Familial systemic lupus erythematosus. Presence of a cross-reactive idiotype in healthy family members.

Halpern, R; Davidson, Anne; Lazo, Aristides; Solomon, Gary; Lahita, Robert G.; Diamond, Betty

doi:10.1172/jci112028

Cited by 70 publications

(19 citation statements)

References 23 publications

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“…The wide distribution of many of these idiotypes in SLE patients, their family members (30,42), and in healthy individuals suggests that the ability to make the idiotype is not unique to patients with lupus. It is likely that IdGNI and IdGN2 are important as targets of immunoregulatory networks, with the B cells that express them being selected for up-regulation in individuals predisposed to develop SLE.…”

Section: Discussionmentioning

confidence: 99%

Idiotypic characteristics of immunoglobulins associated with systemic lupus erythematosus. Studies of antibodies deposited in glomeruli of humans

Kalunian

Panosian‐Sahakian

Ebling

et al. 1989

Arthritis & Rheumatism

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Indirect immunofluorescence with monoclonal antibodies to 6 different idiotypes was used to characterize immunoglobulins deposited in the glomeruli of renal biopsy samples from 32 patients with systemic lupus erythematosus (SLE) and 19 patients with nonlupus immune glomerulonephritis. IdGN2 was present in 75% of the biopsy specimens from SLE patients and in 6% of those from patients with non-lupus nephritis; IdGNl occurred in 38% and 6%, respectively. The other idiotypes were not increased in biopsy samples from patients with SLE. Deposition of IdGN2 was associated with a subendothelial location of Ig and proliferative changes in the glomeruli. In studies of glomerular eluates from 4 immunosuppressed SLE patients, an average of 26% of total Ig and 37% of anti-DNA was composed of IdGN2. Compared with IdGN2-immunoglobulin, IdGN2+ immunoglobulin

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Section: Discussionmentioning

confidence: 99%

Idiotypic characteristics of immunoglobulins associated with systemic lupus erythematosus. Studies of antibodies deposited in glomeruli of humans

Kalunian

Panosian‐Sahakian

Ebling

et al. 1989

Arthritis & Rheumatism

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“…Isoelectric focusing in 8 M urea was performed on all sera as previously described (10) to determine the charge distribution of the serum anti-DNA antibodies. DNA Western blots were performed to detect anti-DNA antibodies that might be complexed in the serum or of too low affinity to be detected by standard assays (11).…”

Section: Methodsmentioning

confidence: 99%

“…DNA Western blots were performed to detect anti-DNA antibodies that might be complexed in the serum or of too low affinity to be detected by standard assays (11). 1 l of each serum was electrophoresed on an isoelectric focusing gel in 8 M urea to dissociate immune complexes and the gels were transferred to nitrocellulose filters and probed with radiolabeled double-stranded DNA as previously described (10). In addition, dot blots were performed in which 0.5 l of selected sera was applied to nitrocellulose substrate.…”

Section: Methodsmentioning

confidence: 99%

An in vitro assay for detection of glomerular binding IgG autoantibodies in patients with systemic lupus erythematosus.

Budhai

Oh²,

Davidson³

1996

J. Clin. Invest.

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The deposition of anti-dsDNA antibodies in the glomerulus is believed to play a critical role in the pathogenesis of nephritis in SLE. However, an absolute correlation between serum levels of anti-dsDNA antibodies and renal disease has not been found. Recently a glomerular binding assay (GBA) has been developed to detect IgG binding to isolated rat glomeruli. We have used the GBA to study sera from four groups of SLE patients: (A) ϩ anti-dsDNA antibodies, active nephritis; (B) Ϫ anti-dsDNA antibodies, active nephritis; (C) ϩ anti-dsDNA antibodies, no nephritis; and (D) Ϫ anti-dsDNA antibodies, no nephritis. The serum antids-DNA antibodies in group A and group C patients could not be distinguished on the basis of isotype, charge, or crossreactivity with histones. Nevertheless, the mean intensity of glomerular immunofluorescence was significantly higher in group A than in the three other patient groups and distinguished between patients with serum anti-dsDNA antibodies who had nephritis and those without clinically apparent nephritis. GBA reactivity was unaffected by DNase treatment of sera, but was partially inhibited by preincubation with dsDNA. These findings are consistent with the hypothesis that some anti-dsDNA antibodies cross-react with glomerular components and that the presence of this crossreactivity is associated with, and may be responsible for, the development of nephritis. In addition, we have identified a group of SLE patients with renal disease and typical renal histopathology and immune deposits who do not have serum anti-dsDNA antibodies or antibodies that directly bind to glomeruli in the GBA. The mechanism of renal immune deposition in these patients remains to be determined. ( J. Clin. Invest. 1996. 98:1585-1593.) Key words: systemic lupus erythematosus • glomerulonephritis • anti-DNA antibodies

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“…Although the data are not yet conclusive, it appears that the germline immunoglobulin genes used to encode autoantibodies exist in nonautoimmune individuals and can be used to encode nonself-reactive antibodies (1)(2)(3)(4). There is still considerable controversy, however, whether autoantibodies are encoded by unmutated germ line genes and produced by circulating B cells that are not specifically activated by antigen (2,(5)(6)(7)(8), or whether they are encoded by somatically mutated genes which because of increased affinity for antigen are selected during a secondary B cell response (9-1 1).…”

Section: Introductionmentioning

confidence: 97%

Molecular characterization of a somatically mutated anti-DNA antibody bearing two systemic lupus erythematosus-related idiotypes.

Davidson

Manheimer-Lory²,

Aranow³

et al. 1990

J. Clin. Invest.

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Familial systemic lupus erythematosus. Presence of a cross-reactive idiotype in healthy family members.

Abstract: Sera of 27 members of 3 human kindreds with familial systemic lupus erythematosus (SLE) were examined for expression of a cross-reactive idiotype present on anti-DNA antibodies of SLE patients.

Cited by 70 publications

References 23 publications

Idiotypic characteristics of immunoglobulins associated with systemic lupus erythematosus. Studies of antibodies deposited in glomeruli of humans

Idiotypic characteristics of immunoglobulins associated with systemic lupus erythematosus. Studies of antibodies deposited in glomeruli of humans

An in vitro assay for detection of glomerular binding IgG autoantibodies in patients with systemic lupus erythematosus.

Molecular characterization of a somatically mutated anti-DNA antibody bearing two systemic lupus erythematosus-related idiotypes.

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