Abstract
Our group previously demonstrated a strong association between elevated plasma soluble CD13 enzyme activity and newly diagnosed extensive chronic GVHD (cGVHD) in children. As cytotoxic anti-CD13 Abs have been documented after blood and marrow transplant (BMT) in association with CMV infection and cGVHD, we hypothesized that soluble CD13 contributes to cGVHD pathogenesis by induction of CD13 reactive Abs and that anti-CD13 Abs could be additional biomarkers for newly diagnosed pediatric extensive cGVHD. Using prospectively collected plasma samples from pediatric allogeneic BMT (allo-BMT) subjects with cGVHD and controls without cGVHD enrolled in a large multi-institution Children's Oncology Group cGVHD therapeutic trial, we evaluated whether soluble CD13 correlates with induction of anti-CD13 Abs. We found that CD13 reactive Abs are present in a proportion of patients after allo-BMT, but did not seem to correlate with the presence of soluble CD13. Anti-CD13 Abs also did not meet our criteria as a diagnostic biomarker for cGVHD. These data do not confirm that induction of CD13 reactive Abs is a mechanism for cGVHD in children nor are part of the pathogenesis of cGVHD associated with elevated soluble CD13. The exact role of CD13 in cGVHD remains to be determined.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Remberger M, Beelen DW, Fauser A, Basara N, Basu O, Ringden O . Increased risk of extensive chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation using unrelated donors. Blood 2005; 105: 548–551.
Kollman C, Howe CW, Anasetti C, Antin JH, Davies SM, Filipovich AH et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood 2001; 98: 2043–2051.
Ratanatharathorn V, Nash RA, Przepiorka D, Devine SM, Klein JL, Weisdorf D et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versushost disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood 1998; 92: 2303–2314.
Nash RA, Antin JH, Karanes C, Fay JW, Avalos BR, Yeager AM et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood 2000; 96: 2062–2068.
Fraser CJ, Bhatia S, Ness K, Carter A, Francisco L, Arora M et al. Impact of chronic graft-versus-host disease on the health status of hematopoietic cell transplantation survivors: a report from the Bone Marrow Transplant Survivor Study. Blood 2006; 108: 2867–2873.
Przepiorka D, Anderlini P, Saliba R, Cleary K, Mehra R, Khouri I et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation. Blood 2001; 98: 1695–1700.
Fujii H, Cuvelier G, She K, Aslanian S, Shimizu H, Kariminia A et al. Biomarkers in newly diagnosed pediatric extensive chronic graft-versus-host disease: A report from the Children's Oncology Group. Blood 2008; 111: 3276–3285.
She K, Gilman AL, Aslanian S, Shimizu H, Krailo M, Chen Z et al. Altered toll-like receptor 9 responses in circulating B cells at the onset of extensive chronic graft-versus-host disease. Biol Blood Marrow Transplant 2007; 13: 386–397.
Luan Y, Xu W . The structure and main functions of aminopeptidase N. Curr Med Chem 2007; 14: 639–647.
Dixon J, Kaklamanis L, Turley H, Hickson ID, Leek RD, Harris AL et al. Expression of aminopeptidase-n (CD13) in normal tissues and malignant neoplasms of epithelial and lymphoid origin. J Clin Pathol 1994; 47: 43–47.
Soderberg C, Sumitran-Karuppan S, Ljungman P, Moller E . CD13-specific autoimmunity in cytomegalovirus-infected immunocompromised patients. Transplantation 1996; 61: 594–600.
Soderberg C, Larsson S, Rozell B, Sumitran-Karuppan S, Ljungman P, Moller E . Cytomegalovirus-induced CD13 specific autoimmunity—a possible cause of chronic graft-versus-host disease. Transplantation 1996; 61: 600–609.
Miklos DB, Kim HT, Miller KH, Guo L, Zorn E, Lee SJ et al. Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission. Blood 2005; 105: 2973–2978.
Svegliati S, Olivieri A, Campelli N, Luchetti M, Poloni A, Trappolini S et al. Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood 2007; 110: 237–241.
Soderberg C, Giugni TD, Zaia JA, Larsson S, Wahlberg JM, Moller E . CD13 (human aminopeptidase N) mediates human cytomegalovirus infection. J Virol 1993; 67: 6576–6585.
Giugni TD, Soderberg C, Ham DJ, Bautista RM, Hedlund KO, Moller E et al. Neutralization of human cytomegalovirus by human CD13-specific antibodies. J Infect Dis 1996; 173: 1062–1071.
Hansen AS, Noren O, Sjostrom H, Werdelin O . A mouse aminopeptidase N is a marker for antigen presenting cells and appears to be co-expressed with major histocompatibility complex class II molecules. Eur J Immunol 1993; 23: 2358–2364.
Falk K, Rotzschke O, Stavanovic S, Jung G, Rammensee HG . Pool sequencing of natural HLA-DR, DQ and DP ligands reveal detailed peptide motifs, constraints of processing, and general rules. Immunogenetics 1994; 39: 230–242.
Acknowledgements
We thank Ruth Milner for her expert statistical help and Dr Kaiji Hu for assistance with Cellomics. This work was supported by Grant RO1-CA84137 from the National Cancer Institute of the National Institutes of Health and by the Canadian Institutes of Health Research/Wyeth Clinical Research Chair in Transplantation. Chair's U10 CA98543.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Cuvelier, G., Kariminia, A., Fujii, H. et al. Anti-CD13 Abs in children with extensive chronic GVHD and their relation to soluble CD13 after allogeneic blood and marrow transplantation from a Children's Oncology Groups Study, ASCT0031. Bone Marrow Transplant 45, 1653–1657 (2010). https://doi.org/10.1038/bmt.2010.15
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2010.15
Keywords
This article is cited by
-
Biomarkers in chronic graft-versus-host disease: quo vadis?
Bone Marrow Transplantation (2018)