An acquired inhibitor to the GPVI platelet collagen receptor in a patient with lupus nephritis.
BACKGROUND
GPVI is a major platelet collagen signaling receptor. In rare cases of immune thrombocytopenic purpura (ITP), autoantibodies to GPVI result in receptor shedding.


OBJECTIVE
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 FcgammaRIIA 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.
Nurden
P
P
CRPP/PTIB, Hôpital Xavier Arnozan, Pessac, France.
Tandon
N
N
Takizawa
H
H
Couzi
L
L
Morel
D
D
Fiore
M
M
Pillois
X
X
Loyau
S
S
Jandrot-Perrus
M
M
Nurden
A T
AT
D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D016466:CHO Cells; D003094:Collagen / Q000737:chemistry; D006224:Cricetinae; D003412:Cricetulus; D003435:Crotalid Venoms / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D037181:Lectins, C-Type / Q000737:chemistry; D008181:Lupus Nephritis / Q000097:blood / Q000378:metabolism*; D051379:Mice; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry
D003435:Crotalid Venoms; D007166:Immunosuppressive Agents; D037181:Lectins, C-Type; D010980:Platelet Membrane Glycoproteins; D011994:Recombinant Proteins; C098341:platelet membrane glycoprotein VI; C028890:convulxin; D003094:Collagen