Ranger A, Ray S, Szak S, Dearth A, Allaire N, Murray R, Gardner R, Cadavid D and Mi S.

Neurology(R) neuroimmunology & neuroinflammation. 2018;5:e417.

DOI: 10.1212/NXI.0000000000000417

Abstract

Objective:

To evaluate whether the anti-LINGO-1 antibody has immunomodulatory effects.

Methods:

Human peripheral blood mononuclear cells (hPBMCs), rat splenocytes, and rat CD4⁺ T cells were assessed to determine whether LINGO-1 was expressed and was inducible. Anti-LINGO-1 Li81 (0.1–30 μg/mL) effect on proliferation/cytokine production was assessed in purified rat CD4⁺ T cells and hPBMCs stimulated with antibodies to CD3 +/– CD28. In humans, the effect of 2 opicinumab (anti-LINGO-1/BIIB033; 30, 60, and 100 mg/kg) or placebo IV administrations was evaluated in RNA from blood and CSF samples taken before and after administration in phase 1 clinical trials; paired samples were assessed for differentially expressed genes by microarray. RNA from human CSF cell pellets was analyzed by quantitative real-time PCR for changes in transcripts representative of cell types, activation markers, and soluble proteins of the adaptive/innate immune systems. ELISA quantitated the levels of CXCL13 protein in human CSF supernatants.

Results:

LINGO-1 is not expressed in hPBMCs, rat splenocytes, or rat CD4⁺ T cells; LINGO-1 blockade with Li81 did not affect T-cell proliferation or cytokine production from purified rat CD4⁺ T cells or hPBMCs. LINGO-1 blockade with opicinumab resulted in neither significant changes in immune system gene expression in blood and CSF, nor changes in CXCL13 CSF protein levels (clinical studies).

Conclusions:

These data support the hypothesis that LINGO-1 blockade does not affect immune function.