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An acquired inhibitor to the GPVI platelet collagen receptor in a patient with lupus nephritis
Author(s) -
NURDEN P.,
TANDON N.,
TAKIZAWA H.,
COUZI L.,
MOREL D.,
FIORE M.,
PILLOIS X.,
LOYAU S.,
JANDROTPERRUS M.,
NURDEN A. T.
Publication year - 2009
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2009.03537.x
Subject(s) - gpvi , platelet , lupus nephritis , systemic lupus erythematosus , platelet activation , antibody , immunology , chemistry , medicine , disease
Summary. Background : GPVI is a major platelet collagen signaling receptor. In rare cases of immune thrombocytopenic purpura (ITP), autoantibodies to GPVI result in receptor shedding. Objectives : To investigate a possible pathogenic role of plasma anti‐GPVI antibody located in a woman with lupus nephritis. Methods : Measured were (i) platelet aggregation to collagen and convulxin, (ii) platelet GPVI expression (flow cytometry and western blotting), (iii) plasma soluble GPVI (sGPVI, dual antibody ELISA), and (iv) plasma anti‐GPVI antibody (ELISA using recombinant sGPVI). Results : In 2006 and early 2007, the patient had a normal platelet count but a virtual absence of platelet aggregation to collagen and convulxin. Her platelets responded normally to other agonists including cross‐linking ITAM‐dependent FcγRIIA by monoclonal antibody, IV.3. Flow cytometry and western blotting showed a platelet deficiency of GPVI. Plasma sGPVI levels were undetectable whereas ELISA confirmed the presence of anti‐GPVI antibody. Sequencing revealed a normal GPVI cDNA structure. The patient’s plasma and the isolated IgG3 fraction activated and induced GPVI shedding from normal platelets. A deteriorating clinical condition led to increasingly strict immunosuppressive therapy. This was globally associated with a fall in plasma anti‐GPVI titres, the restoration of platelet GPVI and the convulxin response, and the loss of her nephrotic syndrome. Conclusions: Our results show that this patient acquired a potent anti‐GPVI IgG3 antibody with loss of GPVI and collagen‐related platelet function. Further studies are required to determine whether anti‐GPVI antibodies occur in other lupus patients with nephritis.