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Biomedical subjects

I Lundberg

Publications and source records attributed to I Lundberg.

At least 19 recordsLinked to original sources
PubMed2001

Autoantibody profiles in the sera of European patients with myositis.

OBJECTIVE: To determine the prevalence of myositis specific autoantibodies (MSAs) and several myositis associated autoantibodies (MAAs) in a large group of patients with myositis. METHODS: A total of 417 patients with myositis from 11 European countries (198 patients with polymyositis (PM), 181 with dermatomyositis (DM), and 38 with inclusion body myositis (IBM)) were serologically analysed by immunoblot, enzyme linked immunosorbent assay (ELISA) and/or immunoprecipitation. RESULTS: Autoantibodies were found in 232 sera (56%), including 157 samples (38%) which contained MSAs. The most commonly detected MSA was anti-Jo-1 (18%). Other anti-synthetase, anti-Mi-2, and anti-SRP autoantibodies were found in 3%, 14%, and 5% of the sera, respectively. A relatively high number of anti-Mi-2 positive PM sera were found (9% of PM sera). The most commonly detected MAA was anti-Ro52 (25%). Anti-PM/Scl-100, anti-PM/Scl-75, anti-Mas, anti-Ro60, anti-La, and anti-U1 snRNP autoantibodies were present in 6%, 3%, 2%, 4%, 5%, and 6% of the sera, respectively. Remarkable associations were noticed between anti-Ro52 and anti-Jo-1 autoantibodies and, in a few sera, also between anti-Jo-1 and anti-SRP or anti-Mi-2 autoantibodies. CONCLUSIONS: The incidence of most of the tested autoantibody activities in this large group of European patients is in agreement with similar studies of Japanese and American patients. The relatively high number of PM sera with anti-Mi-2 reactivity may be explained by the use of multiple recombinant fragments spanning the complete antigen. Furthermore, our data show that some sera may contain more than one type of MSA and confirm the strong association of anti-Ro52 with anti-Jo-1 reactivity.

Antibody Specificity↗
PubMed2001

Increased levels of proinflammatory cytokines and nitric oxide metabolites in neuropsychiatric lupus erythematosus.

OBJECTIVE: To investigate systemic and intrathecal production of proinflammatory cytokines in relation to cerebrospinal fluid (CSF) nitric oxide (NO) release in patients with neuropsychiatric lupus erythematosus (NPLE). METHODS: Thirty patients with NPLE rated as mild, moderate, or severe were studied and CSF was obtained from 21 of these. Cytokine mRNA expressing cells were detected by in situ hybridisation. Soluble cytokines were assessed by enzyme linked immunosorbent assay (ELISA). Nitrite and nitrate were determined by capillary electrophoresis. RESULTS: Patients with NPLE had high numbers of lymphocytes expressing mRNA for tumour necrosis factor alpha (TNFalpha), interferon gamma, and interleukin 10 in blood. The number of peripheral blood TNFalpha mRNA positive cells correlated strongly with the level of NO metabolites in the CSF (r(2)=0.69). Both the number of peripheral blood mononuclear cells expressing mRNA for TNFalpha as well as the CSF level of NO metabolites correlated with NPLE disease severity. CONCLUSION: These data suggest that increased peripheral production of proinflammatory cytokines such as TNFalpha may contribute both to an increased production of NO in the central nervous system and to generation of clinical NPLE. The data also support the possibility that measurements of NO metabolites in CSF may be of value in the diagnosis of neurological symptoms related to SLE.

Adult↗
PubMed2001

MRI guided muscle biopsy confirmed polymyositis diagnosis in a patient with interstitial lung disease.

UNLABELLED: Idiopathic inflammatory myopathies, such as polymyositis (PM), may present with general symptoms such as fever and fatigue and only minimal muscle weakness, making it difficult to make a definite diagnosis and provide adequate treatment. Here a case is described in which interstitial lung disease was the first and most prominent manifestation of PM. Later, when muscle weakness became apparent and inflammatory muscle disease was suspected the first muscle biopsy was non-diagnostic. However, magnetic resonance imaging (MRI) scans of the clinically weak thigh muscles showed high signal on T(2) weighted images, suggesting muscle inflammation more proximal to the first biopsy site. A second biopsy at this site disclosed typical histopathological findings for myositis. After treatment with prednisolone in combination with cyclophosphamide both pulmonary and muscle function improved. CONCLUSION: MRI scans of muscles may be helpful in selection of a site for muscle biopsy in patients with suspected inflammatory myopathy when a first muscle biopsy turns out to be negative. Additionally, patients with interstitial lung disease of unknown cause should be tested for muscular function to exclude an associated inflammatory muscle disorder.

Anti-Inflammatory Agents↗
PubMed2000

Fine mapping of the SLEB2 locus involved in susceptibility to systemic lupus erythematosus.

We have previously reported linkage of systemic lupus erythematosus to chromosome 2q37 in multicase families from Iceland and Sweden. This locus (SLEB2) was identified by linkage to the markers D2S125 and D2S140. In the present study we have analyzed additional microsatellite markers and SNPs covering a region of 30 cM around D2S125 in an extended set of Nordic families (Icelandic, Swedish, and Norwegian). Two-point linkage analysis in these families gave a maximum lod score at the position of markers D2S2585 and D2S2985 (Z = 4.51, PIC = 0.65), by applying a "model-free" pseudo-marker linkage analysis. Based on multipoint linkage analysis in the Nordic families, the most likely location of the SLEB2 locus is estimated to be in the interval between D2S125 and the position of markers D2S2585 and D2S2985, with a peak multipoint lod score of Z = 6.03, assuming a dominant pseudo-marker model. Linkage disequilibrium (LD) analysis was performed using the data from the multicase families and 89 single-case families of Swedish origin, using the same set of markers. The LD analysis showed evidence for association in the single-case and multicase families with locus GAAT3C11 (P < 0.0003), and weak evidence for association was obtained for several markers located telomeric to D2S125 in the multicase families. Thirteen Mexican families were analyzed separately and found not to have linkage to this region. Our results support the presence of the SLEB2 locus at 2q37.

Base Sequence↗
PubMed2000

Immunological changes in human skeletal muscle and blood after eccentric exercise and multiple biopsies.

1. A role of the immune system in muscular adaptation to physical exercise has been suggested but data from controlled human studies are scarce. The present study investigated immunological events in human blood and skeletal muscle by immunohistochemistry and flow cytometry after eccentric cycling exercise and multiple biopsies. 2. Immunohistochemical detection of neutrophil- (CD11b, CD15), macrophage- (CD163), satellite cell- (CD56) and IL-1beta-specific antigens increased similarly in human skeletal muscle after eccentric cycling exercise together with multiple muscle biopsies, or multiple biopsies only. 3. Changes in immunological variables in blood and muscle were related, and monocytes and natural killer (NK) cells appeared to have governing functions over immunological events in human skeletal muscle. 4. Delayed onset muscle soreness, serum creatine kinase activity and C-reactive protein concentration were not related to leukocyte infiltration in human skeletal muscle. 5. Eccentric cycling and/or muscle biopsies did not result in T cell infiltration in human skeletal muscle. Modes of stress other than eccentric cycling should therefore be evaluated as a myositis model in human. 6. Based on results from the present study, and in the light of previously published data, it appears plausible that muscular adaptation to physical exercise occurs without preceding muscle inflammation. Nevertheless, leukocytes seem important for repair, regeneration and adaptation of human skeletal muscle.

Adult↗
PubMed2000

Decreased expression of interleukin-1alpha, interleukin-1beta, and cell adhesion molecules in muscle tissue following corticosteroid treatment in patients with polymyositis and dermatomyositis.

OBJECTIVE: To study the effects of immunosuppressive therapy, in particular, corticosteroids, on morphologic signs of inflammation and expression of cytokines, adhesion molecules, and class I major histocompatibility complex (MHC) antigen in muscle tissue from patients with polymyositis (PM) and dermatomyositis (DM) and to correlate the molecular changes with changes in muscle function. METHODS: Seven patients with PM and 4 patients with DM underwent muscle biopsy before and after 3-6 months of therapy. Ten of the 11 patients were initially treated with prednisolone 30-60 mg/day. The phenotypes of infiltrating inflammatory cells and the expression of interleukin-1alpha (IL-1alpha) and IL-1beta, adhesion molecules, and class I MHC antigen were studied by immunochemistry. Computerized image analysis was used for quantitation of staining. Muscle function was assessed with a muscle function index score. RESULTS: Pronounced improvement of muscle function during the treatment period was noted in 8 of the 11 patients. The changes in muscle function coincided with an almost complete disappearance of inflammatory cells, including CD3+ T cells, in the patients with clinical improvement. These patients also exhibited decreased expression of IL-1alpha, IL-1beta, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), leukocyte function-associated antigen 1alpha, and very late activation antigen 4alpha. Of note, there was persistent expression of IL-1alpha, ICAM-1, and VCAM-1 in capillaries and of class I MHC antigens on muscle fibers in several of the patients who, after corticosteroid treatment, still had muscle weakness despite the disappearance of inflammatory infiltrates. CONCLUSION: Changes in the muscle expression of key molecules in the inflammatory process, such as IL-1alpha and IL-1beta, ICAM-1 and class I MHC antigens, showed a consistent but not complete concordance with changes in and status of muscle function in patients with myositis who received the current standard treatment for the disease. These data indicate that it is possible to further evaluate various therapies for myositis using molecular analysis of muscle biopsy specimens obtained on repeated occasions. In addition, the data demonstrate a dissociation between muscle function and degree of inflammatory infiltration in the affected muscles and suggest that the functional defects are more related to the expression of molecules such as IL-1alpha in muscle capillaries than to the mere presence of inflammatory cells in the affected muscles.

Adrenal Cortex Hormones↗
PubMed2000

A susceptibility locus for human systemic lupus erythematosus (hSLE1) on chromosome 2q.

To identify chromosomal regions containing susceptibility loci for systemic lupus erythematosus (SLE), we performed genome scans in families with multiple SLE patients from Iceland, a geographical and genetic isolate, and from Sweden. A number of chromosomal regions showed maximum lod scores (Z) indicating possible linkage to SLE in both the Icelandic and Swedish families. In the Icelandic families, five regions showed lod scores greater than 2.0, three of which (4p15-13, Z=3.20; 9p22, Z=2.27; 19q13, Z=2.06) are homologous to the murine regions containing the lmb2, sle2 and sle3 loci, respectively. The fourth region is located on 19p13 (D19S247, Z=2.58) and the fifth on 2q37 (D2S125, Z=2.06). Only two regions showed lod scores above 2.0 in the Swedish families: on chromosome 2q11 (D2S436, Z=2. 13) and 2q37 (D2S125, Z=2.18). The combination of both family sets gave a highly significant lod score at D2S125 of Z=4.24 in favor of linkage for 2q37. This region represents a new locus for SLE. Our results underscore the importance of studying well-defined populations for genetic analysis of complex diseases such as SLE.

Animals↗
PubMed2000

Kinetics of anti-fibrillin-1 autoantibodies in MCTD and CREST syndrome.

Using a highly sensitive Radioimmunoassay (RIA), the kinetics of synthesis of anti-fibrillin (Fbn-1) autoantibodies were studied in 17 patients with mixed connective tissue disease (MCTD) and two with CREST syndrome calcinosis, Raynaud's oesophageal dismotility, sclerodectyly and teleangiectasis who were found to be positive for this autoimmune response. IgG autoantibodies specific for recombinant Fbn-1 (rFbn-1) (aa 369-425) were found in all patients excepting one with MCTD, multiple sclerosis, and dermatomyositis. IgM were found in fewer cases. Several kinetics patterns of anti-Fbn-1 autoantibodies were observed: a) long lasting persistence of IgG and IgM autoantibodies up to 14 years; b) fluctuation of antibodies during various periods up to 16 years; c) disappearance of antibody response after several years, and d) patients producing IgG but not IgM autoantibodies. No differences in the synthesis of autoantibodies were observed between MCTD patients with a stable disease, and those developing during the course features of systemic sclerosis (SSc), Sjogren's syndrome, or rheumatoid-like arthritis. In one patient displaying a lupus-like syndrome for 3 years, the appearance of anti-Fbn-1 autoantibodies coincided with the occurrence of MCTD and scleroderma. While the detection of anti-Fbn-1 autoantibodies may be clinically useful in differential diagnosis or eventual prognosis of patients with connective tissue diseases, their role in the pathogenesis of scleroderma syndromes requires further investigation.

Autoantibodies↗
PubMed2000

Association analysis with microsatellite and SNP markers does not support the involvement of BCL-2 in systemic lupus erythematosus in Mexican and Swedish patients and their families.

We have described suggestive linkage between microsatellite markers within the cytogenetic region 18q21-23 and SLE, a region where linkage with other autoimmune diseases has also been detected. The Bcl-2 gene located within this region, is a candidate gene because of its role in apoptosis, a physiological mechanism that could be deregulated in autoimmune disease. Furthermore, several studies have found abnormalities of Bcl-2 expression in SLE patients. We therefore sought to determine if the Bcl-2 gene is involved in SLE by studying members of a large cohort of Mexican SLE patients (n = 378) and 112 Swedish simplex families. Using a microsatellite marker and two single nucleotide polymorphisms located within the gene, we were unable to detect association between Bcl-2 and SLE in either population. We also tested whether combinations of alleles of the Bcl-2 and IL-10.G microsatellites would increase the risk for SLE. Our results do not support such hypothesis. Our findings suggest that linkage between SLE and the 18q21-23 region is due to a gene other than Bcl-2.

Alleles↗
PubMed2000

The safety of a resistive home exercise program in patients with recent onset active polymyositis or dermatomyositis.

The objective was to investigate whether a 12-week resistive home exercise program in addition to conventional medical treatment could be safely performed regarding muscle inflammation, muscle function, and quality of life in patients with active polymyositis (PM) or dermatomyositis (DM). Eleven patients diagnosed with active PM or DM were included. Muscle biopsies and Magnetic Resonance Imaging (MRI) of the thighs were performed. Quality of life, function, and subjective global disease impact (SGDI) were assessed and creatine phosphokinase levels (CPK) were analysed. The patients exercised with the exercise program for 15 minutes and took a 15-minute walk five days a week for 12 weeks. After the exercise period there was no sign of increased muscle inflammation. The group showed significantly improved function and quality of life compared to the start of study. It seems that this exercise program safely can be employed in patients with active PM or DM, and we suggest that physical exercise should be included in the rehabilitation of these patients.

Adult↗
PubMed2000

Increased expression of interleukin 1alpha and MHC class I in muscle tissue of patients with chronic, inactive polymyositis and dermatomyositis.

OBJECTIVE: To investigate if there is a molecular correlate in muscle tissue to the persisting decreased muscle function in patients with chronic, inactive polymyositis (PM) and dermatomyositis (DM). METHODS: Muscle function was assessed using a muscle function index of myositis. To assess disease activity both histopathological investigation of muscle biopsies and magnetic resonance imaging (MRI) scans of the thigh muscles were performed. Inactive chronic disease was defined as persisting muscle weakness and absence of inflammatory infiltrates in muscle biopsy and absence of signs of inflammation on MRI. Expression of interleukin 1alpha (IL-1alpha), IL-1beta,, adhesion molecules, and MHC class I molecules in muscle tissue was investigated with immunohistochemistry. RESULTS: Muscle weakness was confirmed by a reduction of muscle function score. No signs of inflammation typical for myositis were observed. The most striking finding in our study was the strong expression of IL-1alpha and MHC class I molecules in muscle tissue from patients with inactive chronic PM and DM. Increased IL-1alpha expression was evident in capillaries and increased MHC class I expression was detected in muscle fiber membranes. CONCLUSION: IL-1alpha and MHC class I molecules may have an importance in the pathogenesis of the chronic muscle weakness and fatigue in patients with PM and DM.

Adult↗
PubMed1999

Key residues revealed in a major conformational epitope of the U1-70K protein.

Epitopes depending on three-dimensional folding of proteins have during recent years been acknowledged to be main targets for many autoantibodies. However, a detailed resolution of conformation-dependent epitopes has to date not been achieved in spite of its importance for understanding the complex interaction between an autoantigen and the immune system. In analysis of immunodominant epitopes of the U1-70K protein, the major autoantigen recognized by human ribonucleoprotein (RNP)-positive sera, we have used diversely mutated recombinant Drosophila melanogaster 70K proteins as antigens in assays for human anti-RNP antibodies. Thus, the contribution of individual amino acids to antigenicity could be assayed with the overall structure of the major antigenic domain preserved, and analysis of how antigenicity can be reconstituted rather than obliterated was enabled. Our results reveal that amino acid residue 125 is situated at a crucial position for recognition by human anti-RNP autoantibodies and that flanking residues at positions 119-126 also appear to be of utmost importance for recognition. These results are discussed in relation to structural models of RNA-binding domains, and tertiary structure modeling indicates that the residues 119-126 are situated at easily accessible positions in the end of an alpha-helix in the RNA binding region. This study identifies a major conformation-dependent epitope of the U1-70K protein and demonstrates the significance of individual amino acids in conformational epitopes. Using this model, we believe it will be possible to analyze other immunodominant regions in which protein conformation has a strong impact.

Amino Acid Sequence↗
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

Psychosocial characteristics in young men as predictors of early disability pension with a psychiatric diagnosis.

BACKGROUND: There is little knowledge about disability pensions (DPs) in psychiatric diagnoses. The aim of this study was to analyse risk factors among men for receiving an early disability pension with a psychiatric diagnosis. METHODS: The study is based on data from a nationwide survey of 49 285 young Swedish men who were conscripted into military service in 1969/1970. Potential psychosocial and behavioural risk factors were linked to records from the Swedish Social Insurance Board up until 1993. RESULTS: The majority (63.4%) of the men granted a DP during follow-up had a psychiatric diagnosis as the main and/or secondary diagnosis. Among those conscripts analysed (41 702), 599 had been granted a disability pension with a psychiatric diagnosis. Of these, 35.4% had a diagnosis of psychosis, 23.2% an alcohol- or drug-related diagnosis, and 41.4% 'other' psychiatric diagnosis. Receiving a psychiatric diagnosis at conscription, showing low emotional control, unemployment after graduation, and ranking low on an "IQ" test were strong predictors of all categories of DP with psychiatric diagnoses. In multivariate analysis controlling for the effect of all other risk indicators included in the model, DP with non-alcohol- and non-drug-related psychiatric diagnoses was related to low social support at adolescence but not to signs of extrovert deviant behaviour (risky use of alcohol or contact with police and child authorities). In contrast, DP with an alcohol- or drug-related diagnosis had strong associations with signs of extrovert deviant behaviour. The risk pattern of DP without psychiatric diagnoses was similar to that of DP with a psychosis but also, though to a lesser extent, to that of DP with 'other' psychiatric diagnosis. These similarities could be interpreted as showing that the diagnoses on the records of disability pensions have a low sensitivity and/or specificity or, alternatively, that the risk factors found are risk factors for life careers steering toward a disability pension rather than toward the specific health outcomes per se. CONCLUSIONS: The results illustrate the importance of psychosocial factors established in late adolescence in the complex pathway of a decision of an early DP.

Adult↗
PubMed1999

Organophosphate neuropathy due to methamidophos: biochemical and neurophysiological markers.

Neuropathy target esterase (NTE), the putative target enzyme for organophosphate induced delayed polyneuropathy (OPIDP), can be measured in lymphocytes but has rarely been assessed in acute human poisoning. Serum autoantibodies to nervous system proteins develop in hens poisoned with neuropathic insecticides and also have not been studied after human poisoning. Serial lymphocyte NTE (LNTE) was measured in a 16-year-old boy after acute poisoning with methamidophos for evaluation as a predictor of subsequent neuropathy. The profiles of serum autoantibodies to neurofilament triplet proteins, myelin basic protein, and glial fibrillary acidic protein were measured in order to characterize changes occurring as a result of OPIDP. Clinical neuropathy characterized by steppage gate and profound lower extremity weakness, decreased grip and pinch strength, and decreased ulnar and absent tibial compound muscle action potentials developed 2 weeks following poisoning. Sensory examination and nerve conduction studies were normal. On day 3 following poisoning LNTE was depressed (77% compared with subsequent baseline enzyme activity). Marked increases in serum immunoglobulin G (IgG) autoantibodies to glial fibrillary acidic protein and to neurofilament 200 were observed after the development of OPIDP. We conclude that inhibition of lymphocyte NTE is predictive of subsequent OPIDP. Serum autoantibody titers to nervous system proteins may be useful markers of neuropathy.

Adolescent↗