Biomedical subjects

T Vikingsdottir

Publications and source records attributed to T Vikingsdottir.

7 recordsLinked to original sources

PubMed2006

Mannan-binding lectin and complement C4A in Icelandic multicase families with systemic lupus erythematosus.

OBJECTIVE: To determine whether low mannan-binding lectin (MBL) and C4A null alleles (C4AQ0) are associated with systemic lupus erythematosus (SLE) in multicase families with SLE. METHODS: Low MBL level was determined by measuring serum levels and by genotyping for mutant structural (B/C/D, designated as 0) and promoter (LX) alleles (by real-time polymerase chain reaction). C4AQ0 was detected by protein electrophoresis and corroborated with haplotype and genotype analysis. In nine Icelandic families, 24 patients with SLE were compared with 83 first-degree and 23 second-degree relatives without SLE. Twenty four unrelated family members and a population group of 330 Icelanders served as controls. RESULTS: Overall, the frequency of low MBL genotypes (0/0, LX/0 and wild-type/0) tended to be higher in patients with SLE than in their first-degree and second-degree relatives (p = 0.06), but the frequency was similar in the families and in the controls (p = 0.6). The frequency of C4AQ0 was, however, increased in patients and their relatives compared with that in the controls (p = 0.04). The combination of low MBL genotypes and C4AQ0 was found more often in the patients than in their relatives (p = 0.03) and controls (p = 0.02). However, low MBL level was observed only in patients and first-degree relatives in five of the nine multicase families. In these five families, patients with SLE had low MBL genotypes more often (64%) than their first-degree (38%) and second-degree (0%) relatives (p = 0.001), and the patients with SLE also had, accordingly, lower MBL levels than their relatives (p = 0.001). CONCLUSIONS: These findings indicate that low MBL levels can predispose people to SLE and highlight the genetic heterogeneity of this disease.

Adult↗

PubMed2006

The effects of tobacco smoking and rheumatoid factor seropositivity on disease activity and joint damage in early rheumatoid arthritis.

OBJECTIVE: To study the effect of tobacco smoking and rheumatoid factor (RF) isotypes on disease activity and joint damage in early rheumatoid arthritis (RA). METHODS: One hundred early RA patients were followed prospectively for 2 yr. They were evaluated at recruitment and at 6 and 24 months. Sociodemographic information included smoking history, and radiographs of hands and feet were obtained. RF was monitored by IgM- and IgA-specific RF enzyme-linked immunosorbent assay and by agglutination, and serial measurements were also obtained for C-reactive protein. The influence of tobacco smoking and RF positivity on disease outcome was evaluated using multivariate analysis. Covariates for the regression analysis included sex, age, coffee consumption and IgA-RF positivity. RESULTS: A gradient of increase in disease activity was observed from never smokers to former smokers to current smokers during the 2 yr of observation, defined by number of swollen joints (SJC), tender joints (TJC) and visual analogue scale for pain (P<0.001, P=0.02 and P=0.005, respectively), but smoking status did not influence radiological progression. Ever smokers were more often IgA RF positive (P<0.05). IgA RF-positive patients had more active disease (SJC P=0.002, TJC P=0.01) and showed more radiological progression (P<0.0001) compared with IgA RF-negative patients. Of the RF-positive patients 22% had elevated IgM RF without IgA RF and these patients showed similar disease activity and radiological joint progression to the RF-negative patients. None of these associations were explained by possible confounders. CONCLUSION: Tobacco smoking has an adverse effect on patients with early RA and this is possibly immunologically mediated. IgM RF does not predict poorer prognosis in RA unless it is associated with a concomitant elevation of IgA RF.

Adult↗

PubMed2004

Human plasma-derived mannose-binding lectin: a phase I safety and pharmacokinetic study.

Mannose-binding lectin (MBL) is an important component of innate immunity that can bind to certain sugar residues on the surface of many types of pathogenic micro-organisms. On binding, MBL generates opsonic activity mainly through activation of the complement system. Genetically determined MBL deficiency is very common and can be associated with increased susceptibility to a variety of infections, especially in children and immunosuppressed individuals. The potential benefits of MBL reconstitution therapy therefore need to be evaluated. We have carried out a phase I safety and pharmacokinetic study on 20 MBL-deficient healthy adult volunteers. The MBL was prepared from plasma of nonremunerated, voluntary Danish donors tested and found negative for hepatitis B surface antigen, antibodies to human immunodeficiency virus (HIV) and hepatitis C virus. Each volunteer received a total of 18 mg of MBL in three 6 mg doses given intravenously, once weekly over a period of 3 weeks. The volunteers were closely monitored at the University Hospital in Reykjavik for 8 h after each infusion and daily thereafter for 5 days after each infusion. No adverse clinical or laboratory changes were observed in any of the 20 participants, and frequent measurements did not reveal any signs of infusion-associated complement activation. No antibodies to MBL, HIV or hepatitis viruses were observed 24 weeks after the last infusion. Serum MBL levels increased up to normal levels (1200-4500 ng/ml) immediately after each infusion, but the half-life of the infused MBL was highly variable, ranging from 18 to 115 h (mean 69.6). It is concluded that infusion of purified MBL as prepared by Statens Serum Institut (SSI) is safe. However, adults have to be given at least 6 mg twice or thrice weekly for maintaining protective MBL levels assumed to be about 1000 ng/ml.

Adolescent↗

PubMed2001

Low mannose binding lectin predicts poor prognosis in patients with early rheumatoid arthritis. A prospective study.

OBJECTIVE: To determine whether low mannose binding lectin (MBL) is associated with poor prognosis in rheumatoid arthritis (RA) and whether patients with RA have increased frequency of MBL deficiency. METHODS: Patients with recent onset symmetric polyarthritis (< 1 year, median 3 mo) were recruited if they had not been treated longer than 2 weeks with disease modifying drugs. They were reevaluated after 6 months and their disease activity and progression were correlated with their MBL concentration, rheumatoid factor (RF) isotypes, and C-reactive protein (CRP). Sixty-three female patients with advanced RA were also analyzed. RESULTS: Sixty-five patients with early arthritis fulfilled American College of Rheumatology criteria for RA and 52 were followed for 6 months or longer. Low MBL was associated with raised RF, IgA RF in particular (p = 0.02). and also with a combined elevation of IgM and IgA RF (p = 0.035). Patients with low MBL (lowest 25th percentile) showed less improvement after 6 months of treatment than patients in the highest MBL quartile. This applied to the Thompson joint score (p = 0.03) and grip strength (p = 0.004). Low MBL was also significantly associated with radiological joint erosions at recruitment and at 6 month followup (p = 0.039); and the group with advanced RA also showed a significant association between low MBL concentration and radiological damage (p = 0.036). However. neither patient group had increased frequency of MBL deficiency compared to healthy controls. CONCLUSION: Low MBL predicts poor prognosis in patients with early RA.

Adolescent↗

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↗

PubMed1992

Rate-limiting components and reaction steps in complement-mediated haemolysis.

The aims of this study were to identify the rate-limiting components and reaction steps in the integrated activation sequence of the alternative (AP) and classical (CP) pathways of the complement (C) system. In an initial correlation analysis we found that the haemolysis rate in AP was correlated with the concentrations of C5 and IgM. In CP, the haemolysis rate was correlated with the concentrations of C2-C6, factors I and B, and IgM. In order to identify the rate-limiting components, we added single, purified C components and IgM to pooled, normal human serum and measured the resultant change in the haemolysis rate. We found that a large number of different components, rather than a single one, were rate-limiting in AP and CP. In reconstitution experiments we found that in CP the rate-limiting reaction steps are the activation of C4 and C2. In AP we cannot identify the rate-limiting step precisely, but can only state that it is at the C3 activation step or earlier.

Adolescent↗

PubMedDate not supplied

The potential role of mannan-binding lectin in the clearance of self-components including immune complexes.

Mannan-binding lectin (MBL) is a pattern recognition receptor in the innate immune system. It recognizes certain sugar residues arranged in a pattern that enables MBL to bind with sufficient strength. Such sugar patterns are common on the surface of many microorganisms, and MBL has therefore been considered to be an agent that can discriminate between self and nonself. There is, however, increasing evidence supporting that MBL, like many membrane-bound C-type lectin-like receptors, also helps to dispose of various outworn or abnormal body components. Most self-components are protected with sialic acid or galactose that disrupt the pattern of the sugars that MBL can bind, but MBL may be significantly involved in the elimination of self-components that have lost these protective terminal residues. The role of MBL in the clearance of invading pathogens has previously been thoroughly reviewed. Here, we review some findings that support the notion that MBL may contribute to noninflammatory removal of immune complexes and abnormal cells by the reticuloendothelial system. Defects in this clearance mechanism may cause an accumulation of potentially dangerous self-components, thereby increasing the likelihood of chronic inflammation and autoimmunity.

Animals↗