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H J Lakomek

Publications and source records attributed to H J Lakomek.

At least 19 recordsLinked to original sources
PubMed2000

Rheumatoid factors in systemic lupus erythematosus: association with clinical and laboratory parameters. SLE study group.

The prevalence and clinical and laboratory associations of IgM, IgG and IgA rheumatoid factors (RF) were determined in 352 patients with systemic lupus erythematosus (SLE). IgM, IgG, and IgA class RF were detected in 17.9%, 20.5%, and 20.5% of the sera, respectively. RF were associated with sicca syndrome, hypergammaglobulinemia, high titer of antinuclear antibodies, anemia, SSA- and SSB-antibodies, and with the presence of HLA-DR3. RF correlated negatively with nephritis and livedo racemosa. Moreover, we observed an association of RF and parameters of inflammatory activity such as elevated erythrocyte sedimentation rate (ESR) and leukopenia. Analysis of immunoglobulin classes revealed that laboratory parameters of inflammatory activity, SSA- and SSB-antibodies and HLA-DR3 correlated with IgA RF only. IgA RF define a subgroup of SLE patients characterized by distinct autoimmune phenomena and high disease activity in the absence of nephritis.

Antibodies, Antinuclear↗
PubMed2000

IgA and IgG autoantibodies against alpha-fodrin as markers for Sjögren's syndrome. Systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of IgA and IgG autoantibodies against alpha-fodrin in patients with primary and secondary Sjögren's syndrome (SS) and controls. METHODS: An ELISA detecting IgA and IgG antibodies against alpha-fodrin was developed. We examined the prevalence of IgA and IgG antibodies against alpha-fodrin in patients with primary and secondary SS, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) and blood donors. RESULTS: IgA antibodies against alpha-fodrin were detected in 64% of patients with primary SS (n = 85), 47% of patients with secondary SS and SLE (n = 15), and 86% of patients with secondary SS and RA (n = 7). IgA autoantibodies against alpha-fodrin were detected in only one of 160 sera obtained from blood donors and in one of 50 and 2 of 12 sera obtained from SLE and RA patients without sicca syndrome, respectively. The prevalence of IgG antibodies against alpha-fodrin in SS was lower: they were detected in 55% of sera obtained from patients with primary SS, 40% of patients with secondary SS and SLE, and in 43% of patients with secondary SS and RA. Three of 160 sera from blood donors and one of 50 and 5 of 12 sera from SLE and RA patients without sicca syndrome, respectively, contained IgG antibodies against alpha-fodrin. CONCLUSION: IgA rather than IgG antibodies against alpha-fodrin are specific for and frequently observed in primary and secondary SS and are useful markers for this autoimmune disorder.

Adult↗
PubMed1999

Thrombomodulin in systemic lupus erythematosus: association with clinical and laboratory parameters.

Thrombomodulin is an endothelial cell membrane glycoprotein and is detected in plasma and serum after endothelial injury. In our study comprising 311 patients with systemic lupus erythematosus (SLE) clinical and laboratory associations of elevated thrombomodulin serum concentrations were examined. Elevated thrombomodulin concentrations were detected in 7.1% of the SLE patients and were associated with nephritis including the laboratory parameters proteinuria and erythrocyte casts, vasculitis and neurological involvement of the central nervous system. These correlations remained significant after consideration of the influence of renal function. In SLE, the serum thrombomodulin concentration may become a marker to monitor damage of endothelial cells and involvement of the central nervous system.

Enzyme-Linked Immunosorbent Assay↗
PubMed1998

Association of IgA anti-dsDNA antibodies with vasculitis and disease activity in systemic lupus erythematosus. SLE Study Group.

Previously it has been suggested that the presence of antibodies against dsDNA of the IgA class may define a subset of systemic lupus erythematosus (SLE) patients suffering from nephritis and arthritis. Therefore, these autoantibodies were measured in sera of 352 patients with SLE, 81 blood donors, and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgA anti-dsDNA antibodies were found in 19.9% of the sera from patients with SLE, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 36 laboratory parameters was calculated. IgA anti-dsDNA antibodies were found to be associated with parameters of disease activity such as elevated erythrocyte sedimentation rate and consumption of complement component C3, and the clinical parameters vasculitis, with necrosis and erythema, but not with nephritis and arthritis. Therefore, IgA anti-dsDNA antibodies define a subset of SLE patients, and monitoring of IgA anti-dsDNA antibodies may be helpful as a prognostic parameter in patients with SLE.

Antibodies, Antinuclear↗
PubMed1998

IgM anti-dsDNA antibodies in systemic lupus erythematosus: negative association with nephritis. SLE Study Group.

Antibodies against dsDNA of the IgM class were measured in sera of 352 patients with systemic lupus erythematosus, 81 blood donors and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgM anti-dsDNA antibodies were found in 52.3% of the sera from patients with systemic lupus erythematosus, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 37 laboratory parameters was calculated. There was a highly significant negative correlation between IgM anti-dsDNA antibodies and nephritis as well as all the laboratory parameters indicating renal disease (elevated serum creatinine concentration, proteinuria, erythrocyte casts in the urine). IgM anti-dsDNA antibodies indicate protection of lupus patients against the development of lupus nephritis. Further experiments will show whether application of IgM anti-dsDNA antibodies is effective in treating lupus nephritis.

Antibodies, Antinuclear↗
PubMed1997

[The rheumatoid patient as back pain patient. Diagnosis and differential diagnosis of seronegative spondylarthropathies].

Based on an epidemiology study the frequency of back pain in the population was established by forty percent. Otherwise only thirty percent of patients with backache are diagnosed definitely by practitioners. In view of these circumstances the 1991 published diagnosis criteria for spondylarthropathies are a helpful work in definition of spondylarthropathy patients. Furthermore a new described autoantibody specifically for spondylarthropathies seems to be helpful for this diagnosis of these systemic rheumatic diseases.

Arthritis, Rheumatoid↗
PubMed1995

Significance of antibodies to cardiolipin in unselected patients with systemic lupus erythematosus: clinical and laboratory associations. The SLE Study Group.

In a multicentre study anticardiolipin antibodies of the IgG and IgM isotypes were measured by a solid phase enzyme immunoassay in 368 patients with systemic lupus erythematosus (SLE) who were not selected on the basis of features of antiphospholipid syndrome. Clinical and laboratory associations of increased levels of anticardiolipin antibodies were evaluated. IgG and IgM antibodies to cardiolipin were documented in 224 (60.9%) and 128 (34.8%) patients, respectively. Regarding the symptoms of antiphospholipid syndrome, elevated amounts of anticardiolipin IgG were significantly associated with spontaneous abortion (P < 0.001), thrombocytopenia (P < 0.01), livedo reticularis (P < 0.01) and a positive direct Coombs test (P < 0.05), but not with thrombosis or central nervous system diseases such as epilepsy and psychosis. IgM antibodies to cardiolipin were associated with a positive direct Coombs test (P < 0.01), but with no other symptom of antiphospholipid syndrome. The predictive values of anticardiolipin antibody determinations in unselected SLE patients were poor for all features of antiphospholipid syndrome because of high proportions of false-positive and false-negative results. As for other manifestations of SLE, positive correlations between raised antibodies to double-stranded DNA and the occurrence of anticardiolipin antibodies of the IgG isotype were observed, and anticardiolipin IgM was negatively associated with nephritis.

Adolescent↗
PubMed1995

Novel 68 kDa autoantigen detected by rheumatoid arthritis specific antibodies.

OBJECTIVE: To improve the understanding of the pathogenesis of rheumatoid arthritis (RA) by identifying novel, disease specific autoantibodies. METHODS: Total protein preparations from synovial membranes were separated electrophoretically and immunoblotted. Sera from RA patients were screened for predominant immunoreactions by blotting. A 68 kDa antigen target of the most predominant reaction was detected and further characterised. RESULTS: The dominant immunoreaction in most of the RA sera tested was with a 68 kDa antigen. The antigen is probably ubiquitously expressed. It has an isoelectric point of 5.1, is O-glycosylated, and is located in the endoplasmic reticulum, the cytoplasm, or both. Antibodies to the 68 kDa autoantigen were present in 64% of 167 RA patients tested, and could also be detected in seronegative RA patients, but were present in only 1% of 98 patients with other rheumatic diseases. They could not be detected in 55 healthy controls. CONCLUSIONS: Because of its high sensitivity (64%) and specificity (99%), the anti-68 kDa autoantibody not only provides another valuable parameter for diagnosis, but also represents an antibody that may be involved in the pathological mechanisms leading to RA. This hypothesis can be tested by investigating if 68 kDa specific T cells are present in RA patients.

Animals↗
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↗