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N Rautonen

Publications and source records attributed to N Rautonen.

28 records · Page 2Linked to original sources

Serum interleukin-6 concentrations are elevated and associated with elevated tumor necrosis factor-alpha and immunoglobulin G and A concentrations in children with HIV infection.

Hypergammaglobulinemia is one of the most consistent, and usually the first observable abnormality in infants vertically infected with HIV. We have analyzed serum interleukin (IL)-4, IL-6, tumor necrosis factor (TNF)-alpha, and immunoglobulin (Ig) concentrations in 23 HIV-infected and 21 uninfected children. IL-6 and TNF-alpha concentrations in HIV-infected children were significantly higher than those in uninfected children, and mutually correlated. No differences in serum IL-4 levels between infected and uninfected children were observed. There was a correlation between serum IL-6 and IgG and between IL-6 and IgA concentrations. Furthermore, during follow-up changes in IL-6 levels were usually accompanied by corresponding changes in IgG levels. Our data indicate an association between HIV, IL-6, TNF-alpha and hypergammaglobulinemia. Regardless of the source and initial stimulus, continued production of IL-6 and TNF-alpha may result in augmentation in an auto-feedback manner, accompanied by increases in Ig synthesis and, more importantly, HIV replication. Thus, elucidation of the mechanisms responsible for overproduction of these two cytokines in HIV-infected patients is not only interesting from a biologic point of view, but is likely to have important clinical implications as well.

B-Lymphocytes↗

Antibodies to gliadin in children with coeliac disease.

We have measured antibodies to gliadin (AGA), bovine beta-lactoglobulin, and chicken egg ovalbumin with a four-layer solid phase radioimmunoassay (RIA) in 62 children and adolescents with coeliac disease and in 36 healthy controls. The geometric mean titre of IgG AGA in patients at initial diagnosis was more than 100-fold that of controls (p less than 0.0001). Even patients on gluten-free diet had significantly higher IgG AGA titres than the controls (p = 0.0001), the difference being more than 5-fold. All the 42 patients with active disease (30 at initial diagnosis and 12 after gluten challenge) had their IgG AGA titre above 1,000, as compared with 2 (5.7%) of the 35 controls (p less than 0.0001). Both IgG and IgA AGA were quite sensitive and specific in identifying children with coeliac disease; the sensitivities for IgG and IgA AGA were 100% and 95.2%, the specificities 94.3% and 97.2%, respectively. We conclude that determination of IgG and IgA AGA with RIA is suitable for monitoring dietary compliance in children with coeliac disease, and the method is sensitive and specific for screening for coeliac disease in children.

Adolescent↗

Effect of Gm allotypes on IgG2 antibody responses and IgG2 concentrations in children and adults.

Earlier studies have suggested that in adults the n-positive allele of the human IgG2 gene is more productive than the n-negative allele. This superiority was seen to be manifested in IgG2 antibody responses to polysaccharides, in the higher serum concentration of total IgG2 in the n/n than in -/- individuals, and in the higher concentration of n-positive than n-negative IgG2 in heterozygotes. The present study shows that in 1- or 2-year-old children, the concentration of IgG2 was independent of allotype G2m(n), and both alleles of a heterozygote contributed an average of one-half of the total IgG2. On the other hand, the superiority of the n-positive allele was also seen in young children in IgG2 antibody responses induced by the Haemophilus influenzae type b polysaccharide (Hib). The effect of allotype n on antibody responses was evident only when the immunogen was the Hib polysaccharide. When the immunogen was a conjugate of Hib and diphtheria toxoid, the IgG2 antibody responses of n-positive and n-negative vaccinated individuals were almost equal, both in adults and in children.

Adult↗

Influence of the G2m(n) allotype and age on IgG subclass distribution in antibodies to dietary proteins in children with coeliac disease.

In 47 children with coeliac disease, IgG1 was the dominant IgG subclass (mean 61%) in antibodies to gliadin, a protein component of wheat; IgG2 (22%) and IgG3 (15%) were also found. Very little IgG4 (3%) was detected. Both G2m(n)allotype and the age of the patient had an independent effect on the subclass distribution. The effects of these two factors seem similar to those described earlier on responses to polysaccharides; both G2m(n) and age increase the expression of IgG2 antibodies and concomitantly the share of IgG1 is decreased. The average increase in the share of IgG2 brought about by n/n-genotype was 25.3% (95% confidence limits 12.2-38.4%; P less than 0.001) and that brought about by each additional year of age of the patient 1.1% (0.3-1.9%; P = 0.006). IgG antibodies to beta-lactoglobulin and ovalbumin consisted mainly of IgG1 and IgG4. The titres of the IgG subclasses were low and in many cases below detection level. No association with G2m(n) genotype and share of IgG1 or IgG4 could be demonstrated. Age was inversely correlated with the shares of IgG1 in antibodies to beta-lactoglobulin and ovalbumin.

Adolescent↗

One allele [G2m(n)] of the human IgG2 locus is more productive than the other.

Earlier investigators have shown that a high serum concentration of IgG2 and a high IgG2 antibody response to several polysaccharide antigens is associated with the allotype G2m(n) of the IgG2 subclass. We now show that the total IgG2 concentrations are significantly higher in G2m(n) than in G2m(-n) homozygotes (difference of means was 1.26-fold, p = 0.002). Furthermore, in G2m(n) heterozygotes, the G2m(n) allele contributed more than the G2m(-n) allele to specific IgG2 antibody responses and to the total IgG2.

Alleles↗

IgG subclasses of pneumococcal antibodies--effect of allotype G2m(n).

Antibody responses to three pneumococcal polysaccharides (types 3, 14, and 18C) were analysed after vaccination with a 23-valent polysaccharide vaccine. Antibodies to all three polysaccharides could be detected before immunization. Clear cut IgG, IgA, and/or IgM antibody responses to the polysaccharides were seen in three-quarters of the vaccinees. IgG2 was the predominant and IgG1 the second most abundant subclass of anti-pneumococcal IgG antibodies both before and after the vaccination. The relative proportions of IgG2 and IgG1 antibodies exhibited a continuous variation from 1:0 to approximately 0:2. After vaccination, G2m(n)-positive homozygotes had about four times more IgG2 antibodies (anti-14 and anti-18C) than G2m(n)-negative vaccinees. Heterozygotes occupied an intermediate position. The same pattern was seen less clearly in type 3 antibodies after vaccination, and in all three antibodies before vaccination. The G2m(n) allotypes had no detectable effect on the levels of IgG1, IgG4, or IgM antibodies, and possibly a weak effect on IgG3 and IgA antibodies (G2m(n)-positive homozygotes responded strongly).

Adolescent↗

Determination of homozygosity or heterozygosity for the G2m(n) allotype by a monoclonal, precipitating antibody.

Monoclonal antibody SH 21 was found to be a good anti-IgG2m(n) reagent both for the conventional typing (HA inhibition) and for precipitation in polyethylene glycol containing gel. Antibody SH 21, together with monoclonal antibody HP 6014 (anti-IgG2), was used for the discrimination between G2m(+n) homozygotes and heterozygotes in a double diffusion assay, where the two antibodies and a serum sample were placed in corners of a triangle. In the case of a homozygote SH 21 was able to stop the diffusion of IgG2 to a precipitation line, but some IgG2 of a heterozygote was able to diffuse beyond the precipitate, forming a crossed precipitation pattern. The validity of the typing was checked with serum samples from 54 families. All the 33 'obligatory heterozygotes' (G2m(+n) parent(s) of a G2m(-n) child, or the other way round) exhibited the crossed precipitate. The frequency of the G2mn allele in a Finnish population of 297 unrelated adults was 0.409.

Alleles↗

Isotype concentrations of human antibodies to Haemophilus influenzae type b polysaccharide (Hib) in young adults immunized with the polysaccharide as such or conjugated to a protein (diphtheria toxoid).

Antibody responses of young adults to Haemophilus influenzae type b polysaccharide (Hib) or its protein conjugate were studied with special attention to the isotype composition of the antibodies. Three conclusions of interest can be made: 1) Immunoglobulin G (IgG) antibodies in polysaccharide-immunized volunteers displayed the subclass pattern previously found in antibodies to meningococcal type A polysaccharide. IgG1 was the predominant subclass in IgG antibodies of some individuals, IgG2 in others. Still others had the two subclasses in varying but more even proportions. 2) The conjugate vaccine induced a geometric mean response 2 to 3 times higher and an IgG response 4 times higher to Hib than the polysaccharide vaccine. 3) Anti-Hib antibodies induced by the conjugate vaccine still had essentially the same IgG subclass composition as anti-Hib antibodies induced by the polysaccharide. This composition was strikingly different from the composition of the anti-diphtheria toxoid response induced by the same conjugate vaccine.

Antibodies, Bacterial↗

Isotype concentrations of human antibodies to group A meningococcal polysaccharide.

Antibodies to meningococcal group A polysaccharide (MenA) in the sera of 34 vaccinated adults were quantitated by an isotype-resolving solid-phase RIA (IgA, IgM, IgG1, IgG2, IgG3, and IgG4). All individuals had antibodies before vaccination. The geometric mean concentration was 2.9 micrograms/ml. Two weeks after vaccination the mean antibody concentration had trebled. Average proportions of the three isotypes were then as follows: IgA 15%, IgM 48%, IgG 37%. No differences were found between individuals who had been immunized with the polysaccharide 7 to 8 yr earlier and "primary responders." The subclass composition of IgG antibodies was determined in the 24 postvaccination samples with a definite IgG response (greater than 2-fold increase). IgG1 was the predominant subclass in antibodies of some sera and IgG2 in others, but the average proportions of both subclasses were nearly the same. IgG3 and IgG4 were only found in occasional sera, but when present, each subclass accounted for up to 6%. Although the ratio of kappa and lambda chains could not be determined, there was evidence to suggest that it was higher in anti-MenA antibodies than in antibodies to protein antigens.

Adult↗