Ignat, et al: Autoantibody panels in SLE 1761
From the Department of Microbiology/Immunology and Department of
Medicine, Section of Rheumatology, University of Illinois College of
Medicine, Chicago, Illinois, USA.
Supported in part by Campus Research Board, University of Illinois at
Chicago.
G.P. Ignat, MD; A-C. Rat, MD; J. Vo, MD; J. Varga, MD, Professor and
Head, Section of Rheumatology, Department of Medicine; J.J. Sychra,
PhD, Associate Professor, Department of Radiology; M. Teodorescu, MD,
PhD, Emeritus Professor, Department of Microbiology/Immunology.
Address reprint requests to Dr. M. Teodorescu, 6776 Fieldstone Drive,
Burr Ridge, IL 60527. E-mail: oana@uic.edu
Submitted July 31, 2002; revision accepted January 3, 2003.
Recent guidelines on the use of tests for antinuclear anti-
bodies were issued by a committee of the College of
American Pathologists and the American College of
Rheumatology (ACR)
1,2
. According to these guidelines, (1)
measurement of panels of autoantibodies has no clinical
value for the diagnosis and management of patients with
systemic lupus erythematosus (SLE); and (2) measurement
of antibodies against denatured DNA (ssDNA) has no clin-
ical value and should be used only for research purposes.
However, no publication was cited to support these 2 guide-
lines.
Most studies on autoantibodies in patients with SLE have
focused on those considered disease markers and included
in the ACR diagnostic criteria for SLE
3,4
: anti-dsDNA and
anti-Sm. However, other autoantibodies have been used in
the diagnosis of SLE and related syndromes, including anti-
ssDNA (denatured DNA, total DNA or ssDNA), histones,
nRNP, SSA (Ro), SSB (La), ribosomal protein P, and Scl-
70
5
. The presence of multiple autoantibodies in different
assortments and concentrations reflects both the polyclon-
ality and the diversity of the autoimmune response process
in individual patients with SLE
6,7
.
After the diagnosis of SLE is made, only anti-dsDNA
autoantibody concentrations are routinely used as correlates
or predictors of flare and disease activity
8-13
. The problem
Information on Diagnosis and Management of
Systemic Lupus Erythematosus Derived from the
Routine Measurement of 8 Nuclear Autoantibodies
GHEORGHE PAUL IGNAT, ANNE-CHRISTINE RAT, JERRY J. SYCHRA, JACQUELINE VO, JOHN VARGA,
and MARIUS TEODORESCU
ABSTRACT. Objective. To determine the value of routine measurement of a panel of 8 nuclear autoantibodies
(ANA/8) for the diagnosis and management of patients with systemic lupus erythematosus (SLE).
Methods. To estimate disease sensitivity of ANA/8, we studied 25 patients with new SLE and 114
with new and established SLE. To estimate disease specificity, 100 patients with other autoimmune
rheumatic diseases were included. We used computerized statistical analysis of the level of 8 ANA
in relation to clinical activity determined as Systemic Lupus Activity Measure disease activity scores
(DAS). Data were collected retrospectively from the charts of 114 patients with 698 visits and eval-
uated by multiple and piece-wise linear regression analysis (PWLRA) and correlation and cluster
analyses.
Results. The disease sensitivity of the 3 types of SLE profiles identified was 100% for new SLE
patients (n = 25) and 87% for mixed SLE patients; the disease specificity was 98%. Autoantibody
levels of anti-ssDNA, dsDNA, and Scl-70 were the best individual correlates of general and organ-
specific DAS. Twenty-four percent (R
2
) of the variability in the general DAS was explained by the
multiple regression (R = 0.49), with significant contribution made by anti-Scl-70 (ß = 0.39), dsDNA
(ß = 0.17), Sm (ß = 0.10), and SSA (ß = 0.08). PWLRA indicated that for 68% of the 698 clinical
presentations (average 6/patient), the observed DAS and the predicted DAS from autoantibody
levels were both low and clustered; they were partially discrepant for the remaining 32%, which was
explained by the relatively high correlation of DAS with prior changes in autoantibody levels (R =
0.6). The changes in DAS and in anti-dsDNA levels were significantly predicted by the multiple
regression at one prior visit, with anti-ssDNA as the main contributor.
Conclusion. The ANA/8 profile showed ~ 100% sensitivity and ~ 98% specificity for SLE and
correlated with contemporary and subsequent changes in DAS and autoantibody levels. Among
autoantibodies of this profile, anti-ssDNA (ssDNA) was the most sensitive indicator of SLE and the
main contributor to prediction of subsequent changes in DAS. (J Rheumatol 2003;30:1761–9)
Key Indexing Terms:
SYSTEMIC LUPUS ERYTHEMATOSUS ANTINUCLEAR ANTIBODIES
DISEASE ACTIVITY ssDNA
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