Autoantibodies and Autoantigens in the Urine of SLE Patients

Sciascia, Sandra A.; Dickensheets, Harold; Picking, Wendy L.; Robson, Kristina; Wang, Dong; Ye, B. Hilda; Zhu, Liangjin; Stetler, Dean A.

doi:10.1080/08916930410001713016

Cited by 4 publications

(7 citation statements)

References 14 publications

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“…A similar observation was made in a study measuring anti-RNA polymerase I (RNAPI) in the urine of SLE patients [34]. A further study [35] also reported the presence of autoantibodies against RNAPI, DNA, SSB (La), and ribosomal P proteins in the urine of SLE patient. In addition, the presence and relative concentration of urinary autoantibodies correlated with disease activity.…”

Section: Autoantibodiessupporting

confidence: 78%

Immune-Related Urine Biomarkers for the Diagnosis of Lupus Nephritis

Morell

Pérez-Cózar

Marañón

2021

IJMS

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The kidney is one of the main organs affected by the autoimmune disease systemic lupus erythematosus. Lupus nephritis (LN) concerns 30–60% of adult SLE patients and it is significantly associated with an increase in the morbidity and mortality. The definitive diagnosis of LN can only be achieved by histological analysis of renal biopsies, but the invasiveness of this technique is an obstacle for early diagnosis of renal involvement and a proper follow-up of LN patients under treatment. The use of urine for the discovery of non-invasive biomarkers for renal disease in SLE patients is an attractive alternative to repeated renal biopsies, as several studies have described surrogate urinary cells or analytes reflecting the inflammatory state of the kidney, and/or the severity of the disease. Herein, we review the main findings in the field of urine immune-related biomarkers for LN patients, and discuss their prognostic and diagnostic value. This manuscript is focused on the complement system, antibodies and autoantibodies, chemokines, cytokines, and leukocytes, as they are the main effectors of LN pathogenesis.

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Section: Autoantibodiessupporting

confidence: 78%

Immune-Related Urine Biomarkers for the Diagnosis of Lupus Nephritis

Morell

Pérez-Cózar

Marañón

2021

IJMS

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“…Mild lupus nephritis mainly manifests with urine microalbumin and a few to medium proteinuria, small quantities of albumin and equivalent amounts of other proteins are predominant components. However, severe lupus nephritis frequently manifests with nephritic-range proteinuria, which means the large discharge of not only the albumin but also the globulin including ANA and complement, [12][13][14] resulting in the decrease of globulin and complement in serum, therefore, the patients present with negative IFANA in the blood. In this condition, serum IFANA titer cannot reflect the disease activity, but is determined by the difference between ANA production from plasma cell and ANA discharge from urine.…”

Section: Discussionmentioning

confidence: 99%

Analysis of 15 patients with systemic lupus erythematosus manifesting with negative immunofluorescence anti-nuclear antibodies after treatment

Ding

et al. 2011

Lupus

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The purpose of this study was to investigate the clinical and laboratorial characteristics of patients with systemic lupus erythematosus (SLE) manifesting with negative immunofluorescence anti-nuclear antibodies (IFANA) after treatment for the better understanding of negative conversion of IFANA. Demographic characteristics, clinical and laboratory data of hospitalized SLE patients between March 2006 and May 2011 were retrospectively reviewed. Fifteen cases with negative IFANA were identified in 960 patients. All of the 15 patients were severe, 11 patients manifested with nephritic range proteinuria and hypoalbuminemia, 8 patients were complicated with severe infection and all of the patients had been treated with glucocorticoid and immunosuppressant. Anti-ENA antibodies were positive in 4 of 15 patients. Eight patients died after average 1-year follow-up. Collectively, negative IFANA is mainly attributed to nephritic-range proteinuria; and large-dose glucocorticoid, immunosuppressant and severe infection are also important factors for negative IFANA. Antinuclear antibody can be detected in some SLE patients with negative IFANA by changing the detection method and titer. Negative conversion of IFANA often indicates unfavorable prognosis for severe patients.

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“…Subcloning of human RNAPI(S1)-BD (a.a. 245 -457) and -NT (a.a. 1 -141) and production of GST-BD and GST-NT as well as GST-La and GST-P1 fusion proteins were described previously [15]. GST fusion proteins were purified by glutathione -agarose affinity chromatography.…”

Section: Antigensmentioning

confidence: 99%

“…Conversely, immunization of rabbits with anti-dsDNA purified from the sera of SLE patients or lupus mice induced production of anti-RNAPI antibodies directed primarily against the largest subunit (194 kDa; S1) of RNAPI [35,36]. Recently, we reported the presence of anti-RNAPI antibodies and antigens in the urine of SLE patients, many with normal protein excretion rates [15]. The presence and relative quantity of urinary RNAPI antigen correlated with SLE disease status.…”

Section: Introductionmentioning

confidence: 96%

“…SLE patients urinary anti-RNAPI antibodies were directed against S1 (194 kDa), S4 (44 kDa) and S5 (25 kDa), but anti-S1 antibodies were the most prevalent. Rabbit anti-RNAPI immunoaffinity purified on a column prepared with an SLE patient's urine proteins also reacted primarily against RNAPI(S1) [15]. A 35 kDa SLE urinary protein was identified that appeared to be an RNAPI(S1) fragment, reacting with antibodies prepared against recombinant fusion proteins containing either the N-terminal (NT; amino acids, a.a. 1-141) or basic domain (BD; a.a. 245 -457), DNA binding regions of RNAPI(S1).…”

Section: Introductionmentioning

confidence: 97%

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Immunization of nonautoimmune mice with DNA binding domains of the largest subunit of RNA polymerase I results in production of anti-dsDNA and anti-Sm/RNP antibodies

et al. 2007

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Antibodies against the N-terminal (NT) but not the basic domain (BD), DNA binding regions of the largest subunit (S1) of RNA polymerase I (RNAPI) were detected in the sera of MRL-lpr/lpr lupus mice. Antibodies against both RNAPI(S1)-NT and -BD, as well as other systemic lupus erythematosus (SLE) autoantigens (La, ribosomal P proteins and Sm/RNP) were produced by rabbits immunized with anti-DNA antibodies that had been affinity purified from SLE patients. Immunization of nonautoimmune mice (Balb/c) with RNAPI(S1)-NT, RNAPI(S1)-BD, or La in the form of GST fusion proteins, induced production of anti-double-stranded (ds) DNA and anti-Sm/RNP. GST-P1 did not induce an anti-dsDNA response in these mice. These results demonstrate that RNAPI(S1)-NT, RNAPI(S1)-BD and La can participate in an anti-autoantigen/anti-DNA antibody loop during an SLE-like autoimmune response.

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Autoantibodies and Autoantigens in the Urine of SLE Patients

Cited by 4 publications

References 14 publications

Immune-Related Urine Biomarkers for the Diagnosis of Lupus Nephritis

Immune-Related Urine Biomarkers for the Diagnosis of Lupus Nephritis

Analysis of 15 patients with systemic lupus erythematosus manifesting with negative immunofluorescence anti-nuclear antibodies after treatment

Immunization of nonautoimmune mice with DNA binding domains of the largest subunit of RNA polymerase I results in production of anti-dsDNA and anti-Sm/RNP antibodies

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