Study of the effect of anti-rhGAA antibodies at low and intermediate titers in late onset Pompe patients treated with ERT

被引：8

作者：

Fernandez-Simon, Esther ^{[1
]}

Carrasco-Rozas, Ana ^{[1
]}

Gallardo, Eduard ^{[1
,2
]}

Gonzalez-Quereda, Lidia ^{[3
]}

Alonso-Perez, Jorge ^{[1
]}

Belmonte, Izaskun ^{[4
]}

Pedrosa-Hernandez, Irene ^{[4
]}

Montiel, Elena ^{[4
]}

Segovia, Sonia ^{[1
,2
]}

Suarez-Calvet, Xavier ^{[1
]}

Llauger, Jaume ^{[5
]}

Mayos, Mercedes ^{[6
]}

Illa, Isabel ^{[1
,2
]}

Angel Barba-Romero, Miguel ^{[7
]}

Barcena, Joseba ^{[8
]}

Paradas, Carmen ^{[9
]}

Rosario Carzorla, Maria ^{[10
]}

Creus, Carlota ^{[11
]}

Coll-Canti, Jaume ^{[12
]}

Diaz, Manuel ^{[13
]}

Dominguez, Cristina ^{[14
,15
]}

Fernandez-Torron, Roberto ^{[16
]}

Jose Garcia-Antelo, Maria ^{[17
]}

Maria Grau, Josep ^{[18
]}

Lopez de Munain, Adolfo ^{[16
]}

Antonio Martinez-Garcia, Francisco ^{[19
]}

Morgado, Yolanda ^{[20
]}

Moreno, Antonio ^{[21
]}

Moris, German ^{[22
]}

Angel Munoz-Blanco, Miguel ^{[23
]}

Nascimento, Andres ^{[24
]}

Luis Parajua-Pozo, Jose ^{[25
]}

Querol, Luis ^{[26
]}

Rojas, Ricard ^{[26
]}

Robledo-Strauss, Arturo ^{[27
]}

Rojas-Marcos, Inigo ^{[28
]}

Antonio Salazar, Jose ^{[29
]}

Uson, Mercedes ^{[30
]}

Diaz-Manera, Jordi ^{[1
,2
]}

机构：

[1] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, Neuromuscular Disorders Unit, Barcelona, Spain

[2] Ctr Invest Red Enfermedades Raras CIBERER, Madrid, Spain

[3] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Genet, U705 CIBERER, Barcelona, Spain

[4] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Rehabil & Physiotherapy Dept, Barcelona, Spain

[5] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Radiol, Barcelona, Spain

[6] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Resp Dept, Barcelona, Spain

[7] Hosp Gen Albacete, Albacete, Spain

[8] Hosp Univ Cruces, Baracaldo, Spain

[9] Hosp Virgen Rocio, Seville, Spain

[10] Hosp Puerta Hierro, Majadahonda, Spain

[11] Hosp Virgen Nieves, Granada, Spain

[12] Hosp Germans Tries & Pujol, Badalona, Spain

[13] Hosp Cabuenes, Gijon, Spain

[14] Hosp 12 Octubre, Madrid, Spain

[15] Inst Invest I 12, Madrid, Spain

[16] Hosp Univ Donostia, San Sebastian, Spain

[17] Hosp Univ A Coruna, La Coruna, Spain

[18] Hosp Clin Barcelona, Barcelona, Spain

[19] Hosp Clin Univ Virgen Arrixaca, Murcia, Spain

[20] Hosp Univ Virgen Valme, Seville, Spain

[21] Hosp Univ Morales Meseguer, Murcia, Spain

[22] Hosp Univ Asturias, Oviedo, Spain

[23] Hosp Gregorio Maranon, Madrid, Spain

[24] Hosp St Joan de Deu, Barcelona, Spain

[25] Hosp Can Mises, Ibiza, Spain

[26] Hosp Santa Creu & Sant Pau, Barcelona, Spain

[27] Hosp Juan Ramon Jimenez, Huelva, Spain

[28] Hosp Virgen Macarena, Seville, Spain

[29] Hosp Reg Univ Malaga, Malaga, Spain

[30] Hosp Son Llatzer, Palma de Mallorca, Spain

来源：

MOLECULAR GENETICS AND METABOLISM | 2019年 / 128卷 / 1-2期

关键词：

Enzyme replacement therapy; ERT; Late onset Pompe disease; LOPD; Antibodies; ENZYME REPLACEMENT THERAPY; ACID ALPHA-GLUCOSIDASE; DISEASE; IMPACT;

D O I：

10.1016/j.ymgme.2019.07.013

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Late onset Pompe disease (LOPD) is a genetic disorder characterized by slowly progressive skeletal and respiratory muscle weakness. Symptomatic patients are treated with enzyme replacement therapy (ERT) with alglucosidase alpha (rhGAA). Although most of ERT treated patients develop antibodies against rhGAA, their influence on clinical progression is not completely known. We studied the impact of anti-rhGAA antibodies on clinical progression of 25 ERT treated patients. We evaluated patients at visit 0 and, after 1 year, at visit 1. We performed several muscle function tests, conventional spirometry and quantitative muscle MRI (qMRI) using 3-point Dixon analysis of thigh muscles at both visits. We also obtained serum samples at both visits and anti-rhGAA antibodies were quantified using ELISA. Antibody titers higher than 1:200 were identified in 18 patients (72%) of our cohort. Seven patients (28%) did not develop antibodies (0 to < 1:200), 17 patients (68%) developed low to intermediate titers (1:200 to < 1:31,200) and 1 patient (4%) developed high titers ( > 1:31,200). We analyzed the effect of low and intermediate antibody titers in clinical and radiological progression. There were no differences between the results of muscle function tests, spirometry or fat fraction analyzed using qMRI between patients with and without antibodies groups at baseline. Moreover, antibody titers did not influence muscle function test, spirometry results or qMRI results at year 1 visit. Most of the LOPD patients developed antibodies against ERT that persisted over time at low or intermediate levels. However, antibodies at these low and intermediate titers might not influence clinical response to the drug.

引用

页码：129 / 136

页数：8

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