Immunomonitoring of graft-versus-host minor histocompatibility antigen correlates with graft-versus-host disease and absence of relapse after graft.
BACKGROUND
After HLA-identical hematopoietic stem cell transplantation, minor histocompatibility (mH) antigen alloreactivity plays a dominant role in the development of graft-versus-host disease (GVHD) and graft versus leukemia (GVL).


METHODS
We have analyzed the mH alloreactivity (enzyme-linked immunospot [ELISpot] for interferon-gamma[IFN-gamma] assay) from 24 donor/recipient pairs over a period of 2 years of follow-up and correlated such alloreactivity with the development of GVHD or absence of relapse. Circulating specific T cells anti-mH with multimer HLA-peptides were also studied.


RESULTS
We show by ELISpot IFN-gamma assay that alloreactivity during the first 3 months from donor versus recipient or donor versus mismatched identified mH antigens is associated with acute GVHD and GVL effect. In addition, we demonstrate that the donor-versus-recipient reactivity observed after the third month is highly associated with chronic GVHD and GVL (p = 0.0007). Finally, we show by multimer HLA-peptide assay that mH epitope-specific T cells present after 3 months are statistically related to the GVL effect.


CONCLUSIONS
Our results provide a robust method to monitor mH antigen graft-versus-host reaction and suggest that current identified mH have predictive value on GVHD and GVL.
Laurin
David
D
Etablissement Français du Sang Rhône-Alpes, and Immunobiologie et Immunothérapie des Cancers, Centre de Recherche INSERM Albert Bonniot, La Tronche, France.
Hannani
Dalil
D
Pernollet
Martine
M
Moine
Agnès
A
Plumas
Joël
J
Bensa
Jean-Claude
JC
Cahn
Jean-Yves
JY
Garban
Frédéric
F
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D012008:Recurrence; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D014019:Tissue Donors; D014180:Transplantation; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000276:immunology; D055815:Young Adult
D007166:Immunosuppressive Agents; D015778:Minor Histocompatibility Antigens; D007371:Interferon-gamma