IL-7 and IL-10 Serum Levels Are Potential Immune Biomarkers for Acute Graft-Versus-Host Disease Following Unrelated Hematopoietic Stem Cell Transplantation

• Published in: Blood 2014-12, Vol.124 (21), p.5865-5865
• Main Authors: Azevedo, Rita I, Soares, Antonio S, Espada, Eduardo, Camacho, Nadia, Martins, Carlos V, Lourenco, Fernanda, Juncal, Clara, Moreno, Raul, Carmo, Jose A, Lacerda, Joao F
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V124.21.5865.5865

Acute GVHD (aGVHD) remains a major cause of morbidity in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT). Although numerous studies have investigated potential immunologic parameters that could predict for aGVHD, there are no validated immune biomarkers presently used in clinical practice. We are currently performing a prospective analysis of immune reconstitution after allogeneic HSCT in different patient cohorts. The goal of the present study is to detect abnormalities of immune reconstitution associated with an inability to maintain T cell tolerance after allogeneic HSCT and to identify specific immunologic biomarkers predictive of aGVHD. We have thus far accrued 36 unrelated HSCT recipients with a median age of 48 years old (16 females; 20 males). The degree of HLA-matching at the allele level between patients and donors was: 10/10 (n=20), 9/10 (n=15), 8/10 (n=1). Graft source consisted of unmanipulated bone marrow (n=18) or peripheral blood stem cells (n=18). All patients received a reduced-intensity conditioning regimen with fludarabine, melphalan and thymoglobulin (dose dependent on the degree of HLA matching), in association with cyclosporine and mycophenolate mofetil for GVHD prophylaxis. A total of 21 patients (58%) developed grades II-IV aGVHD in the first six months post-transplant. Whole blood and serum samples were collected from HSCT recipients 1, 2, 3 and 6 months post-HSCT. To assess the impact of different immune markers on the occurrence of aGVHD, patients were categorized into 2 groups based on the development or not of grade II-IV aGVHD in the first six months post-HSCT. Our comprehensive 7-colour flow cytometry panel encompasses phenotypic markers for relevant T, B, NK, NKT and dendritic cell subsets, further including intracellular markers for the assessment of proliferation and susceptibility to apoptosis within regulatory (Treg), conventional (Tcon) CD4 T cells and CD8 T cell subsets. Serum concentrations of IL-2, IL-7, IL-10, IL-15, IFN-γ and TNF-α were evaluated with a multiplex cytokine assay. Absolute counts of lymphocytes, total T cells, CD4 Tcon, CD4 Treg and CD8 T cells display similar reconstitution patterns in unrelated HSCT recipients with and without aGVHD. However, we have observed a clear trend for higher levels of γδ T cells, both in terms of frequency and absolute counts, in patients who develop aGVHD, particularly at 1 month post-HSCT (Mann Whitney test, P = 0.0699). Furthermore, we fo