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Biomedical subjects

J Björkander

Publications and source records attributed to J Björkander.

At least 19 recordsLinked to original sources
PubMed1992

Shared HLA class II-associated genetic susceptibility and resistance, related to the HLA-DQB1 gene, in IgA deficiency and common variable immunodeficiency.

Most cases of selective IgA deficiency (IgA-D) and common variable immunodeficiency (CVID) occur sporadically. However, familial clustering is not uncommon, and the two disorders can occur within the same family. We have previously described positive associations with three DR-DQ haplotypes as well as a strong negative association with DRw15,DQw6,Dw2 in IgA-D. Different amino acids at position 57 of the HLA-DQ beta chain were found to be related to susceptibility and resistance to IgA-D. Now we have found identical, although somewhat weaker, positive and negative DR-DQ associations in a large group of CVID patients (n = 86), as well as the same associations with codon 57 of the DQB1 gene. In addition, we have confirmed our earlier observations in an independent group of IgA-D individuals (n = 69), and in sib-pair analysis we have found linkage of the genetic susceptibility to IgA-D to the HLA class II region. In IgA-D individuals not carrying the three overrepresented DR-DQ haplotypes, the same positive association with a non-aspartic acid residue at position 57 of the HLA-DQ beta chain was seen. The previously reported associations with deletions of the HLA class III genes C4A (fourth component of complement) and CYP21P (steroid 21-hydroxylase pseudogene) were, in our groups of immunodeficient individuals, statistically secondary to the association with the DQB1 allele 0201. The shared HLA class II associations in the two humoral immunodeficiencies support the hypothesis that IgA-D and CVID are related disorders. Disease susceptibility and resistance are most closely associated with a gene(s) within the DR-DQ region, alleles of the DQB1 locus being candidate genes.

Alleles↗
PubMed1992

Aberrations in titre and avidity of serum IgM and IgG antibodies to microbial and food antigens in IgA deficiency.

The antibody levels and relative avidity of serum IgM and IgG antibodies against E. coli O antigens, poliovirus type 1 and beta-lactoglobulin were determined with enzyme-linked immunosorbent techniques in IgA deficient (IgAd) patients with frequent respiratory tract infections and healthy IgAd individuals. Healthy individuals with normal immunoglobulin levels served as controls. The IgM antibody levels against the bacterial, viral and food antigens and the IgG antibody levels against the bacterial antigens were significantly higher in the IgAd group with recurrent infections than in the group of healthy IgAd individuals. The symptomatic IgAd group had significantly higher levels of the IgG antibodies against the bacterial antigen, also when compared with controls. In contrast the healthy IgAd individuals had the highest avidities of IgM antibodies to the viral and food antigens. The high avidities of antibodies could be a compensatory host defence mechanism in IgAd. These aberrations may appear as a consequence of increased mucosal exposure in IgAd to antigens such as E. coli or beta-lactoglobulin, but presumably not to poliovirus which is only exceptionally present in the milieux. They could also be a result of the previously suggested dysregulation of antibody responses in IgAd.

Antibody Affinity↗
PubMed1992

Presence of non-maternal antibodies in newborns of mothers with antibody deficiencies.

To explain the mechanism for induction and production of specific antibodies found in the newborn already at birth, without previous known exposure to the antigen, we chose a model that presumably excluded the possibility of specific antibodies being transferred from the mother to the fetus. Specific IgG, IgA, and IgM antibodies against Escherichia coli and poliovirus antigens were determined with ELISA in serum, saliva, and amniotic fluid from hypogammaglobulinemic and IgA-deficient mothers as well as in cord serum, saliva, and meconium from their offspring. All the mothers lacked IgA and some also lacked IgM antibodies, which were found in their healthy newborns. The amniotic fluid from a hypogammaglobulinemic mother lacking IgA contained small amounts of IgA antibodies, which were also found in the neonate, suggesting a fetal origin. There was evidence for the presence of antiidiotypic antibodies to poliovirus in the cord sera. We propose that idiotypic and/or antiidiotypic IgG antibodies transferred via the placenta from the mother to the fetus can initiate specific immune responses seen in the newborn. Thus, it may be that transplacental IgG not only passively protects the newborn, but also actively primes the fetus during fetal life via its content of idiotypic and/or antiidiotypic antibodies.

Agammaglobulinemia↗
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

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↗
PubMed1989

Enhanced IgG1 and IgG3 responses to pneumococcal polysaccharides in isolated IgA deficiency.

Serum IgG subclass-specific antibody concentrations to pneumococcal polysaccharides (PnPs) 1 and 14 were measured in 13 adult patients with isolated IgA deficiency and nine healthy adults immediately before and 4 weeks following immunization with polyvalent pneumococcal vaccine. Samples were analysed by enzyme immunoassay using pooled human serum as a reference preparation. A significant rise in median post-immunization antibody concentrations to PnPs14 was seen for all IgG subclasses, for IgA-deficient patients and for controls. For PnPs1, post-immunization IgG2 and IgG4 antibody concentrations rose significantly in the patient group, and IgG4 antibody concentrations rose significantly in the controls. The median IgG1 and IgG3 antibody concentrations to PnPs1 were significantly higher pre- and post-immunization in IgA-deficient individuals in comparison with controls, as were post-immunization IgG3 antibody concentrations to PnPs14. This enhancement of IgG1 and IgG3 antibody responses to pneumococcal polysaccharide antigens in IgA-deficient patients suggests an alteration in regulation of the normal switching processes in the generation of subclass and isotype diversity or could possibly be due to alteration in the affinity of subclass specific antibody.

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

Assay of specific IgE antibodies to disodium cromoglycate in serum from a patient with an immediate hypersensitivity reaction.

A 29-year-old man with pollen allergy had experienced immediate adverse reactions, such as itching of the eyes, rhinitis, wheezing, and general urticaria, after using disodium cromoglycate (DSCG) eye drops. The local symptoms were reproducible, and skin tests were strongly positive. With serum from the patient, a RAST was developed for the assay of IgE antibodies. The uptake on RAST disks was 6% of the total activity added, which was a significantly higher level than was found in sera from 35 randomly selected blood donors or in sera from 25 patients tolerating DSCG. By addition of DSCG to the patient's serum, 95% of the binding to paper disks could be inhibited. The induction of specific IgE antibodies was proposed to be a result of a combination of electrostatic and hydrophobic interaction of DSCG and a protein carrier. The substance would thus act as a hapten without any covalent binding to the carrier. DSCG may serve as a model for other nonreactive low-molecular-weight substances suspected to elicit type I-like adverse reactions.

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 prophylaxis in patients with antibody deficiency syndromes and anti-IgA antibodies.

Sera from three hundred five patients with immunoglobulin deficiencies were analyzed for the presence of anti-IgA antibodies by using indirect agglutination and enzyme-linked immunosorbent assay (ELISA). Anti-IgA antibodies were observed in 15 of 68 (22%) patients with hypogammaglobulinemia and 53 of 185 (29%) patients with selective IgA deficiency, both groups having serum IgA less than 0.05 g/liter. The highest frequency, 6 of 10 or 60%, was noted for patients with a combined IgA-IgG2 deficiency. No anti-IgA antibodies were detected in 25 patients with serum IgA between 0.05 and 0.27 g/liter and normal amounts of serum IgM and IgG or in 17 patients with hypogammaglobulinemia who had serum IgA of 0.05-0.7 g/liter. The anti-IgA antibodies were primarily of the IgG class, but IgD and IgM anti-IgA were occasionally found. IgE anti-IgA antibodies could not be detected with the presently used technique. The IgG anti-IgA antibodies were mainly of the IgG1 subclass but occasionally also of the subclasses IgG2, IgG3, and IgG4. Of eight patients with anti-IgA antibodies, seven tolerated Ig prophylaxis with a commercial immunoglobulin preparation low in IgA when given either intramuscularly or intravenously. The titers of anti-IgA in the sera of these patients did not rise in relation to the prophylaxis. Only one of the eight patients had a history of previous anaphylactic reactions to IgA-containing blood products. He tolerated six Ig infusions during 5 months with the IgA-depleted preparation without any adverse effects but showed increasing levels of anti-IgA antibodies and ultimately experienced a near-fatal reaction at the seventh infusion.

Antibodies, Anti-Idiotypic↗
PubMed1987

Humoral immunity in nasal mucosa of patients with common variable immunodeficiency.

Humoral immunodeficiency, as reflected by the low serum immunoglobulin (Ig) concentrations in adult patients with common variable immunodeficiency (CVID), was even more severely expressed at the B-cell level in their nasal mucosa. No Ig-producing cells could be detected by immunohistochemistry in 11 of 19 mucosal specimens. The epithelial distribution of secretory component (SC) was normal in all specimens, but a sign of SC-dependent IgM transport was seen in only three. Epithelial IgA was completely lacking. All patients had had recurrent lower respiratory tract infections and 16 had recurrent or chronic infections of the upper respiratory tract. A previous report indicated that the intestinal mucosa is a privileged site for maturation of B cells in patients with CVID; the present study shows that this does not hold true for the nasal mucosa. This difference in B-cell maturation may in part explain the preferential susceptibility to infections in the respiratory tract of patients with CVID.

Adolescent↗
PubMed1987

Immunohistochemical study of nasal mucosa in patients with common variable immunodeficiency.

The presence of immunoglobulin (Ig)-producing cells was studied immunohistochemically in nasal mucosa obtained from adult patients with common variable immunodeficiency. In 11 of 19 biopsy specimens no such cells could be detected and with one exception very few appeared in the others. Distinct sign of epithelial IgM transport mediated by secretory component (SC) was seen in three specimens although the epithelial distribution of SC appeared normal in all cases. All patients had recurrent lower respiratory tract infections and 16 had recurrent infections of the upper respiratory tract. The localization of the infections primarily to the respiratory tract might be explained by the fact that the immunodeficiency, as reflected by the low serum Ig concentrations, was still more severely expressed at the B cell level in the nasal mucosa.

Adolescent↗
PubMed1987

Immunohistochemical study of nasal mucosa in patients with selective IgA deficiency.

Fifteen nasal biopsy specimens from adult patients with selective IgA deficiency were examined in a 'blind' immunohistochemical study for the presence of immunocytes producing various immunoglobulin (Ig) classes. Three groups of patients could be identified. One group had a predominance of IgG- and IgM-producing cells in their nasal mucosa, a second group revealed mainly IgG- and IgD-producing cells, and a third group had very few mucosal immunocytes. The clinical examinations showed that upper respiratory tract infections were most common in patients with few immunocytes while such infections were least common in patients with predominance of IgG and IgM immunocytes. Our results indicated that IgM, in contrast to IgD, acts as a compensatory secretory Ig in some patients with selective IgA deficiency.

Adolescent↗
PubMed1987

Interferon and beta 2-microglobulin in patients with common variable immunodeficiency or selective IgA deficiency.

The production of interferon (IFN) after stimulation of peripheral blood mononuclear cells with Sendai virus or phytohemagglutinin was studied in patients with common variable immunodeficiency (CVID) or selective IgA deficiency. Cells from CVID patients produced significantly more Sendai virus-induced (alpha) and mitogen-induced (gamma) IFN than cells from healthy control subjects. By contrast, some patients with selective IgA deficiency produced subnormal amounts of IFN-alpha. Neither IFN-alpha nor IFN-gamma was detectable in sera from the two categories of patients using radioimmunoassays with sensitivity limits of 5-10 international units per milliliter. With the aid of a more sensitive bioimmunoassay, however, antiviral activity was detected more frequently in sera from patients with CVID than in sera from control individuals. Acid treatment and absorption with anti-IFN-alpha and anti-IFN-beta sera indicated that the antiviral activity was due to IFN, with no preponderance of any particular IFN type. Determination of beta-2-microglobulin (beta 2M) concentrations revealed that CVID patients had markedly, and IgA-deficient patients moderately increased serum levels of this substance, as compared to healthy blood donors. Since IFN enhances the synthesis of beta 2M the finding of increased levels of this substance in CVID would be consistent with the observed hyperproduction of IFN. The present findings are concordant with earlier observations of increased natural killer cell activity in at least some forms of CVID and suggest that increased activity of the IFN/natural killer cell system provides a mechanism which may compensate for the defective B cell function in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗