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Biomedical subjects

R Söderström

Publications and source records attributed to R Söderström.

At least 19 recordsLinked to original sources
PubMed1994

Qualitative and quantitative analyses of the antibody response elicited by Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugates in adults with IgG subclass deficiencies and frequent infections.

Twenty-one IgG subclass-deficient adult patients with repeated infections of the respiratory tract, were immunized with Haemophilus influenzae type b capsular polysaccharide (HibCP) covalently bound to tetanus toxoid (TT). Specific immunoglobulin and IgG subclasses to HibCP and TT were quantified; the biological activities of HibCP antibodies were also investigated. Most patients showed an antibody response similar to that observed in healthy adults, and the bactericidal activity related to the post-immunization levels of HibCP antibodies. No relation was found between immunoglobulin isotype deficiency, the clinical symptoms and the IgG subclass responsiveness, and no relation was observed between HibCP and TT antibody responses. Our data indicate that some, but not all, patients with recurrent infections and IgG subclass deficiency have an abnormal serum antibody response to polysaccharide and protein epitopes of Hib-TT conjugate vaccine. Analysis of the antibody response after vaccination with HibCP-TT conjugate vaccine did not seem to predict the clinical course of such patients.

Adult↗
PubMed1992

Herpesvirus serology, aberrant specific immunoglobulin G2 and G3 subclass patterns and Gm allotypes in individuals with low levels of IgG3.

One objective of this study was to determine whether IgG3-deficient individuals have an increased frequency of reactivated herpesvirus infections. Serum titres to Epstein-Barr virus (EBV) and human herpesvirus-6 were examined in 10 healthy and in 10 symptomatic persons with serum IgG3 < 0.1 g/l. Atypical titres were found in 16% of the IgG3-deficient individuals. Reactivations of these viruses thus do not seem common in IgG3 deficiency. Antigen-specific IgG responses were also determined. A lowered frequency of IgG3 to an EBV-derived peptide was found only in symptomatic, IgG3-deficient individuals. Levels of IgG2 to a bacterial polysaccharide were lowered in the same group, despite normal serum levels of total IgG2. A functional IgG2 deficiency may contribute to symptoms in IgG3 deficiency. The G3(g) allotype, known to be associated with low total IgG3, dominated in IgG3-deficient persons (13/17) independently of presence or absence of symptoms. A linkage of G3(g) to the G2(n) negative allotype, associated with low IgG2, was equally common irrespective of symptoms. G3(g) and absence of G2(n) seem to be one prerequisite for most of IgG3 deficiency combined with low specific IgG2.

Antibodies, Viral↗
PubMed1991

Immunoglobulin subclasses and prophylactic use of immunoglobulin in immunoglobulin G subclass deficiency.

Persistent low serum levels of one or several immunoglobulin G (IgG) subclasses can be found in a high proportion of adult patients with increased susceptibility to infections. It is hard to envision that the low subclass level in itself is responsible for this susceptibility because healthy blood donors have been described who are completely devoid of certain subclasses in serum. This apparent discrepancy may be partly explained by the observation that most subclass-deficient patients have underlying aberrations in T-cell and B-cell interaction and function that may impair their capacity to compensate for even minor deficiencies. A prospective blind crossover study of the effect of prophylactic Ig substitution therapy was done in 43 adult patients with IgG subclass deficiency. The patients were randomized to receive 1 year of therapy with intramuscular Ig 25 mg/kg/wk or 1 year of saline injections. A significant protective effect of the prophylactic Ig therapy was seen with a great reduction in the number of days of infection. In addition, several immunologic parameters were altered after 1 year of Ig therapy. Nineteen of the patients later were included in an open study using 50 mg/kg/wk of Ig. After 6 months of treatment, significant protection against infection was observed, with a reduction of 6.2 days in the number of days per month with infection. This marked effect of prophylactic Ig suggests that the Ig aberrations seen in IgG subclass-deficient patients contributed to their susceptibility to infection. The effect of 25 mg/kg/wk was much less pronounced than that of 50 mg/kg/wk, and normal serum IgG subclass levels were not achieved even during the higher-dose therapy. However, it seems likely that subcutaneous or intravenous administration of larger doses of Ig would allow for more efficient therapy.

Adult↗
PubMed1991

IgG subclass deficiency with or without IgA deficiency.

IgG subclass deficiency (IgGSD) is difficult to define since reference materials vary between laboratories and the clinically relevant cut off levels for the various subclasses are not well known. The diagnosis of IgGSD should be based on more than one determination since the levels vary, due to various factors such as infections, operations, etc. There is a relation between IgGSD and occurrence of frequent infections, but at the same time even total lack of a subclass can be seen in healthy individuals. Infections in the upper and lower respiratory tract predominate. Gm allotypes influence IgG subclass levels. Most IgGSD patients are homozygous in the Gm system. Immunocytes producing IgG3 in the nasal mucosa correlate with serum IgG3 levels, whereas rectal IgG1 producing cells relate to serum IgG1 levels. This may reflect differences in antigen and/or mitogen exposure at the two mucosal sites. IgG2SD is the predominant form of IgGSD among children, whereas after puberty IgG3SD is most common. At the same age period there is a switch in sex distribution from three boys/one girl to one male/three females. Various abnormalities in B and T lymphocyte numbers and function are often found. In a double blind crossover study of Ig prophylaxis over 2 years in 43 IgGSD adult patients a significant decrease in the number of days with infections was seen both in the whole group and among the IgG1 deficient. Days with bronchial constriction were also significantly decreased among the 22 patients who had asthma as well. Acute bronchitis became significantly less frequent in the IgG3 deficient patients during Ig prophylaxis. This was seen in those under the lower range of 0.41 g/liter of Oxelius' early normal material, although many recent reference materials suggest 0.14-0.15 g/liter of IgG3 as the cut off. In a group of 25 consecutive patients with IgGSD + IgA deficiency recurrent respiratory infections were the major problem and lung function impairment was found in 12, and bronchiectasies in 5. Still many individuals with this combined deficiency have been reported to be healthy, again illustrating our limited understanding of these conditions.

Disease↗
PubMed1991

Isotype distribution of mucosal IgG-producing cells in patients with various IgG subclass deficiencies.

The subclass distribution of IgG-producing immunocytes was examined by immunohistochemistry in nasal and rectal mucosa of infection-prone patients with untreated IgG subclass deficiencies. Biopsy specimens from the two sites were obtained in 18 clinically and serologically well-characterized adult subjects; only a nasal or rectal sample was available from nine similar patients. Chronic lung disease was common in the patient groups with selective serum IgG1 deficiency and combined IgG1 and IgG3 deficiency, whereas the other categories of patients had mainly upper airway and other mild infections. Serum IgG2 or IgG3 deficiency was usually expressed also at the cellular level in rectal mucosa, and the proportion of rectal IgG1 cells was significantly correlated with the IgG1 level (r = 0.90, P less than 0.001). Likewise, there tended to be a decreased expression of the actual subclass at the cellular level in nasal mucosa of patients with serum IgG1 or IgG2 deficiency. Conversely, the median nasal proportion of IgG3 cells was remarkably unaffected by a deficiency of this subclass in serum and rectal mucosa. Interestingly, these patients rather tended to have raised IgG3 and reduced IgG2 cell proportions in their nasal mucosa, although this apparent local IgG3 compensation was nevertheless strongly correlated with the serum IgG3 level (r = 0.87, P less than 0.002). These disparities may reflect different antigenic and mitogenic exposure of the two tissue sites; for example, a persistent protein bombardment of the nasal mucosa that could conceivably override locally a B cell maturation defect. The possible clinical consequences of such variable mucosal expression of IgG subclass deficiencies remain to be studied.

Adult↗
PubMed1988

Intravenous immunoglobulin prophylaxis causing liver damage in 16 of 77 patients with hypogammaglobulinemia or IgG subclass deficiency.

Sixteen of 77 patients (21 percent) with common variable immunodeficiency or IgG subclass deficiency contracted non-A, non-B hepatitis in association with intravenous infusions of immunoglobulin. The hepatitis seemed to run a more severe course in these patients than in non-immunodeficient patients. Twelve patients had clinical symptoms, and five died with hepatitis being the cause of death in two and a contributing factor in three. Liver biopsy specimens showed early chronic active hepatitis and cirrhosis. In addition to increases in liver enzymes, 13 patients had increases in alkaline phosphatase levels. All but two patients who contracted hepatitis had been given 50 mg/kg per week or more of intravenous immunoglobulin. Lymphocyte counts, T/B cell ratios, and T-lymphocyte function did not differ between those in whom hepatitis developed and those in whom it did not develop. The hepatitis was associated with more than one batch of a Swedish intravenous immunoglobulin, the immunoglobulin being derived from United States sources as well as from European plasma. Three previous brief reports in the literature have also associated non-A, non-B hepatitis with the intravenous infusion of various immunoglobulins. Biologic materials given to patients, including immunoglobulin, should, whenever possible, be prepared so as to ensure absence of viruses.

Adult↗
PubMed1988

Immunoglobulin subclass deficiency.

IgG subclass deficiency was first noted in 1968. Subnormal levels of one or two, occasionally three IgG subclasses may be relatively common. It has not been determined, however, at what level below the normal range the IgG subclass deficiency is of clinical relevance. It remains important to clarify this point because certain subclass deficiencies may be without relevance of their own. Because patients with decreases of various IgG subclasses often present with a number of diseases, the low immunoglobulin levels may signify the presence of other abnormalities of more biologic significance. IgG subclass deficiency has been noted in about 25% of patients with well-defined food allergy and in patients with asthma, diabetes mellitus, Henoch-Schönlein's purpura, Bechterew's disease, intractable epilepsy of childhood, Friedreich's ataxia and autoimmune cytopenias. Most commonly they have increased frequency of infections especially in the respiratory tract, including sinusitis, otitis media and bronchopneumonia, but also osteomyelitis, meningitis, septicemia and various skin infections. Low levels of various subclasses have been noted in connection with other immunodeficiencies such as ataxia-telangiectasia. In common variable immunodeficiency there is an obvious imbalance in the IgG subclasses. Furthermore IgG subclass deficiency can be seen in relatives of patients with common variable immunodeficiency and in IgA deficiency. They also occur in relatives of patients with systemic lupus erythematosus, diabetes mellitus type 1 and C2 deficiency. In a few cases of subclass deficiency gene deletions have been shown. Subnormal levels of IgG subclasses make a remarkable change in sex distribution around puberty from 3/1 in boys and girls to the reverse sex ratio among adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Immunoglobulin G subclass deficiencies.

Low levels of single or multiple serum immunoglobulin G (IgG) subclasses is a common finding among patients with increased susceptibility to infections. In this investigation we summarize data from studies of 503 subclass-deficient individuals. Low IgG2 levels was the most common deficiency among children, and boys were more often deficient than girls. From the age of 16, females dominated, and the most frequent finding was low IgG3 levels. In vitro T or B lymphocyte dysfunction was demonstrated in 75% of the individuals, suggesting that low subclass levels may be indicators of an underlying defect at the B cell or possibly T cell level. Vaccinations and mucosal biopsies were performed to evaluate which patients may be helped by immunoglobulin substitution therapy.

Adult↗
PubMed1987

Immunoglobulin G subclasses in immunodeficiency.

Immunodeficiencies have been described ranging from stem cell dysfunction to low levels of isolated IgG subclasses. Subclass deficiencies seem in most cases to depend on regulatory defects rather than absence of genes encoding Ig heavy chains. It is, thus, not surprising that low levels of IgG subclasses can be seen in various immunodeficiency syndromes, where regulatory defects of the immune response may be present. Isolated IgG subclass deficiencies, however, are often found among patients with increased susceptibility to e.g. infections. The frequent B and/or T cell abnormalities observed in IgG subclass deficient individuals may explain the increased susceptibility to infections, suggesting that low subclass levels may function as an indicator of a clinically important immunodeficiency.

Adult↗
PubMed1986

IgG subclass deficiencies.

IgG subclasses differ not only in their biochemical and biologic properties, but also in their occurrence as selective deficiencies, alone and in combination. The normal range of IgG subclass concentrations in children and adults is compared with deficiencies found in individuals with repeated respiratory tract infections. Concomitant IgA deficiency is often noted. It is suggested that decreased IgG2 and IgG3 levels in IgA-deficient individuals may increase the risk of recurrent respiratory infection and lung damage. Finally, the efficacy immunoglobulin. prophylaxis in reducing of infection is anecdotally related.

Adult↗
PubMed1986

Correlation between deficiency of immunoglobulin subclass G3 and Gm allotype.

Gm allotypes were investigated in 63 Swedes: 46 females and 17 males, in whom serum IgG3 was below 0.35 g/l. Both monoclonal antibodies and polyclonal antisera were used for the quantification. Concentrations of the other IgG subclasses were within the age-related normal ranges. The distribution of the IgG1 genetic markers G1m(a,x,f) differed markedly from that observed in normal Swedes (p less than 0.001). Thus G1m(a) was present in 60 subjects as compared to an expected 36, and phenotype G1m(-f) in 34 subjects as against an expected 8. The mean IgG3 concentration was numerically lower in the G1m(-f) group than in the G1m(+f) cohort, and individuals with IgG3 levels 0.10 g/l were more frequent in the G1m(-f) group. Among Caucasians, G3mg is in linkage disequilibrium with G1ma and our interpretations is that the haplotype G1ma;ax G2m-n G3mg is markedly increased in individuals with IgG3 deficiency.

Dysgammaglobulinemia↗