Autoimmune rheumatologic diseases

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Distinct Single Cell Gene Expression Signatures of Monocyte Subsets Differentiate Between Tnf-alpha Inhibitor Treatment Response Groups in Rheumatoid Arthritis

Friday, June 16
6:15 PM - 7:30 PM

Work from our group demonstrated that pre-treatment serum type I IFN-β/α ratio>1.3 predicts non-response to anti-TNFα therapy (TNFi) in RA patients. Mechanisms that underlie the IFN-β/α ratio that predicts response are unknown. Effects of IFN on uncommon cell populations may be masked in whole blood or mixed cell populations. We used single cell analysis to investigate whether monocyte gene expression differs significantly between RA patients according to their pre-TNFi serum IFN-β/α ratio. Single classical (CL) and non-classical (NC) blood-derived monocytes were isolated from seropositive RA subjects prior to biologic therapy. Subjects were grouped by pre-TNFi serum IFN-β/α ratio: IFN-β/α>1.3(n=6) and IFN-β/αJAK1,IL1A,TLR2,CD32A,CD36, CXCR3,IL8,IRAK1, and TYK2 expression were retained in the mixed monocyte gene expression model for differentiating between groups. JAK1 and IL1A were also retained in the models from monocyte subsets.TLR9,STAT1, and FCER were retained in the CL model. STAT2 and IFI27 were retained in the NC model. Regression models from the monocyte subsets provided increased discriminatory potential in comparison to the mixed monocyte model. Within-cell co-expression patterns demonstrate biological differences in monocyte subsets of RA patients with an IFN-β/α>1.3, the ratio of type I IFNs which predicts non-response to TNFi.When monocyte subsets were analyzed separately, differentiation by gene expression was strongest and distinct expression signatures were identified, suggesting that further study of monocyte subsets will illuminate molecular differences that determine treatment response to TNFi in RA.

Theresa Wampler Muskardin

Assistant Professor
Mayo Clinic, Department of Medicine and Department of Pediatrics and Adolescent Medicine, Division of Rheumatology

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    Wei Fan

    Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

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      Zhongbo Jin

      University of Florida

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        Mark Jensen

        Department of Immunology and Division of Rheumatology, Mayo Clinic

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          Jessica Dorschner

          Department of Immunology and Division of Rheumatology, Mayo Clinic

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            Yogita Ghodke-Puranik

            Assistant Professor
            Department of Immunology and Division of Rheumatology, Mayo Clinic

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              Betty Ann Dicke

              Mayo Clinic, Department of Medicine, Division of Rheumatology

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                Danielle Vsetecka

                Department of Immunology and Division of Rheumatology, Mayo Clinic

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                  Mayo Clinic Inflammatory Arthritis Clinic Group

                  Mayo Clinic, Department of Medicine, Division of Rheumatology

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                    Timothy Niewold

                    Associate Professor
                    Department of Immunology and Division of Rheumatology, Mayo Clinic

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                      Distinct Single Cell Gene Expression Signatures of Monocyte Subsets Differentiate Between Tnf-alpha Inhibitor Treatment Response Groups in Rheumatoid Arthritis



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