Deletion of the gene encoding CD59a in mice increases disease severity in a murine model of rheumatoid arthritis

Arthritis Rheum. 2004 Sep;50(9):3035-44. doi: 10.1002/art.20478.


Objective: To investigate the roles of CD59a in the protection of joint tissue in the context of murine antigen-induced arthritis (AIA).

Methods: AIA was triggered in CD59a-deficient (CD59a(-/-)) mice and in CD59a-sufficient (CD59a(+/+)) controls; the course and severity of disease were compared between groups. The effects on arthritis of restoring CD59 to the joint in CD59a(-/-) mice by use of a membrane-targeted recombinant CD59 were also explored.

Results: Disease, as assessed clinically by measurement of joint swelling on day 1 (P < 0.0001), day 2 (P < 0.01), and day 7 (P < 0.02) and histologically from indicators of joint damage on day 21 (P < 0.02), was significantly enhanced in CD59a(-/-) mice compared with CD59a(+/+) wild-type controls. Membrane attack complex (MAC) deposition in the arthritic joints of CD59a(-/-) mice was also increased compared with that in the joints of CD59a(+/+) controls. Restitution of CD59 activity in joints of CD59a(-/-) mice was attempted with soluble recombinant rat CD59 (sCD59) or with a novel membrane-targeted rat CD59 derivative (sCD59-APT542). Strong immunohistochemical staining of the synovial membrane and subsynovial tissue was apparent in sCD59-APT542-injected joints, but not in joints injected with untargeted sCD59. Intraarticular administration of sCD59-APT542 markedly ameliorated disease severity in CD59a(-/-) mice, knee swelling was significantly reduced over the time course of the disease, and joint damage, assessed histologically, was significantly milder on day 21 (P < 0.05).

Conclusion: These data firmly implicate the MAC of complement as a major effector of joint damage in the murine AIA model of rheumatoid arthritis (RA), and they provide a rationale for the inhibition of MAC assembly as a therapeutic strategy for RA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • CD59 Antigens / genetics
  • CD59 Antigens / immunology*
  • CD59 Antigens / pharmacology
  • Complement Membrane Attack Complex / immunology
  • Disease Progression
  • Gene Deletion
  • Genetic Predisposition to Disease
  • Male
  • Mice
  • Models, Animal
  • Severity of Illness Index


  • Adjuvants, Immunologic
  • CD59 Antigens
  • Complement Membrane Attack Complex