Immune responses to alglucosidase in infantile Pompe disease: recommendations from an Italian pediatric expert panel

Table 5 Drugs commonly used for immune toleration

Drug	Mechanism	Adverse events
Bortezomib	Proteasome inhibition: blocks protein recycle and production of antibodies in plasma cells^a [55, 56]	Peripheral neuropathy, anemia, neutropenia, thrombocytopenia, gastrointestinal and cardiac side effects [23]
IVIG	Binding to the neonatal Fc receptor (FcRn) which is responsible for recycling of antibodies thus downregulating antibody responses [53, 57, 58] Passive immunity during the period of immune suppression due to other drugs (specially rituximab) [23]	Infusion-associated reactions [59]
Methotrexate	Inhibits folic acid metabolism (which blocks de novo DNA synthesis), thus eliminating dividing B and T cells. Low dose: Induces regulatory B cells rather than cell depletion [60, 61]	Bone marrow and gastrointestinal toxicities, rarely acute pneumonitis, pulmonary fibrosis and renal function impairment [12, 62]
Mycophenolate mofetil	Inhibition of proliferative responses of T and B lymphocytes [12]	Leukopenia, anemia and thrombocytopenia
Rapamycin	Mammalian target of rapamycin (mTOR), which inhibits cell survival and proliferation of B and T lymphocytes, but selectively promotes regulatory T – Treg – cells ^b [63,64,65,66,67]
Rituximab	Monoclonal antibody against CD20 molecule expressed on B cells [12]	Infusion-associated reactions, lymphocytopenia, progressive multifocal leukoencephalopathy [62]

^a In muscle, the ubiquitin-proteasome system is believed to degrade contractile skeletal muscle proteins and may play a critical role in muscle wasting [23]
^b May have an impact on glycogen storage in muscle by influencing the mTor pathway and inhibiting glycogen storage [68]

ISSN: 1824-7288