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Development of autoantibodies before the clinical onset of systemic lupus erythematosus.
N Engl J Med. 2003 Oct 16; 349(16):1526-33.NEJM

Abstract

BACKGROUND

Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored. We investigated the onset and progression of autoantibody development before the clinical diagnosis.

METHODS

The Department of Defense Serum Repository contains approximately 30 million specimens prospectively collected from more than 5 million U.S. Armed Forces personnel. We evaluated serum samples obtained from 130 persons before they received a diagnosis of SLE, along with samples from matched controls.

RESULTS

In 115 of the 130 patients with SLE (88 percent), at least one SLE autoantibody tested was present before the diagnosis (up to 9.4 years earlier; mean, 3.3 years). Antinuclear antibodies were present in 78 percent (at a dilution of 1:120 or more), anti-double-stranded DNA antibodies in 55 percent, anti-Ro antibodies in 47 percent, anti-La antibodies in 34 percent, anti-Sm antibodies in 32 percent, anti-nuclear ribonucleoprotein antibodies in 26 percent, and antiphospholipid antibodies in 18 percent. Antinuclear, antiphospholipid antibodies, anti-Ro, and anti-La antibodies were present earlier than anti-Sm and anti-nuclear ribonucleoprotein antibodies (a mean of 3.4 years before the diagnosis vs. 1.2 years, P=0.005). Anti-double-stranded DNA antibodies, with a mean onset 2.2 years before the diagnosis, were found later than antinuclear antibodies (P=0.06) and earlier than anti-nuclear ribonucleoprotein antibodies (P=0.005). For many patients, the earliest available serum sample was positive; therefore, these measures of the average time from the first positive antibody test to the diagnosis are underestimates of the time from the development of antibodies to the diagnosis. Of the 130 initial matched controls, 3.8 percent were positive for one or more autoantibodies.

CONCLUSIONS

Autoantibodies are typically present many years before the diagnosis of SLE. Furthermore, the appearance of autoantibodies in patients with SLE tends to follow a predictable course, with a progressive accumulation of specific autoantibodies before the onset of SLE, while patients are still asymptomatic.

Authors+Show Affiliations

Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14561795

Citation

Arbuckle, Melissa R., et al. "Development of Autoantibodies Before the Clinical Onset of Systemic Lupus Erythematosus." The New England Journal of Medicine, vol. 349, no. 16, 2003, pp. 1526-33.
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(16):1526-33.
Arbuckle, M. R., McClain, M. T., Rubertone, M. V., Scofield, R. H., Dennis, G. J., James, J. A., & Harley, J. B. (2003). Development of autoantibodies before the clinical onset of systemic lupus erythematosus. The New England Journal of Medicine, 349(16), 1526-33.
Arbuckle MR, et al. Development of Autoantibodies Before the Clinical Onset of Systemic Lupus Erythematosus. N Engl J Med. 2003 Oct 16;349(16):1526-33. PubMed PMID: 14561795.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of autoantibodies before the clinical onset of systemic lupus erythematosus. AU - Arbuckle,Melissa R, AU - McClain,Micah T, AU - Rubertone,Mark V, AU - Scofield,R Hal, AU - Dennis,Gregory J, AU - James,Judith A, AU - Harley,John B, PY - 2003/10/17/pubmed PY - 2003/10/21/medline PY - 2003/10/17/entrez SP - 1526 EP - 33 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 349 IS - 16 N2 - BACKGROUND: Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored. We investigated the onset and progression of autoantibody development before the clinical diagnosis. METHODS: The Department of Defense Serum Repository contains approximately 30 million specimens prospectively collected from more than 5 million U.S. Armed Forces personnel. We evaluated serum samples obtained from 130 persons before they received a diagnosis of SLE, along with samples from matched controls. RESULTS: In 115 of the 130 patients with SLE (88 percent), at least one SLE autoantibody tested was present before the diagnosis (up to 9.4 years earlier; mean, 3.3 years). Antinuclear antibodies were present in 78 percent (at a dilution of 1:120 or more), anti-double-stranded DNA antibodies in 55 percent, anti-Ro antibodies in 47 percent, anti-La antibodies in 34 percent, anti-Sm antibodies in 32 percent, anti-nuclear ribonucleoprotein antibodies in 26 percent, and antiphospholipid antibodies in 18 percent. Antinuclear, antiphospholipid antibodies, anti-Ro, and anti-La antibodies were present earlier than anti-Sm and anti-nuclear ribonucleoprotein antibodies (a mean of 3.4 years before the diagnosis vs. 1.2 years, P=0.005). Anti-double-stranded DNA antibodies, with a mean onset 2.2 years before the diagnosis, were found later than antinuclear antibodies (P=0.06) and earlier than anti-nuclear ribonucleoprotein antibodies (P=0.005). For many patients, the earliest available serum sample was positive; therefore, these measures of the average time from the first positive antibody test to the diagnosis are underestimates of the time from the development of antibodies to the diagnosis. Of the 130 initial matched controls, 3.8 percent were positive for one or more autoantibodies. CONCLUSIONS: Autoantibodies are typically present many years before the diagnosis of SLE. Furthermore, the appearance of autoantibodies in patients with SLE tends to follow a predictable course, with a progressive accumulation of specific autoantibodies before the onset of SLE, while patients are still asymptomatic. SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/14561795/Development_of_autoantibodies_before_the_clinical_onset_of_systemic_lupus_erythematosus_ L2 - http://www.nejm.org/doi/full/10.1056/NEJMoa021933?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -