RT Journal Article
SR Electronic
T1 Characterising the autoantibody repertoire in systemic sclerosis following myeloablative haematopoietic stem cell transplantation
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP annrheumdis-2021-221926
DO 10.1136/ard-2021-221926
A1 Ayoglu, Burcu
A1 Donato, Michele
A1 Furst, Daniel E
A1 Crofford, Leslie J
A1 Goldmuntz, Ellen
A1 Keyes-Elstein, Lynette
A1 James, Judith
A1 Macwana, Susan
A1 Mayes, Maureen D
A1 McSweeney, Peter
A1 Nash, Richard A
A1 Sullivan, Keith M
A1 Welch, Beverly
A1 Pinckney, Ashley
A1 Mao, Rong
A1 Chung, Lorinda
A1 Khatri, Purvesh
A1 Utz, Paul J
YR 2023
UL http://ard.bmj.com/content/early/2023/01/17/ard-2021-221926.abstract
AB 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 were significantly higher in patients who survived event-free to month 54.Conclusions Our results suggest that HSCT favourably alters the autoantibody repertoire, which remains virtually unchanged in CTX-treated patients. Although antibodies recognising secreted proteins are generally thought to be pathogenic, our results suggest a subset could potentially modulate HSCT in scleroderma.Data are available on reasonable request. On publication of this study in a peer-reviewed journal, deidentified array data will be uploaded to the Gene Expression Omnibus (GEO) database.