Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies directed against human cell nuclear factors (HLA-F1 and HLA-F2) that bind to the interferon consensus sequence (ICS) in the promoter region of the HLA-A2 class I gene can be detected in the serum of some patients with systemic lupus erythematosus (SLE). Such antibodies, in gel-shift assays, inhibited the formation of the retarded band corresponding to the HLA-F1/F2-ICS complex irrespective whether purified factors or crude nuclear extracts were used. This inhibitory effect was due to IgG since the SLE serum activity bound to and could be eluted from a protein A-Sepharose column. This effect still persisted after absorption of SLE serum on a DNA-affinity column which removed antibodies directed against protein-free HLA-A2-ICS nucleotide sequence also present in such sera. Western blot analysis further confirmed that SLE serum recognized both HLA-F1 (65 kDa) and HLA-F2 (88 kDa) polypeptides, independently of the presence of the HLA-A2-ICS nucleotidic sequence, as well as other proteins. These results suggest that human sera from some patients with SLE may be used as a convenient source of antibodies directed against DNA-binding proteins regulating gene transcription.
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PMID:Antibodies to HLA class I promoter-binding proteins in sera from patients with systemic lupus erythematosus. 273 69

Major histocompatibility complex (MHC) haplotypes, including HLA-A, -B, -C and -DR and complotypes (BF, C2, C4A and C4B) were determined in a large family with inherited C4 deficiency. The propositus, a 12-year-old girl with complete C4 deficiency and SLE, had the MHC haplotypes HLA-A2,Cw3,-B40,-DR6,BFS,C2C,C4AQO,C4ABQO inherited from her father and HLA-A30,-B8,-DR3,BFF1,C2C,C4AQO,C4BQO from her mother. These haplotypes were identified in several of the healthy relatives, who were thus shown to be carriers of C4 deficiency. Most of the other haplotypes found in the family were not considered to be unusual in the general population. The complete absence of C4 in the patient was confirmed by studies of Chido and Rodgers antigens in the plasma and on the erythrocytes, the absence of plasma C4d fragments and by studies of C4 chain antigens by immunoblotting technique. The results of the genetic analysis, together with the findings in other cases of C4 deficiency, supports the possibility that complete C4 deficiency in itself predisposes to development of SLE without contribution of other MHC gene products.
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PMID:C4 allotypes and HLA-DR antigens in the family of a patient with C4 deficiency. 393 50

The histocompatibility antigens were determined in 170 normal Chinese by a modified micro-lymphocytotoxicity test of Terasaki using 26 typing sera obtained from Behring Laboratories and Stanford University, and the data were compared with those obtained from 36 systemic lupus erythematosus, 30 rheumatoid arthritis, 17 ankylosing spondylitis as well as 45 leprosy patients. In normal individuals HLA-A2,A11 and A9 were dominant in locus A, the frequency were 42.35%, 41.76% and 32.35% respectively. HLA-Bw17, B13 and B5 were dominant in locus B, the frequency were 55.29%, 19.41% and 14.70% respectively. In systemic lupus erythematosus, the frequency of B8, Bw38 and A3 were slightly higher than normal (relative risk > 2); the frequency of Bw21 and B7 were little lower (risk of Bw21 < 0.5, frequency of B7 > 5% in normals but none in patients). In rheumatoid arthritis, the frequency of A28 and A10 (Aw25+26) were slightly lower than normal (risk < 0.5). In ankylosing spondylitis, the frequency of B27 was extremely high (risk = 44.92), Aw24 was also rather high (risk > 2); the frequency of B5, Bw35 and A10 (Aw25+26) was low (risk < 0.5), Bw15 and Bw21 > 5% in normals but none in patients. In leprosy, the frequency of B18 was relatively high (risk > 2); A3, Aw30+31+32, B27 and Bw35 were somewhat low (risk < 0.5). Because of the small sample size, however, the differences were not significant by Chi square analysis except the high frequency of B27 in ankylosing spondylitis (corrected P < 0.001).
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PMID:[Tissue typing of blood lymphocytes in normal Chinese and diseases (author's transl)]. 744 26

The HLA phenotypes were investigated in 30 Jamaican patients with Systemic Lupus Erythematosus (SLE), 30 with Rheumatoid Arthritis (RA) and 40 healthy controls. HLA phenotypes were determined by the microcytoxicity technique, using commercially prepared typing trays. In this study, the HLA phenotypic associations with SLE (HLA-B14, RR 4.3: HLA-A28, RR 4.3) were not statistically significant. However, a statistically significant lack of HLA-A9 (p < 0.01; CP < 0.1) was observed in SLE patients compared to healthy controls. In RA patients, a statistically significant association was noted with HLA-A2 (RR 5.1; CP < 0.01). No HLA class II associations were noted with SLE. Class II associations with RA did not achieve statistical significance but included those previously established in other populations. The preliminary data obtained from this study indicate differences in the patterns of HLA phenotypes in Jamaican patients with SLE and RA compared to those observed in such patients elsewhere. Further studies involving larger groups of patients and typing at the serological, cellular and molecular levels are clearly warranted.
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PMID:Systemic lupus erythematosus, rheumatoid arthritis and HLA phenotypes in Jamaicans. 779 5

Approximately 10% of patients with systemic lupus erythematosus (SLE) develop epileptic seizures. When occurring before the onset of generalized SLE, the seizures are mainly primary generalized. Accordingly, long-term treatment with anti-epileptic drugs may precipitate SLE, or epilepsy and SLE may both occur as manifestations of a genetically determined predisposition. Some patients develop IgA deficiency during phenytoin treatment. This condition is reversible and IgA becomes normalized when phenytoin is withdrawn (drug-induced IgA deficiency). Some epileptic patients have a drug-independent IgA deficiency. Patients with drug-induced IgA deficiency are usually HLA-A2, while those with drug-independent IgA deficiency are HLA-A1,B8. The gene coding for IgA deficiency seems to be located in the HLA complex on chromosome 6. The gene locus for juvenile myoclonus epilepsy and related disorders is also on chromosome 6 and in close relation to the gene locus for the HLA system. Juvenile myoclonic epilepsy may be accompanied by drug-induced IgA deficiency, but there are also cases with other sometimes less-defined epilepsies, associated with this anomaly. It is possible that the relationship between epilepsy and immune disturbances is related to a common genetically determined susceptibility.
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PMID:Immunological aspects of epilepsy. 833 10

The genetic basis of complete C4 deficiency in a patient with SLE was investigated. Previous studies have demonstrated that this patient has two different major histocompatibility complex (MHC) haplotypes that each contain a major deletion and a non-expressed C4 gene. In the present study, non-expression of the C4 genes was explained by the finding of two distinct C4 gene mutations. A previously described two base pair insertion in exon 29 of the C4 gene was detected in the paternal MHC haplotype [HLA-A2, B40, SC00, DR6]. The maternal haplotype [HLA-A30, B18, F1C00, DR3] carried a C4 gene with a one base pair deletion in exon 20 generating a premature stop codon. This mutation was neither found in 10 individuals with known non-expressed C4 genes nor in 9 individuals homozygous for the complotype F1C30. The isotype and allotype specific regions of the patient's C4 genes were sequenced, and both contained C4A3a sequence. In conclusion, two different MHC haplotypes resembling the extended haplotypes [HLA-A2, B40, SC02, DR6] and [HLA-A30, B18, F1C30, DR3] both contained a non-expressed C4A gene that was due to either of two distinct mutations, demonstrating the heterogeneous genetic background of C4 deficiency.
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PMID:Characterization of non-expressed C4 genes in a case of complete C4 deficiency: identification of a novel point mutation leading to a premature stop codon. 979 39

Exposure to silica minerals is associated with silicosis and autoimmune disorders, especially systemic scleroderma. Evidence of this association has been increasingly reported in the last decade. The aim of this paper is to discuss, on the basis of a literature review, the case of a 28-year-old female dental technician who suffered from episodes of weakness, arthralgia, pain, swelling and stiffness of the fingers, dyspnoea with cough, a positive Waaler-Rose reaction, increased rheumatoid factor and normal ESR. She was a non-smoker. A rheumatoid syndrome with lung interstitial disorder, associated with silica exposure from dental ceramic products, was diagnosed. The patient had the HLA-A2-A31, HLA-B51-B18 and HLA-DR3-DR11 haplotypes, some of which are associated with autoimmune disease susceptibility. A 6-month follow-up, with adequate protection and without treatment, showed disappearance of the symptomatology and negative tests for Waaler-Rose reaction and rheumatoid factor. Exposure to silica should, therefore, be sought in the history of any patient with autoimmune or lupus-like syndrome and pulmonary changes. Symptoms associated with silica dust exposure from dental ceramic products should be recognised as being due potentially to an occupational disease, and dental technicians should be protected as workers at risk.
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PMID:Rheumatoid syndrome associated with lung interstitial disorder in a dental technician exposed to ceramic silica dust. A case report and critical literature review. 1195 93

EBV infection is more common in patients with systemic lupus erythematosus (SLE) than in control subjects, suggesting that this virus plays an etiologic role in disease and/or that patients with lupus have impaired EBV-specific immune responses. In the current report we assessed immune responsiveness to EBV in patients with SLE and healthy controls, determining virus-specific T cell responses and EBV viral loads using whole blood recall assays, HLA-A2 tetramers, and real-time quantitative PCR. Patients with SLE had an approximately 40-fold increase in EBV viral loads compared with controls, a finding not explained by disease activity or immunosuppressive medications. The frequency of EBV-specific CD69+ CD4+ T cells producing IFN-gamma was higher in patients with SLE than in controls. By contrast, the frequency of EBV-specific CD69+ CD8+ T cells producing IFN-gamma in patients with SLE appeared lower than that in healthy controls, although this difference was not statistically significant. These findings suggest a role for CD4+ T cells in controlling, and a possible defect in CD8+ T cells in regulating, increased viral loads in lupus. These ideas were supported by correlations between viral loads and EBV-specific T cell responses in lupus patients. EBV viral loads were inversely correlated with the frequency of EBV-specific CD69+ CD4+ T cells producing IFN-gamma and were positively correlated with the frequencies of CD69+ CD8+ T cells producing IFN-gamma and with EBV-specific, HLA-A2 tetramer-positive CD8+ T cells. These results demonstrate that patients with SLE have defective control of latent EBV infection that probably stems from altered T cell responses against EBV.
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PMID:Defective control of latent Epstein-Barr virus infection in systemic lupus erythematosus. 1470 7

T cell dysfunction has been described in systemic lupus erythematosus (SLE). However, the specific phenotype and function of antigen-specific CD8 cells is less clear. Here we determined phenotype and function of Epstein-Barr virus (EBV)-specific CD8 cells at the single-cell level in SLE. HLA-A2-restricted EBV-BMLF-1-specific CD8 cells were enumerated by flow cytometry using tetramers in SLE and healthy control subjects. Antigen-specific CD8 cells were analyzed for expression of differentiation, activation, proliferation, and anti-apoptotic markers. EBV-specific, other virus-specific (specific against a viral peptide pool consisting of cytomegalovirus, EBV and influenza virus peptides), and mitogen-induced CD8 cell function was assessed by INF-gamma ELISPOT assay. Frequencies of EBV-specific CD8 cells tended to be greater in SLE subjects than in healthy control subjects (p=0.07). While over 10% of EBV-specific CD8 cells were capable of producing IFN-gamma in four out of five healthy control subjects, such proportions of EBV-specific CD8 cells capable of IFN-gamma production were observed in only one out of six SLE subjects (p=0.04). In contrast, viral peptide pool-specific and mitogen-induced IFN-gamma-producing T cell function was intact in SLE subjects. Phenotypic analysis revealed EBV-specific CD8 cells to be in an early to intermediate differentiation and resting memory state in both groups. While EBV-specific CD8 cells are similar in phenotype, their frequency tends to be increased, and function appears to be decreased in SLE. Therefore, an impaired EBV-specific CD8 immune response may exist in SLE, potentially contributing to disease pathogenesis.
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PMID:Phenotypic and functional analysis of EBV-specific memory CD8 cells in SLE. 1618 18