The Relation of Immunoglobulin Class, Pattern of Antinuclear Antibody, and Complement-Fixing Antibodies to DNA in Sera from Patients with Systemic Lupus Erythematosus*

Rothfield, Naomi F.; Stollar, B D

doi:10.1172/jci105669

Cited by 166 publications

(51 citation statements)

References 35 publications

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“…We also demonstrated that IL-4 was required for DN Th cell-induced IgG production from CD1c ϩ B cells, since neutralizing anti-IL-4 mAbs block the production of IgG1 and IgG2. The ability of SLE DN T cells to produce IL-4 and provide help for IgG production is consistent with data showing a critical role for IL-4 in murine models of SLE (42) and the role of IgG autoantibodies in the pathogenesis of lupus nephritis (43). It is striking that the three patients with DN T cells secreting the highest levels of IL-4 were the individuals with the lowest disease activity; each of them had a SLEDAI score of 1.…”

Section: Discussionsupporting

confidence: 88%

Human Double-Negative T Cells in Systemic Lupus Erythematosus Provide Help for IgG and Are Restricted by CD1c

Sieling¹,

Porcelli

Duong³

et al. 2000

The Journal of Immunology

118

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To understand the mechanism of T cell help for IgG production in systemic lupus erythematosus (SLE) we investigated the response of CD4- and CD8-negative (double-negative (DN)) T cells because 1) DN T cells are present at unusually high frequency in patients with SLE and can induce pathogenic autoantibodies; 2) the DN T cell repertoire includes cells restricted by CD1 Ag-presenting molecules; and 3) CD1c is expressed on a population of circulating B cells. We derived DN T cell lines from SLE patients and healthy individuals. In the presence of CD1+ APCs, DN T cell lines from SLE patients produced both IL-4 and IFN-γ, whereas DN T cells from healthy donors produced IFN-γ, but no IL-4. In general, cells from patients with highly active disease produced high levels of IFN-γ; cells from those with little activity produced high IL-4. Coculture of CD1c-directly reactive T cells from healthy donors with CD1c+ B cells elicited IgM Abs, but little or no IgG. In contrast, CD1c-directly reactive T cells from SLE patients induced isotype switching, with a striking increase in IgG production. Neutralizing Abs to CD1c inhibited the ability of DN T cells to induce IgG production from CD1c+ B cells, further indicating that CD1c mediated the T and B cell interaction. IgG production was also inhibited by neutralizing Abs to IL-4, correlating with the cytokine pattern of DN T cells derived from these patients. The data suggest that CD1c-restricted T cells from SLE patients can provide help to CD1c+ B cells for IgG production and could therefore promote pathogenic autoantibody responses in SLE.

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Section: Discussionsupporting

confidence: 88%

Human Double-Negative T Cells in Systemic Lupus Erythematosus Provide Help for IgG and Are Restricted by CD1c

Sieling¹,

Porcelli

Duong³

et al. 2000

The Journal of Immunology

118

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“…The punctate fluorescence of nuclear pore complexes was not apparent on rat liver sections used for routine ANA detection. The autoantibody produced a continuous peripheral (rim) labeling, similar to the fluorescence patterns reported for antibodies to DNA and to lamins (1)(2)(3)(4)(5)(6). However, on cultured cells, the peripheral fluorescence was punctate, and thus, it could not be confused with the continuous labeling associated with these antibodies.…”

Section: Discussionsupporting

confidence: 74%

A novel autoantibody causing a peripheral fluorescent antinuclear antibody pattern is specific for nuclear pore complexes

Dagenais

Bibor-Hardy

Senécal

1988

Arthritis & Rheumatism

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We characterized serum from a patient with polymyositis, and found that it produced a peripheral (rim) fluorescent antinuclear antibody pattern on rat liver substrate. Indirect immunofluorescence analysis revealed a punctate pattern at the nuclear surface of PtK2, BHK-21, and HEp-2 cells. This pattern was still present after sequential extraction in situ with non-ionic detergent, DNase, RNase, and high ionic strength buffer (2M NaCI). Immunogold electron microscopic localization was specific for nuclear pore complexes. By immunoblot analysis, the antigens were polypeptides of 200 kd and 130 kd that were enriched in the nuclear fraction.Antinuclear antibodies (ANA) in human sera are routinely detected with indirect immunofluorescence microscopy on substrates such as rat liver sections (1). Among the patterns identified by this method, the peripheral (rim) pattern is of diagnostic importance because of its association with systemic lupus erythematosus (SLE) (1,2). Studies of the antigenic specificity of autoantibodies from sera causing a peripheral ANA pattern have shown a strong association with anti-DNA antibodies (2,3). In addition, autoantibodies to nuclear lamins, observed in sera from 1 patient with linear scleroderma (4) and 5 patients with SLE (5,6), were shown to cause a peripheral ANA pattern because of continuous labeling of the nuclear envelope.Nuclear pore complexes are structures localized at the points of fusion of the double nuclear membranes (7) and are thought to allow molecular exchanges across the nuclear envelope. We report the identification, in serum from a patient with polymyositis, of a novel autoantibody that causes a peripheral ANA pattern on rat liver sections and stains the nuclear envelope of various cell lines. This autoantibody reacts with nuclear pore complexes. PATIENTS AND METHODSPatient LL. The index serum was obtained from a 35-year-old white woman who, in December 1985, developed polymyositis, which was characterized by progressive proximal muscle weakness, elevated levels of serum creatine kinase (4,836 units/liter, normal 24-1 70), myopathic changes evident on electromyogram, and abnormal findings on quadriceps muscle biopsy. ANA were detected by indirect immunofluorescence on cryostat rat liver sections, at a titer of 1: 1,280 and with a peripheral pattern. Esophageal manometry revealed decreased peristaltic pressure in the distal two-thirds of the esophagus.Normal or negative results were noted on the following tests: hemoglobin, leukocyte and platelet

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“…Furthermore, not all antibodies in the glomeruli of SLE patients are anti-DNA. Some of the characteristics of antibodies to DNA that localize in glomeruli are known; they include high avidity for the antigen (4,37), preferential reactivity with dsDNA (4,8), complementfixing Ig isotypes (2,3,5), and cationic charge, which may be important primarily in the initiation of nephritis (7-1 1,38).…”

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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The Relation of Immunoglobulin Class, Pattern of Antinuclear Antibody, and Complement-Fixing Antibodies to DNA in Sera from Patients with Systemic Lupus Erythematosus*

Cited by 166 publications

References 35 publications

Human Double-Negative T Cells in Systemic Lupus Erythematosus Provide Help for IgG and Are Restricted by CD1c

Human Double-Negative T Cells in Systemic Lupus Erythematosus Provide Help for IgG and Are Restricted by CD1c

A novel autoantibody causing a peripheral fluorescent antinuclear antibody pattern is specific for nuclear pore complexes

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

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