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The MHC class I–like Fc receptor promotes humorally mediated autoimmune disease
Shreeram Akilesh, … , Gregory J. Christianson, Derry Roopenian
Shreeram Akilesh, … , Gregory J. Christianson, Derry Roopenian
Published May 1, 2004
Citation Information: J Clin Invest. 2004;113(9):1328-1333. https://doi.org/10.1172/JCI18838.
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Article Autoimmunity

The MHC class I–like Fc receptor promotes humorally mediated autoimmune disease

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Abstract

The MHC class I family–like Fc receptor, FcRn, is normally responsible for extending the life span of serum IgG Ab’s, but whether this molecule contributes to autoimmune pathogenesis remains speculative. To determine directly whether this function contributes to humoral autoimmune disease, we examined whether a deficiency in the FcRn heavy chain influences autoimmune arthritis in the K/BxN mouse model. FcRn deficiency conferred either partial or complete protection in the arthritogenic serum transfer and the more aggressive genetically determined K/BxN autoimmune arthritis models. The protective effects of an FcRn deficiency could be overridden with excessive amounts of pathogenic IgG Ab’s. The therapeutic saturation of FcRn by high-dose intravenous IgG (IVIg) also ameliorated arthritis, directly implicating FcRn blockade as a significant mechanism of IVIg’s anti-inflammatory action. The results suggest that FcRn is a potential therapeutic target that links the initiation and effector phases of humoral autoimmune disease.

Authors

Shreeram Akilesh, Stefka Petkova, Thomas J. Sproule, Daniel J. Shaffer, Gregory J. Christianson, Derry Roopenian

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Figure 1

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FcRn-deficient mice are resistant to serum-transfer arthritis. Data repr...
FcRn-deficient mice are resistant to serum-transfer arthritis. Data represented as the mean ± SE. (A_C) A single injection of 250 ∝l of sera pooled from 6- to 20-week-old arthritic K/BxN animals was injected intraperitoneally into three FcRn_/_ (open circles) and three FcRn+/+ (filled circles) B6 control mice. (A) Ankle width determinations and overall arthritis scores are as described (19). All time points except day 0 were significant at P < 0.05. (B) Digital images of representative ankles of FcRn_/_ and WT mice 6 days after serum transfer. (C) Serial serum samples from A were analyzed for anti-GPI Ig by ELISA (21). Data are representative of two independent experiments. NS, not significant. All other time points were significant at P < 0.05. (D) Ankle width and arthritis scores of B6-FcRn_/_ mice (n = 4_5) injected intraperitoneally with 250 (filled circles), 500 (filled squares), or 1,000 (open squares) ∝l arthritogenic K/BxN or 1,000 ∝l normal B6 mouse serum (open circles). *Ankle width and arthritis score time points were P _ 0.004 and P < 0.01 versus B6 serum, respectively. Other time points versus B6 serum were not significant at P < 0.05.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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