Intrathecal cytokine profile in neuropathy with anti-neurofascin 155 antibody

Objective: To characterize the CSF cytokine profile in chronic inflammatory demyelinating polyneuropathy (CIDP) patients with IgG4 anti-neurofascin 155 (NF155) antibodies (NF155⁺ CIDP) or those lacking anti-NF155 antibodies (NF155⁻ CIDP). Methods: Twenty-eight CSF cytokines/chemokines/growth factors were measured by multiplexed fluorescent immunoassay in 35 patients with NF155⁺ CIDP, 36 with NF155⁻ CIDP, and 28 with non-inflammatory neurological disease (NIND). Results: CSF CXCL8/IL-8, IL-13, TNF-α, CCL11/eotaxin, CCL2/MCP-1, and IFN-γ were significantly higher, while IL-1β, IL-1ra, and G-CSF were lower, in NF155⁺ CIDP than in NIND. Compared with NF155⁻ CIDP, CXCL8/IL-8 and IL-13 were significantly higher, and IL-1β, IL-1ra, and IL-6 were lower, in NF155⁺ CIDP. CXCL8/IL-8, IL-13, CCL11/eotaxin, CXCL10/IP-10, CCL3/MIP-1α, CCL4/MIP-1β, and TNF-α levels were positively correlated with markedly elevated CSF protein, while IL-13, CCL11/eotaxin, and IL-17 levels were positively correlated with increased CSF cell counts. IL-13, CXCL8/IL-8, CCL4/MIP-1β, CCL3/MIP-1α, and CCL5/RANTES were decreased by combined immunotherapies in nine NF155⁺ CIDP patients examined longitudinally. By contrast, NF155⁻ CIDP had significantly increased IFN-γ compared with NIND, and exhibited positive correlations of IFN-γ, CXCL10/IP-10, and CXCL8/IL-8 with CSF protein. Canonical discriminant analysis of cytokines/chemokines revealed that NF155⁺ and NF155⁻ CIDP were separable, and that IL-4, IL-10, and IL-13 were the three most significant discriminators. Interpretation: Intrathecal upregulation of type 2 helper T (Th2) cell cytokines is characteristic of IgG4 NF155⁺ CIDP, while type 1 helper T cell cytokines are increased in CIDP regardless of the presence or absence of anti-NF155 antibodies, suggesting that overproduction of Th2 cell cytokines is unique to NF155⁺ CIDP.