TY - JOUR
T1 - A differential sex-specific pattern of IgG2 and IgG4 subclasses of anti-drug antibodies (ADAs) induced by glatiramer acetate in relapsing-remitting multiple sclerosis patients
AU - Avila, Sandra
AU - Guerrero-García, José de Jesús
AU - Becerril-Villanueva, Enrique
AU - Pérez-Sánchez, Gilberto
AU - Pavón, Lenin
AU - Rojas-Mayorquín, Argelia E.
AU - Mireles-Ramírez, Mario Alberto
AU - Muñoz-Valle, José Francisco
AU - Vallejo-Castillo, Luis
AU - Medina-Rivero, Emilio
AU - Ortuño-Sahagún, Daniel
AU - Pérez-Tapia, Sonia Mayra
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/9
Y1 - 2019/9
N2 - Background: Glatiramer acetate (GA) is a drug for Multiple Sclerosis (MS) treatment. However, its administration induces anti-drug antibodies (ADA). This research evaluated the sex differences in humoral response against GA in RR-MS patients Methods: We analyzed 69 RR-MS patients, 43 treated with GA and 26 treated with IFN-β. In all cases, the serum concentration of IgG antibodies was determined by UPLC, whereas the levels of IgG subclasses (1–4) of anti-GA antibodies and the concentration of IL-6 were detected by Multiplex and IL-10, and IFN-γ were detected by ELISA. Results: The total concentration of IgG antibodies in patients did not differ between treatments, whereas the IgG levels of ADA were higher in male and female patients treated with GA (P ≤ 0.0001). The subclasses of IgG anti-GA antibodies were as follows: IgG4>>IgG3>IgG1>IgG2. Statistical analysis showed differences in the IgG2 (P ≤ 0.01) and IgG4 (P ≤ 0.0001) subclasses by sex in RR-MS patients. Levels of IgG1 subclass in male patients correlated positively with the circulatory levels of IL-6 (rs = 0.587, P ≤ 0.04) and IFN-γ (rs = 0.721, P ≤ 0.001), while IgG2 subclass levels in female patients correlated with serum levels of IFN-γ (rs = 0.628, P ≤ 0.0006). Statistical analysis did not detect correlations between the levels of IgG (1–4) subclasses of anti-GA antibodies and the evaluated clinical parameters. Conclusion: This study showed differences in the levels of IgG2 and IgG4 subclasses of ADA between male and female RR-MS patients. Further studies are necessary to take advantage of the clinical potential of this finding.
AB - Background: Glatiramer acetate (GA) is a drug for Multiple Sclerosis (MS) treatment. However, its administration induces anti-drug antibodies (ADA). This research evaluated the sex differences in humoral response against GA in RR-MS patients Methods: We analyzed 69 RR-MS patients, 43 treated with GA and 26 treated with IFN-β. In all cases, the serum concentration of IgG antibodies was determined by UPLC, whereas the levels of IgG subclasses (1–4) of anti-GA antibodies and the concentration of IL-6 were detected by Multiplex and IL-10, and IFN-γ were detected by ELISA. Results: The total concentration of IgG antibodies in patients did not differ between treatments, whereas the IgG levels of ADA were higher in male and female patients treated with GA (P ≤ 0.0001). The subclasses of IgG anti-GA antibodies were as follows: IgG4>>IgG3>IgG1>IgG2. Statistical analysis showed differences in the IgG2 (P ≤ 0.01) and IgG4 (P ≤ 0.0001) subclasses by sex in RR-MS patients. Levels of IgG1 subclass in male patients correlated positively with the circulatory levels of IL-6 (rs = 0.587, P ≤ 0.04) and IFN-γ (rs = 0.721, P ≤ 0.001), while IgG2 subclass levels in female patients correlated with serum levels of IFN-γ (rs = 0.628, P ≤ 0.0006). Statistical analysis did not detect correlations between the levels of IgG (1–4) subclasses of anti-GA antibodies and the evaluated clinical parameters. Conclusion: This study showed differences in the levels of IgG2 and IgG4 subclasses of ADA between male and female RR-MS patients. Further studies are necessary to take advantage of the clinical potential of this finding.
KW - ADA
KW - Glatiramer acetate
KW - IgG2
KW - IgG4
KW - Male and female differences
UR - http://www.scopus.com/inward/record.url?scp=85068063312&partnerID=8YFLogxK
U2 - 10.1016/j.msard.2019.06.021
DO - 10.1016/j.msard.2019.06.021
M3 - Artículo
C2 - 31272071
AN - SCOPUS:85068063312
SN - 2211-0348
VL - 34
SP - 92
EP - 99
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
ER -