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)

The clinical symptoms of drug-induced lupus (DIL) are similar to those of idiopathic systemic lupus erythematosus. The literature indicates that in patients with DIL, sera generally contain antinuclear antibodies (ANAs); however, ANA-negative DIL has been reported. The list of medications implicated as etiologic agents in DIL continues to grow. This list includes two different types of angiotensin-converting enzyme inhibitors--captopril and enalapril. We report the first case of DIL caused by lisinopril. Our patient had negative results on ANA testing and had histone antibodies (IgG anti-[H2A-H2B]-DNA) mirroring the disease course. Antibodies to the (H2A-H2B)-DNA complex are seen in more than 90% of patients with active DIL, excluding those with DIL due to hydralazine. Thus, it is important to recognize the clinical significance of IgG anti-(H2A-H2B)-DNA antibodies and that negative ANA test results do not preclude the diagnosis of DIL.
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PMID:Antinuclear antibody-negative, drug-induced lupus caused by lisinopril. 1178 Jun 82

An estimated incidence of drug-induced lupus erythematosus caused by all drugs is 15,000 to 20,000 cases a year, and represents approximately 5 to 10% of the total number of patients with systemic lupus erythematosus. Approximately 22% of the patients treated with isoniazid for a mean of 6 months develop antinuclear antibodies. Isoniazid-induced lupus erythematosus affects either sex equally and the most common presenting feature is arthralgia or arthritis with anemia. Fever and pleuritis occur in approximately half of the cases, and pericarditis in approximately 30% of cases. IgG antibody to the (H2A-H2B)-DNA complex appears specific for the isoniazid-induced lupus erythematosus. The drug-induced lupus presenting with cardiac tamponade is a recognized feature of many drugs such as hydralazine, procainamide, and sulfasalazine. Reported here is a case of isoniazid-induced lupus erythematosus presenting with cardiac tamponade. A 73-year-old man was treated with isoniazid for 8 months at a dose of 300 mg a day. The patient responded to the withdrawal of the isoniazid therapy and placement of a pericardial window. The existing literature on the subject is reviewed.
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PMID:Isoniazid-induced lupus erythematosus presenting with cardiac tamponade. 1189 31

Anti-chromatin autoantibodies were one of the first autoantibodies ever detected since they make up the majority of antibodies causing LE Cell formation. Anti-chromatin autoantibodies have had many names over the last few decades: LE cell factor; anti-nucleosome; anti-deoxyribonucleoprotein (DNP); and anti-(H2A-H2B-DNA). These autoantibodies are found in approximately 75% of people with systemic lupus erythematosus and up to 100% of people with drug-induced lupus. They are also found in 20-50% of patients with autoimmune hepatitis type I (lupoid hepatitis). Anti-chromatin are not generally found in any other disease, thus showing very good sensitivity and specificity for patients with lupus, drug-induced lupus and lupoid hepatitis. A number of studies have shown that in patients with lupus, anti-chromatin often correlates better with kidney disease than anti-DNA. Recent genetic analyses of murine models of lupus have identified at least three loci that work together to cause anti-chromatin antibodies and glomerulonephritis in mice. It will be an important breakthrough when the functions of the genes at these loci are identified.
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PMID:Anti-chromatin (anti-nucleosome) autoantibodies. 1284 87

A spontaneous, autoreactive autoantibody called SN5-18 (IgG2b, kappa) binds to a complex of H2A/H2B/dsDNA in chromatin, but erroneously appears to bind dsDNA when the Ab is used in a form that is not highly purified. Because of this finding, we evaluated the antigenic specificity of a prototypic anti-dsDNA Ab, 3H9/Vkappa4, now used widely in transgenic studies of tolerance and autoimmunity. We found that the purified mAb 3H9/Vkappa4 binds chromatin and specifically a complex of H2A/H2B/dsDNA, but not dsDNA in solid phase or in solution. When used in the form of culture supernatant or as a standard protein G preparation, mAb 3H9/Vkappa4 appears to bind dsDNA, apparently due to nuclear proteins in the preparation that assemble on target DNA. Because of the reported role of V(H)CDR3 Arg residues in dsDNA binding and the near identity of the SN5-18 sequence to other dsDNA-specific Ab, we tested the contributions of two V(H)CDR3 Arg residues in SN5-18 to chromatin specificity. We found that both these Arg residues at positions 104 and 106 were required for detectable chromatin binding. These results indicate a role for V(H)CDR3 Arg residues in chromatin specificity of lupus-derived autoantibodies. Further, they provide an explanation for a possible discrepancy in the form of tolerance observed in different anti-DNA Ig transgene models.
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PMID:Chromatin specificity of anti-double-stranded DNA antibodies and a role for Arg residues in the third complementarity-determining region of the heavy chain. 1500 32

The initial novel observation of this study was that most B cells of male BXSB lupus mice bear surface IgG2a(b) of extrinsic origin. To define the surface antigen, we here examine three (NZBxBXSB)F1-derived IgG2a(b) monoclonal antibodies (mAbs) selected for binding to cell surfaces. Surprisingly, all three mAbs bound the nucleosome (nuc) particle, the fundamental unit of chromatin and an early target of autoimmunity in systemic lupus erythematosus. Their tentative dissociation constant (K(d)) for soluble nuc particles was approximately 7 x 10(-10) m. The mAbs bound more weakly to both H2A-H2B-DNA and H3-H4-DNA complexes, and in immunoblot they stained all four core histones. The mAbs detected a surface antigen on all cell lines examined, present on viable cells. When stripped of nuc, and in the presence of DNase I, their binding to cell lines improved. Heparin displaced the antigen from the cell surface. In vivo, the three mAbs stained B cells of several BALB/c mice clearly stronger than the isotype control; this differential staining was significantly reduced in FcgammaRIIB-deficient mice. The results indicate that the three mAbs recognize (a) planted antigen on viable cultured cells and (b) soluble autoantigen in vivo, leading to immune complexes that bind to FcgammaRIIB. Further experiments demonstrated that antinuc IgG2a could be eluted from splenocytes of a male BXSB lupus mouse. Hence, at least part of the extrinsic IgG2a(b) found on BXSB B cells may represent FcgammaRIIB-bound nuc-IgG2a(b) complexes.
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PMID:Antinucleosome autoantibodies bind directly to cell lines in vitro and via the FcgammaRIIB receptor to B lymphocytes in vivo: a role for immune complexes in interactions between antinucleosome IgG2a and B cells of BXSB lupus mice. 1523 81

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the occurrence of numerous autoantibodies directed against nuclear antigens. Anti-histone antibodies (AHA) are as prevalent as their anti-dsDNA counterparts in SLE. Despite their frequency and potential importance, there have not been given much attention to AHA until recently. Nucleosomes, the fundamental repeating units of the chromatin, are formed of complexes of histones and DNA. The nucleosome core particle is composed of a central tetramer of 2 molecules each of H3 and H4 flanked by 2 dimers of H2A and H2B and surrounded by 2 superhelical turns of approximately 146 base pairs of DNA. The full nucleosome contains a molecule of H1 located at the point where DNA enters and exits the nucleosome. Recent studies have shown that the post transcriptional modification of histone changes chromatin structure to regulate transcription and the concept of this mechanism "epigenetics" has become center of attention in the field of basic cell biology. There have been described diverging specificities of AHA. Many attempts to locate antigenic determinants recognized by AHA have been made and H1 and H2B have been thought as common targets in lupus patients. Studies on murine models of lupus have shown several interesting findings. The universal epitope is located on H2B in (NZBxNZW)F1 mice. In addition to core histones, MRL-MP/Fas(lpr) mice develop high titers of autoantibodies to H1. Autoimmunity to chromatin regularly involves humoral immune responses directed against H1. These histones appear to be an early (possibly initial trigger) autoantigen for this autoimmune response in lupus.
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PMID:[Specificities and clinical significance of autoantibodies directed against histones]. 1599 75

Chromatin is the native complex of histones and DNA found in the cell nucleus of eukaryotes. The fundamental subunit of chromatin is the nucleosome, which is composed of a core particle in which 146 bp of helical DNA are wrapped around an octamer made up of two H2A-H2B dimers that surround an H3-H4 tetramer. The prevalence of anti-chromatin (nucleosome) antibodies in systemic lupus erythematosus (SLE) varies from 50% to 90%, being similar to that of the classical positive LE cell. The presence of these antibodies can be used, in conjunction with clinical findings and other laboratory tests, to help in the diagnosis of SLE and drug induced lupus. The presence of anti-chromatin antibodies has also been linked to glomerulonephritis in SLE patients.
Lupus 2006
PMID:Anti-chromatin (anti-nucleosome) antibodies. 1689 74

The generation of autoantibodies against chromatin is a hallmark of the multifactorial autoimmune disease systemic lupus erythematosous (SLE). Impaired clearance of apoptotic cells together with the release of nuclear autoantigens are supposed to contribute to the loss of self-tolerance in SLE. Phospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) are exposed on the surfaces of apoptotic cells and on apoptotic blebs. Also histones/nucleosomes can be detected on apoptotic cells; however, their binding motifs are still unknown. Therefore, we investigated the interaction of PS, PE, phosphatidylcholine (PC), and cardiolipin (CL) with histones H1, H2A, H2B, H3, and H4 by surface plasmon resonance (SPR). Strong binding to phospholipids was found for all histones, with H2A displaying the highest binding affinity to all phospholipids investigated. Hence, phospholipids including PS and PE may contribute to the binding of histones to surfaces and blebs of apoptotic cells. Moreover, histones/nucleosomes complexed to uningested apoptotic membrane structures may foster autoimmunity towards nuclear compounds.
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PMID:Interaction of histones with phospholipids--implications for the exposure of histones on apoptotic cells. 1751 19

Forty-four female patients who met the following criteria were studied. All were referred for rheumatology consultation because of symptoms and a positive antinuclear antibody (ANA) to rule out lupus. None fulfilled the American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) at the time of the initial visit. All had a normal or noncontributory complete blood count, urinalysis, and blood panel. They lacked antideoxyribonucleic acid, anti-Smith (anti-Sm), antiribonucleoprotein (anti-RNP), anti-Ro, anti-La, and antiscleroderma 70 (anti-Scl-70) antibodies, and none had rheumatoid factor, elevated creatine phosphokinase levels, or decreased C3 complement or C4 complement values. We performed additional tests or procedures in an effort to improve diagnostic accuracy. Nine of 44 (20%) had a negative ANA on retesting. All patients were tested for antiribosomal P, antineuronal, antihistone-(H2A-H2B)/deoxyribonucleic acid complex antibody, anti-smooth muscle antibody and antithyroid antibodies, as well as Westergren sedimentation rate. Anticardiolipin antibody, serum protein electrophoresis, bone scanning, or skin biopsies with or without lupus band testing were obtained as clinically indicated. At the 6-month follow-up, 19 patients (43%) fulfilled the ACR criteria for SLE, 14 (32%) fulfilled the ACR criteria for fibromyalgia only, 4 (9%) had seronegative rheumatoid arthritis, 1 (2%) had myasthenia gravis, and 6 (14%) remained undiagnosed; 18/19 diagnosed with SLE had an additional antibody or positive diagnostic test listed above versus 3/25 without SLE (p<0.0001). Additional laboratory and diagnostic testing beyond the routine ANA profile correlated with the evolving diagnosis in 86% of the patients at 6 months.
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PMID:The 'rule out lupus' rheumatology consultation: clinical outcomes and perspectives. 1907 69


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