Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Type I IFN (IFN-I)-regulated gene expression is known to be elevated in blood and skin lesions of patients with two different forms of cutaneous lupus erythematosus (CLE): subacute cutaneous lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE). A positive correlation between Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores of these patients and blood IFN-I signature has also been described. Using samples from a phase 0 longitudinal clinical study, we examined the relationship between IFN-I signatures in skin and blood, total CLASI scores, and autoantibody (autoAb) profiles at weeks 1 and 12 of the study.
Methods: Under informed consent, 37 subjects with DLE and 16 subjects with SCLE were recruited for study participation. 18 of the DLE subjects and 12 of the SCLE subjects also had concomitant SLE. Total CLASI scores for each DLE and SCLE subject were collected at weeks 1 and 12 of the study. Lesional and non-lesional skin biopsies were collected at week 1 and an additional biopsy was collected at week 12 from the same region where the lesional biopsy had been collected. Blood RNA PAXgene tubes along with serum were also collected at each time point. In addition, serum, blood RNA PAXgene, and skin biopsies were collected from healthy volunteers at week 1 only. RNA was extracted from both blood and skin and an IFN-I gene expression score was computed using the following genes: IFI44, IFI44L, IFI27, and RSAD2. Serum was profiled for autoAb specificities at both time points using the ProtoArray® platform.
Results: Gene expression in the skin revealed that the IFN-I score was significantly elevated in both lesional and non-lesional skin biopsies from both the SCLE and DLE subgroups when compared to healthy control biopsies. There was no significant difference between skin IFN-I scores in SCLE versus DLE regardless of concomitant SLE and skin IFN-I scores were strongly correlated to blood IFN-I scores in all subsets with or without SLE. Additionally, a positive correlation between skin IFN-I scores and CLASI scores was noted. Many individuals exhibited a decrease in CLASI and skin IFN signature from week 1 to week 12, although a significant correlation was not found across the cohort. AutoAb signal was longitudinally stable in all subgroups; however, only subjects with concomitant SLE had significantly elevated autoAb signals when compared to healthy controls.
Conclusion: Our findings support previous reports of CLASI correlation with blood IFN-induced gene expression and elevation of autoAb signal in SLE subjects. To our knowledge, however, we are the first to show that skin and blood IFN signatures correlate in the same patient irrespective of their subclass of CLE or if they have concomitant SLE. We also show that IFN-I signature is not only elevated in lesional skin of CLE patients, but also in the apparently healthy, non-lesional skin. Additionally, we found that despite the presence of a systemic blood IFN-I signature in CLE subjects with or without SLE, there was no elevation of autoAbs in the non-SLE CLE subjects.
To cite this abstract in AMA style:Schreiter J, Jordan J, Cesaroni M, Chevrier M, Piantone A, Gourley I, Benson J, Sato T. Results from a Phase 0 Longitudinal Clinical Trial in Cutaneous Lupus Erythematosus: Analysis of the Type I IFN Signature in the Skin and Blood and Its Relationship with Disease Activity Scores and Autoantibody Profiles [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/results-from-a-phase-0-longitudinal-clinical-trial-in-cutaneous-lupus-erythematosus-analysis-of-the-type-i-ifn-signature-in-the-skin-and-blood-and-its-relationship-with-disease-activity-scores-and-au/. Accessed June 19, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/results-from-a-phase-0-longitudinal-clinical-trial-in-cutaneous-lupus-erythematosus-analysis-of-the-type-i-ifn-signature-in-the-skin-and-blood-and-its-relationship-with-disease-activity-scores-and-au/