Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains.

Abstract

MRL/1 and BXSB male mice have a systemic lupus erythematosus (SLE)-like disease similar to but more acute than that occurring in NZB X W mice. The common elements of lymphoid hyperplasia, B-cell hyperactivity, autoantibodies, circulating immune complex (IC), complement consumption, IC glomerulonephritis with gp70 deposition, and thymic atrophy were found in all three kinds of SLE mice. On the basis of these common elements, SLE seen in these mice can be considered a single disease in the same sense that human SLE is one disease. The differences in the SLE expressed in the different mice are no greater than those found in an unselected series of humans with SLE. However, the significant quantitative and qualitative variations in abnormal immunologic expression suggest that different constellations of factors, genetic and/or pathophysiologic, may operate in the three murine strains and that each constellation is capable of leading, via its particular abnormal immunologic consequences, to the activation of common immunopathologic effector mechanisms that cause quite similar SLE-like syndromes. From an experimental point of view, the availability of several inbred murine strains of commonplace histocompatibility types that express an SLE-like syndrome makes possible innumerable manipulations which should help to elucidate the nature and cause(s) of this disorder.

The darker side of follicular helper T cells: from autoimmunity to immunodeficiency

“…43 Moreover, the role of IL-21 is also shown in another model of murine lupus, NZB/W F1 mice, which exhibit clinical features that resemble those of human SLE, including autoantibody production and immune complex-mediated nephritis. 44,45 Upon intranasal administration of anti-CD3 antibodies, NZB/W F1 mice exhibited suppressed lupus development characterized by reduced levels of autoantibodies and diminished glomerulonephritis. 45 It was found that the treatment with anti-CD3 antibody affected the function of CD4 1 CXCR5 1 ICOS 1 T FH cells, characterized by decreased IL-21 and IL-17 production in these mice which was associated with the autoimmune pathologies.…”

Immuno- and genetic therapy in autoimmune diseases

“…Genetic analysis of disease in relation to the development of arthritis and of anti-Sm antibodies has shown that up to ෂ25% develop one or other of these manifestations depending on the colony and without known genetic factor. 54 This observation suggests that unknown environmental factors may be responsible for the development of these features.…”

“…The disease is spontaneous, more severe and develops earlier in females (at ෂ4-5 months of age) 53 ; high titres of IgG anti-DNA antibodies, antinuclear antibodies (ANA) occurs in virtually all females and death results from progressive glomerulonephritis. 54 The disease in the BWF1 mouse is particularly sensitive to the effects of sex hormones; in general, androgens are protective and suppress the production of autoantibodies whereas estrogens are permissive. 55,56 Both NZB and NZW parents contribute genetically to the immune abnormalities that cause disease.…”

“…Both male and female MRL/lpr mice develop high serum levels of immunoglobulins, monoclonal paraproteins, ANA and immune complexes. 54 The mice produce IgM and IgG anti-DNA and die from immune nephritis at a young age (90% dead by 9 months). The mice also produce other autoantibodies including IgG2a anti-chromatin, anti-red blood cells, anti-thyroglobulin, anti-Sm, anti-RNA polymerase and rheumatoid factors autoantibodies.…”

Rheumatic diseases in an MRL strain of mice with a deficit in the functional Fas ligand

“…This gene is also known to induce various forms of rheumatic disease, including glomerulonephritis, vasculitis, and arthritis, in the presence of an MRL genetic background (8)(9)(10). Recently, it was shown that the lpr gene is a deletion mutant of the Fas antigen (1 1).…”