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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which multiple genes appear to play important roles in pathogenesis. Hereditary deficiencies, both complete and partial, of several components of the complement system clearly predispose to lupus. HLA class II alleles appear to mediate specific autoantibodies, many of which are pathogenic. Modern molecular techniques are now providing insight into the specific major histocompatibility complex class II polymorphisms that are associated with different autoantibodies in SLE. Other genetic systems also may be important.
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PMID:Genetics of systemic lupus erythematosus. 145 48

Several of the heterogeneous clinical manifestations of systemic lupus erythematosus have been associated with specific autoantibodies. Associations between HLA class II antigens and autoantibodies to the ribonucleoproteins Ro(SSA) and La(SSB) have been reported in these patients. Because HLA class II molecules present antigen to T cell receptors (TCRs), we have searched for a TCR gene associated with the production of anti-Ro(SSA) antibodies. A pair of restriction fragment length polymorphisms (RFLPs), one of which hybridizes to the TCR constant region C beta 1 and the other to the C beta 2 gene, has been identified, suggesting these may be genotypic markers for an extended region of the TCR beta locus. This RFLP pair occurs in 76% of patients with Ro(SSA) precipitins, 84% of anti-Ro(SSA)-positive patients lacking La(SSB) precipitins, but only 41% of the patients lacking both precipitins (P = 0.0004). This disproportionate occurrence in a subset of lupus patients indicates that these RFLPs are not disease susceptibility markers, but rather are important markers for TCR genes whose products are involved in the production of anti-Ro(SSA) antibodies. The majority of patients who have these RFLPs and HLA class II antigens previously associated with the anti-Ro(SSA) response make this antibody, suggesting that interactions between products of these loci occur in response to Ro(SSA).
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PMID:Anti-Ro(SSA) autoantibodies are associated with T cell receptor beta genes in systemic lupus erythematosus patients. 196 59

Serum levels of IdGN2 (an idiotype enriched in nephritogenic antibodies), IdX (an idiotype not enriched in nephritogenic antibodies), IgG, and anti-DNA were measured in 23 Caucasian patients with lupus nephritis, in age- and sex-matched lupus patients without nephritis, and in similarly matched healthy individuals. Serum levels of IdGN2 were significantly higher in the patients with lupus nephritis than in those without, and they were higher in all lupus patients compared with the healthy control subjects. However, the same observations were true for serum levels of IdX. There were significant positive correlations between the serum levels of IgG, IdGN2, IdX, and anti-DNA. HLA typing at the DR and DQ loci was performed in 105 lupus patients of different races (Caucasian, black, and Asian/Polynesian/Filipino). Serum levels of IdGN2 in 83 of these individuals did not correlate with any of the HLA class II haplotypes currently known to predispose to lupus nephritis. We conclude that the high serum levels of IdGN2, which are characteristic of some patients with lupus nephritis, may often result from polyclonal B cell activation rather than from idiotype-specific upregulation associated with one or more of the class II genes that predispose to nephritis in this disease.
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PMID:Idiotypic characteristics of immunoglobulins associated with human systemic lupus erythematosus. Association of high serum levels of IdGN2 with nephritis but not with HLA class II genes predisposing to nephritis. 211 76

The antigen responsible for autoimmunization in systemic lupus erythematosus is unknown. In spite of this obstacle, we show that T helper (Th) cell lines that are functionally relevant to this disease can be established in vitro. We derived a total of 396 interleukin 2-dependent T-cell lines from the in vivo activated T cells of five patients with lupus nephritis. Only 59 (approximately 15%) of these lines had the ability to selectively augment the production of pathogenic anti-DNA autoantibodies that were IgG in class, cationic in charge, specific for native DNA, and clonally restricted in spectrotype. Forty-nine of these autoantibody-inducing Th lines were CD4+ and expressed the alpha beta T-cell receptor (TCR). The other 10 were CD4-8- (double negative), 3 expressing the alpha beta TCR and 7 expressing the gamma delta TCR. All of the autoantibody-inducing Th lines responded to some endogenous antigen presented by autologous B cells. The autoreactive responses of the CD4+ Th lines were restricted to HLA class II antigens, whereas those of the double-negative cells were not. Endogenous heat shock or stress proteins of the HSP60 family that were expressed by the lupus patients' B cells were involved in stimulating an autoreactive proliferation of the gamma delta Th cells. These studies demonstrate a novel helper activity of certain gamma delta T cells in a spontaneous autoimmune response.
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PMID:Pathogenic anti-DNA autoantibody-inducing T helper cell lines from patients with active lupus nephritis: isolation of CD4-8- T helper cell lines that express the gamma delta T-cell antigen receptor. 214 99

CCLE, a disease entity at the benign end of the lupus spectrum, is characterized by marked photosensitivity and skin lesions in sun-exposed areas. The histopathology of lesions resembles hypersensitivity type IV reactions. We have asked whether an association between class II alleles and CCLE exists. RFLP analysis of HLA-DQA genes revealed a Taq I HLA-DQA1 allelic restriction fragment overrepresented in a group consisting of 26 patients as compared to healthy control individuals. This result was corroborated by typing with oligonucleotide probes. The presence of the DQA1*0102 allele in the patients' group led to a relative risk of 4.57, with a statistical significance of p < 0.05 after correction for 36 comparisons. Although not statistically significant, it is interesting that all patients possess in at least one of their HLA-DQA1 alleles a nucleotide sequence coding for the amino acid glutamine at position 34 of the DQ alpha molecule. The expected frequency of these alleles in the control population amounts to 82%. The HLA-DRB1*16 allele, which is found in linkage disequilibrium with the HLA-DQA1*0102 allele, is also observed at an increased frequency in the patient's group, though the association was not significant after correction for the number of comparisons. However, no associations of CCLE with alleles at the HLA-DPB1 locus was found. The association of CCLE with certain HLA class II alleles points to an involvement of HLA-DQ and/or -DR molecules in the pathogenesis of the disease. Alternatively, genetic loci in linkage disequilibrium may code for elements which contribute to the development of CCLE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association between chronic cutaneous lupus erythematosus and HLA class II alleles. 788 95

The objective of this study was to investigate whether an octamer transcription factor gene (OTF3) located within the MHC region of chromosome 6 is involved in determining susceptibility to systemic lupus erythematosus (SLE) in a Spanish population. An OTF3 HindIII polymorphism was characterized by restriction fragment length polymorphism analysis of polymerase chain reaction amplified genomic DNA in 69 patients with SLE and 60 controls. No differences in the OTF3 allelic or genotypic distribution between healthy controls and patients with SLE were found. In the group of patients with diffuse proliferative glomerulonephritis, where we have previously detected the strongest MHC association, we did not observe OTF3 linkage either. In conclusion, the OTF3 gene does not appear to be associated with SLE in the Spanish population. This might be due to the distance of the gene from the HLA class II-III region where more relevant autoimmune-related genes are located.
Lupus 1995 Oct
PMID:Lack of association between the MHC linked OTF3 gene and systemic lupus erythematosus. 856 33

The cause of toxic oil syndrome (TOS) has not yet been definitively determined, but some genetic susceptibility factors (certain HLA antigens and female sex) have been identified in 236 patients. Similarities with genetic factors for scleroderma and hydralazine-induced lupus (i.e. in TOS female sex and HLA-A24, Pcorrected = 0.00001 and DR4, Pcorrected = 0.04, respectively) may provide a clue to the responsible xenobiotic and its pathogenesis, and may also help in understanding the basis of the related eosinophilia-myalgia syndrome associated with tryptophan ingestion. In this paper it is also established that a human class I antigen (HLA-A24) and, independently, an HLA class II haplotype (DR4-DQ8, Pcorrected = 0.04) and arginine 52 in the alpha-DQ chains (Pcorrected = 0.03) are associated with TOS susceptibility, similarly to insulin-dependent diabetes. This further supports the classification of TOS as an autoimmune disease. Also, the increased frequency of a particular set of low-frequency HLA class I antigens in chronic TOS patients (i.e. B27, B37, B38 and B49) and the probable decrease in the frequency of HLA-B homozygotes in surviving patients (Pcorrected = 0.008) may provide an objective model to explain the maintenance of the HLA polymorphism: less frequent HLA alleles may be more advantageous in the event of unexpected human contact with unusual xenobiotics (not only microbes); however, other mechanisms working together to preserve and generate HLA polymorphism may coexist.
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PMID:Frequencies of HLA-A24 and HLA-DR4-DQ8 are increased and that of HLA-B blank is decreased in chronic toxic oil syndrome. 880 34

Antibodies to fibrin-bound tissue plasminogen activator (tPA) have been found in autoimmune diseases with vascular injury, such as systemic lupus erythematosus and scleroderma. The purpose of this study was to determine whether patients with primary pulmonary hypertension (PPH) have an immunogenetically determined response to fibrin-bound tPA. Antibodies to fibrin-bound tPA were determined in three patient groups: 45 adults with PPH, 41 children with PPH, and 40 children with anatomically large congenital pulmonary to systemic communications (PHT+shunt). The frequencies of the HLA class II (DRB1,3,4,5, and -DQB1) alleles in these three patient groups were compared with those of 51 healthy Caucasian control subjects. Fibrin-bound tPA antibodies were found in four of 45 (9%) adults with PPH, four of 41 (10%) children with PPH, and one of 40 (2.5%) children with PHT-shunt. HLA class II typing, which was available for seven of nine Caucasians with fibrin-bound tPA antibodies, revealed that six of seven (86%) patients typed HLA-DQ7 (DQB1*0301) and one typed HLA-DQ6. The 86% frequency of HLA-DQ7 in the antibody positive patients was significant compared with the 29% frequency in the healthy control subjects (p = 0.007, p corrected [pc] = 0.05, OR = 14.4). Of interest, these antibody-positive patients, although lacking antiphospholipid antibodies, shared an amino acid epitope, common to HLA-DQB1*06,07 and 08 subtypes, which was previously reported to be associated with the lupus anticoagulant. In conclusion, antibodies to fibrin-bound tPA and HLA-DQ7, and possibly the same epitope associated with the lupus anticoagulant, defined a small subset of children and adults with PPH.
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PMID:Primary pulmonary hypertension, tissue plasminogen activator antibodies, and HLA-DQ7. 900 24

The antiphospholipid syndrome (APS) is an autoimmune thrombophilic disorder in which thromboembolism and thrombocytopenia occur. The antiphospholipid antibodies in these patients may cause acquired activated protein C resistance, whereas hereditary activated protein C resistance results from a common single point mutation in coagulation factor V (factor VLeiden). In a family of 11 members with 4 normal subjects, autoimmune thrombocytopenia was documented in 6 patients. Three out of these were found to have thrombocytopenia associated with primary APS. In addition, these 3 subjects were also heterozygous for the factor VLeiden. Only in this group of individuals did life threatening thromboembolic complications occur, while other thrombocytopenic family members showed no thrombotic manifestations. Genetic studies revealed no linkage between APS and HLA class II alleles. Taken together, we present a family with autoimmune thrombocytopenia, which is associated with primary APS in at least 50% of thrombocytopenic individuals. The coexistence of both APS and factor VLeiden in thrombocytopenic subjects, led to an increased number of thrombotic events, suggesting a critical role of combined acquired and hereditary activated protein C resistance in the development of thrombosis in this family. Since no association between APS and specific HLA groups was found, other underlying risk factors for the development of APS must be considered.
Lupus 1998
PMID:Familial coexistence of primary antiphospholipid syndrome and factor VLeiden. 960 41

Autoantibody production is commonly associated with particular HLA class II phenotypes. The aim of the present study was to investigate whether the presence of antiphospholipid (APL) antibodies and other autoantibodies in women with unexplained recurrent miscarriage was associated with particular human leukocyte antigen (HLA)-DR or -DQ alleles or linked epitopes which have previously been reported as being associated with the recurrent miscarriage syndrome or the presence of APL. In a total of 123 Danish and Czech women with recurrent miscarriage, serum was investigated for six different APL antibodies including anticardiolipin (ACL) antibody. Antinuclear antibodies (ANA), anti-zona pellucida antibodies and anti-sperm antibodies were also investigated. The women were HLA-DR and -DQ typed by DNA-based methods. The frequency of HLA-DR phenotypes did not differ significantly between APL antibody positive recurrent miscarriage patients and APL antibody negative recurrent miscarriage patients or healthy controls. Among ACL antibody positive recurrent miscarriage patients, significantly more were positive for the HLA-DR3 phenotype and negative for the HLA-DR2 phenotypes compared with healthy controls (P < 0.05). Among ANA positive recurrent miscarriage women, 55% carried the HLA-DR3 phenotype compared with 28% of ANA negative patients (P < 0.05) and 21% of healthy controls (P < 0.002). In conclusion, among recurrent miscarriage women, the HLA-DR3 phenotypes seem to predispose to formation of ACL antibodies and ANA. The association between APL antibodies and particular HLA alleles and HLA-linked epitopes reported in studies of patients with lupus erythematosus (e.g. HLA-DR7 and -DR4) could not be confirmed in patients with recurrent miscarriage.
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PMID:Studies on associations between human leukocyte antigen (HLA) class II alleles and antiphospholipid antibodies in Danish and Czech women with recurrent miscarriages. 988 8


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