Background:A subgroup of lupus patients present with mild symptoms and immunologic features, while they do not meet classification criteria for SLE. This disease state can be referred to as “incomplete systemic lupus erythematosus” (iSLE). Up to 55% of iSLE patients progress to SLE. Furthermore, previous research has shown that iSLE might overlap with early primary Sjögren’s disease (pSS).(1) Unfortunately, there are no predictive markers available for progression to classifiable disease. Type-I interferon (IFN) plays an important role in disease initiation of both SLE and pSS.(2,3) Myxovirus-resistance protein A (MxA) is a GTP-ase that has previously be demonstrated to correlate strongly with IFN-type I expression. Furthermore, interferon-inducible chemokines IFN-γ induced protein 10 (IP-10), and B-cell activating factor (BAFF), that are both inducible by IFN, are of interest, because it is demonstrated that these proteins are increased prior to the diagnosis of SLE.(4)Objectives:To find predictive markers that identify patients with incomplete systemic lupus erythematosus (iSLE) who are at the highest risk to progress to classifiable systemic lupus erythematosus (SLE) or primary Sjögren’s syndrome (pSS).Methods:Patients with iSLE (ANA ≥ 1:80, ≥ 1 clinical SLICC criterion, but not fulfilling the criteria, and disease manifestation <5 years) were included in a longitudinal observational study. Every half year, clinical status was evaluated and regular immunological serologic assessment was performed. Annually, interferon (IFN)-gene expression was determined by RT-PCR in whole blood using 14 genes. These genes represented 3 IFN-related modules. Some genes were mainly inducible by IFN-type I, others by IFN-type II. Furthermore, IFN-related mediators Myxovirus resistance protein A (MxA), interferon-gamma-induced protein 10 (IP-10) and B-cell activating factor (BAFF) were measured.Results:Of 38 included iSLE patients, 6 had developed SLE and 1 develop pSS (18%) after median follow up of 36 months. The 7 patients who developed SLE/pSS were all women, and were younger at baseline than those who remained having iSLE (median 26 years, IQR 20-29 vs. median 42 years, IQR 30-56, p=0.0009). Over time, these patients had significantly lower complement 3 (p<0.0001) and complement 4 levels (p=0.005), higher IFN-gene expression (p=0.007), and lower neutrophil counts (p=0.033) (see Figure 1.). No difference was found between IFN-type I and IFN-type II inducible genes. Levels of MxA, IP-10 and BAFF did not differ between patients who remained iSLE and who progressed to SLE/pSS.Figure 1.Conclusion:Gender, age at diagnosis, persistent low complement levels, and high IFN-gene expression can help to identify iSLE patients at the highest risk of progressing to classifiable disease.References:[1]Md Yusof MY, et al. Prediction of autoimmune connective tissue disease in an at-risk cohort: Prognostic value of a novel two-score system for interferon status. Ann Rheum Dis. 2018;1–8.[2]Yao Y, et al. Type I interferons in Sjögren’s syndrome. Autoimmun Rev. 2013;12(5):558–66.[3]Crow MK. Type I Interferon in the Pathogenesis of Lupus. J Immunol [Internet]. 2014;192(12):5459–68.[4]Lu R, et al. Dysregulation of innate and adaptive serum mediators precedes systemic lupus erythematosus classification and improves prognostic accuracy of autoantibodies. J Autoimmun. 2016;74:182–93.Disclosure of Interests:None declared
Modular Transcriptional Repertoire Analyses of Adults With Systemic Lupus Erythematosus Reveal Distinct Type I and Type II Interferon Signatures