[Recombinant Ro-, La- and U1-n-RNP antigens: detection of autoantibodies with ELISA and clinical association in SLE].
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Antibody Specificity↗
Biomedical subjects
K Hartung
Publications and source records attributed to K Hartung.
Expansion of the liver-associated macrophage system in systemic lupus erythematosus-prone NZB/W mice.
Systemic lupus erythematosus is characterized by profound changes of the immune system. We report on alterations of the macrophage system in the murine NZB/W model of this disease. A greatly increased number of mature macrophages was isolated from the liver of NZB/W mice as compared to BALB/c mice and several other inbred strains used as healthy controls. In addition, the macrophage precursor compartment in the liver of NZB/W mice was expanded severalfold as measured by proliferation of light-fraction nonadherent nonparenchymal cells (NPCs) in response to colony-stimulating factors. Functional properties of the macrophages isolated from various anatomic sites of the lupus-prone mice were tested. Production of monokines by macrophages from liver, spleen, and peritoneal cavity, calculated on a per cell basis, was in the same range as in several healthy control strains tested. Yet the overall production of these immunoregulatory molecules by the increased liver macrophage system, the body's largest compartment of macrophages, is likely to result in increased levels of circulating monokines in the plasma of lupus-prone NZB/W mice. Indeed, significantly elevated levels of interleukin-6, interleukin-1, and colony-stimulating activity could be demonstrated in the plasma of these mice both spontaneously and after stimulation with lipopolysaccharide. A possible contribution of the expansion of the macrophage system to the development of the disease is discussed.
Animals↗
Polymorphism of the DQA1 promoter region (QAP) and DRB1, QAP, DQA1, DQB1 haplotypes in systemic lupus erythematosus. SLE Study Group members.
We have investigated the DNA polymorphism for the DQA1 promoter region (QAP) and HLA-class II DRB1, DQA1, and DQB1 genes in 178 central European patients with Systemic lupus erythematosus (SLE) using polymerase chain reaction and Dig-ddUTP labeled oligonucleotides. Increased frequencies of DRB1*02 and *03 are confirmed by DNA typing. In addition, the frequencies of DQA1*0501, *0102 and DQB1*0201, *0602 alleles are increased in the patients as compared to controls. The strongest association to SLE is found with DRB1*03 and DOB1*0201 alleles (p < 10(-7), p corr. < 10(-5) and p < 10(-6), p corr. < 10(-4), respectively). By investigating the DQA1 promoter region in the SLE patients we have detected nine different QAP variants. Increased frequencies of QAP1.2 and QAP4.1 are observed in patients as compared to controls (p < 0.05, p corr. = n.s.). Analysis of linkage disequilibria demonstrates a very strong association between QAP variants and DQA1, DRB1 alleles. Certain QAP variants are completely associated with DQA1 and DRB1 alleles, whereas others can combine with different DQA1 and DRB1 alleles. All DRB1*02-positive patients and controls carry QAP1.2, and all DRB1*03-positive patients and controls carry QAP4.1. Conversely, the QAP1.2 variant appears only in DRB1*02 haplotypes, while the QAP4.1 variant can be observed in DRB1*03, *11, and *1303 haplotypes. Based on the strong linkage disequilibria between DRB1-DQA1-DQB1 genes and between DRB1-QAP-DQA1, we have deduced the four-point haplotypes for DRB1-QAP-DQA1-DQB1 in patients and controls. Two haplotypes DRB1*02-QAP1.2-DQA1*0102-DQB1*0602 and DRB1*03-QAP4.1-DQA1*0501-DQB1*0201 are significantly increased in patients as compared to controls (p < 0.01, p corr. = n.s., RR = 1.8 and p < 10(-7), p corr. < 10(-5), RR = 3.1, respectively). The analysis of relative risks attributed to the various alleles of QAP, DQA1, and DQB1 as well as the investigation of the deduced DRB1-QAP-DQA1-DQB1 haplotypes leads to the conclusion that QAP4.1 and DQA1*0501 on the DR3 haplotypes are probably not involved in SLE susceptibility.(ABSTRACT TRUNCATED AT 400 WORDS)
Alleles↗
DR2 haplotypes (DRB1, DQA1, DQB1) associated with systemic lupus erythematosus.
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Gene Frequency↗
Polymorphism of the tumor necrosis factor beta gene in systemic lupus erythematosus: TNFB-MHC haplotypes.
We investigated the Nco I restriction fragment length polymorphism (RFLP) of the tumor necrosis factor beta (TNFB) gene in 173 patients with systemic lupus erythematosus (SLE), 192 unrelated healthy controls, and eleven panel families, all of German origin. The phenotype frequency of the TNFB*1 allele was significantly increased in patients compared to controls (63.6% vs 47.1%, RR = 1.96, p < 0.002). The results of a two-point haplotype statistical analysis between TNFB and HLA alleles show that there is linkage disequilibrium between TNFB*1 and HLA-A1, Cw7, B8, DR3, DQ2, and C4A DE. The frequency of TNFB*1 was compared in SLE patients and controls in the presence or absence of each of these alleles. TNFB*1 is increased in patients over controls only in the presence of the mentioned alleles. Therefore, the whole haplotype A1, Cw7, B8, TNFB*1, C4A DE, DR3, DQ2 is increased in patients and it cannot be determined which of the genes carried by this haplotype is responsible for the susceptibility to SLE. In addition, two-locus associations were analyzed in 192 unrelated healthy controls for TNFB and class I alleles typed by serology, and for TNFB and class II alleles typed by polymerase chain reaction/oligonucleotide probes. We found positive linkage disequilibrium between TNFB*1 and the following alleles: HLA-A24, HLA-B8, DRB1*0301, DRB1*1104, DRB1*1302, DQA1*0501, DQB1*0201, DQB1*0604, and DPB1*0101. TNFB*2 is associated with HLA-B7, DRB1*1501, and DQB1*0602.
Base Sequence↗
A novel HLA-DRB1-DR2 allele associated with HLA mistyping.
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Alleles↗
No direct correlation between HLA-DPB1 and antibodies against recombinant Ro (SS-A)/La (SS-B) proteins in systemic lupus erythematosus. SLE Study Group.
We investigated the association of HLA-DPB1 alleles with the occurrence of autoantibodies against Ro (SS-A) or La (SS-B) using recombinant 52 kD-Ro, 60 kD-Ro and La proteins in 177 German patients with systemic lupus erythematosus (SLE). A significant increase in the frequency of DPB1*0101 is observed in SLE patients compared to healthy controls (Pcorr.. < 0.004). Antibodies against 52 kD-Ro, 60 kD-Ro and La are tested by ELISA and are found with a frequency of 25.4%, 33.9% and 17.5% in the patients, respectively. An association with HLA-DPB1*0101 is observed for antibodies against La (P < 0.01) and 52 kD-Ro (P < 0.01), but not for 60 kD-Ro in the absence of La/52 kD-Ro. Since there is a strong linkage disequilibrium between DPB1*0101 and DR3 in the normal population and in SLE patients, and since there is an association between DR3 and SLE, as well as between DR3 and the occurrence of recombinant Ro/La antibodies in SLE patients, we investigated whether DPB1*0101 is associated per se or via linkage disequilibrium with DR3. DPB1*0101 in the absence of DR3 is not more common in patients than in controls and not in patients with autoantibodies to Ro and La than without autoantibodies. We conclude that there is no evidence for a direct involvement of DPB1*0101 in the production of Ro/La autoantibodies in SLE patients.
Alleles↗
Drug-related lupus in a patient with rheumatoid arthritis under sulfasalazine treatment.
The induction of lupus-like syndromes with the appearance of single-stranded DNA antibodies is a well-known complication of drug therapy. In this report we present a patient with an erosive seropositive rheumatoid arthritis developing the clinical and serological features of systemic lupus erythematosus including the occurrence of double-stranded DNA antibodies under sulfasalazine treatment.
Adult↗
Complement split product C3d as an indicator of disease activity in systemic lupus erythematosus.
In order to investigate, if complement levels can be used as an indicator of clinical activity in systemic lupus erythematosus (SLE), levels of C3, C4, CH50, and C3d were measured in 79 patients, 41 with inactive, 31 with moderately active and 7 with severely active disease. Our study shows that C3d, and particularly the C3d/C3 ratio, provide sensitive markers for disease activity in SLE. Since C3d is a direct measurement of complement turnover, it reflects complement activation better than C3, C4 and CH50.
Adolescent↗
DNA typing for HLA-DPB1-alleles in German patients with systemic lupus erythematosus using the polymerase chain reaction and DIG-ddUTP-labelled oligonucleotide probes. Members of SLE Study Group.
Genomic DNA of 178 German Caucasian patients with systemic lupus erythematosus are studied for HLA-DP locus by using PCR and DIG-ddUTP-labelled oligonucleotide probes. A significant increase of DPB1*0101 is observed in SLE patients compared with healthy controls (chi 2 = 15.27, p.c. < 0.004). DPB1*0501 and *0901 are also slightly increased (chi 2 = 5.85, P < 0.05, p.c. = NS; chi 2 = 5.64, P < 0.05, p.c. = NS). There is no significant difference in frequency of DP alleles between male and female patients. Since a linkage disequilibrium between HLA-B, DR and DP loci is found in our SLE patients, an analysis is performed assessing the relative importance of these HLA-markers to SLE. The results show that the increase of DPB1*0101 in SLE patients is associated with the HLA-B8, DR3 haplotype and it suggests a more important role for HLA-B8, DR3 or genes within this haplotype than for DPB1*0101 in the genetic predisposition for SLE.
Alleles↗
[Causes of kyphotic and lordotic curvature of the spine with cuneiform vertebral deformation in swine].
Clinical, radiographic and pathological findings demonstrate that kyphosis in 11 weaned pigs with formation of wedge shaped vertebrae can be caused by congenital malformation, traumatic lesion (fracture), inflammation (osteomyelitis), metabolic bone disease or abnormal body posture following chronically painful diseases. Lordosis in 2 weaned pigs with cuneiform deformations of the dorsal part of vertebrae was also caused by developmental malformations or abnormal body posture (polyarthritis). No evidence of heredity in the group of congenital vertebral malformations was found.
Animals↗
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↗
MHC associations of autoantibodies against recombinant Ro and La proteins in systemic lupus erythematosus. Results of a multicenter study. SLE Study Group.
Antibodies against recombinant 52 kD-Ro, recombinant 60 kD-Ro and recombinant La protein were determined by ELISA in over 300 central European patients with systemic lupus erythematosus (SLE). A strong association with HLA-DR3 was found for antibodies against 52 kD-Ro and La, but not for recombinant 60 kD-Ro antibodies in the absence of antibodies against 52 kD-Ro or La. Ro/La negative SLE patients still showed an increased frequency of HLA-DR3 as compared to healthy controls. These results indicated that the preferential formation of Ro and La antibodies was not due to an unspecific stimulatory effect of HLA-DR3 but that the antibody response to certain defined proteins (52 kD-Ro and La) was influenced by MHC genes in SLE. Furthermore, the association of SLE with HLA-DR3 was independent of the effects of DR3 on the formation of 52 kD-Ro and La antibodies.
Antibody Specificity↗
Expanded macrophage precursor populations in BXSB mice: possible reason for the increasing monocytosis in male mice.
The BXSB mouse spontaneously develops an autoimmune disease that resembles human systemic lupus erythematosus (SLE). During their lifetime, male BXSB mice show an increasing monocytosis in the peripheral blood as opposed to their female littermates. This monocytosis is unique among autoimmune-prone mice. To test the hypothesis that alterations at the stem cell level may be responsible for this monocytosis, myeloid bone marrow precursor cells were examined in both male and female BXSB mice from 4 to 40 weeks of age. The number of M-CSF responding stem cells (CFU-M) and the number of GM-CSF responding stem cells (CFU-GM) were higher than in all other inbred mouse strains tested. In addition, male BXSB mice developed a progressive increase of CFU-M and CFU-GM in the bone marrow during their lifetime, which paralleled the peripheral blood monocytosis. The monocytosis in male BXSB mice is the result of a further expansion of the strain-specific high number of macrophage precursors by intrinsic factors, which may be attributed to the influence of the Yaa factor. The sex-specific expanded mononuclear phagocyte system may promote the autoimmune process and may be one reason for the dramatic course of murine SLE in male BXSB mice.
Animals↗
A new HLA-DPB1 allele from a patient with systemic lupus erythematosus.
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Alleles↗
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↗
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↗
[Radiation exposure of the hands and feet during x-ray studies in small animals].
In early years of radiology, many severe radiation injuries in radiologists were registered. Unfortunately, there are still cases of skin lesions of the hands of veterinarians. The main reason for this is careless handling during the examination. First of all the veterinarian should try to stay out of the primary beam. In addition, he must be aware that lead gloves are no protection against primary rays. In contrast, the risk of placing the feet in the primary beam is relatively low. Monitoring of radiation shows, that, if veterinarians are aware of the hazards, there is no danger of radiation damage. Advice for reducing the exposure dose to the hands is given.
Animals↗