Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T. activity in the blood. If left untreated, TTP may lead to severe organ dysfunction and even death due to common thrombosis. Plasma exchange offers emerged as the preferred treatment for TTP as it is effective in filtering the pathogenic antibodies while providing active ADAMTS 13 protease. The current treatment regimens consisting of plasma exchange and corticosteroids have effectively decreased mortality from 90% to less than 20%[2, 3]. Still, a significant number of individuals are refractory to treatment or relapse after the 1st episode of TTP. These individuals are treated with intensification of the plasma exchange routine, improved doses of corticosteroids and second-line cytotoxic providers such as vincristine or cyclophosphamide. Rituximab is definitely a monoclonal chimeric antibody against CD20, a molecule that is indicated on all mature B cells, but not long lived plasma cells. The FDA authorized rituximab in the beginning for the treatment of Non-Hodgkin Lymphoma. More recently it was approved for the treatment of autoimmune diseases such as rheumatoid arthritis [4] and ANCA-associated vasculitis [5], and was found useful in the treatment of chronic immune thrombocytopenia [6]. Rituximab causes a rapid (within 2C4 weeks) and profound decrease in circulating B cells through multiple mechanisms (antibody-mediated cell cytotoxicity, complement activation and apoptosis). The decrease in B cells continues for a number of months following a typical four weekly infusions of rituximab. The antibody forming plasma cells are not affected by rituximab, hence the overall immunoglobulin levels remain within FJX1 normal limits [7]. There is some evidence that B cell depletion may lead to moderate decrease in autoantibody levels [4, 7] but that cannot fully clarify the restorative effect of rituximab. It has been suggested that removal of B cells efficiently deprives the immune system from important auto-antigen showing and inflammatory cytokine generating cells, therefore abrogating the autoimmune response. Given the profile and mode of action of rituximab and its performance in autoimmune diseases, it emerged as a stylish candidate for the treatment of TTP. Several initial tests and case series reported that rituximab was well tolerated and effective in individuals with TTP including the ones with recurrent or refractory disease [8, 9]. A phase II trial of rituximab as 1st line treatment suggested that when added onto the standard of care, rituximab decreases the pace of relapse from 57% in historic controls to only 10%[10]. Subsequently, a randomized phase III medical trial comparing rituximab to placebo was initiated but terminated early due to slow subject accrual (clinicaltrials.gov; “type”:”clinical-trial”,”attrs”:”text”:”NCT00799773″,”term_id”:”NCT00799773″NCT00799773). In this problem of the journal, Froissart et al [11] asked whether rituximab is effective in the treatment of refractory/relapsing TTP. Individuals with low ADAMTS 13 activity ( 10%) who experienced suboptimal response to Methoxyresorufin standard treatment in the acute phase of TTP or relapsed after the initial episode were treated with rituximab. Rituximab, in contrast to common practice and in order to circumvent the problem with daily plasma exchange, was given in 3 Methoxyresorufin doses within the span of a week with the 4th dose given two weeks later on. The individuals were recruited prospectively; but instead of an active comparator group, historical settings treated with a variety of regimens including cytotoxic medications (cyclophosphamide, vincristine) were used. The biologic effect of rituximab was serious as expected with the B cell populace become undetectable in the blood within a few days of infusion. More importantly anti-ADAMTS 13 antibodies virtually disappeared and ADAMTS 13 activity normalized within 3 months after initiation of treatment. The medical results were equally encouraging: only one out of 22 individuals did not respond to rituximab. Rituximab-treated individuals accomplished remission quickly, within the 1st month after initiation of treatment, with no patient relapsing within the 1st year as opposed to 9.4% relapses in the control group. Of notice, the variations between rituximab and control treatment were not as apparent after 12 months as B cell populace recovered. The importance of this study lies within the fact that rituximab proved very efficacious, even more so than cytotoxic treatments, in Methoxyresorufin inducing a quick remission that lasted for over a 12 months in all individuals. This is just like published experience previously. Moreover, rituximab-treated sufferers didn’t need the usage of cytotoxic splenectomy or medications, staying away from potentially serious unwanted effects connected with these thus.