Characterising the autoantibody repertoire in systemic sclerosis following myeloablative haematopoietic stem cell transplantation

作者：Burcu Ayoglu, Michele Donato, Daniel E. Furst, Leslie J. Crofford, Ellen Goldmuntz, Lynette Keyes-Elstein, Judith A. James, Susan Macwana, Maureen D. Mayes, Peter A. McSweeney, Richard A. Nash, Keith M. Sullivan, Beverly Welch, Ashley Pinckney, Rong Mao, Lorinda Chung, Purvesh Khatri, Paul J. Utz · 发表于：Annals of the Rheumatic Diseases · 年份：2023 · DOI：10.1136/ard-2021-221926 · 被引用次数：23 · 研究领域：Systemic Sclerosis and Related Diseases、Liver Diseases and Immunity、Inflammatory Myopathies and Dermatomyositis

OBJECTIVES: Results from the SCOT (Scleroderma: Cyclophosphamide Or Transplantation) clinical trial demonstrated significant benefits of haematopoietic stem cell transplant (HSCT) versus cyclophosphamide (CTX) in patients with systemic sclerosis. The objective of this study was to test the hypothesis that transplantation stabilises the autoantibody repertoire in patients with favourable clinical outcomes. METHODS: We used a bead-based array containing 221 protein antigens to profile serum IgG autoantibodies in participants of the SCOT trial. RESULTS: Comparison of autoantibody profiles at month 26 (n=23 HSCT; n=22 CTX) revealed antibodies against two viral antigens and six self-proteins (SSB/La, CX3CL1, glycyl-tRNA synthetase (EJ), parietal cell antigen, bactericidal permeability-increasing protein and epidermal growth factor receptor (EGFR)) that were significantly different between treatment groups. Linear mixed model analysis identified temporal increases in antibody levels for hepatitis B surface antigen, CCL3 and EGFR in HSCT-treated patients. Eight of 32 HSCT-treated participants and one of 31 CTX-treated participants had temporally varying serum antibody profiles for one or more of 14 antigens. Baseline autoantibody levels against 20 unique antigens, including 9 secreted proteins (interleukins, IL-18, IL-22, IL-23 and IL-27), interferon-α2A, stem cell factor, transforming growth factor-β, macrophage colony-stimulating factor and macrophage migration inhibitory factor w...