The following article features coverage from the 17th Annual WORLDSymposium meeting. Click here to read more of MPR’s conference coverage.

For patients with Fabry disease (FD), mast cell stabilizers appear to have the potential to control infusion related reactions (IRRs) and possibly allow for the safe reintroduction of agalsidase in patients who previously received enzyme replacement therapy (ERT), according to research presented at the 17th Annual WORLDSymposium.

FD is a rare, X-linked lysosomal disorder characterized by a GLA mutation which results in either a lack of or a defective α-galactosidase A (GalA) enzyme. Currently, standard therapy for this condition includes ERT plus agalsidase, a recombinant human α-GalA enzyme. IRRs caused by an immune response against this exogenous enzyme are marked by symptoms such as fever, pain, vomiting, diarrhea, rigors, as well as angioedema.

This study analyzed the reports of 8 patients with FD who developed IRRs in order to better understand the mechanisms causing these reactions. Of the total patients, 6 presented with NCI-CTC grade 3 criteria for hypersensitivity and acute reactions while 2 presented with grade 2 criteria. Seven of the patients had negative tests for agalsidase specific immunoglobulin E (IgE) as well as normal levels of tryptase. Neutralizing antibodies with titers between 1:20 and 1:500 were found in 6 patients and no significant correlation between IRRs and anti-drug antibodies was observed. Differences in major immune cell types (T cells, dendritic cells, and NK cells) were not significant when comparing reactors and non-reactors.

Peripheral blood samples were obtained pre- and post-infusion in patients who experienced IRRs in order to perform immunophenotyping. The study authors compared their results to the results of other FD patients who did not experience IRRs. “Circulating dendritic cells were drastically reduced during IRRs suggesting possible sequestration to the sites of inflammation,” the study authors stated. They added, “An increase in NK cells and decrease in T cells were also observed.” Additionally, nonspecific degranulation of mast cells was observed, marked by significant increases in cytokines IL-4, IL-8, and TNF-α. Standard premedications plus mast cell stabilizers were successfully used to manage all IRRs and therapy was not interrupted.

“Taken together, the results indicate crosstalk between immune cells resulting in IgE independent mast cell specific allergic inflammation,” the authors concluded. They added, “Mast cell stabilizers could be used to control IRRs and for safe reintroduction of agalsidase in patients previously treated with ERT.”


Limgala RP, Flykry J, Veligatla V, Goker-Alpan O. Mast cell stabilizers in management of IgE independent mast cell activation in infusion related reactions in patients with Fabry disease. Presented at: 17th Annual WORLDSymposium; February 8-12, 2020. Abstract 140.