Autoantibodies before the Clinical Onset of Systemic Lupus Erythematosus
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《新英格兰医药杂志》
To the Editor: The article by Arbuckle and colleagues (Oct. 16 issue)1 raises three points that need clarification. What percentage of the patients with systemic lupus erythematosus (SLE) had a positive test for antinuclear antibodies at a dilution of 1:80? In clinical practice, almost all patients with SLE have a positive test for antinuclear antibodies at this dilution. The authors screened for SLE at a higher dilution (1:120), thus reducing the sensitivity of the test. The criteria of the American College of Rheumatology for the diagnosis of SLE do not discriminate between this condition and the antiphospholipid syndrome, which is an important cause of lupus in the absence of antinuclear antibodies.
What percentage of positive results for double-stranded DNA autoantibodies on enzyme-linked immunosorbent assay (ELISA) were confirmed by the crithidia indirect immunofluorescence assay? ELISA often detects low-affinity and weakly positive double-stranded DNA autoantibodies that have limited biologic and clinical significance.2 The crithidia indirect immunofluorescence assay is a more specific test for SLE.
Peter Kelleher, Ph.D.
Imperial College
London SW10 9NH, United Kingdom
References
Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003;349:1526-1533.
Egner WT. The use of laboratory tests in the diagnosis of SLE. J Clin Pathol 2000;53:424-432.
The authors reply: Available serum samples were initially screened for antinuclear antibodies at a dilution of 1:40, and 92 percent of the patients and 9 percent of the controls were found to be positive. With the use of this threshold, antinuclear antibodies were detected a mean (±SD) of 3.27±0.25 years before diagnosis. The improved specificity of the 1:120 dilution1 was used for the analysis presented. Of the 130 patients studied, 126 had one or more autoantibodies detected 3.85±2.52 years before diagnosis. Of the 72 with samples available before the first clinical symptom developed, 72 had one or more autoantibodies at that time (3.05±2.23 years before the symptoms developed).
Experiments not reported in our article demonstrated a nearly perfect association between positivity or negativity for anti–double-stranded DNA on ELISA2 and the presence or absence of anti–double-stranded DNA on crithidia immunofluorescence. (All 45 serum samples with definitive results were concordant in the two assays. Two samples that were equivocal on ELISA were negative on crithidia immunofluorescence.) Of the 633 serum samples from patients and the 260 control serum samples tested, the 42 with equivocal results for anti–double-stranded DNA on ELISA were retested by crithidia immunofluorescence, with the following results: 39 samples from patients were negative, 1 sample from a patient was positive, and 2 control samples were negative.
Judith A. James, M.D., Ph.D.
Micah T. McClain, Ph.D.
Melissa R. Arbuckle, M.D., Ph.D.
John B. Harley, M.D., Ph.D.
Oklahoma Health Center
Oklahoma City, OK 73104
jamesj@omrf.ouhsc.edu
References
Tan EM, Feltkamp TE, Smolen JS, et al. Range of antinuclear antibodies in "healthy" individuals. Arthritis Rheum 1997;40:1601-1611.
Avina-Zubieta JA, Galindo-Rodriguez G, Kwan-Yeung L, Davis P, Russell AS. Clinical evaluation of various selected ELISA kits for the detection of anti-DNA antibodies. Lupus 1995;4:370-374.
What percentage of positive results for double-stranded DNA autoantibodies on enzyme-linked immunosorbent assay (ELISA) were confirmed by the crithidia indirect immunofluorescence assay? ELISA often detects low-affinity and weakly positive double-stranded DNA autoantibodies that have limited biologic and clinical significance.2 The crithidia indirect immunofluorescence assay is a more specific test for SLE.
Peter Kelleher, Ph.D.
Imperial College
London SW10 9NH, United Kingdom
References
Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003;349:1526-1533.
Egner WT. The use of laboratory tests in the diagnosis of SLE. J Clin Pathol 2000;53:424-432.
The authors reply: Available serum samples were initially screened for antinuclear antibodies at a dilution of 1:40, and 92 percent of the patients and 9 percent of the controls were found to be positive. With the use of this threshold, antinuclear antibodies were detected a mean (±SD) of 3.27±0.25 years before diagnosis. The improved specificity of the 1:120 dilution1 was used for the analysis presented. Of the 130 patients studied, 126 had one or more autoantibodies detected 3.85±2.52 years before diagnosis. Of the 72 with samples available before the first clinical symptom developed, 72 had one or more autoantibodies at that time (3.05±2.23 years before the symptoms developed).
Experiments not reported in our article demonstrated a nearly perfect association between positivity or negativity for anti–double-stranded DNA on ELISA2 and the presence or absence of anti–double-stranded DNA on crithidia immunofluorescence. (All 45 serum samples with definitive results were concordant in the two assays. Two samples that were equivocal on ELISA were negative on crithidia immunofluorescence.) Of the 633 serum samples from patients and the 260 control serum samples tested, the 42 with equivocal results for anti–double-stranded DNA on ELISA were retested by crithidia immunofluorescence, with the following results: 39 samples from patients were negative, 1 sample from a patient was positive, and 2 control samples were negative.
Judith A. James, M.D., Ph.D.
Micah T. McClain, Ph.D.
Melissa R. Arbuckle, M.D., Ph.D.
John B. Harley, M.D., Ph.D.
Oklahoma Health Center
Oklahoma City, OK 73104
jamesj@omrf.ouhsc.edu
References
Tan EM, Feltkamp TE, Smolen JS, et al. Range of antinuclear antibodies in "healthy" individuals. Arthritis Rheum 1997;40:1601-1611.
Avina-Zubieta JA, Galindo-Rodriguez G, Kwan-Yeung L, Davis P, Russell AS. Clinical evaluation of various selected ELISA kits for the detection of anti-DNA antibodies. Lupus 1995;4:370-374.