Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Platelet-associated antibodies, cellular immunity and FCGR3a genotype influence the response to rituximab in immune thrombocytopenia.

Authors: Cooper, N  Stasi, R  Cunningham-Rundles, S  Cesarman, E  McFarland, JG  Bussel, JB 
Citation: Cooper N, etal., Br J Haematol. 2012 Aug;158(4):539-47. doi: 10.1111/j.1365-2141.2012.09184.x. Epub 2012 Jul 6.
Pubmed: (View Article at PubMed) PMID:22775462
DOI: Full-text: DOI:10.1111/j.1365-2141.2012.09184.x

Rituximab is widely used in autoimmune diseases including immune thrombocytopenia (ITP), although the mechanism of effect remains unclear. This study describes the effects of rituximab on platelet-associated antibodies (PA-APAs), B and T cell counts and clonality ( IGHV and TRG@ gene rearrangements), FCGR3A (FcgammaRIIIa) and FCGR2A (FcgammaRIIa) polymorphisms and correlation to anti-CD40 ligand (CD40L) response. PA-APA levels fell more frequently in responders (6/8) than in non-responders (2/10: P = 0.08-0.15). Two responders had no PA-APAs. Two non-responders with a fall in PA-APAs had very high CD8 levels. One non-responder had a B cell clone, one responder and one non-responder had a T cell clone. 15/16 patients had the same responses to rituximab and antiCD40L. Patients with FCGR3A V/V polymorphisms were more likely to respond to rituximab (P = 0.03). In summary, the fall in PA-APAs in responders confirms the humoural effect of rituximab. Failure to respond in patients with very high CD8 levels, despite PA-APA fall indicates a role for T cell-mediated platelet/megakaryocyte destruction. Concordance of response to anti-CD40L suggests autoantibody-producing cells are under T cell control. Finally, the effect of FCGR polymorphisms on response confirms the importance of FCGR-mediated depletion of B cells in autoimmunity. This has implications on the pathology of ITP as well as the immunological effect of B cell depletion.


Disease Annotations
Objects Annotated

Additional Information

RGD Object Information
RGD ID: 11040770
Created: 2016-03-15
Species: All species
Last Modified: 2016-03-15
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.