Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined 18 families with infants who had neonatal lupus erythematosus (NLE) syndrome to determine whether abnormalities in C4 phenotypes and genotypes were an additional risk factor for this syndrome. Fifteen of 18 mothers of infants with NLE (83%) had C4 null allotypes compared with 36% of population controls (p = less than .001). This increased frequency was due mainly to the presence of C4A null allotypes (11/18, 61%). C4 gene abnormalities, i.e., deletion or probable duplication, were present in 100% (16/16) of mothers of infants with NLE. The most common molecular genetic abnormality in mothers of infants with NLE in this study was deletion of C4A genes. Duplication of C4A and C4B loci was also commonly seen. Duplication of C4A genes was detected only in mothers of infants with complete congenital heart block (CCHB), and duplication of C4B was detected only in mothers of infants with dermatitis. No significant increase in C4A or C4B null allotypes or protein deficiencies was noted in mothers of infants with neonatal lupus when compared with anti-Ro(SS-A)-positive mothers delivered of clinically normal infants. Fathers of infants with NLE showed a trend toward increase in C4B null allotypes when compared with population controls (75%, 3/4, p = .06). The two infants with CCHB examined were C4B protein-deficient, in contrast to infants with lupus dermatitis, who had frequent C4B null allotypes but no C4B protein deficiency. C4B null allotypes were not seen in unaffected siblings of infants with NLE and in only 1 of 7 anti-Ro(SS-A)-positive mothers who delivered clinically normal infants. We conclude that inheritance of C4A null allotypes is not predictive of increased risk of neonatal lupus when present in anti-Ro(SS-A)-positive women. Examination of paternal and maternal C4 genes of additional infants with NLE, in particular those with CCHB, and of normal infants born to anti-Ro(SS-A)-positive mothers--and of the normal infants' parents--is required to determine if abnormal C4B genes are a critical factor rendering susceptibility to the NLE syndrome.
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PMID:Neonatal lupus erythematosus syndrome: analysis of C4 allotypes and C4 genes in 18 families. 154 98

A female patient with disfiguring lupus erythematosus profundus (LEP) from the age of 13 years was found to have an isolated partial C4 deficiency, with reduced levels of both allotypes, C4A and C4B. A genetic basis for the hypocomplementaemia was confirmed by a family study of complement and HLA types which revealed heterozygous null alleles for C4A and C4B in the proband. Marked improvement in her cutaneous lesions occurred with thalidomide.
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PMID:Lupus erythematosus profundus with partial C4 deficiency responding to thalidomide. 187 7

Deficiencies in proteins of the classic complement pathway are particularly frequent in patients with autoimmune diseases, notably systemic lupus erythematosus (SLE). The C4 component is a polymorphous glucoprotein coded by two closely linked genes, C4A and C4B, located within the HLA complex. C4, and in particular the C4A isotype plays a major role in maintaining immune complexes in solution. Fifty percent of patients with SLE are homozygous or heterozygous to the silent allele C4 AQO. Hereditary CE deficiency is often complicated by lupus-related diseases which may be associated with repeated infections. The biological particularity of SLE associated with complement protein deficiencies is the frequency of anti-SSA (Ro) antibodies.
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PMID:[Lupus and protein deficiencies of the classical complement pathway]. 223 85

Previous studies of patients with systemic lupus erythematosus (SLE) have shown an increased frequency of certain major histocompatibility complex (MHC) markers, including HLA-DR2, DR3, and C4AQ0 (C4A-null), in Caucasian patients. However, most of these studies were of randomly selected, unrelated patients; families were not included, and haplotypes were not determined. In order to define more accurately the possible role of MHC genes in lupus susceptibility, HLA-A, B, C, and DR, as well as BF, C2, C4A, C4B, and GLO, markers were determined in 62 Caucasian patients of known ethnic background, and in the members of their families. The distributions of extended haplotypes (fixed combinations of HLA-B, DR, and complotype alleles), fragments thereof, and individual alleles were determined in SLE patients and controls. The MHC distributions in all patients were compared with haplotypes in a normal Caucasian population. There were no statistically significant differences between the frequencies of any MHC marker, fragment, or extended haplotype in the patients compared with the controls. The patients were categorized into 2 groups of European ancestry (English/Irish; other Europeans), and each group was compared with a group of ethnically matched controls. There was a statistically significantly increased frequency of the alleles C4AQ0 and DR3 and the complotype SC01 in SLE patients of English/Irish descent as compared with ethnically matched controls. The increase in C4AQ0 and DR3 could be accounted for by the fact that they were part of the extended haplotype [HLA-B8;SC01;DR3] and/or its fragment (SC01;DR3). No increase in any MHC marker was observed in the other patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of ethnicity on major histocompatibility complex complement allotypes and extended haplotypes in patients with systemic lupus erythematosus. 236 33

A range of drugs including hydralazine, isoniazid, procainamide and penicillamine cause toxic side effects which resemble systemic lupus erythematosus (SLE). Deficiencies of C1, C4 and C2 are associated with idiopathic SLE, and these defects may compromise the ability of the patient to deal with immune complexes. Immune complexes with protein as antigen, such as has been reported to be diagnostic of procainamide-induced SLE, interact more with the C4A isotype of C4 than the C4B isotype. It is shown that hydralazine, isoniazid and penicillamine inhibit the covalent binding of C4 to a complement-activating surface and that the drugs themselves become covalently bound to C4. For each of these drugs, C4A is inhibited more than C4B, and it is suggested that this is an important contributory factor in the development of the toxic side effects to these drugs involving immune-complex deposition. For procainamide, it is shown that the hydroxylamine metabolite rather than the drug itself inhibits the covalent binding reaction of C4. Hydralazine, isoniazid and procainamide are metabolised by the polymorphic N-acetyltransferase, and slow acetylators are at increased risk of drug-induced lupus. For procainamide, oxidation to the hydroxylamine form is an alternative metabolic route of increased importance in slow acetylators, and it is suggested that investigation of C4 type in susceptible patients could provide a means of identifying those at greatest risk of immunotoxicity.
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PMID:Drug-induced immune-complex disease. 252 48

21 patients with systemic lupus erythematosus induced by long-term treatment with hydralazine were investigated to see whether susceptibility to this syndrome was associated with deficiency of the classical pathway complement protein, C4. 16 of 21 (76%) patients had one or more C4 null (ie, non-productive) alleles compared with 35 of 82 normal subjects (43%). This difference was significant. The HLA-DR4 antigen, known to be in linkage disequilibrium with the C4B null allele, was also significantly more frequent in the patients (14 of 21 patients compared with 31 of 81 normal subjects). Susceptibility to hydralazine-induced lupus, as in idiopathic systemic lupus erythematosus, may depend partly upon genetically determined C4 levels.
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PMID:Complement system protein C4 and susceptibility to hydralazine-induced systemic lupus erythematosus. 256 18

The role of HLA and complement genes was studied in 13 patients with subacute cutaneous lupus erythematosus. Genetic markers and by combining the major histocompatibility complex class I (HLA-A, -B, and -C), class II (HLA-DR), and class III (properdin factor B [BF] and C4) phenotyping with DNA level analysis of the C4 region. Of our patients, 54% had DR2 antigens and 50% had DR3 antigens, when the frequencies in the controls were 25% and 33%, respectively. The DR3 antigen was associated with annular skin lesions that were associated with a younger age at onset, whereas the DR2 antigen was associated with papulosquamous skin lesions and an older age at onset. The frequency of C4 null alleles was 83% in the patients and 50% in the controls. The null alleles were found in both C4A and C4B loci and were not associated with any special major histocompatibility complex haplotype. The DNA studies showed that the null phenotype mostly resulted from a gene deletion. A highly increased frequency of complement C4 null alleles may be a predisposing factor for cutaneous lupus erythematosus and especially of the subacute cutaneous type.
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PMID:Subacute cutaneous lupus erythematosus. Genetic markers and clinical and immunological findings in patients. 265 45

Two genes, C4A and C4B, encoding the fourth component of the complement system are linked to the HLA complex. C4 defects or C4 'null' genes can predispose to an autoimmune disease, lupus erythematosus (LE). We have used Southern blotting techniques to analyse genomic DNA from 23 patients with LE and from healthy controls, to evaluate the molecular basis of the C4 null phenotypes. In addition to the high frequencies of C4 null phenotypes and HLA-B8. DR3 antigens, confirming earlier results, we observed that among the patients both the C4A and C4B null phenotypes mostly resulted from gene deletions. Among the controls only the C4A null phenotypes were predominantly the result of gene deletions. In all cases these C4 gene deletions also extended to a closely linked pseudogene, 21-hydroxylase A (21-OHA). Altogether, 52% of the patients and 26% of the controls carried a C4/21-OHA deletion.
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PMID:C4 null phenotypes among lupus erythematosus patients are predominantly the result of deletions covering C4 and closely linked 21-hydroxylase A genes. 326 Sep 57

A patient who presented with urticarial vasculitis, recurrent angio-oedema and gastro-intestinal symptoms in association with a 'lupus-like' disorder is documented. Other 'auto-immune' phenomena such as Sjogren's-like syndrome and polyarthritis were present in association with antibodies to RNP, low C4 and a null allele was demonstrated at the C4B locus. Response to varied therapies was poor and unsustained.
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PMID:Hypocomplementaemic urticarial vasculitis, angio-oedema and 'lupus-like' disease: association with C4B null allele. 349 4

Eight families (121 individuals) with two or more members affected with systemic lupus erythematosus (SLE) were analyzed for histocompatibility antigens (HLA-A, B, C, DR, MT, and MB) and complement antigens (C4A, C4B, and BF). These data were correlated with serological markers (antinuclear antibodies, single- and double-stranded anti-DNA, anti-SM, anti-nRNP, anti-Ro [SS-A], anti-La [SS-B], and biological false-positive tests for syphilis and clinical features. Fifteen members had SLE, and 19 had other immune diseases (subacute cutaneous lupus erythematosus, discoid lupus erythematosus, hypothyroidism, insulin-dependent diabetes mellitus, primary Sjogren's syndrome, immune thrombocytopenic purpura, rheumatoid arthritis, and multiple sclerosis). Twenty-three healthy relatives (seroreactors) had significant titers of circulating antibodies, as did 2 of 17 spouses. There was an increased frequency of null C4 alleles in those individuals with SLE (60%) and healthy relatives (50%) as compared with spouses (24%). Multivariate analysis showed a significant association between SLE and female sex (P =.006), whereas there was no significant association revealed between female sex and other immune diseases. Patients with SLE also had a higher frequency of either C4A or C4B null alleles (P = .01) than those with immune diseases. The C4A homozygous null phenotype was more common in SLE patients than in seroreactors (P = .02). There was a higher frequency of HLA-DR2 and DR3 in individuals with SLE than in those with immune disease (P = .08), seroreactors (P = .02) and normal relatives (P = .002). One totally C4-deficient patient with SLE was identified. These families demonstrate an important association between SLE and the C4 null allele and the HLA-DR2 and DR3. These risk factors, however, cannot account for the development of disease in all individuals.
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PMID:Null alleles of the fourth component of complement and HLA haplotypes in familial systemic lupus erythematosus. 387 10


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