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. CONCLUSION: Recipient B cell persistence may contribute to the frequency and/or severity of cGVHD after RICT.
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. CONCLUSION: Recipient B cell persistence may contribute to the frequency and/or severity of cGVHD after RICT.
Authors: P Kier; E Penner; S Bakos; P Kalhs; K Lechner; B Volc-Platzer; J Wesierska-Gadek; G Sauermann; H Gadner; W Emminger-Schmidmeier Journal: Bone Marrow Transplant Date: 1990-08 Impact factor: 5.483
Authors: L M Griffith; J P McCoy; C D Bolan; D F Stroncek; A C Pickett; G F Linton; A Lundqvist; R Srinivasan; S F Leitman; R W Childs Journal: Br J Haematol Date: 2005-03 Impact factor: 6.998
Authors: Marijke R Canninga-van Dijk; Hanneke M van der Straaten; Rob Fijnheer; Cornelus J Sanders; Jan G van den Tweel; Leo F Verdonck Journal: Blood Date: 2004-07-13 Impact factor: 22.113
Authors: Dimitrios Daoussis; Stamatis-Nick C Liossis; Athanassios C Tsamandas; Christina Kalogeropoulou; Alexandra Kazantzi; Chaido Sirinian; Maria Karampetsou; Georgios Yiannopoulos; Andrew P Andonopoulos Journal: Rheumatology (Oxford) Date: 2009-05-15 Impact factor: 7.580