Session Type: Abstract Submissions (ACR)
The type I interferon (IFN-I) signature, describing expression in PBMC of a large set of gene transcripts induced by IFN-I, and increased serum IFNα functional activity are characteristic of many patients with systemic lupus erythematosus (SLE) and are candidate biomarkers of disease activity. However, previous studies have not consistently demonstrated whether IFNα activity is useful for monitoring disease activity and assessing the effect of therapy in lupus patients.
From a cohort of 60 lupus patients with available serum data of IFNa activity, 15 were identified who experienced a) at least 1 severe flare as determined by the SELENA-SLEDAI instrument, and b) had a follow-up visit no longer than 3 months after the occurrence of a severe flare. In the 15 patients identified, there were 21 occurrences of a severe flare, with a follow-up visit no longer than 3 months later. IFNα activity at the time of those visits was measured using an in vitro reporter assay in which WISH epithelial cell line cells (highly responsive to stimulation with IFN-I) were cultured with patient sera and relative expression of IFIT1 and IFI44, IFN-I-responsive genes, was quantified using RT-PCR. The IFN-I score was calculated by converting relative expression values to IFN units/ml, using a standard curve acquired from dose response stimulations of WISH cells with 1-100 units/ml of recombinant IFNα. Clinical improvement was defined according to the SLE Responder Index (SRI) as: 1) improvement in SLEDAI by at least 4 points; 2) no 2 B or 1 A as recorded in the BILAG; 3) no increase in Physician Global Assessment by more than 0.3 points.
Out of 21 severe flares identified, 12 fulfilled the clinical improvement criteria (responses) during the next visit (<3 months). In those cases, IFNα score decreased significantly (from a median of 12.67 to 2.3, p=0.005), and there was also a significant decrease in the SLEDAI score (from a median of 13 to 5, p=0.0025). The remaining 9 cases which did not fulfill the clinical improvement criteria (no responses) showed statistically unchanged IFNα and SLEDAI scores. Immunosuppressive therapies were similar in both groups, including mycophenolate mofetil in 10/12 responses and in 5/9 non-responses. Pulse steroids were used in 6/12 responses and 4/9 non-responses. Only 1 pulse steroid therapy in each group was given less than 7 days before serum was obtained for IFNa levels.
Our data indicate that a decrease in IFN-I serum activity following a severe clinical flare may be a sensitive and reliable tool for monitoring the disease state of lupus patients and confirming the effectiveness of therapies used to treat severe flares.
E. E. Jacek,
K. A. Kirou,
M. K. Crow,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-ifn%ce%b1-activity-in-systemic-lupus-erythematosus-drops-in-response-to-immunosuppressive-therapy-only-when-there-is-concurrent-clinical-response/