Anti-thymocyte globulins capable of binding to T and B cells reduce graft-vs-host disease without increasing relapse.
Anti-thymocyte globulin (ATG) is polyclonal, containing Ab specificities capable of binding to various immune-cell subsets implicated in the pathogenesis of GVHD, including T cells, B cells, natural killer cells, monocytes/macrophages, neutrophils and DC. We wished to determine which ATG specificities are important for GVHD prevention. We measured day 7 serum levels of 23 ATG specificities in 120 hematopoietic cell transplant recipients whose myeloablative conditioning included 4.5 mg/kg ATG (thymoglobulin). High levels of ATG specificities capable of binding to T- and B-cell subsets were associated with a low likelihood of acute GVHD (aGVHD). High levels of these ATG specificities were associated with increased rates of viral but not bacterial or fungal infections. They were not associated with an increased risk of malignancy relapse; on the contrary, high levels of ATG specificities capable of binding to regulatory T cells and invariant NKT cells were associated with a low risk of relapse. In conclusion, high levels of ATG antibodies to Ag(s) expressed on T and B cells are associated with a low risk of aGVHD and a high risk of viral but not bacterial or fungal infections. These antibodies have neutral or beneficial effects on relapse.
Department of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 1N4. mhoeghpe@ucalgary.ca
M
M
Hoegh-Petersen
M A
MA
Amin
Y
Y
Liu
A
A
Ugarte-Torres
T S
TS
Williamson
P J
PJ
Podgorny
J A
JA
Russell
A
A
Grigg
D
D
Ritchie
J
J
Storek
D000328:Adult; D000368:Aged; D000416:Alberta / Q000453:epidemiology; D000741:Anemia, Aplastic / Q000628:therapy; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D015994:Incidence; D007938:Leukemia / Q000517:prevention & control / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000517:prevention & control / Q000628:therapy; D009894:Opportunistic Infections / Q000453:epidemiology / Q000209:etiology / Q000821:virology; D055502:Secondary Prevention; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014777:Virus Diseases / Q000453:epidemiology / Q000209:etiology / Q000821:virology; D055815:Young Adult
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; C512542:thymoglobulin