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

Mult Scler Relat Disord. 2019 Sep:34:92-99. doi: 10.1016/j.msard.2019.06.021. Epub 2019 Jun 18.

Abstract

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.

Keywords: ADA; Glatiramer acetate; IgG2; IgG4; Male and female differences.

MeSH terms

  • Adult
  • Female
  • Glatiramer Acetate / therapeutic use*
  • Humans
  • Immunoglobulin G / blood*
  • Immunosuppressive Agents / therapeutic use*
  • Interferon-gamma / blood
  • Male
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Multiple Sclerosis, Relapsing-Remitting / therapy*
  • Sex Characteristics*

Substances

  • Immunoglobulin G
  • Immunosuppressive Agents
  • Glatiramer Acetate
  • Interferon-gamma