scholarly journals Breaking Tolerance to Double Stranded DNA, Nucleosome, and Other Nuclear Antigens Is Not Required for the Pathogenesis of Lupus Glomerulonephritis

2004 ◽  
Vol 199 (2) ◽  
pp. 255-264 ◽  
Author(s):  
Samuel T. Waters ◽  
Marcia McDuffie ◽  
Harini Bagavant ◽  
Umesh S. Deshmukh ◽  
Felicia Gaskin ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Antinuclear Antibody ◽  
Early Mortality ◽  
Chromosome 1 ◽  
Chronic Glomerulonephritis ◽  
Chromosome 4 ◽  
Double Stranded Dna ◽  
Nuclear Antigens ◽  
Dsdna Antibody ◽  
Lupus Glomerulonephritis

In lupus-prone NZM2328 mice, a locus Cgnz1 on chromosome 1 was linked to chronic glomerulonephritis, severe proteinuria, and early mortality in females. A locus Adnz1 on chromosome 4 was linked to antinuclear antibody (ANA) and anti–double stranded DNA (dsDNA) antibody (Ab) production. In this investigation, two congenic strains, NZM2328.C57L/Jc1 (NZM.C57Lc1) and NZM2328.C57L/Jc4 (NZM.C57Lc4), were generated by replacing the respective genetic intervals containing either Cgnz1 or Adnz1 with those from C57L/J, a nonlupus-prone strain. The NZM.C57Lc1 females had markedly reduced incidence of chronic glomerulonephritis and severe proteinuria. NZM.C57Lc4 females had chronic glomerulonephritis and severe proteinuria without circulating ANA, anti-dsDNA, and antinucleosome Ab. These data confirm the linkage analysis. Unexpectedly, NZM.C57Lc1 females had little anti-dsDNA and related Ab, suggesting the presence of a second locus Adnz2 on chromosome 1. The diseased NZM.C57Lc4 kidneys had immune complexes by immunofluorescence and electron microscopy. The eluates from these kidneys did not contain ANA, anti-dsDNA, and antinucleosome Ab, indicative of the presence of non–anti-dsDNA nephritogenic Ab. Thus, breaking tolerance to dsDNA and chromatin is not required for the pathogenesis of lupus nephritis. These results reaffirm that anti-dsDNA and related Ab production and chronic glomerulonephritis are under independent genetic control. These findings have significant implications in the pathogenesis of systemic lupus erythematosus.

scholarly journals Cgnz1 allele confers kidney resistance to damage preventing progression of immune complex–mediated acute lupus glomerulonephritis

2013 ◽  
Vol 210 (11) ◽  
pp. 2387-2401 ◽  
Author(s):  
Yan Ge ◽  
Chao Jiang ◽  
Sun-Sang J. Sung ◽  
Harini Bagavant ◽  
Chao Dai ◽  
...  
Keyword(s):  
Immune Complex ◽  
Organ Damage ◽  
Distal Region ◽  
Chromosome 1 ◽  
Chronic Glomerulonephritis ◽  
Female Mice ◽  
Inflammatory Parameters ◽  
Stage Renal Disease ◽  
End Stage ◽  
Lupus Glomerulonephritis

Cgnz1 and Agnz1 on the distal region of mouse chromosome 1 are associated with chronic glomerulonephritis (cGN) and acute GN (aGN). NZM2328.Lc1R27 (R27) was generated by introgressing a C57L/J region where Cgnz1 is located to NZM2328. R27 female mice developed aGN mediated by immune complex (IC) deposition and complement activation without progression to cGN with severe proteinuria. End stage renal disease (ESRD) was not seen in R27 mice as old as 15 mo. Thus, aGN and cGN are under separate genetic control, and IC-mediated proliferative GN need not progress to cGN and ESRD. NZM2328 and R27 female mice have comparable immune and inflammatory parameters. In contrast to NZM2328, R27 mice were resistant to sheep anti–mouse GBM serum-induced nephritis, supporting the hypothesis that aGN is mediated by autoimmunity and resistance to the development of cGN is mediated by end organ resistance to damage. Thus, autoimmunity should be considered distinct from end organ damage. The Cgnz1 region has been mapped to a 1.34 MB region with 45 genes. Nine candidate genes were identified. Clinical relevance of these observations is supported by case studies. Clinical implications and the significance to human lupus and other diseases are presented.

scholarly journals A case of Lemierre syndrome combined with a suspected systemic lupus erythematosus flare

2019 ◽  
Vol 7 ◽  
pp. 2050313X1987178 ◽  
Author(s):  
Teruhiro Fujii ◽  
Yuko Iwabuchi ◽  
Takahito Moriyama ◽  
Keiko Uchida ◽  
Kosaku Nitta
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Antinuclear Antibody ◽  
Activity Index ◽  
Immunosuppressive Treatment ◽  
Young Patients ◽  
Systemic Lupus ◽  
Lemierre Syndrome ◽  
Dsdna Antibody ◽  
Antibody Levels

Lemierre syndrome develops in healthy young patients as a result of bacteremia after oral cavity infection. It causes thrombophlebitis in the internal jugular vein. Infection can easily occur during immunosuppressive treatment in patients with systemic lupus erythematosus and become severe. We present a case of Lemierre syndrome in a patient with systemic lupus erythematosus. A 56-year-old woman presented with fever, left lower toothache, and skin symptoms from the left neck to the anterior chest. Clinical presentation and laboratory investigations revealed Lemierre syndrome. The inflammation and thrombus disappeared with antibiotic and anticoagulant therapies. However, transient hypocomplementemia and elevated antinuclear antibody levels were observed during treatment; therefore, a concomitant systemic lupus erythematosus flare was considered. In systemic lupus erythematosus patients with Lemierre syndrome, complement and antinuclear antibody levels are modified, so other indicators should be precisely evaluated, such as levels of urinary protein, sediment, serum creatinine and anti-dsDNA antibody, and systemic lupus erythematosus disease activity index.

scholarly journals Immunization with a Peptide Surrogate for Double-stranded DNA (dsDNA) Induces Autoantibody Production and Renal Immunoglobulin Deposition

1998 ◽  
Vol 188 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Chaim Putterman ◽  
Betty Diamond
Keyword(s):  
Immune Response ◽  
Lupus Erythematosus ◽  
Inbred Strains ◽  
Autoantibody Production ◽  
Peptide Antigen ◽  
Double Stranded Dna ◽  
Dsdna Antibody ◽  
Antigen Peptide ◽  
Peptide Display ◽  
Dsdna Antibodies

Anti–double-stranded DNA (dsDNA) antibodies are the serologic abnormality characteristically associated with systemic lupus erythematosus (SLE) and may play an important role in disease pathogenesis. Although the anti-dsDNA antibodies present in SLE are indicative of an antigen-driven response, the antigen has not been conclusively identified. By screening a phage peptide display library, we demonstrated previously that the decapeptide DWEYSVWLSN is specifically bound by the pathogenic murine IgG2b anti-dsDNA antibody R4A. To investigate the possibility that a protein antigen might trigger lupus-like autoimmunity, we immunized BALB/c mice with DWEYSVWLSN in adjuvant. Mice developed significant titers of IgG anti-dsDNA antibodies 2–3 wk after the initial immunization. Immunized mice also developed antibodies against some other lupus autoantigens, and immunoglobulin deposition was present in renal glomeruli at 49 d. Although an immune response to peptide and dsDNA was evident in BALB/c mice, there was little response in other inbred strains. This study demonstrates that lupus-like anti-dsDNA reactivity can be generated in nonautoimmune mice by immunization with a peptide antigen. Peptide-induced autoimmunity may prove useful in understanding the spreading of antigenic specificities targeted in SLE. However, most importantly, the demonstration that a peptide antigen can initiate a SLE-like immune response opens a new chapter on the potential antigenic stimuli that might trigger SLE.

scholarly journals Spontaneous soft tissue haemorrhage in systemic lupus erythematosus

Reumatismo ◽  
2016 ◽  
Vol 68 (4) ◽  
pp. 199 ◽  
Author(s):  
M.C. Abdulla
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Soft Tissue ◽  
Lupus Erythematosus ◽  
Antinuclear Antibody ◽  
Low Grade ◽  
Systemic Lupus ◽  
Double Stranded Dna ◽  
Positive Antinuclear Antibody ◽  
Clinical Presentations ◽  
Retinal Haemorrhages

Diversity in clinical presentations and complications of systemic lupus erythematosus (SLE) make the diagnosis and management challenging. The mechanisms of haemorrhagic manifestations in SLE have not been well elucidated. A 47-year-old woman with no comorbidities was admitted after suffering fatigue and low grade fever for six months. She had bilateral soft tissue haemorrhage over the forearm and intra retinal haemorrhages. She was assessed and diagnosed as having SLE based on positive antinuclear antibody, strongly positive anti double stranded DNA, thrombocytopenia and low C3 and C4 levels. We describe a case of spontaneous bilateral soft tissue haemorrhage in SLE and discuss the various mechanisms causing bleeding in lupus.

scholarly journals Comparison of antinuclear antibody profiles obtained using line immunoassay and fluorescence enzyme immunoassay

2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110143
Author(s):  
Jaehyeok Jang ◽  
Sinyoung Kim ◽  
Hyon-Suk Kim ◽  
Kyung-A Lee ◽  
Jungyong Park ◽  
...  
Keyword(s):  
Enzyme Immunoassay ◽  
Lupus Erythematosus ◽  
Antinuclear Antibody ◽  
Diagnostic Performance ◽  
Antinuclear Antibodies ◽  
Lower Sensitivity ◽  
Systemic Lupus ◽  
Nuclear Antigens ◽  
Good Agreement ◽  
Strong Agreement

Objective LIA-ANA-Profile-17S is a multiplex line immunoassay that simultaneously detects 17 antinuclear antibodies (ANAs) against extractable nuclear antigens (ENAs). We evaluated the utility of LIA-ANA-Profile-17S as a supplement to ANA indirect immunofluorescence (IIF) and EliA ENA (a fluorescence enzyme immunoassay) for diagnosis of ANA-associated rheumatic diseases. Methods Sera were collected from 245 patients referred for an ANA IIF test. LIA-ANA-Profile-17S results were compared with those of EliA ENA. The kappa coefficients, agreement rates, and diagnostic performance of these tests were assessed for systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SjS). Results We observed almost perfect interassay agreement for antibodies against Ro52/Ro60, CENP-B, and Scl-70 (kappa = 0.91, 0.97, and 1.00, respectively); strong agreement for anti-SS-B/La antibody (kappa = 0.81); and relatively low agreement for other antibodies, including those against dsDNA, Sm, RNP, and Jo-1. For SLE diagnosis, LIA-ANA-Profile-17S showed lower sensitivity and similar specificity compared with EliA ENA. The sensitivity and specificity of these two assays were similar for SjS diagnosis. Conclusions The specificity of LIA-ANA-Profile-17S was enhanced when combined with ANA IIF and was comparable with that of EliA ENA. LIA-ANA-Profile-17S showed relatively good agreement with EliA ENA. In combination with ANA IIF, these assays showed enhanced diagnostic performance.

Guidelines for Clinical Use of the Antinuclear Antibody Test and Tests for Specific Autoantibodies to Nuclear Antigens

2000 ◽  
Vol 124 (1) ◽  
pp. 71-81 ◽  
Author(s):  
Arthur Kavanaugh ◽  
Russell Tomar ◽  
John Reveille ◽  
Daniel H. Solomon ◽  
Henry A. Homburger
Keyword(s):  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Antinuclear Antibody ◽  
Clinical Decision Making ◽  
Antibody Test ◽  
Disease Diagnosis ◽  
Test Results ◽  
Appropriate Use ◽  
Nuclear Antigens ◽  
Systemic Rheumatic Diseases

Abstract The following guideline presents a series of recommendations based on published medical literature for use of the antinuclear antibody (ANA) test and tests for specific autoantibodies to nuclear antigens in the diagnostic evaluation, prognostic assessment, and monitoring of patients with systemic rheumatic diseases. The guideline emphasizes the need for clinical evaluation to improve the usefulness of test results in patient management. Consideration is given to appropriate use of the generic ANA test in the initial evaluation of patients with signs and symptoms of a systemic rheumatic disease, the evaluation of patients suspected of having lupus erythematosus, use in clinical situations in which the ANA test is required to establish a disease diagnosis, and identification of clinical situations in which the ANA test has little value. Sections are also devoted to recommendations aimed at improving the analytic methods used to detect and measure ANA and specific autoantibodies to nuclear antigens and to the appropriate use of tests for specific autoantibodies in several disease situations that commonly occur in patients with suspected or documented systemic rheumatic diseases. Emphasis is placed on the use of these tests only in situations in which the test results can be expected to provide information necessary for clinical decision making. Those tests of limited medical usefulness and situations in which test results are likely to be misleading are also identified.

scholarly journals Diseases caused by reactions of T lymphocytes towards incompatible structures of the major histocompatibility complex. VI. Autoantibodies characteristic of systemic lupus erythematosus induced by abnormal T-B cell cooperation across I-E.

1982 ◽  
Vol 155 (5) ◽  
pp. 1555-1560 ◽  
Author(s):  
F M van Rappard-van der Veen ◽  
A G Rolink ◽  
E Gleichmann
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Host Reaction ◽  
Systemic Lupus ◽  
Double Stranded Dna ◽  
Histocompatibility Complex ◽  
Nuclear Antigens ◽  
Hla Dr ◽  
Do So ◽  
Autoantibody Formation

By induction of a suitable graft-vs-host reaction (GVHR) in H-2-different F1 mice, one can induce the production of autoantibodies characteristic of systemic lupus erythematosus (SLE). The purpose of the present study was to define the intra-H-2 differences in the F1 recipients that are capable of triggering this process. A GVHR was induced in [B10.A(2R) x B10.A(4R)]F1 mice by injecting 10(8) lymphocytes from either parental strain. Whereas the donor B10.A(4R) induced a massive formation of autoantibodies to thymocytes, erythrocytes, nuclear antigens, and double-stranded DNA, the donor B10.A(2R) failed to do so. The intra-H-2 genetics of these two parent leads to F1 combinations are such that the observed autoantibody formation after the injection of B10.A(4R) T cells must have been triggered exclusively by the incompatible I-Ek subregion of the [B10.A(2R) x B10.A(4R)]F1 recipients. Because I-E appears to be the murine analogue of HLA-D/DR, this finding is of interest with respect to the increased frequency of certain HLA-DR alleles in SLE patients, as discussed.

scholarly journals When systemic lupus erythematosus affects vision: a rare presentation of this condition

2020 ◽  
Vol 13 (1) ◽  
pp. e229382
Author(s):  
Tiago Gama Ramires ◽  
Luísa Vieira ◽  
Nuno Riso ◽  
Maria Francisca Moraes-Fontes
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Blurred Vision ◽  
Rare Presentation ◽  
Complement Components ◽  
Oral Ulcers ◽  
Dsdna Antibody ◽  
Rare Manifestation ◽  
Retinal Vascular Tortuosity

A 23-year-old woman with fever, oral ulcers, arthalgias and weight loss of 2-week duration suddenly developed blurred vision, with reduced visual acuity, cotton wool exudates and retinal vascular tortuosity. Laboratory testing revealed anaemia, lymphopaenia, positive antinuclear antibody and high anti-dsDNA antibody titre with low complement components. There was no evidence of infection, clinching the diagnosis of lupus retinopathy. Steroid therapy alone was highly effective and was also accompanied by a normalisation of haemoglobin and lymphocyte counts, after which azathioprine was added. Hydroxychloroquine was introduced after resolution of retinal changes. Immunosuppressive therapy was progressively tapered over the course of 12 months and then discontinued, and the patient remains in remission 48 months after the initial presentation. Our patient exemplifies a very rare manifestation of systemic lupus erythematosus. We emphasise the importance of its early detection and complexity of treatment in order to reduce visual morbidity.

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