Restoration of C1q levels by bone marrow transplantation attenuates autoimmune disease associated with C1q deficiency in mice.
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.
Cortes-Hernandez
Josefina
J
Rheumatology Section, Eric Bywaters Centre, Faculty of Medicine, Imperial College, London, UK.
Fossati-Jimack
Liliane
L
Petry
Franz
F
Loos
Michael
M
Izui
Shozo
S
Walport
Mark J
MJ
Cook
H Terence
HT
Botto
Marina
M
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
D015922:Complement C1q