Cj. Kootstra et al., EFFECTIVE TREATMENT OF EXPERIMENTAL LUPUS NEPHRITIS BY COMBINED ADMINISTRATION OF ANTI-CD11A AND ANTI-CD54 ANTIBODIES, Clinical and experimental immunology, 108(2), 1997, pp. 324-332
Mice with chronic graft-versus-host disease (GVHD), induced by injecti
on of DBA/2 lymphocytes in (C57BL10DBA/2) F-1 hybrids, develop a synd
rome resembling systemic lupus erythematosus (SLE) with immune complex
glomerulonephritis. In this model we evaluated the role of interactio
ns between CD11a (LFA-1 alpha) and CD54 (intercellular adhesion molecu
le-1 (ICAM-1)) molecules on leucocytes in the development of renal dis
ease in systemic autoimmunity. Two weeks after induction of GVHD, when
anti-nuclear autoantibodies were detected in the circulation and immu
ne complexes had formed in the glomeruli, mice were injected twice per
week with rat anti-CD11a and anti-CD54 MoAbs, or with their vehicle P
BS, or with control rat IgG. MoAb treatment significantly lowered albu
minuria and increased survival compared with control mice with GVHD. I
n the glomeruli of MoAb-treated mice there was markedly less binding o
f immunoglobulin and C3, while anti-renal tubular epithelium autoantib
odies, but not anti-glomerular basement membrane autoantibodies, were
significantly lowered in the circulation 4 weeks after disease inducti
on. In addition, MoAb treatment inhibited the glomerular influx of CD1
1a(+) cells and decreased development of histological abnormalities in
the kidneys. Both rat IgG- and MoAb-treated mice developed anti-rat i
mmunoglobulin antibodies. Furthermore, a marked splenomegaly with an i
ncrease of the T cell compartment was observed in MoAb-treated mice wi
th GVHD. These results show that CD11a/CD54 interactions are crucial f
or the full-blown development of lupus nephritis in this model. Treatm
ent aimed at blocking the activity of these molecules profoundly atten
uated the development of renal disease in chronic GVHD even if started
when first symptoms of SLE (i.e. anti-nuclear autoantibodies in sera
and glomerular binding of immunoglobulins) were already detectable.