1. Assessing the Role of Anti rh-GAA in Modulating Response to ERT in a Late-Onset Pompe Disease Cohort from the Italian GSDII Study Group
- Author
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Anna Galvagni, G. Marrosu, Silvia Bonanno, Cristina Sancricca, Sabrina Ravaglia, Rachele Piras, Giulia Ricci, Tiziana Mongini, Gabriele Siciliano, Virginia Bozzoni, Serenella Servidei, Alberto Lerario, Roberta Telese, Massimiliano Filosto, Lorenzo Maggi, Elena Pegoraro, Maria Antonietta Maioli, Liliana Vercelli, Serena Gallo Cassarino, Alessandro Padovani, Antonio Di Muzio, Paola Tonin, Stefano Cotti Piccinelli, Maurizio Moggio, Michele Sacchini, Antonio Toscano, Maria Alice Donati, Claudio Semplicini, Olimpia Musumeci, and Filomena Caria
- Subjects
Male ,030213 general clinical medicine ,Vital Capacity ,Anti rh-GAA antibodies ,Glycogen storage diseases II ,GSD II ,LOPD ,Pompe disease ,Gastroenterology ,Severity of Illness Index ,Cohort Studies ,0302 clinical medicine ,Glycogen storage disease type II ,Pharmacology (medical) ,biology ,Glycogen Storage Disease Type II ,Antibody titer ,General Medicine ,Enzyme replacement therapy ,Middle Aged ,Antibodies, Anti-Idiotypic ,Titer ,Settore MED/26 - NEUROLOGIA ,Anti-Idiotypic ,Italy ,030220 oncology & carcinogenesis ,Cohort ,Female ,Antibody ,Cohort study ,Adult ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Antibodies ,03 medical and health sciences ,FEV1/FVC ratio ,Internal medicine ,medicine ,Humans ,Enzyme Replacement Therapy ,alpha-Glucosidases ,business.industry ,nutritional and metabolic diseases ,medicine.disease ,biology.protein ,business - Abstract
Patients with late-onset Pompe disease (LOPD) receiving enzyme replacement therapy (ERT) may develop IgG antibodies against alglucosidase alpha (anti-rhGAA) in the first 3 months of treatment. The exact role of these antibodies in modulating efficacy of ERT in this group of patients is still not fully understood. To assess whether anti rh-GAA antibodies interfere with ERT efficacy, we studied a large Italian cohort of LOPD patients. We analyzed clinical findings and performed serial measurements of IgG anti rh-GAA antibody titers from 64 LOPD patients treated with ERT. The first examination (T0) was completed on average at 17.56 months after starting ERT, while the follow-up (T1) was collected on average at 38.5 months. Differences in T0–T1 delta of the six-minute walking test (6MWT), MRC sum score (MRC), gait, stairs and chair performance (GSGC) and forced vital capacity (FVC) were considered and then related to the antibody titers. Almost 22% of the patients never developed antibodies against GAA, while 78.1% had a positive titer (31.2% patients developed a low titer, 43.8% a medium titer and 3.1% a high titer). No statistical significance was found in relating the T0–T1 delta differences and antibody titers, except for MRC sum score values in a subgroup of patients treated < 36 months, in which those with a null antibody titer showed a greater clinical improvement than patients with a positive titer. Our results confirm that in a large cohort of LOPD patients, anti rh-GAA antibody generation did not significantly affect either clinical outcome or ERT efficacy. However, in the first 36 months of treatment, a possible interference of low-medium antibody titers with the clinical status could be present. Therefore, a careful and regular evaluation of antibody titers, especially in cases with evidence of clinical decline despite ERT, should be performed.
- Published
- 2019