the state of the Fc part in immunoglobulin preparations.

In vivo Behaviour of Gamma Globulin Preparations

Metabolic properties of standard gamma globulin (St-GG) and of several gamma globulin (GG) preparations for intravenous use were analyzed in radioactive tracer studies. The in vivo behaviour of St-GG was investigated in 16 probands and found to be comparable to that of normal IgG. The kinetics of the resorption of St-GG from intramuscular deposits, its elimination from the intravascular compartment and from the body were studied in 2 probands. Metabolic properties of GG preparations for intravenous use were compared with those of St-GG in 3-4 probands after simultaneous injection of 125I- and 131I-labelled tracer doses. Important differences in the half-times of intravascular survival, in the rates of catabolism and in the distribution in the body were noticed for most of the preparations for intravenous use except for an improved acid-treated (pH 4) GG, the in vivo behaviour of which was similar to that of St-GG.

Evaluation of the Effects of the Gammaglobulin Preparation on the Infections in Patients with Hematological Malignancy

Evaluation of the Effects of the Gammaglobulin Preparation on the Infections in Patients with Hematological Malignancy

Inhibition of fertility in mice by passive immunization with antibodies to isolated zonae pellucidae.

A chromatographically purified preparation of gamma globulin produced against isolated zonae pellucidae of mice was used to immunize mice. A single 2.5 mg dose totally inhibited fertility for a minimum of 11 days.

Precipitating antibodies against Neisseria meningitidis in normal sera and their possible origin.

Crossed immunoelectrophoresis was used to study precipitating antibodies against Neisseria meningitidis in sera from 214 normal persons and in human gammaglobulin. A polyspecific meningococcal antigen preparation and a corresponding rabbit antiserum constituted the reference system. All the sera contained one to five precipitins against N. meningitidis which could be identified and quantified by means of the reference system. The precipitin score, which expresses the number and titre of precipitins in each serum, increased with age. More than 25 precipitins were found in the gammaglobulin preparation, including antibodies against the groupspecific polysaccharides A, B and C. Absorption of three of the five normally occurring precipitins (nos. 4, 19, 22) with antigens from various bacteria showed that precipitins nos. 4 and 19 could be completely absorbed by antigens from other Neisseria species, but not by antigens from other genera. This indicates that these two precipitins may have been induced by non-pathogenic Neisseria species or by meningococci. The finding of protective antibodies in gammaglobulin might indicate the possibility of its use in prophylaxis or therapy meningococcal infections.

Effect of intravenously applicable globulin on phagocytosis of bacteria by human polymorphonuclear leukocytes.

Three gamma-globulin (IgG) preparations were prepared by enzymatic digestion with plasmin [IgG (plasmin)] or pepsin [IgG (pepsin)] and by polyethylene glycol (PEG) fractionation [IgG (PEG)] and their efficacy was compared in terms of the ability to promote phagocytosis in vitro of three strains of pyogenic bacteria, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae, by human polymorphonuclear leukocytes. IgG (plasmin) had the composition of IgG : Fab : Fc=60 : 26 : 14 ; IgG (pepsin), IgG : F (ab')2 : Fc=8 : 77 : 15 and IgG (PEG), 90% or more IgG. In the phagocytosis test, IgG (PEG) was the most efficient and IgG (plasmin) more than IgG (pepsin) though agglutinin titers of these were much the same. The F (ab')2 fragments were almost inefficient in spite of their agglutinin titer similar to those of the IgG preparations. The Fab and Fc fragments showed neither agglutinin titer nor the ability to promote phagocytosis. Since it has been confirmed by a previous study (ref. 16) on the phagocytosis mechanism that these differences in phagocytic effects result from a phagocytotic mechanism in which antigen bound to antibody at its Fab portion is phagocytized through receptors for Fc and complement present on the polymorphonuclear leukocyte surface, it may be concluded that an IgG preparation desirable for clinical use is that which contains intact IgG molecules as much as possible.

Distribution of IgG subclasses in commercial and some experimental gamma-globulin preparations.

The IgG subclass distribution was determined in six commercial and in four experimental human gamma-globulin preparations. The concentrations of IgG subclasses were measured in a modified radiommunoassay using subclass-specific antisera. In commercial gamma-globulins, the distribution of the subclasses corresponded roughly to the distribution in normal human serum. A considerable enrichment of the IgG 4 was found in experimental lots prepared either from the ethanol fraction III or from the rivanol-precipitable IgG.

Concentration of intravenously administered gammaglobulin preparations in dog skin (author's transl)

Chemical modification of standard gammaglobulin with enzyme treatment (pepsin) or stabilization (beta-propiolactone) is able to influence elimination, fragmentation and organ distribution of intravenously administered gammaglobulins as shown in 36 dogs after i.v. application of allogenic and xenogenic gammaglobulin preparations. Pepsin-gammaglobulin was eliminated and fragmented most rapidly. Gammaglobulin concentrations of all preparations in the skin showed as slower decrease than comparable blood concentrations. The highest skin concentrations 10 days after i.v. application were found for beta-propiolactone gammaglobulin with 6.2 +/- 1.6 microgram/g compared to a blood level of 7.9 +/- 0.9 microgram/ml.

IgA in commercial gamma-globulin preparations.

The presence of anti-IgA has been related to adverse reactions to injection or infusion of IgA-containing material. In this study IgA was demonstrated in all of the investigated commercial gamma-globulin preparations. In the material from a few producers it was, however, very low. By immuno-gel filtration it could be shown that the IgA consisted of aggregates as well as a 7S component and fragments. By immunoelectrophoresis-immunofluorescence IgG-IgA complexes could also be detected. The IgA aggregates could be almost completely degraded by reduction-alkylation. It is implied that such changed IgA in gamma-globulin preparations for injection may increase the risk of immunization against IgA.

Improved compatibility of ALG therapy by application of aggregate free globulin.

Horse anti-human lymphocyte globulin (ALG) solutions contain, like human gamma-globulin preparations, a varying amount of IgG aggregates, which increase during longer periods of storage. Aggregate formation does not impair the immunosuppressive potency of ALG, as has been shown by prolongation of skin allograft survival time in primates. Deaggregated ALG, which can be obtained by ultracentrifugation at 100,000 g over 2 h, is less immunogenic than aggregate containing ALG. The clinical compatibility of ALG was significantly improved by ultracentrifugal deaggregation.

Evidence for the clonal abortion theory of B-lymphocyte tolerance.

This paper deals with the behavior of adult mouse bone marrow cells placed in tissue culture with or without antigen, and subsequently assessed for immune competence after adoptive transfer into lethally X-irradiated, syngeneic hosts. Attention was focussed on B lymphocytes through using hapten human gamma globulin (HGG) preparations as putative tolerogens in tissue culture, the T-cell-independent antigens DNP-POL and NIP-POL as challenge injections in adoptive hosts, and numbers of hapten-specific PFC in host spleens for the quantitation of immune competence. It was found that the capacity of bone marrow cells to mount an adoptive immune response rose by a factor of about fivefold over 3 days in tissue culture. This rise was completely abolished by the presence in the culture of hapten-HGG conjugates with about one mole of hapten per carrier molecule. The prevention of the emergence of immune competence amongst maturing B cells was termed clonal abortion tolerogenesis. Dose-response studies showed the lowest effective antigen concentration to be between 2.5 times 10- minus 10 and 2.5 times 10- minus 9 M, and a standard concentration of 2.5 times 10- minus 8 M was chosen as producing near maximal effects. The tolerance was antigen-specific and time-dependent, being maximal only when antigen was present continuously as the cultured cells was maturing. It did not depend on the presence of T lymphocytes in marrow, and was not of an "infectious" type. In contrast to tolerogenesis of mature B lymphocytes by high antigen concentrations, it could not be abolished by lipopolysaccharide. We speculate that clonal abortion may be a tolerance mechanism of great physiological significance for self-recognition, and discuss the results in the framework of other recent tolerance models, including those involving receptor blockade and suppressor T cells.

Viral hepatitis and hepatitis B antigen: recent advances.

SummaryRecent advances in hepatitis research have shed new light on the etiology, pathogenesis, epidemiology and prevention of type B hepatitis infection. The so-called ‘Dane’ particle is probably the complete hepatitis B virion; its outer coat is the hepatitis B (Australia) antigen (HB Ag) and its inner core is an immunologically distinct particle. Subtypes of HB Ag (a, d, y, w and r) are useful indices for epidemiological surveys. Concepts of epidemiology have changed: type B hepatitis is transmissible by contact as well as by inoculation. The presence of HB Ag in blood is indicative of the presence of hepatitis B virus. Tests to detect antigen and use of voluntary blood donors have played a major role in the decreased incidence of post transfusion hepatitis. A special hepatitis B gammaglobulin preparation and a heat-inactivated hepatitis B vaccine have proved to be effective in preliminary studies.

Anti-gamma globulins and chronic infection: comparative studies of the immune response to various bacteria and gamma globulin preparations.

A study of the relationship of clinical states associated with prolonged infection (bacterial endocarditis and osteomyelitis) and generation of serum anti-gamma globulins was made with particular reference to quantitative amounts of staphylococcal protein A in various infecting strains. No correlation between individual strain amounts of protein A and presence of anti-gamma globulins was detected. Thirty-eight rabbits were immunized intravenously with various strains of bacteria (Staphylococcus aureus, enterococci, Streptomyces viridans, pneumococci, pseudomonas, and Escherichia coli) for periods of 6 weeks, and antibacterial as well as anti-gamma globulin antibodies were assayed. No single group or strain of bacteria stood out as being more prone to produce anti-gamma globulins than others tested. Most rabbits developed anti-gamma globulins reacting with human gamma globulins, whereas the specificity for rabbit gamma globulin appeared more restricted. In 16 rabbits immunized with eight different strains of S. aureus, quantitative elevation of serum gamma globulin above 2.5 g per 100 ml often seemed to be correlated with presence of detectable serum anti-gamma globulins. By contrast 15 rabbits immunized with autologous or isologous rabbit gamma globulins in many instances developed extremely high titers of anti-gamma globulins showing primary specificity for human rather than rabbit gamma globulin. These studies further amplify the remarkably heterogeneous anti-gamma globulin reactivity associated with various types of immune response.

Immunonephelometric determination of fibrinogen and its derivatives in plasma

An immunonephelometric method for determination of fibrinogen and fibrin degradation products in plasma is described. Test plasms are diluted 1/600 in a solution containing 17 g NaCl and 3.8 g trisodium citrate/100 ml. To 3 cm 3 of this mixture 0.2 cm 3 of a concentrated antifibrin gamma globulin preparation is added. The reading of this sample minus the γ-globulin blank in a Thorp Nephelometer is directly proportional to the fibrinogen content of the plasma or to its FDP concentration in terms of intact fibrinogen. This paper examines the mechanism, accuracy and reproducibility of this method.

Gamma Globulin Solution for Intravenous Administration: Trials in Healthy Volunteers

AbstractA preparation of gamma globulin was administered intravenously to 88 healthy subjects at 95 occasions in doses of 10–50 ml. In two instances the injection was discontinued because of increased pulse rate and blood pressure and increased respiratory frequency. In one case urticaria appeared after the injection. Otherwise no side effects of importance were observed.

A controlled trial on therapy for newborns weighing 750-1 250 g. I. Clinical findings and mortality in the newborn period.

SummaryA controlled therapeutic trial was performed in newborns with birthweight of 750‐1 250 g. 40 infants (the “treatment” group) received an i.v. infusion with glucose and NaHCO3 from the 1st to the 4th‐7th day of life, and increasing amounts of human milk from the 2nd day of life. They also received, during the newborn period, 3 antibiotics (sodium penicillin G 500 000 U + methicillin 100 mg + colistin sulf. 8 mg per kg/day), a gamma globulin preparation (0.5 ml/day for 3 days) and fresh human plasma (3 ml every 2nd day in the first 5 days of birth). 40 infants (the “control” group) received only oral feeding with 10% glucose and human milk, starting in the 2nd day of life, and i.m. kanamycin (20 mg/kg/day for 5 days).No difference between treated and control babies was observed with respect to the following findings: neonatal mortality rate and survival curve on the whole series; neonatal mortality rate in babies with birthweight above or below 1.04 kg, with gestational age below 28 weeks, with above or below median respiratory rate or arterial pH on admission, with or without marked abnormality on chest film, and in males or females (but, in subjects with gestational age above 27 weeks, a significantly lower mortality rate was found in controls); postmortem findings; incidence of apnoeic spells, tremors and cloni, and pattern of muscular tonus. Bradycardia associated with 2: 1 atrioventricular block was observed in 6 controls in the 2nd day of birth. No adverse effects presumably due to the therapeutic procedures so contrasted were demonstrated.It was concluded that in the present series of newborns with very low weight: (a) the massive anti‐infectious therapy was not superior to the administration of a single broadspectrum antibiotic; (b) the administration of fresh human plasma was not effective in preventing hemorrhage (but further evaluation is needed); (c) the routine i.v. infusion with glucose and NaHCO3 did not improve neonatal survival as compared with oral feeding.However, previous studies, as well as observations on the present series reported elsewhere (11), have shown that several biochemical abnormalities commonly seen in orally fed newborns with very low weight can be prevented or corrected, at least in part, by the early infusion with glucose and NaHCO3. Since some of these abnormalities are potentially dangerous to the central nervous system, the final evaluation of this therapy must await long‐term follow‐up studies in survivors. It is therefore suggested that, before such studies are available, the early i.v. infusion with glucose and NaHCO3 should be given routinely to newborns with very low weight.

Rubella antibody levels in commercial gamma globulin preparations.

Rubella antibody levels in commercial gamma globulin preparations. S J Millian, A Kogon, and S KleinCopyRight https://doi.org/10.2105/AJPH.61.2.353 Published Online: August 29, 2011

Clinical Evaluation of a New Intravenous Gamma Globulin.

Excerpt Existing intramuscular gamma globulin preparations cannot provide immediate replacement therapy by infusion of large doses. Previous attempts to produce an intravenous gamma globulin by aci...