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

Publication ,  Journal Article
Ayoglu, B; Donato, M; Furst, DE; Crofford, LJ; Goldmuntz, E; Keyes-Elstein, L; James, J; Macwana, S; Mayes, MD; McSweeney, P; Nash, RA; Mao, R ...
Published in: Ann Rheum Dis
May 2023

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.

Duke Scholars

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Published In

Ann Rheum Dis

DOI

EISSN

1468-2060

Publication Date

May 2023

Volume

82

Issue

5

Start / End Page

670 / 680

Location

England

Related Subject Headings

  • Transplantation, Autologous
  • Scleroderma, Systemic
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • Cyclophosphamide
  • Autoantibodies
  • Arthritis & Rheumatology
  • 3204 Immunology
  • 3202 Clinical sciences
  • 1117 Public Health and Health Services
 

Citation

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MLA
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Ayoglu, B., Donato, M., Furst, D. E., Crofford, L. J., Goldmuntz, E., Keyes-Elstein, L., … Utz, P. J. (2023). Characterising the autoantibody repertoire in systemic sclerosis following myeloablative haematopoietic stem cell transplantation. Ann Rheum Dis, 82(5), 670–680. https://doi.org/10.1136/ard-2021-221926
Ayoglu, Burcu, Michele Donato, Daniel E. Furst, Leslie J. Crofford, Ellen Goldmuntz, Lynette Keyes-Elstein, Judith James, et al. “Characterising the autoantibody repertoire in systemic sclerosis following myeloablative haematopoietic stem cell transplantation.Ann Rheum Dis 82, no. 5 (May 2023): 670–80. https://doi.org/10.1136/ard-2021-221926.
Ayoglu B, Donato M, Furst DE, Crofford LJ, Goldmuntz E, Keyes-Elstein L, et al. Characterising the autoantibody repertoire in systemic sclerosis following myeloablative haematopoietic stem cell transplantation. Ann Rheum Dis. 2023 May;82(5):670–80.
Ayoglu, Burcu, et al. “Characterising the autoantibody repertoire in systemic sclerosis following myeloablative haematopoietic stem cell transplantation.Ann Rheum Dis, vol. 82, no. 5, May 2023, pp. 670–80. Pubmed, doi:10.1136/ard-2021-221926.
Ayoglu B, Donato M, Furst DE, Crofford LJ, Goldmuntz E, Keyes-Elstein L, James J, Macwana S, Mayes MD, McSweeney P, Nash RA, Sullivan KM, Welch B, Pinckney A, Mao R, Chung L, Khatri P, Utz PJ. Characterising the autoantibody repertoire in systemic sclerosis following myeloablative haematopoietic stem cell transplantation. Ann Rheum Dis. 2023 May;82(5):670–680.

Published In

Ann Rheum Dis

DOI

EISSN

1468-2060

Publication Date

May 2023

Volume

82

Issue

5

Start / End Page

670 / 680

Location

England

Related Subject Headings

  • Transplantation, Autologous
  • Scleroderma, Systemic
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • Cyclophosphamide
  • Autoantibodies
  • Arthritis & Rheumatology
  • 3204 Immunology
  • 3202 Clinical sciences
  • 1117 Public Health and Health Services