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Int J Mol Sci. 2017 Oct 12;18(10). pii: E2127. doi: 10.3390/ijms18102127.

The Immunogenicity of Branded and Biosimilar Infliximab in Rheumatoid Arthritis According to Th9-Related Responses.

Author information

1
Department of Rheumatology, Azienda Ospedaliera-Polo Universitario Luigi Sacco, Milan 20157, Italy. rossella.talotta@asst-fbf-sacco.it.
2
Department of Biomedical and Clinical Sciences, Azienda Ospedaliera-Polo Universitario Luigi Sacco, Milan 20157, Italy. angyberzi@gmail.com.
3
Department of Rheumatology, University of Padua, Padua 35100, Italy. adoria@unipd.it.
4
Department of Rheumatology, Azienda Ospedaliera-Polo Universitario Luigi Sacco, Milan 20157, Italy. alberto.batticciotto@hsacco.it.
5
Department of Rheumatology, Azienda Ospedaliera-Polo Universitario Luigi Sacco, Milan 20157, Italy. mariachiara.ditto@hsacco.it.
6
Department of Rheumatology, Azienda Ospedaliera-Polo Universitario Luigi Sacco, Milan 20157, Italy. atzenifabiola@gmail.com.
7
Department of Rheumatology, Azienda Ospedaliera-Polo Universitario Luigi Sacco, Milan 20157, Italy. sarzi@tiscali.it.
8
Department of Biomedical and Clinical Sciences, Azienda Ospedaliera-Polo Universitario Luigi Sacco, Milan 20157, Italy. daria.trabattoni@unimi.it.

Abstract

Our objective was to evaluate the immunogenicity of branded and biosimilar infliximab by detecting changes in T-helper-9 (Th9) percentages induced by an in vitro stimulation test.

METHODS:

Peripheral blood mononuclear cells collected from 55 consecutive rheumatoid arthritis (RA) outpatients (15 drug free, 20 successfully treated with branded infliximab, 20 branded infliximab inadequate responders) and 10 healthy controls were cultured, with or without 50 μg/mL of infliximab originator (Remicade®) or 50 μg/mL of infliximab biosimilar (Remsima®) for 18 h. Th9 lymphocytes were identified by means of flow cytometry as PU.1 and IRF4-expressing, IL-9-secreting CD4⁺ T cells. Furthermore, the markers CCR7 and CD45RA were used to distinguish naïve from memory IL-9 producer cells.

RESULTS:

Under unstimulated conditions, the drug-free RA patients had the highest percentages of Th9 lymphocytes. Following stimulation with branded infliximab, the percentages of PU.1 and IRF4-expressing Th9 cells, CCR7⁺, CD45RA- (central memory) and CCR7-, CD45RA- (effector memory) cells significantly increased in the group of inadequate responders, but no significant variation was observed after exposure to the biosimilar of infliximab.

CONCLUSIONS:

Th9 cells seem to be involved in the immune response to the epitopes of branded, but not biosimilar, infliximab, and this may depend on the recall and stimulation of both central and effector memory cells.

KEYWORDS:

Th9 lymphocytes; biosimilars; infliximab; rheumatoid arthritis

PMID:
29023386
PMCID:
PMC5666809
DOI:
10.3390/ijms18102127
[Indexed for MEDLINE]
Free PMC Article

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