IgG anti-cardiolipin antibodies in murine lupus.
The frequency and nature of IgG anti-cardiolipin and anti-ds-DNA antibodies among MRL/lpr, MRL/+ and NZB/W F1 mice (murine lupus strains) and non-autoimmune inbred strains of mice (NIH/Swiss and Balb/c) were analysed by ELISA. High titres of anti-ds-DNA were detected in autoimmune strains (MRL/lpr, 69%; MRL/+, 50%; and NZB/W, 80% positive), whereas anti-cardiolipin antibodies were detected only in MRL/lpr (69%) and MRL/+ (17%) mice. IgG subclass analysis of these antibodies in 20 MRL/lpr sera revealed that all four subclasses were represented. When tested for fine antigenic specificity, anti-cardiolipin antibodies in MRL/lpr and MRL/+ mice bound to acidic phospholipids rather than to neutral phospholipids and were not inhibited by DNA. In MRL/lpr mice, anti-cardiolipin antibodies were first detected at 2 months, peaked around 5 months and then declined preterminally. To determine whether complications associated with anti-cardiolipin antibodies were present in MRL/lpr mice, blood counts were performed and litter sizes were determined. Although no significant decreases in the red and white blood cell counts were observed in MRL/lpr mice, platelet counts were significantly lower compared with NIH/Swiss (P < 0.001) and Balb/c (P < 0.005) mice. MRL/lpr mice had significantly fewer pups per delivery compared with a normal strain (MRL/lpr, 5.3+2.6; NIH/Swiss, 72 +/- 2.1; P < 0002). These observations indicate that the serological characteristics of IgG anti-cardiolipin antibodies in MRL/ lpr mice are similar to those of anti-cardiolipin antibodies in humans with lupus. Whether these autoantibodies are pathogenetically related to thrombocytopenia and a small litter size in MRL/lpr mice remains to be determined.
Gharavi
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The Hospital for Special Surgery, Cornell University Medical Center, New York, NY 10021, USA.
Mellors
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RC
Elkon
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KB
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000097:blood* / Q000145:classification; D000974:Antibodies, Antinuclear / Q000097:blood; D000918:Antibody Specificity; D005260:Female; D007074:Immunoglobulin G / Q000097:blood* / Q000145:classification; D008098:Litter Size; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology*; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology
D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G