title: Restoration of C1q levels by bone marrow transplantation attenuates autoimmune disease associated with C1q deficiency in mice.
abstract: C1q deficiency in both humans and mice is strongly associated with autoimmunity. We have previously shown that bone marrow transplantation (BMT) restored C1q levels in C1q-deficient (C1qa(-/-)) mice. Here, we studied the effect of BMT on autoimmunity in C1qa(-/-) mice. Following irradiation, young C1qa(-/-) or wild-type MRL/Mp mice received bone marrow cells (BMC) from strain-matched wild-type or C1qa(-/-) animals. C1q levels increased rapidly when C1qa(-/-) mice received BMC from wild-type mice. Conversely, they decreased slowly in wild-type mice transplanted with C1qa(-/-) BMC. C1qa(-/-) animals transplanted with C1qa(-/-) BMC demonstrated accelerated disease when compared with wild-type mice given wild-type BMC. In contrast, a significant delay in the development of autoantibodies and glomerulonephritis was observed in C1qa(-/-) mice reconstituted with wild-type BMC, and the impaired clearance of apoptotic cells, previously described in C1qa(-/-) mice, was rectified. Moreover, the autoimmune disease was accelerated in wild-type mice given C1qa(-/-) BMC compared to animals transplanted with wild-type cells. These results provide supporting evidence that BMT may be a therapeutic option in the treatment of autoimmunity associated with human C1q deficiency.
authors.affiliation: Rheumatology Section, Eric Bywaters Centre, Faculty of Medicine, Imperial College, London, UK.
authors.forename: Josefina
authors.initials: J
authors.lastname: Cortes-Hernandez
authors.forename: Liliane
authors.initials: L
authors.lastname: Fossati-Jimack
authors.forename: Franz
authors.initials: F
authors.lastname: Petry
authors.forename: Michael
authors.initials: M
authors.lastname: Loos
authors.forename: Shozo
authors.initials: S
authors.lastname: Izui
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Walport
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
authors.forename: Marina
authors.initials: M
authors.lastname: Botto
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D016026:Bone Marrow Transplantation; D015922:Complement C1q / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010587:Phagocytosis / Q000276:immunology / Q000502:physiology; D013154:Spleen / Q000378:metabolism
chemical_list: D015922:Complement C1q