Waldenstroms Macroglobulinemia
IVIG and Rituximab Research

IVIG and the Rituximab IgM Flare In Waldenstrom’s Macroglobulinemia

Research related with IVIG and the Rituximab IgM Flare In Waldenstrom’s Macroglobulinemia Is concerned with Triggering of IL-6 obtained through MAPK Pathways and PI3K/AKT and indication of Monocytic Activation of Fcgriia
Researchers had previously made an experiment on WM patient with the help of paradoxical flare in serum IgM levels following IVIG administration and/or rituximab. It results after some hours of execution and 40% to 70% of the patients were affected. Due to paradoxical flare, Waldenstrom’s Macroglobulinemia patient may result to aggravation, and/or symptomatic hyperviscosity of other IgM mediated morbidities. Direct execution of Waldenstrom’s Macroglobulinemia cells with the help of rituximab or IVIG does not give desirable result of further IgM release. Patients IL-6 goes up having rituximab and are induced with IgM flare.

Methods and Patients:

In the presence or absence of rituximab or IVIG, researchers have performed the studies of WM cells with the help of transwell system using granulocytes or monocytes.After induction of rituximab, Granulocyte, monocyte cell lysates and supernatants were collected for further research. IL-6 levels were experimented with real-time RT-PCR and multiplex assays . siRNAs to target FcgRIIB,FcgRiiA,FcgRIA,FcgRIBand FcgRIIA were taken to hit downFcy receptors on primary monocytes.Real-time RT-PCR and flow cytoetry confirmed Fcy receptor expression following siRNA transfection. When proteins of simulated monocytes of rituximab are analyzed alongside arrays of phospho antibody it shows signs of western blotting.


A considerable growth in IgM release was experimented following combination of primary WM cells along with co-incubation and monocytes with IVIG or rituximab. This growth was related to IL-6 release and may be restricted by IL-6 antibodies. The stimulation of IL-6 was reduced significantly after the induction of rituximab of monocytes with the help of siRNA hit of FcgRIIA. Ingenuity pathway and Phospho-body experimented discovered that PI3K/AKT and MAPK pathways were participated in showing signs by rituximab stimulation of monocytes with FcgRIIA. Western blotting of AKT, ERK1/2, PI3k & p38MAPK with phosphor specific antibodies resulted in an increase of their phosphorylation.Moreover, production of IL-6 were reduced for AKT, ERK1/2, PI3k & p38MAPK.


So with the above data the conclusion is that the IVIG and/or rituximab associated IgM flare experimented in WM patients results in positive activeness of the MAPK and PI3K/AKT pathways and negative response discovered by IL-6 with the induction of bystander monocytes done by way of FcgRIIA binding. These pathways were restricted to release IL-6 from rituximab induced monocytes by inhibitors. Thus the studies provide an outline for research of pre-emptive therapies for restricting IgM flare in Waldenstrom’s Macrogloblunemia patients for the consideration of IVIG therapy and/or rituximab.