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PubMed1996

Severe Guillain-Barré syndrome in childhood treated with human immune globulin.

Thirteen children with severe Guillain-Barré syndrome were treated with human immune globulin. Patients received a mean total dose of 1.9 gm/kg of human immune globulin for 2 or 5 days. To evaluate the relationship between the response to human immune globulin and electrodiagnostic findings, we compared the clinical outcome of 3 groups of children. The first group consisted of 9 children with electrophysiologic evidence of a mean amplitude of the compound motor action potentials larger than 10% of the lower limit of normal. The second group of 4 children had inexcitable motor nerves. Children in the second group required longer periods to improve one functional grade (mean 67.3 days vs 18.8 days) and to reach grade 2 (219 days vs 32.7 days). Moreover, children in the second group were more disabled after 3 and 6 months, and they all remained with distal atrophy and weakness after 7 months of follow-up. Furthermore, the outcome of children in the second group was no different from that of a historic control of 5 untreated children with severe Guillain-Barré syndrome and similar electrophysiologic findings. Human immune globulin treatment in children with severe Guillain-Barré syndrome is safe, easy to administer, and does not increase the number of relapses. Nevertheless, it does not seem to benefit children with low mean compound motor action potential amplitude.

Child↗

PubMed2006

Anti-endotoxin hyperimmune globulin attenuates portal cytokinaemia, phagocytic cell priming, and acute lung injury after lower limb ischaemia-reperfusion injury.

OBJECTIVES: Acute limb ischaemia is a common and often lethal clinical event. Reperfusion of an ischaemic limb has been shown to induce a remote gut injury associated with transmigration of endotoxin into the portal and systemic circulation, which in turn has been implicated in the conversion of the sterile inflammatory response to a sepsis syndrome, after lower torso ischaemia-reperfusion injury. This study tests the hypothesis that an anti-endotoxin hyperimmune globulin attenuates ischaemia-reperfusion (I/R) associated sepsis syndrome. DESIGN: Prospective, randomised placebo controlled trial, animal experiment. MATERIALS AND METHODS: Experimental porcine model, bilateral hind limb I/R injury, randomised to receive anti-endotoxin hyperimmune globulin or placebo. RESULTS: Bilateral hind limb I/R injury significantly increased intestinal mucosal acidosis, portal endotoxaemia, plasma cytokine (TNF-alpha, IL-6, IL-8) concentrations, circulating phagocytic cell priming and pulmonary leukosequestration, oedema, and capillary-alveolar protein leak. Conversely, pigs treated with anti-endotoxin hyperimmune globulin (IgG) 20mg/kg at onset of reperfusion had significantly reduced portal endotoxaemia, early circulating phagocytic cell priming, plasma cytokinaemia and attenuation of acute lung injury. CONCLUSIONS: Endotoxin translocation across a hyperpermeable gut barrier, phagocytic cell priming and cytokinaemia are key events of limb I/R injury induced systemic inflammation and acute lung injury. This study shows that an anti-endotoxin hyperimmune globulin attenuates portal endotoxaemia, which may reduce early phagocytic cell activation, cytokinaemia and ultimately acute lung injury.

Animals↗

PubMed2006

Acute rejection risk in kidney transplant recipients on steroid-avoidance immunosuppression receiving induction with either antithymocyte globulin or basiliximab.

Immunosuppression with rapid discontinuation of corticosteroids, usually with induction therapy, is safe in kidney transplant recipients. In 89 patients, we induced immunosuppression with basiliximab or rabbit antithymocyte globulin (17 and 72 patients, respectively). Selection criteria for basiliximab were age (>or=65 years), history (malignancy; chronic infection), and type 1 diabetes mellitus (eligible for pancreas transplant). Steroids were administered through posttransplantation day 4 (five doses); maintenance immunosuppression was with tacrolimus and mycophenolate mofetil. At last follow-up (average, 286 days), most patients were steroid-free (antithymocyte globulin, 90%; basiliximab, 88%). Protocol biopsies were performed at 1, 4, and 12 months posttransplantation. The overall risk of biopsy-proven acute rejection was 12%. At 6 months posttransplantation, acute rejection-free survival was 93% for antithymocyte globulin, 65% for basiliximab (P<.001). Median time to biopsy-proven acute rejection was 27 and 71 days, respectively. The low incidence of biopsy-proven acute rejection with steroid-avoidance immunosuppression may be further reduced with antithymocyte globulin.

Acute Disease↗

PubMed2002

Respiratory outcomes in high-risk children 7 to 10 years after prophylaxis with respiratory syncytial virus immune globulin.

PURPOSE: Respiratory syncytial virus infections have been implicated in the development of asthma. We evaluated the long-term effects of respiratory syncytial virus immune globulin, an effective prophylactic agent for the prevention of these infections in children, on respiratory and allergic outcomes in children at high risk of chronic airway disease. SUBJECTS AND METHODS: Thirteen children at high risk of respiratory disease (mean [+/-SD] age, 8.6 +/- 1.1 years) were evaluated using pulmonary function and allergy skin testing 7 to 10 years after they had received prophylaxis with respiratory syncytial virus immune globulin. For comparison, 26 high-risk control children (mean age, 8.5 +/- 0.9 years) were also evaluated. Health outcomes data were collected from all subjects. The children were matched for age and gestational age. There were more boys, and a lesser frequency of a lower respiratory tract infection with respiratory syncytial virus (P <0.001) in the group that had been treated prophylactically than in the controls. The ratio of the forced expiratory volume in 1 second to forced vital capacity was significantly better in children who had received immune globulin (median, 0.88; interquartile range, 0.81 to 0.91) than in the controls (median, 0.76; interquartile range, 0.67 to 0.86; P = 0.02). Children were also less atopic (2 of 13) in the respiratory syncytial virus immune globulin group than in the control group (13 of 26, P <0.04) and were less likely to have missed school (P = 0.006) or have had an asthma attack (P = 0.03). CONCLUSION: The results suggest that prophylaxis of respiratory syncytial virus infections in infancy may have long-term effects on respiratory and immunologic parameters relevant to the development of asthma. Larger-scale studies are needed.

Bronchial Provocation Tests↗

PubMed1997

Altered binding of serum thyroid hormone to thyroxine-binding globulin in women with functional hypothalamic amenorrhea.

OBJECTIVE: To further characterize hypothyroidemia with decreased serum concentrations of total triiodothyronine and total T4 in women with functional hypothalamic amenorrhea. DESIGN: Cohort study. SETTING: University of California San Diego Clinical Research Center. PATIENT(S): 8 women with functional hypothalamic amenorrhea (hypogonadotropic or normogonadotropic amenorrhea of at least 6 months duration) and 9 normal cycling women in the early follicular phase of their cycles. INTERVENTION(S): 24-hour frequent blood sampling. MAIN OUTCOME MEASURE(S): Comparison of levels of thyroid hormones and binding proteins between functional hypothalamic amenorrhea and normal cycling women. Measurements of serum free T4, free triiodothyronine, total T4, total triiodothyronine, reverse triiodothyronine, thyroid-binding globulin, albumin, and prealbumin levels and determination of T4 binding and binding affinity to each of the three binding proteins. RESULT(S): The results confirmed reduced levels of total triiodothyronine and total T4, but revealed no significant difference in free triiodothyronine and free T4, as well as reverse triiodothyronine, levels between functional hypothalamic amenorrhea and normal cycling women. Although serum levels of thyroid hormone-binding proteins were similar between normal cycling women and functional hypothalamic amenorrhea, a significant decrease in T4 bound to thyroid-binding globulin along with a decrease in apparent affinity of thyroid-binding globulin for T4 was present in functional hypothalamic amenorrhea. No differences in prealbumin- or albumin-T4 interactions were found. CONCLUSION(S): In functional hypothalamic amenorrhea, a reduced thyroid-binding globulin binding affinity appears to explain the disparity between normal levels of free triiodothyronine, free T4, and binding proteins in the face of reduced levels of total triiodothyronine and total T4.

Adult↗

PubMed1985

Cutaneous manifestations of serum sickness in patients receiving antithymocyte globulin.

We have prospectively evaluated the cutaneous manifestations of serum sickness in thirty-five patients treated with horse antithymocyte globulin for bone marrow failure. Twenty-one patients (21/35) were treated with antithymocyte globulin (15 mg/kg/day) for 10 days, and fourteen of thirty-five patients were treated with antithymocyte globulin (15 mg/kg/day) for 14 days and then every other day for an additional 14 days. Clinical evidence of serum sickness developed in thirty patients and included fever and malaise (100%), cutaneous eruptions (93%), arthralgias and myalgias (67%), gastrointestinal complaints (67%), and lymphadenopathy (13%). Cutaneous findings consisted of morbilliform eruptions (n = 19), urticaria (n = 1), or a combination of these two reaction patterns (n = 8). Cutaneous manifestations of serum sickness began on day 7 +/- 1 and lasted for 12 +/- 2 days for the group as a whole. Biopsies of lesional skin revealed mild perivascular lymphohistiocytic infiltrates by light microscopy in these leukopenic patients. Direct immunofluorescence microscopy of lesional skin from patients with serum sickness demonstrated immunoreactants in seven of nine subjects (78%). Immunoreactants were confined to the walls of dermal blood vessels and consisted of IgM (7/9), C3 (6/9), IgE (5/9), and IgA (4/9). IgG (horse or human) was not identified in any of these specimens. Twenty-one patients (21/28) also developed an erythematous eruption on the sides of the fingers, toes, palms, and soles 12 to 48 hours prior to their morbilliform eruption. This study describes the cutaneous manifestations of human serum sickness occurring during therapy with horse antithymocyte globulin, documents a cutaneous sign of serum sickness, and suggests that the cutaneous eruptions associated with human serum sickness are immunologically mediated.

Antilymphocyte Serum↗

PubMed1997

Immune globulins are effective in severe pediatric Guillain-Barré syndrome.

The effect of high-dose intravenous immune globulins was evaluated in an open prospective multicenter study of 26 children with severe Guillain-Barré syndrome. They presented with mild to moderate flaccid weakness of extremities, with cranial nerve involvement (20) and sensory impairment (22). All children rapidly deteriorated in 2-16 days (mean 6) to become bedridden, and 2 children also developed respiratory failure requiring artificial ventilation (Disability Grading Scale 4-5). Immune globulins were then administered at a total dose of 2 gm/kg, on 2 consecutive days, without adverse effects requiring discontinuation of therapy. Marked and rapid improvement was noted in 25 children, who improved by 1 to 2 Disability Grade Scales < or = 2 weeks after the infusion. Twenty were able to walk independently by 1 week, and 1 could be weaned off a ventilator. Eighteen children recovered by 2 weeks. The rest recuperated in a period of four months, including a child who was artificially ventilated for 4 weeks. The uniform rapid improvement and recovery associated with immune globulins contrasts with the slow recovery course in severe natural cases. We conclude that immune globulins are effective and safe in severe childhood-onset Guillain-Barré syndrome and therefore may serve as the initial treatment of choice.

Adolescent↗

PubMed2002

Functional properties of oat globulin modified by a calcium-independent microbial transglutaminase.

Oat globulin was modified by a calcium-independent microbial transglutaminase (TG). The TG-polymerized protein had higher solubility than the control at acidic pH and had improved water- and fat-binding properties. Incubation of 10% (w/v) oat globulin dispersions in the presence of TG at 37 degrees C led to the formation of a well-developed viscoelastic gel network with a microstructure characterized by thick strands and large clusters. The TG-induced gels had higher modulus values, lower loss tangent values, and lower frequency dependency than the heat-induced gels. The TG-induced gel system has the characteristics of classical polymer gel with permanent "chemical" cross-links, whereas the heat-denatured system has the characteristics of a temporary "physical" gel with breakable cross-links. Fourier transform infrared spectroscopy showed marked shift and intensity changes in several major bands, suggesting pronounced changes in protein conformation during TG-induced gelation. Aggregation of protein molecules was also indicated by the progressive increases in two infrared bands (1679-1682 and 1622-1625 cm(-)(1)) associated with the formation of intermolecular beta-sheets and strands. Results suggest that new food polymers with unique functionality can be produced from oat globulin treated with TG and that elastic gels can be formed near neutral pH, instead of the alkaline pH required for thermally induced oat globulin gels.

Avena↗

PubMed2003

Nutritional and physiological responses of young growing rats to diets containing raw cowpea seed meal, protein isolate (globulins), or starch.

The nutritional and physiological effects of raw cowpea (Vigna unguiculata (L) Walp.) seed meal, protein isolate (globulins), or starch on the metabolism of young growing rats have been evaluated in 14-day trials. Wet and dry weight gain, feed conversion efficiency, and lipid and protein accretion were significantly reduced as a result of inclusion of seed meal, globulins, or starch in the diet, with growth retardation being most marked with the seed meal. The proportional weights of the small intestine and pancreas were increased by meal diets, and serum cholesterol levels were slightly reduced. The globulins and raw starch also increased relative small intestine weights but had no effect on the pancreas or serum constituents. The effects of cowpeas on rats appeared to be due primarily to the combined actions of globulins, resistant starches, protease inhibitors, and possibly fiber and non-starch polysaccharides on intestinal and systemic metabolism.

Animal Nutritional Physiological Phenomena↗

PubMed2004

Effect of pH and ionic strength modifications on thermal denaturation of the 11S globulin of sunflower (Helianthus annuus).

Helianthinin, the main storage protein of sunflowers, has low water solubility and does not form a gel when heated; this behavior is different from other 11S globulins and limits its food applications. To understand this particular behavior, changes on helianthinin association-dissociation state induced by modifications in pH and ionic strength were analyzed. The influence of these different medium conditions on its thermal stability and tendency to form aggregates was also studied. Helianthinin behavior at different pH values and ionic strengths is similar to other 11S globulins except that it remains in a trimeric form at pH 11. Helianthinin thermal stability is higher than other 11S globulins but is lower than oat 11S globulin. Alkaline pH produces a 10 degrees C decrease of its denaturation temperature and also of the cooperativity of denaturation process, but it does not affect the denaturation activation energy. The decrease in thermal stability with the pH increase is also manifested by its tendency to form aggregates by SH/SS interchange reactions. When thermal treatments at alkaline pH are performed, all helianthinin subunits form aggregates, characterized by a higher proportion of beta-polypeptides than alpha-polypeptides, which is an indication that aggregation is accompanied by dissociation. Treatments at 80 degrees C are sufficient to induce aggregation but not to produce denaturation, and in these conditions hexameric forms remain after the treatment.

2S Albumins, Plant↗

PubMed2006

Gene families encoding isoforms of two major sesame seed storage proteins, 11S globulin and 2S albumin.

Sesame (Sesamum indicum L.) seed has been recognized as a nutritional protein source owing to its richness in methionine. Storage proteins have been implicated in allergenic responses to sesame consumption. Two abundant storage proteins, 11S globulin and 2S albumin, constitute 60-70 and 15-25% of total sesame proteins, respectively. Two gene families separately encoding four 11S globulin and three 2S albumin isoforms were identified in a database search of 3328 expressed sequence tag (EST) sequences from maturing sesame seeds. Full-length cDNA sequences derived from these two gene families were completed by PCR using a maturing sesame cDNA library as the template. The amino acid compositions of these deduced storage proteins revealed that the richness in methionine is attributed mainly to two 2S albumin isoforms and partly to one 11S globulin isoform. The presence of four 11S globulin and three 2S albumin isoforms resolved in SDS-PAGE was confirmed by MALDI-MS analyses. The abundance of these isoforms was in accord with the occurrence frequency of their EST sequences in the database. A comprehensive understanding of these storage proteins at the molecular level may also facilitate the identification of allergens in crude sesame products that have caused severe allergic reactions increasingly reported in the past decade.

Albumins↗

PubMed2003

The addition of sirolimus to cyclosporine and steroids inhibits the anti-equine antibody response in renal transplant recipients treated with antithymocyte globulin.

Polyclonal antibodies, such as equine antithymocyte globulin (ATGAM), are known to induce antibody formation. This study evaluated the in vivo effect of sirolimus on antibody formation associated with the use of equine antithymocyte globulin in renal transplant recipients. Recipients of either a living-related donor or cadaveric renal allograft received azathioprine (AZA) (n = 15), mycophenolate mofetil (MMF) (n = 12), or sirolimus (n = 15) in addition to baseline immunosuppression with corticosteroids, cyclosporine, and equine antithymocyte globulin. Immediately before transplantation and weekly for at least 1 month, sequential serum specimens were tested for the presence of human anti-equine antibody using an enzyme-linked immunosorbent assay (ELISA). Anti-equine antibody formation was significantly different among the three treatment groups. Fewer patients receiving MMF (17%, p = 0.007 vs. AZA) and sirolimus (13%, p = 0.003 vs. AZA) developed anti-equine antibody compared with AZA (66%). There was no significant difference (p = 0.81) in the sensitization to equine antithymocyte globulin when comparing the patients receiving MMF or sirolimus. In the sensitized patients, high anti-equine antibody titers (>1 : 500) were more common in those receiving AZA (n = 3) than MMF (n = 0) or sirolimus (n = 1). Compared to AZA, sirolimus, when given in combination with cyclosporine A, significantly reduced anti-equine antibody formation to a degree similar to MMF.

Adrenal Cortex Hormones↗

PubMedDate not supplied

Removal of anticomplementary activity from human immune serum globulins by treatment with purified human plasmin.

Human immune serum globulin preparations were treated with highly purified human plasmin to remove their anticomplementary activity. The extent of anticomplementary activity removed and the amount of fragmentation obtained from immune serum globulin preparation depended upon the amount of plasmin added and the length of incubation time. The enzymatic reaction was stopped by removing plasmin with bentonite adsorption. Two types of plasmin-treated immune serum globulin that may be used for intravenous injection were obtained. One was a more fragmented product (35 to 45%) with lower anticomplementary activity, the other was a less degraded product (15 to 20%) with slightly higher anticomplementary activity. Antibody content of the former preparation was somewhat reduced while that of the latter preparation was virtually unchanged from the untreated immune serum globulin.

Complement System Proteins↗

PubMed1990

Hemolysis after intravenous immune globulin therapy: relation to IgG subclasses of red cell antibody.

A patient with chronic idiopathic thrombocytopenic purpura (ITP), a 28-year-old group A, Rh-positive woman, also had hemolytic anemia. At that time, her red cells typed as group A, but the serum typed as group O. This typing followed intravenous high-dose immune globulin therapy, (400 mg/kg for 5 successive days) and was attributable to A antibody of the IgG type, composed of IgG1, IgG2, IgG3, and IgG4, in the immune globulin preparation, which had been given for treatment of ITP. All lots of commercial human plasma preparation products (heat-treated human plasma protein, albumin, factor VIII or IX products, and immune globulin) examined were found to contain A and/or B antibodies of the IgM or IgG type, with titers of 1 to 1024. Twelve of the 20 lots of immune globulin contained RBC antibodies of the IgG type. Subclass IgG1 was found in all 12 of these lots, and all four subclasses, including IgG3, were detected in 8 lots. All 8 showed antibody titers higher than 64.

ABO Blood-Group System↗

PubMed1975

Hepatitis B immune globulin--prevention of hepatitis from accidental exposure among medical personnel.

The role of anti-HBs antibody in reducing the probability of hepatitis after accidental exposure to serum from patients with hepatitis or carriers of HBs Ag was studied prospectively among 712 medical workers. One fourth of the workers were anti-HBs positive and less than one per cent of them developed hepatitis, in contrast to 11 per cent among those who were anti-HBs negative. Three coded immune-serum globulin preparations of varying anti-HBs titer were randomly assigned. Among 251 persons passively immunized with globulin having a conventionally low anti-HBs titer, hepatitis developed in 17 (seven per cent) within six months. Comparative rates among those receiving intermediately high titer and high titer globulin, respectively, were five per cent (11 of 208) and two per cent (5 of 253). The significantly lower incidence among the latter (P less than 0.05) was offset by six additional cases, all in recipients of high titer globulin, detected when follow-up was extended to nine months.

Adult↗

PubMed1993

A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis.

BACKGROUND: Dermatomyositis is a clinically distinct myopathy characterized by rash and a complement-mediated microangiopathy that results in the destruction of muscle fibers. In some patients the condition becomes resistant to therapy and causes severe physical disabilities. METHODS: We conducted a double-blind, placebo-controlled study of 15 patients (age, 18 to 55 years) with biopsy-proved, treatment-resistant dermatomyositis. The patients continued to receive prednisone (mean daily dose, 25 mg) and were randomly assigned to receive one infusion of immune globulin (2 g per kilogram of body weight) or placebo per month for three months, with the option of crossing over to the alternative therapy for three more months. Clinical response was gauged by assessing muscle strength, neuromuscular symptoms, and changes in the rash. Changes in immune-mediated muscle abnormalities were determined by repeated muscle biopsies. RESULTS: The eight patients assigned to immune globulin had a significant improvement in sores of muscle strength (P < 0.018) and neuromuscular symptoms (P < 0.035), whereas the seven patients assigned to placebo did not. With crossovers a total of 12 patients received immune globulin. Of these, nine with severe disabilities had a major improvement to nearly normal function. Their mean muscle-strength scores increased from 74.5 to 84.7, and their neuromuscular symptoms improved. Two of the other three patients had mild improvement, and one had no change in his condition. Of 11 placebo-treated patients, none had a major improvement, 3 had mild improvement, 3 had no change in their condition, and 5 had worsening of their condition. Repeated biopsies in five patients of muscles whose strength improved to almost normal showed an increase in muscle-fiber diameter (P < 0.04), an increase in the number and a decrease in the diameter of capillaries (P < 0.01), resolution of complement deposits on capillaries, and a reduction in the expression of intercellular adhesion molecule 1 and major-histocompatibility-complex class I antigens. CONCLUSIONS: High-dose intravenous immune globulin is a safe and effective treatment for refractory dermatomyositis.

Adolescent↗

PubMed2000

Abnormal myocardial mechanics in Kawasaki disease: rapid response to gamma-globulin.

BACKGROUND: The time course and rate of recovery of myocardial dysfunction in association with Kawasaki disease in response to intravenous gamma-globulin is unknown and may provide mechanistic clues. METHODS AND RESULTS: The acute changes in myocardial contractility in 25 patients with Kawasaki disease were evaluated by noninvasive stress-shortening and stress-velocity analysis. Echocardiograms were performed before and then daily for 4 days during which the patients received gamma-globulin 1.6 to 2 g/kg. Before treatment, contractility was abnormally low (<2 SD) in 14 patients (56%). Contractility increased significantly (2 SD increase) in 17 (68%), including 13 of 14 with depressed contractility and 4 whose initial contractility fell within normal limits. Of the 14 patients with depressed contractility, 8 (57%) normalized within 24 hours and a further 5 (35.7%) normalized within 6 months. A clinical response to treatment (fall in C-reactive protein by 50% and/or resolution of fever within 4 days) was seen in 22 patients (88%). Contractility increased in 17 of the 22 clinical responders and was normal before therapy in the other 5. The 3 patients who did not respond clinically also had no change in contractility with gamma-globulin therapy. Long-term (more than 12 months) follow-up was available in 19 patients. All patients had normal contractility at late follow-up. CONCLUSIONS: More than half the patients with Kawasaki disease have abnormal contractility at presentation. Myocardial response to gamma-globulin therapy is associated with rapid improvement in myocardial mechanics, with a high concordance between the clinical and myocardial response to therapy. The speed of recovery suggests that depressed contractility in patients with Kawasaki disease is caused by a rapidly reversible process such as circulating toxins or activated cytokines. Long-term outcome is good even in those patients with slow recovery of myocardial function.

Child, Preschool↗

PubMed1976

Photoaffinity site-specific covalent labeling of human corticosteroid-binding globulin.

A method was developed for the synthesis of high-specific-activity 21-diazo-21-[6,7-(3)H]deoxycorticosterone, an analog of corticosterone. This analog was used as a photoaffinity label of a high affinity steroid-binding protein, human corticosteroid-binding globulin. Based on direct binding studies and crosscompetition experiments, this diazo derivative exhibited the requisite affinity (within a factor of 1.5 times that of corticosterone) and site specificity to qualify as an affinity labeling legand. Irradiation of corticosteroid-binding globulin with the 21-diazo derivative resulted in irreversible binding to corticosteroid-binding globulin, identified by polyacrylamide gel electrophoresis. Specificity of covalent binding to corticosteroid-binding globulin was established by competition analysis with various steroids. Irreversibility of photodependent binding was shown by persistence of the complex on electrophoresis (in contrast to the noncovalently linked complex), and resistance to exchange with corticosterone or pregnanediol and to solvent extraction. Site specificity of covalent binding was inferred from the effects of a scavenger, Tris-HC1, and fluorescence quenching of a neighboring tryptophan.

Affinity Labels↗