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Biomedical subjects

H Valdimarsson

Publications and source records attributed to H Valdimarsson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Elevation of only one rheumatoid factor isotype is not associated with increased prevalence of rheumatoid arthritis--a population based study.

OBJECTIVE: To analyse the relationship between different rheumatoid factor (RF) isotype patterns and the prevalence of RA. METHODS: Serum samples, collected between 1973 and 1983 from nearly 14,000 randomly selected individuals, were screened for elevation of RF. In 1987, 173 RF positive and 156 matched RF negative participants were evaluated clinically. RESULTS: Participants with elevation of only one RF isotype, most commonly IgM, did not have significantly higher prevalence of RA than the RF negative controls. Of the 17 RF positive individuals who were diagnosed with RA, 14 (82%) had a combined elevation of IgM and IgA RF. CONCLUSION: In contrast to a combined elevation of IgM and IgA RF, elevation of only one RF isotype may not be a significant risk factor for the development of RA.

Adult↗
PubMed2000

Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis.

OBJECTIVES: Smokers have an increased incidence of rheumatoid factor (RF) and rheumatoid arthritis (RA) and one report has also indicated that smoking may also adversely influence the severity of RA. METHODS: Sixty-three women with advanced RA answered a structured questionnaire that included detailed information about their smoking history. The women were also evaluated clinically and radiologically. RESULTS: Heavy smoking (>/= 20 pack-yr) was associated with rheumatoid nodules (P: = 0.01), a higher HAQ score (P: = 0.002) and a lower grip strength (P: = 0.01). Smoking was also associated with more radiological joint damage (P: = 0.02). A positive correlation was observed between smoking and RF levels, in particular IgA RF and a combined elevation of IgM and IgA RF. CONCLUSIONS: Smoking has an adverse effect on disease progression in patients with RA. An association was also observed between smoking and those RF types that predispose to RA and have the highest diagnostic specificity for this disease.

Adult↗
PubMed2000

A prospective study on the incidence of rheumatoid arthritis among people with persistent increase of rheumatoid factor.

OBJECTIVES: To study the stability of rheumatoid factor (RF) increases and to compare the incidence of rheumatoid arthritis (RA) in people with transient or persistent increase of one or more RF isotypes. METHODS: From an original cohort of nearly 14 000 participants in a population study, 135 previously RF positive persons were recruited in 1996 and evaluated according to the 1987 ACR criteria. The observation time ranged from 9-22 years (mean 16. 5). Blood samples were obtained from all participants at entry and again in 1996. RESULTS: About 40% of the participants who had only one raised RF isotype in the original sample had become RF negative in 1996 compared with only 15% of those with increase of two or three RF isotypes (p=0.002). The seven participants who developed RA during the study period all had persistently raised RF. Six of the 54 participants with more than one RF isotype raised in 1996 developed RA, corresponding to an annual incidence of 0.67%, which was 7.5 times higher than observed in the other participants (p=0. 045). CONCLUSION: Symptom free persons with persistently raised RF have greatly increased risk of developing RA. This suggests that dysregulation of RF production is a predisposing factor in RA.

Arthritis, Rheumatoid↗
PubMed2000

[Allergy and asthma in Icelandic children - an epidemiological study.].

OBJECTIVE: The prevalence of allergy and asthma is increasing in Western industrialized countries. The etiology of allergy is multifactorial and only partly understood. In an effort to gather information about asthma and allergy in the pediatric population in Iceland, we have evaluated on a regular basis a cohort of randomly selected children born in 1987. MATERIAL AND METHODS: The first part of the study included 179 children at the age of 18-23 months (mean age 20 months). Of these, 161 children were re-evaluated at four years of age and 134 at eight years. The evaluation included a standardized questionnaire, clinical examination and skin-prick tests. Asthma, eczema, allergic rhinoconjunctivitis and food allergy were diagnosed according to established criteria. RESULTS: At 20 months of age 42% of the children were diagnosed with asthma or allergic disorders, 45% at four years and 34% at the age of eight years. Initially asthma and eczema were most common, but the prevalence and severity of eczema had decreased at four years of age and the prevalence of asthma decreased between four and eight years. No child was diagnosed with allergic rhinoconjunctivitis before two years of age but 7% of four year olds and 10% at the age of eight years. A quarter of the children had at some stage symptoms compatible with more than one allergic disorder. Two-thirds of the children who were diagnosed with eczema and/or asthma before two years of age, were symptom free at eight years. Thirty-eight percent of eight year old children with allergic symptoms had positive skin-prick tests to the allergens used, most commonly to cats. Seventy three percent of eight year old children with allergy and/or asthma, had a first degree relative with a history of allergies. CONCLUSIONS: As in other Western industrialized societies asthma and allergic disorders are common health problems amongst children in Iceland. However, the majority of children with allergic manifestations during the first two years of life, became symptom free before the age of eight years. Conversely, 50% of eight year olds with asthma or allergies were symptom free during the first two years of their life. This suggests that the mechanisms causing allergic symptoms may not be uniform in different age groups.

English Abstract↗
PubMed1999

Enzyme immunoassays for measuring complement-dependent prevention of immune precipitation (PIP) and solubilization of preformed antigen-antibody complexes (SOL).

We have developed simple and sensitive enzyme-based methods for evaluating the ability of serum complement to prevent immune complex precipitation (PIP) or to solubilize preformed immune complexes (SOL). Alkaline phosphatase, serving both as antigen and label, is added to goat IgG anti-alkaline phosphatase antibodies, with serum present throughout the assay (PIP), or added after immune complex formation (SOL). After incubation at 37 degrees C for 1 h followed by centrifugation, the enzyme activity of the supernatant, reflecting the amount of immune complexes in solution, is measured by colorimetry. Results are expressed with reference to a standard serum pool assigned 100 arbitrary units (AU). Intra- and inter-assay variabilities are within 10%. The normal ranges were 67-133 AU for PIP and 72-129 AU for SOL. These methods have been standardized for clinical use in relation to impaired complement function and immune complex disease, and adapted for measuring complement mediated binding of immune complexes to erythrocytes. They are sensitive, easy to perform and do not require expensive facilities. By measuring the interaction of complement with immune complexes, these methods may highlight aspects of the classical and the alternative pathway that are different from those detected using haemolysis as an endpoint.

Alkaline Phosphatase↗
PubMed1999

Is an epitope on keratin 17 a major target for autoreactive T lymphocytes in psoriasis?

Psoriasis is a T cell-mediated inflammatory skin disease that has been associated with infections by group A beta-haemolytic streptococci. In a previous study of patients with active psoriasis we demonstrated an increased frequency of circulating Th1-like cells that responded to 20 amino acid (aa) streptococcal M-peptides sharing sequences with human keratin. These cells disappeared after ultraviolet B (UVB)-induced clinical remission. Using T cells from the blood of 17 psoriatic patients and 17 healthy controls we have now compared the numbers of interferon-gamma (IFN-gamma)-producing cells induced by seven 18-20 aa keratin peptides and five corresponding M-peptides. The most frequent and strongest responses were observed to a peptide from keratin 17 that shares ALEEAN sequence with M-protein. The responses to this peptide were stronger than to the corresponding M-peptide containing the ALEEAN sequence. After UVB treatment T cell responses to all the M- and keratin peptides were abolished, while responses to the positive control antigen streptokinase/streptodornase (SK/SD) were not affected. These findings are consistent with the notion that aa sequences which keratin has in common with M-protein may be a major target for autoreactive T cells in psoriasis.

Amino Acid Sequence↗
PubMed1998

An enzyme based assay for the measurement of complement mediated binding of immune complexes to red blood cells.

A new in vitro method is presented for measuring directly the ability of sera to induce binding of immune complexes (ICs) to erythrocytes (ICRB assay). The assay measures the binding of alkaline phosphatase (AP)-anti-alkaline phosphatase (anti-AP) complexes formed in the presence of the test sera to the complement receptor 1 (CR1) on normal human red blood cells (RBCs). By using a standard serum source, the assay can also be used to measure the IC binding ability of RBCs from different donors. As compared to the traditional CH50 method, the ICRB assay generally showed more pronounced abnormality in 10 individuals tested, of whom 5 had primary deficiency of classical pathway components. Seven out of ten individuals had systemic lupus erythematosus (SLE) and 2/10 had other rheumatic diseases without primary complement deficiency. The ICRB measured in samples from 9 other patients with SLE was significantly decreased when compared to values from 80 normal individuals. ICRB in serum samples from a C2 deficient SLE patient collected during plasma infusion treatment reflected closely the rising amount of C2 in the serum. Using RBCs from different donors ICRB activity correlated well with the numbers of CR1 as measured by a flow cytometric assay (FCA). These methods should be valuable for measuring the overall IC clearance capacity of the blood and have the advantage that the use of radioactive isotopes is avoided.

Animals↗
PubMed1998

Participation of factor B in residual immune complex red cell binding activity observed in serum from a C2-deficient systemic lupus erythematosus patient may delay the appearance of clinical symptoms.

OBJECTIVE: To investigate whether participation of factor B (FB) in immune complex transport might explain long periods of clinical remissions in a homozygous C2-deficient patient with systemic lupus erythematosus (SLE) treated regularly with plasma infusions. METHODS: Immune complex red cell binding (ICRB) was assayed as enzyme activity, C3d by enzyme-linked immunosorbent assay, and FB by immunoelectrophoresis. RESULTS: C2-deficient sera showed low-grade ICRB, which correlated with levels of FB. This activity could be blocked with antibodies to C1q, C4, or FB, but not by antibodies to C2. C3d levels in the patient's plasma changed during infusion, followed by a gradient increase during remission. Comparison of ICRB, C3d, and FB suggested an inverse relationship between FB levels and clinical symptoms. CONCLUSION: In C2 deficiency, FB may interact with C4 to provide a low-grade ICRB. This activity could be clinically significant in patients with C2 deficiency and explain why they are less prone to SLE than patients with C1q or C4 deficiency.

Antibodies↗
PubMed1998

Combined elevation of IgM and IgA rheumatoid factor has high diagnostic specificity for rheumatoid arthritis.

The diagnostic value of measuring rheumatoid factor (RF) by agglutination or isotype-specific enzyme-linked immunosorbent assay (ELISA) was compared. The study included 70 patients with rheumatoid arthritis (RA) and 205 patients with various other rheumatic conditions. Of the RA patients, 74% were RF-positive by agglutination and 90% had one or more RF isotypes elevated by ELISA compared to 14% and 22%, respectively, of the other patients. Strikingly, 70% of the RF-positive RA patients had an elevation of two or more RF isotypes compared to only 16% of the other RF-positive patients (P < 0.0001). Furthermore, a combined elevation of IgM and IgA RF was found in 52% of the RF-positive RA patients, but only in two (4%) of the other RF-positive patients (P < 0.0001). It is concluded that a combined elevation of IgM and IgA RF is highly specific for RA and is very rarely found in rheumatic diseases other than RA. Isotype-specific RF assays are therefore diagnostically superior to agglutination tests. The detection of the RA-specific RF isotype pattern may be particularly helpful early in the course of RA even before the disease is fully differentiated.

Adult↗
PubMed1998

Reconstitution of opsonizing activity by infusion of mannan-binding lectin (MBL) to MBL-deficient humans.

Mannan-binding lectin (MBL, previously named mannan-binding protein, MBP) is a serum collectin, which activates complement upon binding to microbial carbohydrates. This results in opsonization of the microorganisms as well as direct complement-mediated killing. Clinical evidence indicates that MBL has an important role in the innate immune defence against various pathogens. Genetically determined MBL deficiency is associated with increased susceptibility to infections. We have infused two MBL-deficient individuals with clinical grade MBL, purified from pooled donor plasma, in doses sufficient to attain normal concentration of MBL in serum. This resulted in normalization of complement-mediated opsonization. An initial rapid decrease in the serum concentration of MBL was followed by a slower decline with an estimated half-life of about 6 days. No adverse effects were observed and anti-MBL antibodies could not be detected following several MBL infusions. One of the two MBL recipient, a two-year-old girl, who had been suffering from repeated infections from the age of 4 months, was given a total of six MBL infusions. She has subsequently remained healthy for more than three years.

Adult↗
PubMed1998

Does smoking stimulate rheumatoid factor production in non-rheumatic individuals?

Smoking has been associated with increased incidence of rheumatoid arthritis (RA), joint damage and positive rheumatoid factor (RF). Here we report an analysis of the association between smoking and IgM, IgG and IgA RF in a cohort of non-rheumatic individuals participating in a prospective longitudinal study of the incidence and significance of elevated RF. From the initial cohort of nearly 14,000 randomly selected individuals aged 52-80 years, 109 RF-positive and 187 RF-negative non-rheumatic participants were recruited. All participants were tested for RF at least twice at an interval ranging from 4 to 13 years. Of the RF-negative participants 21.9% were active smokers compared to 34.1% of IgM RF-positive (p=0.035), 20.8% of IgG RF-positive (N.S.) and 34.4% of IgA RF-positive participants (p=0.047). Smoking was most prevalent (44.8%) amongst participants with elevation of both IgM and IgA RF (p=0.008), and smokers were also significantly more likely to have a persistent elevation of RF than non-smokers (p=0.024). These findings indicate that smoking may influence the immune system, leading to increased production of IgM and IgA RF.

Aged↗
PubMed1998

Isotypes and opsonophagocytosis of pneumococcus type 6B antibodies elicited in infants and adults by an experimental pneumococcus type 6B-tetanus toxoid vaccine.

Streptococcus pneumoniae is a major respiratory pathogen of infants, children, and the elderly. Polysaccharide vaccines have been useful in adult populations but do not elicit protective immunity in infants and young children. To enhance their immunogenicity, vaccines of pneumococcal polysaccharides conjugated to proteins are being developed. In this study antibody levels and opsonic activities were compared in sera of infants and adults injected with pneumococcal polysaccharide type 6B (Pn6B) conjugated to tetanus toxoid (TT) (Pn6B-TT). Healthy infants were injected with Pn6B-TT; group A was injected at 3, 4, and 6 months of age, and group B was injected at 7 and 9 months of age. A booster injection was given at 18 months. Adults were injected once. Antibodies were measured by enzyme-linked immunosorbent assay and radioimmunoassay, and their functional activities were measured by opsonophagocytosis of radiolabelled pneumococci. In adults, increases in immunoglobulin M (IgM), IgG, IgA, IgG1, and IgG2 to Pn6B were observed. Infants reached adult levels of IgG1 anti-Pn6B after the primary injections. After the booster injection the infant groups had total IgG- and IgM-Pn6B antibody levels similar to those of adults. After the booster injection, IgG1 was the dominant infant anti-Pn6B isotype and at a level higher than in vaccinated adults, but IgA and IgG2 antibodies remained at very low levels. Opsonic activity increased significantly after Pn6B-TT injections; the highest infant sera showed opsonic activity comparable to that of vaccinated adults. Overall, opsonic activity correlated best with total and IgG anti-Pn6B antibodies (r = 0.741, r = 0.653, respectively; n = 35) and was highest in sera with high levels of all Pn6B antibody isotypes. The results indicate the protective potential of a pneumococcal 6B polysaccharide protein conjugate vaccine for young infants.

Adult↗
PubMed1997

Circulating T cells of patients with active psoriasis respond to streptococcal M-peptides sharing sequences with human epidermal keratins.

Psoriasis is a T-cell mediated inflammatory skin disease which has been associated with group A, beta-haemolytic streptococcal infections. Four 20 a.a. long M6-peptides sharing 5-6 a.a. sequences with human epidermal keratins were identified. To investigate the role of potentially cross-reactive T cells in the pathogenesis of psoriasis, interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) responses of circulating T cells to these peptides were analysed by ELISPOT and RT-PCR in 14 psoriatic patients, 12 healthy individuals and six patients with atopic dermatitis (AD). Untreated psoriatic patients' responses were significantly higher to these peptides than healthy and AD controls, while responses to a control M6-peptide, not sharing sequences with keratin, were negligible in all groups. No difference was found in response to streptokinase/streptodornase (SK/SD). M6-protein and peptides exclusively elicited IFN-gamma production, with little IL-4 production, even in AD patients. Interferon-gamma responses to all the M6-peptides were abolished after successful treatment of psoriatic patients, but responses to SK/SD were unaffected. The results indicate that active psoriasis is associated with Th1-like cells responding to streptococcal M6-peptides sharing sequences with human epidermal 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.

Adult↗
PubMed1997

Immune responses of infants vaccinated with serotype 6B pneumococcal polysaccharide conjugated with tetanus toxoid.

BACKGROUND: Streptococcus pneumoniae is a major cause of meningitis, bacteremia, pneumonia and otitis media. Pneumococcal polysaccharides are not immunogenic in infants, but improved immunogenicity of polysaccharide-protein conjugates has been demonstrated. Antibiotic-resistant pneumococci have increased the need for an effective vaccine. OBJECTIVE: To study the safety and immunogenicity of a pneumococcal type 6B polysaccharidetetanus toxoid conjugate (Pn6B-TT) in infants and to assess the function of antibodies. METHODS: Healthy infants were injected, Group A at 3, 4 and 6 months (n = 21) and Group B at 7 and 9 months (n = 19). Booster injection was given at 18 months. Antibodies were measured by enzyme-linked immunosorbent assay and radioimmunoassay, and functional activity was measured by opsonization of radiolabeled pneumococci. Nasopharyngeal cultures were obtained. RESULTS: No significant adverse reactions were observed. Pn6B-IgG (enzyme-linked immunosorbent assay) increased to a geometric mean of 0.62 microgram/ml (P = 0.367, compared with prevaccination titers) in Group A at 7 months and 1.22 micrograms/ml (P < 0.001) in Group B at 10 months. Total Pn6B antibodies (radioimmunoassay) were 44 ng of antibody N/ml (P < 0.053) in Group A and 211 ng of antibody N/ml (P < 0.001) in Group B. A smaller increase in IgM and IgA anti-Pn6B was observed. Reinjection at 18 months elicited booster responses in total and IgG anti-Pn6B; 62% of those in Group A and 79% of those in Group B had > 300 ng of antibody N/ml. Opsonic activity, after initial and booster vaccinations, correlated with Pn6B-antibody titers. Three infants with nasopharyngeal cultures repeatedly positive for serogroup 6 had poor serum IgG responses. CONCLUSION: Our results demonstrate that Pn6B-TT is safe, elicits functional antibodies and memory responses in infants.

Antibodies, Bacterial↗
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↗
PubMed1997

IgA rheumatoid factor correlates with changes in B and T lymphocyte subsets and disease manifestations in rheumatoid arthritis.

OBJECTIVE: To analyze the relationship between lymphocyte subsets, different rheumatoid factor (RF) isotypes, and clinical features in patients with rheumatoid arthritis (RA). METHODS: Patients with established RA (n = 95) were examined clinically and blood samples were collected for measurements of RF by ELISA and for analysis of lymphocyte subsets by flow cytometry. RESULTS: IgA RF positive patients had more severe disease and higher prevalence of extraarticular manifestations than the other patients. Patients with elevated IgA RF had a higher percentage of CD5+ B cells and of CD4+CD45RO+ T cells compared to the other patients with RA or controls. High percentage of CD4+CD45RO+ T cells was also significantly associated with extraarticular manifestations. Patients with the sicca syndrome had significantly higher ratio of CD5+ B cells than patients without or with other types of extraarticular manifestations. CONCLUSION: Different disease manifestations in RA may be associated not only with certain RF isotypes and RF isotype combinations but also with changes in lymphocyte subsets in the blood. The relative increase of CD4+CD45RO+ T cells in the blood of IgA RF positive patients with RA might reflect preferential recruitment of CD8+CD45RO+ T cells to inflammatory sites.

Adult↗