Background/Purpose:  Interferon (IFN) signature has been established in the peripheral blood of the patients with systemic lupus erythematosus (SLE) by transcriptome analyses, indicating a role of the IFN pathway in the pathogenesis of SLE. On the other hand, contribution of the IFN pathway to anti-neutrophil cytoplasmic antibodies (ANCA) – associated vasculitis (AAV) has not been established. We previously reported association of a single nucleotide polymorphism in interferon regulatory factor 5 (IRF5) gene with susceptibility to myeloperoxidase (MPO)-ANCA-positive AAV in a Japanese population, suggesting a potential role of the IFN pathway in AAV. In the present study, we conducted a transcriptome analysis to examine the contribution of the IFN pathway to AAV and compared the results with those of SLE.

Methods:  Total RNA was extracted from the whole blood of Japanese individuals including 6 patients with microscopic polyangiitis (MPA), 8 patients with SLE and 14 healthy controls using the PAXgene kit. The mRNA levels of the IFN signature genes, previously reported to be differentially expressed in SLE, were analyzed using the Agilent SurePrint G3 Human GE microarray. P values were calculated by Welch’s t-test, and Benjamini-Hochberg false discovery rate (FDR) correction was applied for multiple testing.

Results: In MPA, 68 (17.3%) among the 392 probes for the IFN signature genes were upregulated (P_FDR<0.05 and fold change [FC] ≥1.5), showing significant enrichment when compared with 1515 (7.6%) upregulated probes among the 20053 probes in total (Fisher’s exact test P value=9.8E-11). In SLE, 159 out of 392 IFN signature probes (40.6%) were upregulated. Of particular interest, although upregulation of IFN signature gene probes was observed both in SLE and MPA, the sets of upregulated genes showed substantial difference. Cluster analysis showed differential expression patterns in IFN signature genes between MPA and SLE. Principal component analysis using the IFN signature probes confirmed distinct MPA and SLE clusters. When the expression levels of each probe was compared between SLE and MPA, 3228 (16.1%) probes were upregulated in SLE compared with MPA. Among such differentially expressed genes, IFN signature genes showed significant enrichment (115 out of 392 genes, 29.3%, P=3.4E-11).

Conclusion: Although IFN signature was observed also in the peripheral blood of MPA, a substantial proportion of IFN signature genes were differentially expressed between MPA and SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-signature-genes-are-differentially-expressed-between-microscopic-polyangiitis-and-systemic-lupus-erythematosus-peripheral-blood-transcriptomes/