title: Autoantibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity.
abstract: Systemic lupus erythematosus (SLE) is characterized by multiple autoantibodies and complement activation. Recent studies have suggested that anti-nuclear antibody (ANA) positivity may disappear over time in some SLE patients. Anti-double-stranded DNA (dsDNA) antibody titers and complement levels may vary with time and immunosuppressive treatment, while the behavior of anti-extractable nuclear antigen (ENA) over time is less well understood. This study sought to determine the correlation between historical autoantibody tests and current testing in patients with SLE. Three hundred and two SLE patients from the ACR Reclassification of SLE (AROSE) database with both historical and current laboratory data were selected for analysis. The historical laboratory data were compared with the current autoantibody tests done at the reference laboratory and tested for agreement using percent agreement and Kappa statistic. Serologic tests included ANA, anti-dsDNA, anti-Smith, anti-ribonucleoprotein (RNP), anti-Ro, anti-La, rheumatoid factor (RF), C3 and C4. Among those historically negative for immunologic markers, a current assessment of the markers by the reference laboratory generally yielded a low percentage of additional positives (3-13%). However, 6/11 (55%) of those historically negative for ANA were positive by the reference laboratory, and the reference laboratory test also identified 20% more patients with anti-RNP and 18% more with RF. Among those historically positive for immunologic markers, the reference laboratory results were generally positive on the same laboratory test (range 57% to 97%). However, among those with a history of low C3 or C4, the current reference laboratory results indicated low C3 or C4 a low percentage of the time (18% and 39%, respectively). ANA positivity remained positive over time, in contrast to previous studies. Anti-Ro, La, RNP, Smith and anti-dsDNA antibodies had substantial agreement over time, while complement had less agreement. This variation could partially be explained by variability of the historical assays, which were done by local laboratories over varying periods of time. Variation in the results for complement, however, is more likely to be explained by response to treatment. These findings deserve consideration in the context of diagnosis and enrolment in clinical trials.
authors.affiliation: Division of Rheumatology, Johns Hopkins University School of Medicine, 1830 E. Monument Street, Baltimore, MD 21205, USA. ippolitoa@mail.nih.gov
authors.forename: A
authors.initials: A
authors.lastname: Ippolito
authors.forename: D J
authors.initials: DJ
authors.lastname: Wallace
authors.forename: D
authors.initials: D
authors.lastname: Gladman
authors.forename: P R
authors.initials: PR
authors.lastname: Fortin
authors.forename: M
authors.initials: M
authors.lastname: Urowitz
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authors.initials: V
authors.lastname: Werth
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authors.initials: M
authors.lastname: Costner
authors.forename: C
authors.initials: C
authors.lastname: Gordon
authors.forename: G S
authors.initials: GS
authors.lastname: Alarcón
authors.forename: R
authors.initials: R
authors.lastname: Ramsey-Goldman
authors.forename: P
authors.initials: P
authors.lastname: Maddison
authors.forename: A
authors.initials: A
authors.lastname: Clarke
authors.forename: S
authors.initials: S
authors.lastname: Bernatsky
authors.forename: S
authors.initials: S
authors.lastname: Manzi
authors.forename: S-C
authors.initials: SC
authors.lastname: Bae
authors.forename: J T
authors.initials: JT
authors.lastname: Merrill
authors.forename: E
authors.initials: E
authors.lastname: Ginzler
authors.forename: J G
authors.initials: JG
authors.lastname: Hanly
authors.forename: O
authors.initials: O
authors.lastname: Nived
authors.forename: G
authors.initials: G
authors.lastname: Sturfelt
authors.forename: J
authors.initials: J
authors.lastname: Sanchez-Guerrero
authors.forename: I
authors.initials: I
authors.lastname: Bruce
authors.forename: C
authors.initials: C
authors.lastname: Aranow
authors.forename: D
authors.initials: D
authors.lastname: Isenberg
authors.forename: A
authors.initials: A
authors.lastname: Zoma
authors.forename: L S
authors.initials: LS
authors.lastname: Magder
authors.forename: J
authors.initials: J
authors.lastname: Buyon
authors.forename: K
authors.initials: K
authors.lastname: Kalunian
authors.forename: M A
authors.initials: MA
authors.lastname: Dooley
authors.forename: K
authors.initials: K
authors.lastname: Steinsson
authors.forename: R F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.forename: T
authors.initials: T
authors.lastname: Stoll
authors.forename: M
authors.initials: M
authors.lastname: Weisman
authors.forename: M
authors.initials: M
authors.lastname: Petri
mesh_terms: D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002986:Clinical Trials as Topic; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007118:Immunoassay / Q000266:history* / Q000379:methods*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D015415:Biomarkers