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. 2013 Feb;6(1):74-76.
doi: 10.1093/ckj/sfs162. Epub 2012 Dec 20.

Homozygous FCGR3A-158F mutation is associated with delayed B-cell depletion following rituximab but with preserved efficacy in a patient with refractory lupus nephritis

Guillaume Seret  1 , Catherine Hanrotel  2 , Boutahar Bendaoud  3 , Yannick Le Meur  4 , Yves Renaudineau  3
Affiliations

Homozygous FCGR3A-158F mutation is associated with delayed B-cell depletion following rituximab but with preserved efficacy in a patient with refractory lupus nephritis

Guillaume Seret et al. Clin Kidney J. 2013 Feb.

Abstract

Rituximab (RTX), an anti-CD20 monoclonal antibody, has shown promising results in a small group of systemic lupus erythematosus (SLE) patients treated for lupus nephritis (LN). However, such observations were not confirmed in the double-blind LUNAR study. Accordingly, the factors associated with the clinical response remain to be characterized. We report the case of a young woman with known LN successfully re-treated with RTX and steroids and homozygous for the low-affinity FCG3RA 158F genotype. Although B-cell depletion was delayed, complete remission with anti-DNA antibody negativity and proteinuria normalization were maintained for 5 years. The implications for disease pathogenesis and clinical monitoring are discussed.

Keywords: B-cell depletion; FCGR3A; lupus nephritis; rituximab.

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Figures

Fig. 1.
Fig. 1.
Longitudinal variations of (A) proteinuria; (B) C3c and C4 complement fractions; (C) anti-dsDNA Ab, anti-C1q Ab and anti-alpha actinin (ACT) Ab and (D) percentage of peripheral blood B cells in a lupus nephritis patient re-treated with RTX and compared with 14 primary Sjögren's syndrome patients treated with RTX. The 14 SS patients displayed the three FCGR3A genotypes (5 were F/F, 9 were V/F and 1V/V). Of particular note, the SS patient who achieved B-cell depletion at 2 weeks was FCGR3A 158F/F. In the figure, allele-specific PCR is showing an FCGR3A 158F/F genotype.
See this image and copyright information in PMC

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