eFigure. Anti-RNP IgG levels in DLE Patients and Their Subsets Correlate With CLASI Activity Scores
Kim A, O’Brien J, Tseng L, Zhang S, Chong BF. Autoantibodies and Disease Activity in Patients With Discoid Lupus Erythematosus. JAMA Dermatol. 2014;150(6):651-654. doi:10.1001/jamadermatol.2013.8354
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Serologic markers mirroring disease activity in patients with discoid lupus erythematosus (DLE) are unknown. Identifying them would help predict disease course, guide treatment, and clarify the etiology of DLE. Because autoantibodies have been associated with systemic lupus erythematosus (SLE) disease activity,1 we investigated associations between autoantibodies and disease activity measures in patients with DLE.
Patients recruited from University of Texas Southwestern Medical Center outpatient clinics provided written informed consent to this cross-sectional pilot study, which was approved by the university’s institutional review board. Patients with clinicopathologic diagnoses of DLE were included. Patients with other cutaneous lupus erythematosus subtypes (besides acute cutaneous lupus erythematosus) were excluded.
Levels of IgG autoantibodies were quantified by means of enzyme-linked immunosorbent assays (antinuclear antibodies [ANAs], antiribonucleoprotein [anti-RNP], anti–double-stranded DNA [anti-dsDNA] [Inova Diagnostics], anti–single-stranded DNA [anti-ssDNA] [ORGENTEC Diagnostika]) or QUANTAPlex fluorescent immunoassays (anti-Scl-70, anti-Smith, anti-SS-A [52 kDa], anti-SS-A [60 kDa], anti-SS-B) (Inova).
The Cutaneous Lupus Disease Area and Severity Index (CLASI) activity score was the primary disease activity measure. Secondary disease activity indices included CLASI damage score, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, numbers of oral lupus medications prescribed, SLE criteria,2 concentrations of C3 and C4, erythrocyte sedimentation rate, and level of C-reactive protein. All indices except C3, C4, erythrocyte sedimentation rate, and C-reactive protein, which were recorded if measured within 3 months of serum collection, were collected at study visits.
Correlations were calculated by means of the Spearman rank correlation. The DLE subgroup analyses (eg, DLE with SLE or positive for ANAs) were preplanned. P < .005 was declared significant to account for multiple comparisons.
Characteristics of patients with DLE and their subsets are presented in Table 1. In all patients with DLE, level of anti-RNP IgG correlated strongly with CLASI activity scores (Table 2, eFigure in Supplement). Results of tests for ANA, anti-RNP, anti-dsDNA, and anti-ssDNA IgG significantly correlated with SLEDAI scores, numbers of SLE criteria and oral medications used, C3, and C4, except anti-ssDNA IgG and SLEDAI scores. Patients with DLE who tested positive for ANA or who also had SLE demonstrated significant associations between the levels of anti-RNP IgG and CLASI activity scores, and between the levels of ANA, anti-RNP, anti-dsDNA, and anti-ssDNA IgG and several systemic disease activity measures (Table 2).
Results of anti-RNP IgG tests correlated with skin disease activity in patients with DLE. Because patients with DLE who were positive for ANA or who also had SLE demonstrated similar findings, we postulate that when circulating anti-RNP IgG levels surpass a threshold amount, they parallel skin disease activity in patients with DLE. Whereas anti-RNP antibody levels have not been associated with DLE, patients with DLE with SLE have shown upregulated anti-RNP antibody levels.3 Our observation of anti-RNP antibody levels trending with DLE skin disease activity raises the question of whether they contribute to skin disease progression or are by-products of inflammation. Mechanistic studies investigating whether anti-RNP antibodies exacerbate skin disease in lupus-prone mice are being planned.
There were multiple correlations of levels of ANA, anti-RNP, anti-dsDNA, and anti-ssDNA IgG with systemic disease activity measures in all patients with DLE with or without ANA positivity or SLE. Elevated levels of ANA, anti-RNP, anti-dsDNA, or anti-ssDNA IgG in patients with DLE could prompt initiation of oral medication use, which can diminish their levels. Use of quinacrine hydrochloride decreased anti-dsDNA antibody levels in patients with SLE.4 Prospective studies tracking autoantibody levels and disease activity in patients with DLE receiving oral lupus medications may validate this hypothesis.
Limitations of this study include collection of complement levels, erythrocyte sedimentation rate, and C-reactive protein levels, which were not always collected at study visits. Because they fluctuate often, levels may not be accurately reflected. Enzyme-linked immunosorbent assays and fluorescent immunoassays are very sensitive, leading to high false-positive rates.5 However, they were selected because they provided continuous values used in correlation analyses. Because of the study’s cross-sectional design, a causal relationship between autoantibody level and disease progression cannot be determined.
This study highlights associations of levels of ANA, anti-RNP, anti-dsDNA, and anti-ssDNA IgG with disease activity in patients with DLE. Longitudinal and functional studies would help elucidate their biomarker potential and contribution to disease etiology.
Corresponding Author: Benjamin F. Chong, MD, University of Texas Southwestern Medical Center, Department of Dermatology, 5323 Harry Hines Blvd, Dallas, TX 75309-9069 (email@example.com).
Accepted for Publication: September 14, 2013.
Published Online: April 30, 2014. doi:10.1001/jamadermatol.2013.8354.
Author Contributions: Dr Kim and Mr O’Brien served as co–first authors, each with equal contribution to the manuscript. Dr Chong had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Kim, O’Brien, Chong.
Acquisition of data: Kim, O’Brien, Tseng, Chong.
Analysis and interpretation of data: Kim, O’Brien, Zhang, Chong
Drafting of the manuscript: Kim, O’Brien, Chong.
Critical revision of the manuscript for important intellectual content: Kim, O’Brien, Tseng, Zhang, Chong
Statistical analysis: Kim, O’Brien, Zhang, Chong.
Obtained funding: Chong.
Study supervision: Chong.
Conflict of Interest Disclosures: Dr Chong is an investigator for Celgene Corporation, Amgen Incorporated, and Daavlin Corporation. No other disclosures are reported.
Funding/Support: The research reported in this article was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award K23AR061441.
Role of the Sponsor: The National Institute of Arthritis and Musculoskeletal and Skin Diseases had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Additional Contributions: Rose Ann Cannon, Department of Dermatology, University of Texas Southwestern Medical Center, assisted in the manuscript preparation, and Elisa Song, BA, Department of Dermatology, University of Texas Southwestern Medical Center, provided technical support. Jack Cohen, DO; Melissa Costner, MD; Rebecca Vasquez, MD; Julie Song, MD; Sandra Victor, BS; Department of Dermatology, University of Texas Southwestern Medical Center, and Azza Mutwally, MBB; and Valerie Branch, MS; Department of Internal Medicine, University of Texas Southwestern Medical Center, aided in the recruitment of patients. They were not compensated for their contributions to this study.