Search PubMed⌕ Search

Biomedical subjects

K Steinsson

Publications and source records attributed to K Steinsson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Increased number of interleukin-10-producing cells in systemic lupus erythematosus patients and their first-degree relatives and spouses in Icelandic multicase families.

OBJECTIVE: To evaluate the production of interleukin-10 (IL-10) as well as levels of IgG and antinuclear antibodies (ANA) in systemic lupus erythematosus (SLE) patients and their first-degree relatives and spouses in Icelandic SLE multicase families. METHODS: IL-10 production was studied by enzyme-linked immunospot assay of freshly isolated peripheral blood mononuclear cells. Total IgG and ANA were also investigated. Subjects consisted of 23 SLE patients and 47 of their first-degree relatives in 9 Icelandic multicase families. Subjects were ethnically matched by a group of healthy controls. A separate study investigated 12 SLE patients (also from SLE multicase families) and their spouses and a matched group of healthy controls. A predefined protocol was used to obtain both clinical and laboratory data, including information about SLE and other autoimmune disorders. RESULTS: The SLE patients had a significantly higher number of IL-10-producing cells compared with both first-degree relatives and healthy controls (P = 0.0005 and P < 0.0001, respectively). First-degree relatives also had a significantly higher number of IL-10-producing cells compared with healthy controls (P = 0.01). This was also true for the spouses of SLE patients, who had a higher number of IL-10-producing cells compared with matched healthy controls (P = 0.02). CONCLUSION: SLE patients and their first-degree relatives, as well as a limited number of healthy spouses of SLE patients, had increased numbers of spontaneous IL-10-producing cells. These data support the hypothesis that IL-10 production may be genetically determined, and may predispose one toward development of SLE. This has previously been suggested by studies of SLE patients and their relatives in another ethnic population, using another method for measuring IL-10 production. Although these data are based on a small number of observations, they suggest that not only genetic but also environmental factors may be of importance in determining IL-10 production, since the spouses of SLE patients also had an increased number of IL-10-producing cells.

Autoantibodies↗
PubMed1999

A comparison of genome-scans performed in multicase families with systemic lupus erythematosus from different population groups.

Systemic lupus erythematosus is a disease of unknown etiology. Multiple genetic factors are believed to be involved in its pathogenesis. In addition, and due to genetic heterogeneity, these factors and/or their combinations may be different in different ethnic groups, while some might be shared between populations. We have performed genome scans in multicase families from three different population groups, two from Northern Europe, with a high degree of homogeneity, and the third from a recently admixed population of Mexican Mestizos. Although our family material is relatively small, the results presented here show that using family sets from well defined populations are sufficient to detect susceptibility loci for SLE. Our results also reveal the chromosomal regions most likely to contain susceptibility genes for SLE.

Ethnicity↗
PubMed1999

Genetic analysis of the contribution of IL10 to systemic lupus erythematosus.

OBJECTIVE: To study the contribution of the IL10 gene to the susceptibility to systemic lupus erythematosus (SLE). METHODS: Analysis by fluorescent-semiautomated genotyping of a dinucleotide repeat located in the promoter region of the IL10 locus (microsatellite G). RESULTS: No significant difference was found in the frequencies of the microsatellite alleles of 330 Mexican patients with SLE compared to 368 controls from the same population. Two-point linkage analyses were carried out using 13 Mexican, 13 Swedish, and 8 Icelandic families with 2 or more cases with SLE. No linkage was revealed between IL10 and SLE, using a variety of parameter settings. CONCLUSION: Our results do not support that the IL10 gene contributes to the susceptibility to SLE in the populations we studied.

Dinucleotide Repeats↗
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

A study of the association of HLA DR, DQ, and complement C4 alleles with systemic lupus erythematosus in Iceland.

OBJECTIVE: To perform an exploratory analysis of the relative contribution of single MHC genes to the pathogenesis of systemic lupus erythematosus (SLE) in a homogenous white population. METHODS: MHC class II alleles and C4 allotypes were determined in 64 SLE patients and in ethnically matched controls. HLA-DR and DQ typing was performed by polymerase chain reaction amplification with sequence specific primers. C4 allotypes were determined by agarose gel electrophoresis. RESULTS: The frequency of C4A*Q0 was significantly higher in patients than in controls (46.9% v 25.3%, p = 0.002). HLA-DRB1, DQA1, and DQB1 alleles in the whole group of SLE patients were not significantly different from those of controls. On the other hand increase in DRB1*03 was observed in the group of patients with C4A*Q0, as compared with patients with other C4A allotypes (p = 0.047). There was no significant correlation between severe and mild disease, as judged by the SLEDAI, and HLADR, DQ alleles and comparing the patients with C4A*Q0 with those with other C4A allotypes there was no significant difference regarding clinical manifestations. CONCLUSION: The results are consistent with the argument that C4A deficiency contributes independently to susceptibility and the pathogenesis of SLE. C4A*Q0 in SLE patients in Iceland shows weaker linkage disequilibrium with DR3 genes than reported in most other white populations and emphasises the role of ethnicity.

Adolescent↗
PubMed1998

C4AQ0 superimposed on a primary defect increases the susceptibility to systemic lupus erythematosus (SLE) in a family with association between C4AQ0 and SLE.

OBJECTIVE: To investigate the association of C4AQ0 with increased incidence of systemic lupus erythematosus (SLE) or positive serology (28%) in an extended Icelandic family, and whether this can be explained by impaired complement function in handling immune complexes (IC). METHODS: The ability of the classical pathway to opsonize nascent IC [alkaline phosphatase (AP)-anti-AP] and bind them to human erythrocytes was evaluated by the new ICRB assay. The capacity of erythrocytes from family members to bind nascent IC was also measured by a modification of the ICRB assay. IC levels were measured by complement consumption assay, C3d by a sandwich ELISA, factor B by immunoelectrophoresis, and the alternative pathway function by a hemolytic assay. RESULTS: Family members with homozygous or heterozygous C4AQ0 (47%) showed no impaired complement dependent opsonization of IC and binding to erythrocytes. Their factor B and alternative pathway function was normal. Fifty-six percent of the family members (n=18) had abnormally high IC levels, seemingly independent of C4AQ0. However, 6 of the 7 individuals with high IC levels and SLE symptoms had C4AQ0 compared to 2 of 11 symptom-free individuals with high IC levels. CONCLUSION: Our results suggest that the susceptibility for SLE in this family may result from 2 different defects, one leading to elevated IC levels, and another associated with C4AQ0 without detectable impairment in the complement dependent IC transport mechanism. Individuals with both abnormalities have increased susceptibility to SLE.

Antigen-Antibody Complex↗
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↗
PubMed1995

Psychiatric disorders among subjects with systemic lupus erythematosus in an unselected population.

The prevalence of lifetime psychiatric disorders was investigated among all known systemic lupus erythematosus (SLE) patients in Iceland. The participation rate was 81%. Over 49% of the subjects received a lifetime psychiatric diagnosis. The number of diagnoses per person was 2.3. The most common disorder among those with a disorder was phobia (56%), followed by generalized anxiety (12%). Agoraphobia with and without panic, simple, social phobia, and alcohol abuse were found to be more common among the SLE patients in comparison with a population sample (p < 0.02; p < 0.0001; p < 0.001; p < 0.0001; p < 0.05, respectively). A possible explanation of the high rate of phobia may be related to the nature of clinical disfiguring facial skin rashes which may lead to social withdrawal.

Adult↗
PubMed1995

Raised IgA rheumatoid factor (RF) but not IgM RF or IgG RF is associated with extra-articular manifestations in rheumatoid arthritis.

In rheumatoid arthritis (RA) seropositivity has been associated with poor prognosis including bone erosions and extra-articular manifestations. However, findings have been conflicting on the association between individual rheumatoid factor (RF) isotypes and extra-articular manifestations. In this study the occurrence of extra-articular manifestations was examined in the context of the RF isotype patterns rather than individual RF isotypes. IgM, IgG and IgA RF was measured by ELISA in 74 patients with RA and the findings correlated with the presence or absence of extra-articular manifestations. Of the IgA RF positive patients 80% had one or more extra-articular manifestations. In contrast, only 21% of patients with raised IgM and/or IgG RF but normal IgA RF had some extra-articular manifestations and 27% of the seronegative patients. It is concluded that the previously reported association between raised RF and extra-articular manifestations in RA can largely be attributed to the IgA RF isotype.

Adult↗
PubMed1995

A study of the major histocompatibility complex in a Caucasian family with multiple cases of systemic lupus erythematosus: association with the C4AQ0 phenotype.

OBJECTIVE: In an epidemiological survey of systemic lupus erythematosus (SLE) in Iceland several families with multiple cases were identified. In one family, 35 individuals (family members and spouses) in 3 generations were studied clinically, tested for autoantibody formation, and typed for HLA and toxicity complement phenotypes. METHODS: Typing for HLA-A, B, C, DR, and DQ was performed by microlymphocytotoxic assay. In selected samples HLA-DR typing by polymerase chain reaction amplification with sequence specific primers was performed. C4 allotypes were defined by agarose gel protein electrophoresis followed by immunofixation with goat antisera. RESULTS: Five family members fulfilled 4 or more criteria for SLE. Additionally, 5 family members had clinical manifestations or positive serology but did not fulfill 4 ARA criteria. The mean age at onset of symptoms was 22 yrs (8-40). Other autoimmune diseases were not documented in family members. C4A null seemed to be highly associated with disease in this family. All except one patient with SLE and all those with clinical manifestations and positive serology had C4A null in the homozygous or heterozygous form. The individual with SLE and not carrying C4A null had both HLA haplotypes identical. It is noteworthy that there were 5 different C4A null bearing haplotypes involved, of which 3 originated from the spouses. CONCLUSION: Our results are consistent with the argument that C4A deficiency plays a role in the pathogenesis of SLE. There is, however, the possibility of an unidentified environmental or another genetic factor being involved.

Adolescent↗
PubMed1994

Giant cell arteritis in Iceland. An epidemiologic and histopathologic analysis.

OBJECTIVE: To investigate the incidence and clinical and histopathologic features of giant cell (temporal) arteritis (GCA) in the Caucasian population of Iceland. METHODS: All patients diagnosed between 1984 and 1990 were included. Case ascertainment for the study was done in 2 ways: 1) a computerized search from all hospitals and primary care clinics for the diagnosis of GCA, and 2) a review of all temporal artery biopsies performed during the 7-year period. RESULTS: One hundred thirty-three patients with GCA were identified. All fulfilled the 1990 American College of Rheumatology criteria for the classification of GCA. The incidence rate for the population 50 years and older was 27/100,000 (36/100,000 and 18/100,000 for women and men, respectively). Clinical findings included the following: mean age at diagnosis 72.5 years for women and 70.3 years for men, new headache 63.2%, abnormal temporal artery on palpation 43.6%, mean erythrocyte sedimentation rate 88 mm/hour, symptoms of polymyalgia rheumatica 48.1%, and visual disturbances 14.3%. A total of 744 patients underwent temporal artery biopsy during the 7-year period; 16.8% had a positive biopsy result. All 133 patients with the diagnosis of GCA underwent a temporal artery biopsy; 94% had a positive result. Histopathologic findings from the positive biopsies included a fragmented internal elastic lamina in 99.2%, giant cells in 65.6%, and fibrinoid necrosis in 12%. CONCLUSION: Compared with previous epidemiologic surveys, this study shows a high incidence of biopsy-proven GCA in Iceland.

Aged↗
PubMed1994

Systemic sclerosis in Iceland. A nationwide epidemiological study.

OBJECTIVES: To investigate the incidence, prevalence and clinical features of systemic sclerosis (SS) in Iceland. METHODS: All patients diagnosed with SS from 1975-90 were included. Retrieval for the study began in 1980 and was carried out by computerised search from registers of all hospitals and health care clinics and death registration files, and with personal communication with doctors in Iceland. RESULTS: Over a 16 year period from 1975-90, 15 new cases were found with an incidence of 0.7 and 0.05/100,000, for females and males at risk respectively, and 0.38 for both sexes. At the end of 1990 there were 18 patients alive with SS, 13 with limited and five with diffuse cutaneous involvement. The age standardised prevalence was 11.9 and 1.5/100,000 for females and males at risk respectively. The crude prevalence rate for both sexes was 7.1/100,000. There were five deaths, two patients died of SS related causes, one had SS renal disease. The relative risk of death was similar to that in the general population. The calculated five year survival rate was 100% and the 10 year survival rate 81%. No HLA antigen association was found. CONCLUSION: Compared with previous surveys this study shows a low incidence of systemic sclerosis and a high proportion of patients with limited cutaneous involvement.

Adolescent↗
PubMed1994

[Diffuse connective tissue diseases (DCTD)--a review].

The diffuse connective tissue diseases constitute a group of inflammatory diseases with the potential of involvement of many organ systems. The etiopathogenesis is thought to be multifactorial, involving the interaction between particular genetic background and exogenous agents. Recently theories regarding inherited defects in the clearing of immune complexes have been put forward. Serological markers are important diagnostic tools in many of these diseases and emphasize the role of autoimmunity. Epidemiological studies have demonstrated an increase in incidence in some of these diseases and because of selection bias many epidemiological studies may overestimate the severity of these diseases. Therapy aims at modulating and suppressing inflammation. A step towards more directed immune modulation is the use of cyclosporin A and monoclonal antibodies against various surface antigens and mediators in inflammation.

Antigen-Antibody Complex↗
PubMed1993

Splenic uptake of immune complexes in man is complement-dependent.

We have examined the effects of hereditary homozygous C2 deficiency on the processing of radiolabeled soluble immune complexes (IC). A patient with C2 deficiency was studied before and after treatment with fresh frozen plasma (FFP). Hepatitis B surface Ag (HBsAg):anti-HBsAg immune complexes were prepared in vitro using Ag radiolabeled with 123I, and injected intravenously. Dynamic and static gamma-scintigraphy was performed to delineate the sites and kinetics of complex clearance. The patient was initially studied when her C2 level and CH50 were zero, and again 1 wk later after treatment with 12 units of FFP, which normalized these parameters. Before treatment there was rapid uptake of complexes by the liver (t90% [time for 90% uptake] = 13.6 min) and rapid clearance from the circulation (t1/2 = 6.8 min). No splenic uptake was detected, and there was no binding of complexes to erythrocyte CR1. Between 30 and 60 min there was release of 11% of the tracer from the liver. In the second study, performed after normalization of classical pathway complement activity, the t1/2 of IC clearance increased to 9.8 min, and t90% was 27 min. Twenty percent of injected complexes now localized to the spleen, and there was no longer any release of complexes between 30 and 60 min. The kinetics of IC processing and the sites of uptake in this posttherapy study were closely similar to two normal subjects studied in parallel, with a maximum of 72% of injected complexes binding to erythrocytes. These observations indicate that the uptake of immune complexes in the spleen in humans is complement-dependent, and suggest that the observed predisposition to SLE in patients with complement deficiency may be related to abnormal processing of immune complexes.

Antigen-Antibody Complex↗
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↗
PubMed1993

Pain and pain problems among subjects with systemic lupus erythematosus in Iceland.

This population study includes the majority of all systemic lupus erythematosus (SLE) patients in Iceland (n = 65). The study lists various self-rated pain descriptions both from a 54-item pain questionnaire and from the somatisation section of the Diagnostic Interview Schedule (DIS). Results show SLE patients to have significantly more joint and chest pain than does another patient group; to use analgesics more frequently; to have been in hospital more often during the past 10 years and to believe they know the reason for their pain. Also listed are factors that patients have found to increase and decrease SLE pain.

Adult↗