Rise In Immunoglobulin Research Articles

Long term prognosis of patients with cystic fibrosis in relation to early detection by neonatal screening and treatment in a cystic fibrosis centre.

A study was undertaken to evaluate whether an early diagnosis by neonatal screening may improve the long term prognosis of patients with cystic fibrosis and to assess the influence of expert management started immediately after the diagnosis. Comparative clinical follow up in three birth cohorts of patients with cystic fibrosis was performed at the Cystic Fibrosis centre in Groningen in close collaboration with paediatricians in general hospitals in the north-eastern part of the Netherlands. The first birth cohort (n = 19) was detected by screening and the two other cohorts were detected clinically, one (n = 30) consisting of patients born during the screening programme and the other (n = 32) of patients born during the six years immediately after the screening programme ended. The total number of patients in the three birth cohorts included all patients with cystic fibrosis born in this area during a 12 year period. Cumulative survival rates and the variation with time of lung function, the levels of immunoglobulins, and growth patterns were used as main outcome measures. Patients born during the screening programme but detected clinically appeared to have a reduced life expectancy compared with patients detected by screening. The patients detected by screening showed less deterioration in lung function (annual decrease 1.2% of FEV1 % pred), a smaller increase in immunoglobulin levels, and minimal catch-up growth compared with an annual decrease of 3.25% of FEV1 % pred in the non-screened birth cohort of the same age, a higher rise in immunoglobulins leading to increased levels at the end of the observation period, and catch-up growth for weight as well as height. Differences between patients treated in a cystic fibrosis centre and those not referred to a specialist centre were smaller but similar, in favour of treatment at a cystic fibrosis clinic. Expert management started immediately after an early diagnosis of cystic fibrosis by neonatal screening results in important beneficial effects on the outcome and clinical course of the condition. The institution of very early treatment may be critical for the outcome and long term prognosis for most patients with cystic fibrosis. Neonatal screening programmes for cystic fibrosis should be introduced more widely.

Octavalent Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine

An octavalent Pseudomonas aeruginosa conjugate vaccine was synthesized by covalently coupling the O-polysaccharide (O-PS) moiety derived from lipopolysaccharides of Habs serotypes 1, 2, 3, 4, 5, 6, 11 and 12 to toxin A. Adipic acid dihydrazide was used as a spacer molecule to facilitate conjugation. The vaccine was composed of 37% (w/w) O-PS and 63% toxin A, devoid of enzymatic activity characteristic of toxin A, non-toxic for mice and guinea pigs, and non-pyrogenic. The vaccine elicited a significant rise in immunoglobulin G antibody levels to all serotypes of lipopolysaccharide contained in the vaccine and to toxin A. Serotypes 6, 10 and 11 were most immunogenic in mice whereas serotypes 1 and 5 engendered the lowest antibody response. Antitoxin A antibody was able to neutralize the cytotoxicity of toxin A. Immunization of mice with the vaccine conferred significant protection against subsequent challenge with all P. aeruginosa serotype strains contained in the vaccine.

Effect of cholecystokinin and of its antagonist, of atropine, and of food on the release of immunoglobulin A and immunoglobulin G specific antibodies in the rat intestine

Cholecystokinin has previously been shown to produce a rise in immunoglobulin A (IgA) antibodies in the intestinal fluid of human volunteers. Whether the source of these antibodies was pancreatic, biliary, or mucosal had not been defined. The object of the present investigation was to study factors involved in regulating the release of IgA and IgG antibodies from the intestinal mucosa. Hooded-Lister rats were sensitized to ovalbumin. After the sensitization protocol, which lasted 21 days, the rats were anesthetized and a segment of intestine 10 cm long was isolated and perfused in vivo. This segment was flushed with normal saline for 30 min to remove all pancreatic, biliary, and other secretions. It was found in this model that after the intravenous injection of cholecystokinin-octapeptide there was a rise of IgA and IgG antibodies within 2.5 min. Significantly increased secretion of IgA lasted for 10 min, and increased secretion of IgG lasted for 20 min. The cholecystokinin antagonist proglumide reduced the secretions of both immunoglobulins. Atropine reduced baseline IgA secretion by one-half. Intragastric protein hydrolysate, which left the body through the severed end of the duodenum, also raised IgA and IgG levels significantly in the perfused intestine. Control animals receiving intragastric normal saline did not have an elevation of IgA or IgG levels. The phenomena described here demonstrate that the rate of IgA release from the mucosa is influenced by endocrine and nervous stimuli. The rate of IgG release is, as far as could be ascertained, only under endocrine control and not significantly influenced by the cholinergic antagonist atropine.

Frozen deglycerolyzed blood prevents transfusion-acquired cytomegalovirus infections in neonates.

Frozen deglycerolyzed blood (FDB) was used for routine transfusions to 63 low birth weight newborns (less than or equal to 1500 g) over a 12-month period in an effort to decrease transfusion-acquired cytomegalovirus (CMV) infections. Nine of the 63 infants also received nonfrozen blood products (platelets, liquid blood). Seventy-two percent of the donor blood units were CMV-seropositive. Urine cultures and serum titers for anti-CMV antibody (immunoglobulins G and M) were obtained prior to the initial transfusion and sequentially throughout the study. No infant (0 of 54) who received only FDB acquired CMV, whereas 3 of 9 infants (33%) who received non-frozen blood and FDB acquired CMV, as evidenced by CMV viruria and/or a 4-fold rise in immunoglobulin G anti-CMV antibody titers. These results suggest that transfusions with frozen deglycerolyzed blood decrease the risk in low birth weight infants of acquiring CMV, regardless of the CMV serologic status of the donor.

Immunoglobulins in prolonged ruptured membranes

Concentrations of immunoglobulins G, M, and A were studied in maternal and cord serum of patients with prolonged premature rupture of membranes, as well as in properly matched control patients. None of the patients studied showed any evidence of clinical chorioamnionitis or other prenatal infections. Cases were divided into term premature rupture of membranes and term controls and preterm (<34 gestational weeks) premature rupture of membranes and preterm controls. In the term group, with 12 to 24 hours of premature rupture of membranes, maternal immunoglobulins M and A, and cord immunoglobulin A were significantly increased. With a duration of premature rupture of membranes of more than 24 hours, levels of immunoglobulins M and A in maternal serum and levels of immunoglobulins G and A in cord serum showed significant elevations. Levels of cord immunoglobulin M from both subgroups of patients with premature rupture of membranes showed a trend upward but were not significantly higher than those in control patients. In the preterm group, with 12 to 24 hours of premature rupture of membranes, only cord immunoglobulin A was significantly increased. With premature rupture of membranes of ≥72 hours, only maternal immunoglobulin G increased significantly and remained elevated; immunoglobulins M and A in cord serum were also significantly increased. The significant rise in immunoglobulins in patients with premature rupture of membranes may indicate subclinical maternal and fetal infection. This suggests the possibility that subclinical infections may play a role in the etiology of premature rupture of membranes.

Pancreozymin and Secretin Enhance Duodenal Fluid Antibody Levels to Cow's Milk Proteins

Duodenal fluid was collected from normal volunteers before and after stimulation with pancreozymin-cholecystokinin and secretin. Protein content, proteolytic enzyme activities, and antibody activities against cow's milk proteins, alpha-casein, and beta-lactoglobulin B, were measured in the duodenal fluid. After pancreozymin-cholecystokinin stimulation, immunoglobulin A and immunoglobulin M antibody activities rose to peak levels in 5-10 min. The increase in protein content and proteolytic enzyme activities after pancreozymin-cholecystokinin stimulation paralleled the increase in antibody activity against the two cow's milk proteins. Secretin, in spite of its known dilutional effect on duodenal fluid enzyme concentration, also produced a rise in immunoglobulin M and immunoglobulin A antibody activities. Only a slight increase in immunoglobulin G antibody activity was noted after both pancreozymin-cholecystokinin and secretin. It is suggested that, pancreozymin-cholecystokinin and secretin, in addition to their well-established effects on the release of digestive enzymes, also stimulate release of specific antibodies against food proteins. Release of antibody coincident with food intake may act in preventing the inadvertent absorption of antigenic food proteins.

Lymphocyte Subpopulations in Chronic Lymphocytic Leukemia (CLL)

The blood lymphocytosis in CLL is caused mainly by a rise of immunoglobulin (Ig)-bearing leukemic lymphocytes. Most cells carry Fc-receptors, while the percentage with receptors for human complement is very low with the present technique. The leukemic lymphocytes carry only one of the light chain types, which suggests a monoclonal origin. CLL patients with lymphocytes expressing kappa light chains may have a more benign disease than lambda-CLL. T-lymphocyte levels are high during the early course of the disease but decrease with its progression and are low in patients with "active" disease.

Does nonspecific T-lymphocyte stimulation of B lymphocytes occur during reversal reaction in borderline leprosy?

Serum immunoglobulins G, A, and M were estimated in 14 patients with border-line cases of leprosy at commencement of treatment and subsequently when they developed 'reversal reaction'. There was a significant increase in all immunoglobulin levels during the reaction, with a subsequent fall; the postreaction values for IgG and IgA were below the base-line figures. Additonal investigations in six patients indicated that the rise was a nonspecific one, not brought about by an increase in antimycobacterial antibodies. It seems likely that the rise in immunoglobulins during reaction is due to nonspecific T-lymphocyte stimulation of B lymphocytes.