Spataro Federico, Ria Roberto, Chaoul Nada, Solimando Antonio Giovanni, Desantis Vanessa, Vacca Angelo, Di Bona Danilo, Girolamo Attilio Di, Macchia Luigi
Post Graduate School in Allergology and Internal Medicine "Guido Baccelli", Department of Precision and Regenerative Medicine and Ionian Area-(DiMePRe-J), School of Medicine, Aldo Moro University of Bari, Bari, 70124, Italy.
Guido Baccelli Unit of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area-(DiMePRe-J), School of Medicine, Aldo Moro University of Bari, Bari, 70124, Italy.
Orphanet J Rare Dis. 2024 Dec 27;19(1):491. doi: 10.1186/s13023-024-03516-z.
Mucopolysaccharidosis (MPS) type 1 S and type 2 are rare lysosomal storage disorders characterized by impaired enzyme production, resulting in glycosaminoglycans accumulation within lysosomes. Enzyme Replacement Therapy (ERT) with laronidase and idursulfase are first line treatments, respectively. However, infusion-related hypersensitivity reactions (HR) may lead to ERT discontinuation. Thus, desensitization can be performed to restore ERT.
We report on a two-year follow-up after a combined desensitization approach in two MPS patients experiencing HR to ERT. This approach consists of intravenous rapid desensitization combined with the subcutaneous allergen immunotherapy-like desensitization with the culprit recombinant enzyme.
The first patient, suffering from MPS type I, underwent to the combined desensitization approach, and subsequently tolerated weekly standard laronidase infusions for 13 months when HR occurred again. Then, a monthly omalizumab (anti-IgE monoclonal antibody) administration was implemented allowing the patient to restore ERT. The second patient, diagnosed with MPS type 2, was subjected to a similar combined desensitization strategy with idursulfase, and achieved a total desensitization after one year, confirmed by negative skin tests. Thus, he continued standard ERT infusions without HR occurrence.
The combined desensitization approach proved effective in conferring immunotolerance for at least one year in both MPS patients, also demonstrated by the negative skin tests in one patient. However, when immunotolerance to ERT is lost, omalizumab administration can be a valid option in restoring ERT.
1型S型和2型黏多糖贮积症（MPS）是罕见的溶酶体贮积病，其特征是酶产生受损，导致溶酶体内糖胺聚糖积累。分别使用拉罗尼酶和艾度硫酸酯酶进行酶替代疗法（ERT）是一线治疗方法。然而，与输注相关的超敏反应（HR）可能导致ERT中断。因此，可以进行脱敏治疗以恢复ERT。
我们报告了两名对ERT发生HR的MPS患者采用联合脱敏方法后的两年随访情况。该方法包括静脉快速脱敏，结合使用致病重组酶进行皮下过敏原免疫疗法样脱敏。
第一名患有1型MPS的患者接受了联合脱敏方法，随后在HR再次出现时耐受了每周一次的标准拉罗尼酶输注13个月。然后，每月给予奥马珠单抗（抗IgE单克隆抗体），使患者能够恢复ERT。第二名被诊断为2型MPS的患者接受了类似的艾度硫酸酯酶联合脱敏策略，一年后实现了完全脱敏，皮肤试验阴性证实了这一点。因此，他继续进行标准ERT输注，未再发生HR。
联合脱敏方法在两名MPS患者中均有效诱导了至少一年的免疫耐受，其中一名患者的皮肤试验阴性也证明了这一点。然而，当对ERT的免疫耐受丧失时，给予奥马珠单抗可能是恢复ERT的有效选择。
