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L Truedsson

Publications and source records attributed to L Truedsson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Synergetic effect between interleukin-1 receptor antagonist allele (IL1RN*2) and MHC class II (DR17,DQ2) in determining susceptibility to systemic lupus erythematosus.

We investigated whether IL1RN alleles separately or in combination with MHC class II variants, contribute to susceptibility to SLE and to analysed if IL1RN alleles are markers of disease severity. We investigated 81 patients from a defined area in southern Sweden diagnosed between 1981-1992 and 10 consecutive Caucasian families with multiple cases of SLE. As control group 189 healthy blood donors was used. PCR amplification of defined gene sequences was used in determining the IL1RN polymorphism as well as the MHC class II variants. The IL-1RA levels were measured by an immunoassay. We found an increased frequency of IL1RN*2 in both the epidemiological cohort and in the multicase families (P < 0.01). Alone IL1RN*2 and MHC class II (DR17,DQ2) separately increased the SLE risk moderately. The occurrence of IL1RN*2 and MHC class II variants DR17 and DQ2 together increased the risk to develop SLE by a sevenfold. The IL-1RA gene polymorphism did not correlate with disease severity or with renal involvement. We found an association between IL1RN*1 and arthritis (P < 0.001). Serum level of IL-1RA did not correspond to any specific IL1RN allele. An increased frequency of IL1RN*2 suggests the presence of a gene, implemented in SLE-susceptibility, in the IL1RN region of chromosome 2. IL1RN*2 and specific variants of MHC class II act in synergy to increase disease susceptibility. IL1RN*1 may be a marker of risk for development of arthritis.

Alleles↗
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

Characterization of non-expressed C4 genes in a case of complete C4 deficiency: identification of a novel point mutation leading to a premature stop codon.

The genetic basis of complete C4 deficiency in a patient with SLE was investigated. Previous studies have demonstrated that this patient has two different major histocompatibility complex (MHC) haplotypes that each contain a major deletion and a non-expressed C4 gene. In the present study, non-expression of the C4 genes was explained by the finding of two distinct C4 gene mutations. A previously described two base pair insertion in exon 29 of the C4 gene was detected in the paternal MHC haplotype [HLA-A2, B40, SC00, DR6]. The maternal haplotype [HLA-A30, B18, F1C00, DR3] carried a C4 gene with a one base pair deletion in exon 20 generating a premature stop codon. This mutation was neither found in 10 individuals with known non-expressed C4 genes nor in 9 individuals homozygous for the complotype F1C30. The isotype and allotype specific regions of the patient's C4 genes were sequenced, and both contained C4A3a sequence. In conclusion, two different MHC haplotypes resembling the extended haplotypes [HLA-A2, B40, SC02, DR6] and [HLA-A30, B18, F1C30, DR3] both contained a non-expressed C4A gene that was due to either of two distinct mutations, demonstrating the heterogeneous genetic background of C4 deficiency.

Adult↗
PubMed1998

Adverse reactions during endovascular treatment of aortic aneurysms may be triggered by interleukin 6 release from the thrombotic content.

PURPOSE: It has been shown that endovascular aortic aneurysm repair might induce a significant inflammatory response, mainly involving tumor necrosis factor (TNF-alpha) release. This study determined in vitro whether these inflammatory responses could depend on white blood cell (WBC) activation caused by the aneurysmal mural thrombus. METHODS: Mural thrombus specimens obtained from 10 different aortic aneurysms were weighed, homogenized, and assayed for interleukin 1beta (IL-1beta), interleukin 6 (IL-6), TNF-alpha, and soluble TNF receptor (sTNFRI). RESULTS: Only high amounts of IL-6 (mean, 2973 pg/mL) were found. In contrast, after the addition of healthy donor WBCs to the thrombus mass supernatants, elevated levels of TNF-alpha (mean, 523 pg/mL) were seen. Theoretically, WBCs were stimulated by IL-6, resulting in TNF-alpha release. In additional experiments, it was proven that stimulated WBCs, induced by thrombus mass supernatants, synthesize TNF-alpha (mean, 796 pg/mL), and monoclonal antibodies against IL-6, prevented such TNF-alpha production (mean, 62 pg/mL). CONCLUSION: The biologic responses during endovascular repair may be explained by a release of IL-6 from the aneurysmal thrombus, causing WBC stimulation and production of TNF-alpha. More complex processes cannot be excluded, but the present findings suggest that restrictions of manipulations within the aneurysm may be advisable.

Aortic Aneurysm, Abdominal↗
PubMed1998

Expression of properdin in complete and incomplete deficiency: normal in vitro synthesis by monocytes in two cases with properdin deficiency type II due to distinct mutations.

Three properdin deficiency phenotypes have been reported--complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin protein (type III)--all associated with increased susceptibility to meningococcal disease. Expression of properdin by monocytes was examined in type I deficiency and in two unrelated cases with type II deficiency, one from a Swedish and one from a Danish family. The properdin gene in the Danish family contained a point mutation in exon 8 causing a Gln316-->Arg substitution, distinct from a point mutation in exon 4 previously found in the Swedish family. Both genes coded for physicochemically abnormal properdin molecules with changed hydrophilicity. Monocytes from all the properdin-deficient individuals produced properdin mRNA in a normal fashion. In type I deficiency no intracellular or secreted properdin was found, indicating rapid intracellular degradation. Monocytes from the males with type II deficiency expressed and secreted properdin normally. Properdin in sera with type II deficiency showed abnormal oligomerization with a relative decrease in properdin trimers and tetramers. Our findings suggest that the low concentration of circulating properdin in type II deficiency is caused by increased extracellular catabolism. Analysis of properdin expression by monocytes in a female carrier in the family with properdin deficiency type I provided direct evidence of lyonization at the cellular level.

Amino Acid Sequence↗
PubMed1998

HLA-Cw alleles associated with HLA extended haplotypes and C2 deficiency.

There are four MHC-linked complement genes, BF, C2, C4A and C4B, that are inherited as single DNA units, known as complotypes. Extended haplotypes were initially defined by studying the distribution of complotypes in relation to HLA-B and HLA-DR loci in Caucasian families. In order to analyze the distribution of HLA-Cw alleles in relation to extended haplotypes, we studied a large panel of MHC homozygous and heterozygous cell lines representing previously described Caucasian-derived extended haplotypes and 14 patients with complete C2 deficiency. HLA alleles were assigned using sequence-specific oligonucleotide probe hybridization (SSOP). Family analysis served to assign haplotypes for heterozygous samples. We found distinctive HLA-Cw alleles for each independent extended haplotype. Their association in each instance was statistically significant. All patients with C2 deficiency carrying the haplotype [HLA-B18, S042, DR2] were associated with HLA-Cw*1203. These conserved allelic combinations may become an important tool for the study of human evolution and may contribute to the expeditious selection of prospective donors in clinical transplantation.

Alleles↗
PubMed1998

Reference typing report for complement receptor 1 (CR1).

A total of 100 Chinese blood donors (50 from Shen-Zhen and 50 from Taiwan) were studied by the participants in addition to 9 reference samples. A new nomenclature for the CR1 structural alleles was recommended by the participants which would use a numbering system, e.g. CR1*1. The structural allele frequencies in the Chinese were: CR1*1 (190 kD) 0.96, CR1*2 (220 kD) 0.03, CR1*3 (160 kD) 0.01 and CR1*4 (250 kD) 0.00. The HindIII expression polymorphism was also studied and the high expressing allele had a gene frequency of 0.71 while the low expressor gene frequency was 0.28. Erythrocyte copy numbers were quantified and compared between laboratories with good correlation (R = 0.55-0.88). The mean (+/- SD) erythrocyte copy number was 463 (+/- 229) in the Taiwan donors and 446 (+/- 207) in the Mainland Chinese.

Alleles↗
PubMed1997

Relationship between protein complotypes and DNA variant haplotypes: complotype-RFLP constellations (CRC).

From the study of 52 families and 15 homozygous typing cells, 234 MHC complement haplotypes were characterized for features in the DNA of the complotype region: C2/Sst I (2.75, 2.70, 2.65, and 2.40 kb), BF/Taq I (6.6 and 4.5 kb), C4 5'/Bgl II (15 and 4.5 kb), C4 5'/Taq I (7.0, 6.4, 6.0 and 5.4 kb) and C4 3'/Xba I/BamH I (11 and 4 + 7 kb) restriction fragment length polymorphisms (RFLP's), by the presence or absence of C4A, C4B, CYP21A and CYP21B genes and by duplications. Nineteen (of over 1000 theoretically possible) complotype-RFLP constellations (CRC's) were found. The 9 CRC's with two C4 and CYP21 genes were designated A through I. CRC's Bdup and Ddup were like B and D but had duplicated C4B-CYP21B genes. The remaining CRC's had deletions of C4 and/or CYP21 genes and were designated Bdel, Cdel and the like. Individual complement alleles and complotypes were nor randomly distributed among the CRC's. Some complotypes, such as SC01, SC02 and FIC30, were restricted to only 1 CRC; others, such as SC31, FC31, and SC30, were found in several CRC's. Some of the CRC's contained a single complotype, others contained several. Remarkably, there are about 30 CRC-specified complotypes with frequencies of .01 or higher and 14 of .02 or higher. A number of evolutionary origins of complement alleles and complotypes are suggested by the relationships among CRC's. Approximate normal frequencies of the undeleted CRC's were A = .27, B = .19, Bdup = .02, C = .17, D = .07, Ddup = .02, E = .06, F = .05, and G = .02. Thus, CRC's without deletions accounted for 88% of normal complotypes. Since the frequency of Bdel, with a deletion of C4A, was .12, 10 CRC's accounted for all observed normal caucasian MHC haplotypes.

Chromosome Mapping↗
PubMed1997

Tumor necrosis factor-alpha and interleukin-6 release from white blood cells induced by different graft materials in vitro are affected by pentoxifylline and iloprost.

Inflammatory mediators such as cytokines produced by white blood cells (WBCs) at the site of implantation are important for the biocompatibility of vascular grafts. The aim of the present study was to demonstrate the tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) release from WBCs incubated with expanded polytetrafluoroethylene (ePTFE) or woven Dacron grafts. In a second series the effects of pentoxifylline (PTX) and iloprost (ILO), both known to inhibit white blood cell function, on this release were determined. Woven Dacron grafts induced significantly higher release of both TNF-alpha and IL-6 compared to ePTFE. TNF-alpha was detectable first after 2 h, whereas IL-6 was seen after 4 h. Maximum values were reached at 6 and 12 h, respectively. The addition of an endotoxin gave more pronounced patterns of cytokine release not influenced by time. Preincubation with both PTX and ILO at final concentrations of 100 and 10 micrograms/mL, respectively, reduced significantly the TNF-alpha release without differences between the two graft materials, whereas the effect on the IL-6 release varied and was graft material-dependent. In conclusion, graft material-dependent induction of TNF-alpha and IL-6 from WBCs was demonstrated. PTX and ILO influenced the cytokine release. It might be suggested that graft material-induced cytokine production could contribute to intimal hyperplasia in vivo. The present findings encourage further studies regarding graft material-induced WBC alterations and the role of pharmacologic agents influencing this function.

Biocompatible Materials↗
PubMed1997

Endovascular abdominal aortic aneurysm repair induces significant alterations in surface adhesion molecule expression on donor white blood cells exposed to patient plasma.

OBJECTIVE: To determine the response of white blood cells in endovascular aortic aneurysm repair. MATERIALS AND METHODS: Seven patients treated with an endoluminal procedure (AAA-E) and seven patients undergoing conventional surgery (AAA-C) were included (all males, aged 52-80 years). A panel of monoclonal antibodies against CD11a, CD11b, CD11c, CD18 and L-selectin was used. To determine the surface receptors on both circulating and sequestered white blood cells, plasma from the patients and cells from healthy donors were combined for flow-cytometry. RESULTS: The expression of CD11a adhesion molecules only showed slight variations regarding granulocytes, but was more pronounced on monocytes, however, without significant differences between the two patient groups, CD11b, CD11c and CD18 molecules on both granulocytes and monocytes were significantly upregulated 60 min after the endovascular procedure compared to conventional aneurysm repair, and L-selectin molecules were by this time correspondingly cleaved off. CONCLUSION: Endovascular aneurysm repair differed significantly from conventional aneurysm surgery with peak adhesion molecule expression 60 min after balloon deflation, probably caused by release of tumour necrosis factor-alpha (TNF-alpha).

Aged↗
PubMed1997

Modest release of adipsin/factor D by liposuction when using the superwet or tumescent technique.

Human adipsin is recognized to be identical to factor D, which plays an important role in activation of the alternative complement pathway. Since adipsin/factor D is present in high amounts in adipose tissue, liposuction theoretically could result in an increased release of this serine protease into the bloodstream. In the present study, adipsin/factor D was measured in 22 patients undergoing syringe-assisted liposuction using the superwet or tumescent technique. Despite a relatively high mean aspirate volume (2648 ml), only a very modest increase in adipsin/factor D concentration was found during liposuction. All values before, during, and after liposuction were within the range found in healthy blood donors. Furthermore, there was no correlation between adipsin/factor D values and C3 activation products. We conclude that liposuction with the present techniques results in a very modest release of adipsin/factor D that is not associated with increased complement activation.

Complement Activation↗
PubMed1996

Molecular characterization of properdin deficiency type III: dysfunction produced by a single point mutation in exon 9 of the structural gene causing a tyrosine to aspartic acid interchange.

Inherited properdin deficiency is an X-linked recessive disorder clinically manifested by susceptibility to meningococcal disease. Deficiency of properdin is characterized by complete absence (type I), very low level presence (type II), or the presence of a dysfunctional properdin protein in serum as found in one Dutch family (type III). To better understand the dysfunctional protein on the molecular level, samples from three members of the Dutch family were analyzed by direct genomic sequencing. The sequence of the complete gene, including 10 exons and 9 introns, covering about 6500 bases was determined. The dysfunctional properdin was found to be caused by a single T to G mutation in exon 9, which gives rise to a substitution of a tyrosine by an aspartic acid residue at position 387. This change to a hydrophilic amino acid affects the function of the properdin molecule, although the oligomerization of dysfunctional properdin molecules was similar to that of normal properdin. In binding studies with C3b and properdin in serum, no properdin deposition was detected with the type III deficient serum. Inhibition studies with different decapeptides revealed distinct inhibitory sequences, and indicated also that the part of properdin containing the type III mutation was not directly involved in the binding to C3b. The mutation most likely causes conformational changes that make the properdin molecule dysfunctional by affecting its binding to C3b.

Amino Acid Sequence↗
PubMed1996

Surface adhesion molecule expression on human blood cells induced by vascular graft materials in vitro.

The expression of surface adhesion molecules on granulocytes, monocytes (CD11a, CD11b, CD11c, CD18, L-selectin), and platelets (P-selectin, gpIIb-IIIa) was determined after incubation with different graft surfaces [expanded polytetrafluoroethylene (ePTFE) or woven Dacron]. Woven Dacron grafts upregulated the CD11b and CD11c surface antigens on both granulocytes and monocytes. Both graft materials demonstrated increased expression of CD11a and CD18 adhesion molecules on white blood cells at 30 min, followed by a downregulation. Maximum L-selectin expression was seen at 120 min on granulocytes and at 90 min on monocytes without differences between the graft materials. A rapid downregulation of gpIIb-IIIa complexes on platelets was noticed, while no expression of platelet P-selectin molecules was observed. In conclusion, both graft materials induced alteration of the white blood cell adhesion molecule expression, but the intensity and time course were dependent on the cell type and the graft material, suggesting that different mechanisms might be implicated. The expression of platelet surface antigens was less clearly influenced. The clinical significance of an enhanced cell surface antigen receptor expression caused by woven Dacron (CD11b, CD11c) has to be further studied. However, determination of adhesion molecule expression might offer possibilities to predict biocompatibility.

Blood Platelets↗
PubMed1996

Aortobifemoral surgery induces complement activation and release of interleukin-6 but not tumour necrosis factor-alpha.

The aim of the present study was to determine the inflammatory response by an extended analysis of complement in 16 patients undergoing aortobifemoral bypass surgery. The patients were randomized to receive either a bifurcated expanded polytetrafluoroethylene graft (n = 8; group I) or a collagen-impregnated knitted Dacron graft (n = 8; group II) to determine whether differences in graft surface properties might influence the inflammatory response during and after the procedure. The following components of complement: C1q, C4, C3, C3d, C5a and terminal complement complexes were all analysed. C-reactive protein and interleukin-6 were also determined to assess the acute phase response. The complement data were corrected for haemodilution, which was assessed from alpha 2-macroglobulin concentrations. A significant decrease of C1q (P < 0.0001) and an increase in C5a (P < 0.0005) was observed in both groups. C4 and C3 levels showed slight fluctuations in group I, whereas in group II these proteins increased significantly (P < 0.05, P < 0.005, respectively) between 2 and 7 days after surgery. Terminal complement complexes remained unchanged in both groups. Interleukin-6 levels peaked at 12-24 h and the C-reactive protein at 24-72 h. Higher interleukin-6 levels (P < 0.05) were found in group II 6 h after surgery compared with group I; no release of tumour necrosis factor-alpha was identified. An early inflammatory response was found in all patients. The patterns of the complement proteins varied with a C1q depletion and a C5a increase, interpreted as complement activation. Whether the variations between the two graft groups represent any differences in graft surface properties has to be further elucidated.

Aged↗
PubMed1996

Biological responses differ considerably between endovascular and conventional aortic aneurysm surgery.

OBJECTIVES: To determine the inflammatory responses in endovascular abdominal aortic aneurysm (AAA) repair and their relation to clinical findings. DESIGN: Prospective non-randomised study. SETTING: University Hospital, Department of Surgery. PATIENTS AND METHODS: Seven patients treated with an endoluminal procedure (AAA-E) and seven patients undergoing conventional surgery (AAA-C) were included. Inflammatory parameters were assessed by measurements of the cytokines interleukin (IL)-1 beta, IL-6, IL-8 and Tumour Necrosis Factor-alpha (TNF-alpha); analyses of complement proteins C1q, C4, C3, C5a and Terminal Complement Complexes (TCC); haematologic parameters and determination of C-reactive protein (CRP). RESULTS: In six of seven patients in the AAA-E group blood pressure decreases were recorded during introduction of the device. IL-6 and CRP levels were found to be significantly higher in AAA-C patients compared to the AAA-E group. On the other hand, high TNF-alpha levels were recorded in the AAA-E group. Less consumption of the complement proteins C1q, C4 and C3 was observed in AAA-E compared to AAA-C patients. Increased C5a levels were recorded in the AAA-C group, whereas only slight fluctuations were noticed in the AAA-E group. TCC levels were unchanged in both groups. CONCLUSION: Endovascular aortic aneurysm repair induced a significant inflammatory response, mainly involving TNF-alpha and differing from the findings during open AAA repair. These inflammatory responses were probably related to blood pressure decreases during the procedures. On the other hand, conventional repair induced responses related to the more extensive surgical trauma and reperfusion injury.

Aged↗
PubMed1996

Transplantation with allogenic bone marrow from a donor with systemic lupus erythematosus (SLE): successful outcome in the recipient and induction of an SLE flare in the donor.

OBJECTIVE: To investigate the transfer of autoimmunity by allogenic bone marrow transplantation. METHODS: Bone marrow transplantation was performed in a 43 years old man with acute myeloid leukaemia (AML) in remission. The donor was his HLA identical brother who had a mild systemic lupus erythematosus (SLE). Autoantibodies, including antinuclear, anti-C1q, and anticardiolipin antibodies, were measured before and after transplantation. RESULTS: Transient mild graft versus host disease (GvHD) developed in the recipient in the weeks following transplantation. The donor had persistently high concentrations of anti-C1q antibodies to the collagenous region of the complement component C1q. Three months after transplantation the recipient developed antiC1q antibodies that persisted for two months. No other autoantibodies and no SLE-like manifestations appeared. Chronic GVHD started five months posttransplant and responded to intensified immunosuppressive treatment. Three years post-transplant the patient was in unmaintained remission. Within a few weeks after bone marrow donation the donor's disease was exacerbated with development of severe pulmonary alveolitis which required treatment with cyclophosphamide. CONCLUSIONS: When bone marrow transplantation was performed in a patient with AML with bone marrow from an HLA identical brother who had SLE, no evidence of transfer of disease was obtained. However, the recipient temporarily produced anti-C1q antibodies which was a characteristic feature of the donor's SLE and was probably produced by the transplant. The flare of the donor's SLE might be related to the bone marrow tap.

Adult↗
PubMed1996

TNF microsatellites in systemic lupus erythematosus-a high frequency of the TNFabc 2-3-1 haplotype in multicase SLE families.

TNFa, TNFb and TNFc microsatellites were analyzed in 102 SLE patients recruited from a defined area in Southern Sweden. Furthermore we studied 27 SLE patients belonging to 10 multiplex families in which a majority of the members were living within the same area in Southern Sweden. As a control population 98 healthy blood donors from the same region was used. The TNFa2 allele was found more often in the SLE patients (48%) than in the normal controls (33%) (P < 0.01). A low frequency of the TNFa4 allele (10%) vs 16% in controls was observed. The family study showed that the TNFabc haplotype 2-3-1 was more common in SLE associated haplotypes than in non-SLE haplotypes (P < 0.001). The 2-3-1 haplotype was associated with the extended haplotype MHC haplotype [HLA-B8,SC01,DR17]. The results suggest that TNF haplotypes do not constitute special markers of susceptibility to SLE but reflect the increased frequencies of specific intact haplotypes already known to be associated with the disease.

Adolescent↗