Biomedical subjects

I Jónsdóttir

Publications and source records attributed to I Jónsdóttir.

At least 19 recordsLinked to original sources

PubMed2001

The frequency of CLA+ CD8+ T cells in the blood of psoriasis patients correlates closely with the severity of their disease.

Psoriasis is thought to be a T cell-mediated skin disease and the cutaneous lymphocyte antigen (CLA) is an important skin homing epitope for T cells. We have studied the relationship between disease severity (PASI) and phenotypic analysis of T cells in the blood of 36 patients with psoriasis focusing on the expression of CLA, VLA-4 and CD25 on CD4+ and CD8+ T cells. The patients had a higher frequency of circulating CLA+ CD8+ cells than healthy controls. Furthermore, a much stronger correlation was observed between PASI and the frequency of CLA+ CD8+ than CLA+ CD4+ T cells. The frequency of CLA+D8+ T cells correlated more strongly with redness, thickness and scaling of the skin lesions than the total affected body surface area. In contrast to CLA the T cell expression of VLA-4 did not demonstrate any such correlation. Finally, the expression of the activation marker CD25 on CD8+ T cells showed a strong correlation with disease severity in patients with moderate to severe psoriasis (PASI > 10) but such correlation was not observed for CD4+ T cells. These findings support the notion that circulating CLA+ CD8+ T cells may play an important role in the pathogenesis of psoriasis.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1999

Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections.

Host defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) of Escherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans.

Adjuvants, Immunologic↗

PubMed1999

Intranasal immunization with pneumococcal polysaccharide conjugate vaccines protects mice against invasive pneumococcal infections.

Host defenses against Streptococcus pneumoniae depend largely on opsonophagocytosis mediated by antibodies and complement. Since pneumococcus is a respiratory pathogen, mucosal immune responses may play a significant role in the defense against pneumococcal infections. Thus, mucosal vaccination may be an alternative approach to current immunization strategies, but effective adjuvants are required. Protein antigens induce significant mucosal immunoglobulin A (IgA) and systemic IgG responses when administered intranasally (i. n.) with the glyceride-polysorbate based adjuvant RhinoVax (RV) both in experimental animals and humans. The immunogenicity and efficacy of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 was studied in mice after i.n. immunization with RV. Antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA) and compared to antibody titers induced by parenteral immunization. The PNCs induced significant systemic IgG and IgA antibodies after i.n. immunization only when given with RV and, for serotype 1, serum IgG titers were comparable to titers induced by subcutaneous immunization. In addition, i.n. immunization with PNC-1 in RV elicited detectable mucosal IgA. These results demonstrate that RV is a potent mucosal adjuvant for polysaccharides conjugated to proteins. A majority of the PNC-1-immunized mice were protected against both bacteremia and pneumonia after i.n. challenge with a lethal dose of serotype 1 pneumococci, and protection correlated significantly with the serum IgG titers. Similarly, the survival of mice immunized i.n. with PNC-3 in RV was significantly prolonged. These results indicate that mucosal vaccination with PNC and adjuvants may be an alternative strategy for prevention against pneumococcal infections.

Administration, Intranasal↗

PubMed1997

Is psoriasis induced by streptococcal superantigens and maintained by M-protein-specific T cells that cross-react with keratin?

The evidence that T lymphocytes play a key role in the pathogenesis of psoriasis is now compelling. Eruption of psoriatic skin lesions coincides with epidermal infiltration and activation of T cells, and spontaneous or treatment-induced resolution of the lesions is preceded by the reduction or disappearance of epidermal T cells. An upregulation has also been demonstrated for various molecules associated with T-cell mediated inflammation, and treatments selectively directed against T cells have proved very effective. Infections with group A beta-haemolytic streptococci have been associated with onset of acute psoriasis and exacerbation of chronic psoriasis. Such infections are also frequently accompanied by erythematous skin rashes. Also, recent reports indicate that streptococcal superantigens can induce expression of cutaneous lymphocyte antigens (CLA), believed to play a major role in enabling T cells to migrate to the skin. Furthermore, T-cell lines isolated from psoriatic lesions may show strong reactivity to streptococcal antigens. We have postulated that psoriasis is an autoimmune disease mediated by T cells reacting to epitopes that are common to streptococcal M-proteins and keratins. To investigate this possibility, circulating T cells from 12 patients with active psoriasis, paired controls, and six patients with atopic dermatitis were challenged in vitro with five synthetic 20aa (amino acid) M-peptides: production of IFN-gamma and IL-4 was analysed by ELISPOT and RT-PCR techniques. Four of these peptides shared five to six aa sequences with several type I keratins and one did not. In 10 of the 12 psoriasis patients, measurable IFN-gamma production could be induced by one or more of the four peptides that share sequences with keratins. A borderline response was observed in only four of the 18 controls: the dermatitis patients were all negative. The only peptide that shared 6aa with keratins was the one that induced a response in the psoriatic patients most frequently, and four of them showed the strongest response to this peptide while none of the controls reacted to it. In all instances negligible responses were observed to the control peptide that did not share sequences with keratins. Except for PHA-stimulated controls, IL-4 responses could not be detected by either ELISPOT or RT-PCR and there was generally good agreement between the two techniques. A marked reduction in the M-peptide-induced IFN-gamma responses was observed in the psoriasis patients during remission induced by UVB treatment, while their responses to streptokinase-streptodornase were not affected. Thus, active psoriasis is associated with a Th1 type response to short peptides with epitopes shared by streptococcal M-protein and keratin. This is consistent with the hypothesis that psoriasis may be induced and exacerbated in susceptible individuals by M-protein-specific Th1-like cells that cross-react with human epidermal keratin.

Animals↗

PubMed1995

Psoriasis: a T-cell-mediated autoimmune disease induced by streptococcal superantigens?

Psoriasis is a T-cell-mediated disease that can be triggered by infection with group A beta-haemolytic streptococci. It is proposed that psoriatic skin lesions are initiated by exotoxin-activated T cells, and persist because of specific T cells that react both with streptococcal M protein and a skin determinant, possibly a variant of keratin. As discussed here by Helgi Valdimarsson and colleagues, cytokines released by the superantigen (SAg)-stimulated T cells could induce or enhance the expression of the crossreactive autoantigen, leading to the rescue and activation of autoreactive T cells. In this way, the SAg-determined T-cell receptor V beta phenotype would be maintained by T cells in psoriatic lesions.

Autoimmune Diseases↗

PubMed1995

Selective increase of IgA rheumatoid factor in patients with gluten sensitivity.

An increased prevalence of raised autoantibodies, including rheumatoid factor, has been reported in patients with gluten sensitivity. However, rheumatoid factor has only been measured in small groups of patients and the findings have been conflicting. In this study IgM, IgG and IgA rheumatoid factor was measured in 89 patients with dermatitis herpetiformis and 22 patients with coeliac disease and compared with 89 normal controls. There was an increased prevalence of elevated IgA rheumatoid factor in the patients with dermatitis herpetiformis (13.5%; p = 0.036) and coeliac disease (18.2%; p = 0.078), while no such increase was found for the IgM or IgG rheumatoid factor isotypes. This selective increase of IgA rheumatoid factor suggests that rheumatoid factor production in patients with gluten sensitivity primarily results from immunological activation in the gut mucosa.

Adult↗

PubMed1994

Opsonization and antibodies to capsular and cell wall polysaccharides of Streptococcus pneumoniae.

Opsonin-dependent phagocytosis is believed to be the major defense mechanism against Streptococcus pneumoniae. In addition to type-specific antibodies to pneumococcal capsular polysaccharides (PPS), most persons also produce antibodies to cell wall polysaccharide (CWPS), which may be detected in antibody assays due to contamination of PPS antigens. Antibodies to CWPS and PPS from common serotypes were analyzed in relation to opsonic activity before and after vaccination of healthy adults. A highly significant relationship was generally found between opsonization and pneumococcal antibody levels, and this correlation increased markedly by neutralization of CWPS antibodies. This applied in particular for IgG2, which showed no correlation without neutralization. Adsorption of PPS antibodies almost abolished the opsonic activity, whereas removal of CWPS antibodies had no effect. These findings indicate that opsonization of pneumococci is almost exclusively mediated by PPS antibodies and emphasize the importance of neutralizing CWPS antibodies when immunity to this organism is evaluated.

Adult↗

PubMed1994

High molecular weight growth hormone (> 160 kD) in human serum characterized with monoclonal antibodies.

Human growth hormone (hGH) was analyzed by six monoclonal antibodies (Mabs) and a polyclonal antiserum (Pas) before and after molecular sieve chromatography of sera from healthy subjects. Their hGH levels were between < 0.2 and 0.4 ng/ml as determined with Pas. The six Mabs reacted with five distinct epitopes and bound to a hGH fragment corresponding to the amino acid sequence 15-125. Two of the Mabs showed reduced binding to 20-kD hGH. The binding of Mabs to dimeric forms of hGH varied. Human GH levels in unfractionated sera as determined with Mabs were < 3.1-390 ng/ml. After molecular sieve chromatography of the sera, one peak of hGH-immunoreactive material of high molecular weight (> 160 kD) and one at the elution volume of monomeric hGH were determined with Pas and Mabs. The major part of the high molecular weight hGH (> 160 kD) seemed to consist of 22-kD hGH molecules, since Pas and all Mabs detected the hGH immunoreactivity (> 160 kD) in a similar manner. This high molecular weight hGH (> 160 kD) was distinguishable from the identified, receptor-like hGH-binding protein in serum.

Adult↗

PubMed1993

Cerebrospinal fluid dynorphin-converting enzyme activity is increased by voluntary exercise in the spontaneously hypertensive rat.

The activity in cerebrospinal fluid (CSF) of dynorphin-converting enzyme (DCE) has been studied after voluntary exercise in the spontaneously hypertensive (SH) rat. The exercise consisted of spontaneous running in wheels for 4-5 weeks and the average running distance during the last two weeks was 4.0 km/24h. CSF samples were obtained under anaesthesia from the cisterna magna after penetration of the atlanto-occipital membrane. DCE transforms the members of the dynorphin family of opioid peptides into Leu-enkephalin-Arg6. In the present investigation a radioimmunoassay was used for quantitation of Leu-enkephalin-Arg6 release from dynorphin A1-17 and dynorphin B1-13. The rats that were running had a DCE activity (vs. both substrates) in CSF that was approximately 6-12 times higher than in animals not given the running opportunity. A statistically significant correlation between the two prodynorphin-derived substrate peptides was found in terms of DCE activity. We therefore propose that a single enzyme activity may be responsible for the hydrolysis of dynorphin B1-13 and dynorphin A1-17. Furthermore, a significant correlation was also found between running activity and DCE activity 12-14 h before the CSF was withdrawn. Besides measurement of DCE activity by radioimmunoassay, the formation of Leu-enkephalin-Arg6 was identified by reversed-phase micro-column liquid chromatography and plasma desorption mass spectrometry. The experiment shows that voluntary exercise affects opioid peptidergic mechanisms.

Amino Acid Sequence↗

PubMed1993

Dermatitis herpetiformis--an autoimmune disease due to cross-reaction between dietary glutenin and dermal elastin?

Dermatitis herpetiformis (DH), is associated with skin eruptions and granular depositions of IgA in the papillary dermis, but this is not a feature of coeliac disease (CD). The specificity of the IgA in the skin is unknown. High molecular weight glutenin (HMW-g), a component of gluten, has been shown to have structural similarities to human elastin. This paper reports immunoadsorption studies which suggest that human serum may contain antibodies which cross-react with HMW-g and elastin. DH patients had significantly lower levels of IgA antibodies to HMW-g and to elastin than both CD patients and healthy controls. Furthermore, introduction of a gluten-free diet (GFD) was associated with a further reduction in the amount of IgA antibodies to elastin in the DH patients. This diet-associated decrease of elastin antibodies was restricted to the IgA isotype. A significant correlation was observed between IgA antibodies to HMW-g and elastin in healthy controls and CD patients, while no such correlation was found in patients with DH. These findings could indicate that HMW-g induces production of antibodies to elastin, which are deposited in the skin, and that when the antigenic stimulus is removed, these antibodies are further reduced due to continuous dermal deposition. It is postulated that DH may be an autoimmune disease due to cross-reactivity between dietary glutenin and dermal elastin.

Adult↗

PubMed1993

Reciprocal changes in complement activity and immune-complex levels during plasma infusion in a C2-deficient SLE patient.

Although systemic lupus erythematosus (SLE) is abnormally common in individuals with complement deficiency, conclusive evidence has been lacking for a direct causal relationship between disease manifestations and a missing complement component. A patient with C2 deficiency and SLE has been treated with 56 courses of fresh frozen plasma (FFP) infusions over a period of 8 years. Each infusion, involving a total of 12 units of FFP administered in equal doses over 4 consecutive days, has consistently resulted in a transient restoration of the classical pathway of complement, and a full clinical remission lasting 6-8 weeks. This report is concerned with changes in the levels of immune complexes, C2 and C3d during an infusion cycle. Four progressively rising peaks in C2 and C3d were observed during the 4 days of the plasma infusion, and these peaks coincided with four reciprocally descending troughs in the levels of immune complexes. Identical fluctuations have been consistent in all the plasma-infusion cycles that have so far been monitored, and their consistent association with clinical remissions indicates a causal relationship between the C2 restoration and clinical remissions in this C2-deficient SLE patient.

Antigen-Antibody Complex↗

PubMed1992

Do adults with high gliadin antibody concentrations have subclinical gluten intolerance?

Gliadin antibodies of the IgG and IgA isotypes and IgG subclasses were measured in 200 adults who were randomly selected from the Icelandic National Register. Those with the highest gliadin antibody concentrations were invited with negative controls to participate in a clinical evaluation. Neither the study subjects nor the physicians who recorded and evaluated the clinical findings were aware of the antibody levels. Significantly higher proportion of the gliadin antibody positive individuals reported unexplained attacks of diarrhoea (p = 0.03), and IgA gliadin antibodies were associated with increased prevalence of chronic fatigue (p = 0.0037). The gliadin antibody positive group also showed significantly decreased transferrin saturation, mean corpuscular volume and mean corpuscular haemoglobin compared with the gliadin antibody negative controls. Serum folic acid concentrations were significantly lower in the IgA gliadin antibody positive individuals. On blind global assessment 15 of the 48 participants were thought to have clinical and laboratory features that are compatible with gluten sensitive enteropathy, and 14 of these were in the gliadin antibody positive group (p = 0.013). Complaints that have not been associated with gluten intolerance had similar prevalence in both groups with the exception of persistent or recurrent headaches that were more common in the gliadin antibody positive group. These findings raise the possibility that a subclinical form of gluten intolerance may be relatively common.

Adult↗

PubMed1991

Serum levels and molecular sizes of growth hormone during pregnancy in relation to levels of lactogens, insulin-like growth factor I and insulin-like growth factor binding protein-1.

Growth hormone (GH), placental lactogen (PL), prolactin (PRL), insulin-like growth factor I (IGF-I) and IGF binding protein-1 (IGFBP-1) were determined in serum by radioimmunoassays (RIAs) in 12 women during pregnancy. GH and PL were analyzed by two monoclonal antibodies (Mab 3 and Mab 1) raised against pituitary GH. Serum IGFBP-1 had reached maximum levels at midpregnancy while PRL, PL and IGF-I increased continuously during pregnancy. Mab 1, which cross-reacts with PL, measured consistently higher levels of PL in serum than a commercial PL RIA (p less than 0.01) due to interference of cross-reacting serum proteins in the Mab 1 RIA. The GH-specific Mab 3 showed decreasing GH levels in unfractionated serum throughout gestation, but detected GH-immunoreactive proteins of approximately 40-200 kD after molecular sieve chromatography of pooled serum from late pregnancy. It is suggested that the formation of GH complexes of large molecular mass account for the successive disappearance of monomeric GH during pregnancy.

Adult↗

PubMed1990

Cyclosporin A in psoriatic arthritis: an open study.

Eight patients with psoriatic arthritis entered an open study to determine the efficacy of oral cyclosporin A for their treatment. The starting dose was 3.5 mg/kg daily. Findings after the first six months are reported. One patient withdrew from the study after five months because of tremors, general malaise, and lack of improvement. Seven patients continued through the study, and marked improvement was found after two months in all clinical indices. The skin lesions improved in a parallel fashion. The cyclosporin A dose had to be reduced temporarily by 25% in three patients because of an increase in serum creatinine of more than 50%. A rise in diastolic blood pressure in three patients responded to treatment. The study suggests that cyclosporin A effectively treats arthritic manifestations of psoriasis as well as psoriatic skin lesions.

Adult↗

PubMed1990

Monoclonal antibodies reveal circulating growth hormone of high molecular weight not detectable by conventional assays.

A radioimmunoassay based on a monoclonal antibody. Mc-ab 1, which was raised against growth hormone but cross-reacted with human placental lactogen yielded higher GH immunoreactivity levels in serum than one based on a polyclonal antiserum. This discrepancy was noted in subjects with normal GH secretion as well as in patients with GH insufficiency. To characterize this GH immunoreactivity detected by Mc-ab 1, affinity purification and molecular sieve chromatography of serum were performed. High molecular weight proteins with GH immunoreactivity were found with both techniques. These proteins were associated with carbohydrates. Affinity cross-linking showed specific binding of radiolabelled GH to high molecular weight proteins in the serum. After fractionation of serum, the GH immunoreactivity became detectable by the polyclonal antiserum assay as well as by an immunoradiometric assay. GH immunoreactive material with an approximate mass of 80 kD was subjected to isoelectric focusing. When GH immunoreactive fractions at pH 5 were re-chromatographed, GH immunoreactivity was recovered in the elution volume corresponding to monomeric GH. Our results show that sera from normal subjects as well as from patients with deficient GH secretion contain notable amounts of high molecular weight GH which is undetectable by antibodies generally used for GH measurements, but which can be revealed after fractionation of serum.

Acromegaly↗

PubMed1986

Purification of pituitary and biosynthetic human growth hormone using monoclonal antibody immunoadsorbent.

This report describes the purification of human growth hormone from crude pituitary extract and lysate of recombinant E. coli by an immunoadsorbent purification with monoclonal antibody coupled to solid phase. By a single-immunoaffinity chromatography step pure hGH can be obtained from either origin as revealed by SDS-PAGE followed by silver staining or immunoblotting. An additional ion-exchange chromatography step results in homogeneous 22 kDa hGH preparations. Furthermore, this method may be used for isolation of a pituitary hGH variant which has higher binding affinity for this monoclonal antibody than the major 22 kDa form. This study clearly illustrates the potential of monoclonal antibody immunoadsorbents for purification of different molecular forms of hGH.

Antibodies, Monoclonal↗

PubMed1984

Immunochemical characterization of charge isomers of bacteria-derived human growth hormone with monoclonal antibodies.

Monoclonal antibodies were used to study the immunochemical nature of charge isomers of bacterially produced methionyl human growth hormone. After isoelectric focusing of the hormone the 12 monoclonal antibodies reacted similarly in immunoblotting experiments and none of them could discriminate between the two isolated charge isomers in ELISA. This indicates that the generation of charge isomers of met-hGH does not result in loss of the determinants recognized by the monoclonal antibodies and that the conformation of the two main charge isomers is identical within these determinants.

Antibodies, Monoclonal↗

PubMed1984

Monoclonal antibodies to antigens associated with transitional cell carcinoma of the human urinary bladder. I. Determination of the selectivity of six antibodies by cell ELISA and immunofluorescence.

Spleen cells from BALB/c mice immunized with cells derived from transitional cell carcinomas (TCC) of the human urinary bladder were fused with mouse myeloma Sp 2/0 Ag14 cells. Monoclonal antibodies from six established hybridomas were investigated for specificity in a cell ELISA and in indirect immunofluorescence against a large panel of fixed intact cells. Three of the antibodies reacted with half or more of the eight bladder tumors and with a few unrelated tumors. They did not react at all with malignant or normal cells of hematopoietic origin. A fourth antibody reacted with seven of eight bladder tumors. It also reacted weakly with a prostatic carcinoma, with five of six malignant or transformed B cell lines, and with a subpopulation of normal lymphocytes, but not with any of the other cells on the test panel. These four antibodies did not react with cells derived from normal urothelium. The results suggest that these antibodies might recognize cell-type-restricted antigens associated with malignancy. Another antibody reacted with almost all urothelium-derived cells. It also reacted with three of three melanomas but not with any other cells on the panel. The sixth antibody reacted with 32 of the 37 cells tested. The spectrum of reactivities displayed by the antibody suggested that it recognizes HLA antigens.

Antibodies, Monoclonal↗