Systemic Lupus Erythematosus
Association of serum nitrate and nitrite levels with longitudinal assessments of disease activity and damage in systemic lupus erythematosus and lupus nephritis
Article first published online: 28 DEC 2007
Copyright © 2008 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 58, Issue 1, pages 263–272, January 2008
How to Cite
Oates, J. C., Shaftman, S. R., Self, S. E. and Gilkeson, G. S. (2008), Association of serum nitrate and nitrite levels with longitudinal assessments of disease activity and damage in systemic lupus erythematosus and lupus nephritis. Arthritis & Rheumatism, 58: 263–272. doi: 10.1002/art.23153
- Issue published online: 28 DEC 2007
- Article first published online: 28 DEC 2007
- Manuscript Accepted: 21 SEP 2007
- Manuscript Received: 14 FEB 2007
- Arthritis Foundation
- University Research Committee at the Medical University of South Carolina
- Medical University of South Carolina General Clinical Research Center. Grant Number: NIH grant 5-M01-RR-01070
- NIH. Grant Numbers: K08-AR-002193, AI-047469, AR-045476, AR-04745
- Ralph H. Johnson VAMC (Medical Research Service Career Development award, Reserve Educational Assistance Program, and Merit Review grants)
Reactive intermediate production is an essential component of the innate immune response that is induced during disease activity in murine lupus. This study was undertaken to determine whether a marker of systemic nitric oxide (NO) production correlates with prospectively studied disease activity in human systemic lupus erythematosus (SLE) and lupus nephritis patients.
Eighty-three SLE patients and 40 control subjects were studied longitudinally. The SLE group included 23 patients with lupus nephritis documented by renal biopsy and 26 with a history of lupus nephritis. During each visit, following a 24-hour low-nitrate diet, traditional markers of disease activity and damage were determined. Serum nitrate plus nitrite (NOx) levels were determined by chemiluminescence detection.
NOx levels were higher in SLE patients than in controls during the first visit. In univariate longitudinal analyses, NOx levels were associated with SLE Disease Activity Index scores. In multivariate analyses, NOx levels were associated with serum levels of C3 and creatinine and the urinary protein:creatinine ratio. Among patients with lupus nephritis, those with proliferative lesions had higher NOx levels, and higher NOx levels were associated with accumulation of renal damage and lack of response to therapy.
This is the first study to prospectively demonstrate longitudinal associations between serum NOx levels and markers of SLE and lupus nephritis disease activity. The more pronounced association with proliferative lupus nephritis and with longitudinal response to lupus nephritis therapy provides a rationale for the study of reactive intermediates as biomarkers of disease activity and therapeutic targets in proliferative lupus nephritis.