Association of mixed hematopoietic chimerism with elevated circulating autoantibodies and chronic graft-versus-host disease occurrence.
BACKGROUND
Use of a reduced-intensity conditioning regimen before an allogeneic hematopoietic cell transplantation is frequently associated with an early state of mixed hematopoietic chimerism. Such a coexistence of both host and donor hematopoietic cells may influence posttransplant alloreactivity and may affect the occurrence and severity of acute and chronic graft-versus-host disease (GVHD) as well as the intensity of the graft-versus-leukemia effect. Here we evaluated the relation between chimerism state after reduced-intensity conditioning transplantation (RICT), autoantibody production, and chronic GVHD (cGVHD)-related pathology.


METHODS
Chimerism state, circulating anticardiolipin, and antidouble stranded DNA autoantibody (Ab) titers as well as occurrence of cGVHD-like lesions were investigated in a murine RICT model.


RESULTS
We observed a novel association between mixed chimerism state, high levels of pathogenic IgG autoantibodies, and subsequent development of cGVHD-like lesions. Furthermore, we found that the persistence of host B cells, but not dendritic cell origin or subset, was a factor associated with the appearance of cGVHD-like lesions. The implication of host B cells was confirmed by a host origin of autoantibodies.


CONCLUSIONS
Recipient B cell persistence may contribute to the frequency and/or severity of cGVHD after RICT.
INSERM U645, University of Franche-Comte, EFSB-FC, IFR133, Besançon, France.
Sylvain
S
Perruche
Aliette
A
Marandin
François
F
Kleinclauss
Régis
R
Angonin
Stéphanie
S
Fresnay
Marie Hélène
MH
Baron
Pierre
P
Tiberghien
Philippe
P
Saas
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D018183:Transplantation Chimera / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018793:Interleukin-13; D007371:Interferon-gamma