PubMed Health⌕ Search

Biomedical subjects

H J Lakomek

Publications and source records attributed to H J Lakomek.

At least 19 recordsLinked to original sources
PubMed1992

The genetic basis of Ro and La antibody formation in systemic lupus erythematosus. Results of a multicenter study. The SLE Study Group.

Antibodies against Ro and La, including recombinant La and recombinant 60 kD-Ro, were determined by counter immunoelectrophoresis and ELISA in over 300 central European systemic lupus erythematosus (SLE) patients. The presence of both Ro and La antibodies was strongly associated with the MHC haplotype B8-C4AQ0-DR3-DQ2, the association being strongest for DR3. After exclusion of all B8-DR3 positive patients only DR3 positive patients still showed an increased incidence of Ro and La antibodies, suggesting DR3 as the primary association factor. High titers of La antibody, but not of 60 kD-Ro antibody, were also significantly associated with the presence of DR3. Other DR and DQ antigens or heterozygous DQ combinations were not significantly associated with Ro and La antibodies.

Antibodies, Antinuclear↗
PubMed1992

Major histocompatibility complex haplotypes and complement C4 alleles in systemic lupus erythematosus. Results of a multicenter study.

In a multicenter study more than 300 central European systemic lupus erythematosus (SLE) patients were examined for HLA-B, HLA-DR, and complement C4 phenotypes. For 174 SLE patients MHC haplotypes were determined by family segregation analysis, and for 155 patients C4 gene deletions were determined by TaqI restriction fragment length polymorphism. Two haplotypes, B8-C4AQ0-C4B1-DR3 and B7-C4A3-C4B1-DR2, were identified as risk factors for SLE. These findings were confirmed by applying the haplotype frequency difference (HFD) method, which uses nontransmitted haplotypes from the family study as internal controls. Furthermore, only HLA-DR2, but not DR3, B7, or B8, was significantly increased in SLE patients independently of the two risk haplotypes. C4A gene deletions, but not silent C4AQ0 alleles, were increased in SLE patients and neither C4BQ0 alleles nor C4B gene deletions were increased. The observed frequencies of homozygosity and heterozygosity for the two haplotypes and the frequencies of homozygotes for C4AQ0 and C4A deletions did not differ from the expected values, indicating that the risk for SLE is conveyed by single allele effects. In conclusion, there are two MHC-linked susceptibility factors for Caucasian SLE patients carried by the haplotypes B7-DR2 and B8-DR3. The results argue against C4Q0 alleles being the decisive factors increasing susceptibility to SLE.

Alleles↗
PubMed1992

MHC gene products and anticardiolipin antibodies in systemic lupus erythematosus results of a multicenter study. SLE Study Group.

Anticardiolipin antibodies (aCL) and HLA-DR antigens were determined in 314 central European patients with systemic lupus erythematosus (SLE). Both HLA-DR4 and DR7 were increased in aCL-positive patients, and aCL were significantly associated with DRw53. The association between DRw53 and aCL was also apparent in those 17 patients with SLE and the anticardiolipin syndrome. There was no association between aCL and HLA-DQ or C4 alleles in SLE.

Antibodies, Anticardiolipin↗
PubMed1992

[Cutaneous lupus erythematosus and cardiolipin antibodies. Incidence and clinical significance].

In recent years, the importance of antiphospholipid antibodies in systemic lupus erythematosus and various other dermatological and internal diseases has been recognized. Characteristic symptoms associated with these antibodies are venous and arterial thrombosis, recurrent fetal loss, thrombocytopenia, and haemolytic anaemia. Two antiphospholipid antibody subgroups that are clinically relevant can be discerned: anticardiolipin antibodies and lupus coagulant. In this study, 51 clinically well-characterized patients with predominantly cutaneous lupus erythematosus were screened for the presence of anticardiolipin antibodies. Anticardiolipin antibodies could be detected in only three patients. These data suggest that, in patients with cutaneous lupus erythematosus, anticardiolipin antibodies should be measured only in the presence of symptoms associated with antiphospholipid antibodies.

Antiphospholipid Syndrome↗
PubMed1991

Testing for association in SLE families.

Systemic lupus erythematosus (SLE) is a complex disease which is partly determined by genetic factors which influence susceptibility to the disease phenotype. In this association study we try to define the high risk haplotypes which are responsible for this disease, together with other environmental factors. In many other association studies a set of SLE patients is compared to a set of controls. The basic assumption about the underlying population is that the disease and control sample should originate from the same genetic population, which is not always completely satisfied in many studies. Therefore, we analyse our family data by applying the Haplotype Frequency Difference (HFD) Method, which constructs its internal control group from those haplotypes not transmitted to the affected individual. Results partially conform with other studies, showing that the haplotypes B8 DR3 as well as B7 DR2 have a high positive association with SLE. When the DR locus was analyzed alone, we found besides the alleles DR2 and DR3 a negative association for DR1, DR5, and DR6.

Adult↗
PubMed1991

Ankylosing spondylitis: an autoimmune disease?

Identification of several autoantibodies in serum samples from patients with ankylosing spondylitis or suspected ankylosing spondylitis is reported. Five antibodies associated with ankylosing spondylitis were identified by applying cytoimmunofluorescence and immunoblotting techniques to antigen pools from insect tissue. At least one of these antibodies was found in 82% of serum samples from patients with ankylosing spondylitis. A 36 kD drosophila antigen, which showed the most common and most dominant reaction, was further purified and isolated. Thirty two (34%) of the serum samples from 95 patients with definite ankylosing spondylitis and 12 (28%) of the serum samples from 43 patients with suspected ankylosing spondylitis reacted with this antigen. Antibodies purified from the 36 kD antigen reacted specifically with a 69 kD antigen present in separations of total protein preparations from human lymphocytes and HeLa cells. The 36 kD antibody was not found in 29 patients with rheumatoid arthritis nor in 38 apparently healthy controls. The prevalence of the 36 kD antibody was comparable in HLA-B27 positive and negative patients. In addition, the same immunoreaction was found in patients with so called 'seronegative' spondylarthropathies, particularly of the ankylosing spondylitis-type, suggesting that this antibody is specific for ankylosing spondylitis or other 'seronegative' spondylarthropathies with the typical clinical and radiological changes of ankylosing spondylitis.

Antibody Specificity↗
PubMed1991

Cloning and expression of antigenic epitopes of the human 68-kDa (U1) ribonucleoprotein antigen in Escherichia coli.

Autoantibodies directed against the 68-kDa (U1) ribonucleoprotein antigen are mainly found in sera of patients with mixed connective tissue disease. The corresponding cDNA was fragmented into four regions coding for the major antigenic epitopes A', B', C' and D'. All the epitopes were subcloned and expressed as fusion proteins with the glutathione S-transferase in Escherichia coli using the novel expression system pGEX that allows very high yields of recombinant proteins after a single-step purification. The sera of patients with the autoimmune disease were analyzed for the expressed recombinant proteins by an immunoblotting technique. All positive sera showed a patient-specific behavior and could be divided into four groups regarding recognition of the four antigenic epitopes of the 68-kDa (U1) ribonucleoprotein antigen. The epitope B' was reactive to all patient sera positively tested and classified as the marker antigenic epitope for the mixed connective tissue disease.

Cloning, Molecular↗
PubMed1991

Immunoglobulin allotypes in systemic lupus erythematosus--results of a central European multicenter study. SLE Study Group.

Immunoglobulin heavy chains (G1m, G2m, G3m, A2m) and kappa light chain (Km) allotype and phenotype frequencies were examined in 323 central European Caucasian patients with systemic lupus erythematosus (SLE). No significant differences were found between the different allotype or phenotype frequencies of the SLE patients and a control group of healthy individuals. Our results indicate that Gm, A2m and Km allotypes do not represent susceptibility factors for SLE in Caucasians.

Gene Frequency↗
PubMed1990

[Scleroderma].

Sclerodermas may occur in two basic forms: localized sleroderma (LSc) and systemic scleroderma (SSc). Pseudoscleroderma as well as overlap syndromes have to be differentiated from these two variants. From the clinical point of view, localized scleroderma can be subdivided into type I = plaque-like LSc (= morphea), type II = linear LSc, and type III = deep LSc. According to the degree of the cutaneous involvement, systemic scleroderma can likewise be classified into type I = sclerodactylia, type II = acrosclerosis, and type III = scleroderma with primary involvement of the trunk (diffuse scleroderma). In LSc, we never find systemic involvement; SSc, in contrast, is almost always associated with Raynaud's phenomenon, changes of the esophagus, as well as an increased titer of antinuclear antibodies (Hep-2 cell test). Only 23% of our patients with LSc showed elevated ANA titers. We present and discuss data of 56 patients with LSc and 52 patients with SSc. Evidence in the literature as well as our own findings suggest that the pathogenesis of LSc is different from that of SSc. The influence of various mediators and cytokines on the collagen metabolism might be regarded as a theoretical approach in order to develop new therapeutic regimens. This is even more important since there is still no efficient mode of treatment for neither localized nor systemic scleroderma.

Antibodies, Antinuclear↗
PubMed1990

[Lupus erythematosus].

Our paper summarizes the clinical and photobiological studies on lupus erythematosus (LE) performed at the Department of Dermatology, University of Düsseldorf, during the last 5 years. A total of 190 LE cases were examined and classified according to the various cutaneous forms of LE. Except for lupus erythematosus tumidus (LET), we found a female predominance in all other groups. Discoid lupus erythematosus (DLE) is the most common variant of cutaneous LE. Subacute cutaneous lupus erythematosus (SCLE), a less common type, is characterized by the presence of Ro-antibodies, although this marker does not correlate with the degree of photosensitivity. The rare LET is an extremely photosensitive form of LE, which clearly prefers the male sex.

Adolescent↗
PubMed1989

[Livido racemosa in detection of anti-phospholipid antibodies].

Livedo reticularis and antiphospholipid antibodies have previously been found to be associated with a subgroup of patients with systemic lupus erythematosus. We present a case of livedo reticularis accompanied by antiphospholipid antibodies, in which no other signs of any systemic or cutaneous disease could be detected.

Adult↗
PubMed1988

Epitope mapping with a recombinant human 68-kDa (U1) ribonucleoprotein antigen reveals heterogeneous autoantibody profiles in human autoimmune sera.

Several cDNA fragments encoding parts of the (U1)RNP specific 68-kDa autoantigen were expressed in Escherichia coli and the fusion proteins were used as substrate for localization of the autoreactive epitopes. We have identified a region of approximately 30 amino acids reacting with more than 90% (16 of 17) of all human anti-p68 sera tested, regions which carry only a few and a region with no autoepitopes. Comparative analysis of epitopes recognized on partially degraded fusion proteins indicated that the anti-p68 autoimmune response is polyclonal. It involves generation of antibodies to several epitopes including one in a region with retroviral gag protein homology speculated to play a role in the initiation of the autoimmune response. Each of the 17 sera tested contained a different set of autoantibody specificities. These data are not consistent with random mutation as a sole mechanism of anti-p68 autoantibody induction and argue for an Ag-driven autoimmune response.

Antibodies, Antinuclear↗
PubMed1988

A recombinant autoantigen derived from the human (U1) small nuclear RNP-specific 68-kd protein. Expression in Escherichia coli and serodiagnostic application.

A human liver complementary DNA expression library was screened using sera from patients with high titers of autoantibodies, to search for clones expressing major autoantigens that are relevant in connective tissue diseases. One of the clones isolated expressed a major epitope(s) that was immunoreactive with anti-U1 RNP sera, as shown by several techniques. Affinity-purified autoantibodies from the cloned RNP protein specifically recognized the 68-kd U1 RNP protein of HeLa cell nuclear extracts. All sera containing anti-U1 RNP antibodies detected by immunodiffusion, counterimmunoelectrophoresis, or immunoblotting also recognized the cloned RNP protein. The RNP antigen-expressing bacterial colonies and the partially purified cloned RNP fusion protein have been applied to fast and sensitive immunologic assays for the detection and quantification of anti-U1 RNP antibodies.

Autoantigens↗
PubMed1988

Lung function disturbances versus respiratory muscle fatigue in patients with systemic lupus erythematosus.

In 23 consecutive patients (mean age, 38.6 years) with systemic lupus erythematosus (SLE) and in 17 healthy subjects (mean age, 37.5 years) fatigue of respiratory (diaphragm, musculi intercostales externi) and leg muscles (musculus gastrocnemius) was determined comparatively by electromyography. Additionally, routine lung function parameters, including maximum inspiratory (PImax) and expiratory (PEmax) mouth pressures, were measured. The SLE patients showed lower values of vital capacity (VC), total lung capacity (TLC), thoracic gas volume (TGV), FEV1, PImax and PEmax than the healthy controls, while FEV1/VC, residual volume and specific airway conductance were not significantly different in either group. Lung compliance, corrected for TGV, was normal in the SLE group. Breathing through stenoses with increasing resistances resulted in fatigue of the diaphragm in 73% of the SLE group and in 41% of the control group. The corresponding values of the external intercostal muscles were 74% (SLE group) and 29% (control group). Electromyographic signs of respiratory and leg muscle fatigue occurred at lower loads in the SLE group than in the healthy subjects. The pattern of lung function data in patients with SLE was characteristic neither of lung restriction nor of airway obstruction. Respiratory muscle weakness can explain the decrease in TLC, VC, TGV, FEV1, PImax and PEmax.

Adult↗
PubMed1987

[Significant association of HLA-B8 with systemic lupus erythematosus and with specific serological markers].

Analysis of the HLA antigens of the A, B and C locus of 87 patients with systemic lupus erythematosus (SLE) revealed a significant elevation for HLA-B8 of 64% as compared to 22% in a healthy control group (n = 1850) (P less than 0.000001). Owing to the known linkage disequilibrium of this genetic marker with the HLA-A1 antigen, the HLA phenotype A1, B8 was found in 55% of the SLE patients (P less than 0.000001). Moreover, a significant association of the HLA-B8 in 82% (P less than 0.025) of Ro antibody-positive SLE patients (n = 22) and in 84% (P less than 0.025) of Ha antibody-positive patients (n = 19) was striking. A more frequent occurrence of this HLA antigen could also be detected in patients with a persistent nDNA antibody elevation and in patients with manifestation of the disease before the 40th year of life as compared to patients who manifested it later. An association of the HLA-B8 antigen with a raised disease activity of SLE can be inferred.

Adult↗
PubMed1987

Attempts towards a serological diagnosis of ankylosing spondylitis.

Polytene chromosomes of salivary glands as well as nuclear proteins from Kc-cells of Drosophila melanogaster have been used as substrate to identify and evaluate the diagnostic value of crossreacting antibodies present in sera of AS patients. The diagnostic significance of the recently described anti-93D antibody (Lakomek et al., 1984) was confirmed by screening sera of patients with definite or suspected AS using cytoimmunofluorescence on the polytene chromosomes. In addition, four new antibodies could be identified in AS sera by immunoblotting. Simultaneous detection of these antibodies supports the diagnosis of AS and is most useful in diagnosis of early stages of this disease.

Adult↗