Immune profiling of responses to influenza vaccination in patients with myeloproliferative neoplasms

Abstract

Myeloproliferative neoplasms (MPNs) are associated with immune dysregulation and increased susceptibility to infection, emphasizing the importance of vaccination for patients. This pilot study evaluated immune responses to influenza vaccination in MPN patients compared with healthy donors using mass cytometry and serology. We observed diminished CXCR5+ B-cell, CXCR3+ T-cell, activated CD127+ memory T-cell subsets, and a trend toward lower hemagglutinin inhibition titer in MPN patients. These results indicate that patients with MPN exhibit distinct responses to influenza vaccination suggestive of impaired migration to lymphoid organs and T-cell maturation which may impact the development of protective immunity.

Keywords: immunology; myeloproliferative disease; vaccines.

FIGURE 1

Workflow and major immune differences between MPN patients and Healthy controls. (A) Study design and experimental and data analysis workflow. (B) HAI titers in cohorts. Median titer for MPN is 21.3 and for Healthy 32.0. C–D) UMAP dimensionality reduction coloured (C) by major gated populations and (D) by cell density in cohorts. (E) Differentially abundant immune cell populations in cohorts. Those with multiple comparison‐adjusted p‐value < 0.05 and absolute log2 foldchange > 1 are shown in green. Those above the foldchange threshold are annotated regardless of their p‐value.

FIGURE 2

Specific immune cell differences in cohorts and correlates of immune protection. (A) Quantification of T cell subset frequencies gated for activation and migration markers CD127, CCR2 and CXCR3, in MPN patients and Healthy controls. (B) Quantification of B cell subset frequencies gated for a migration marker, CXCR5. (C) Quantification NK cells gated for a maturation marker, CD57, and monocyte subsets and dendritic cells gated for an activation marker, CD11b. (D) Characterisation of Lin‐populations in MPN and Healthy, gated for immune markers: HLA‐DR, CD45RA and CD123. Adjusted p‐values: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. (E) Correlates of immune protection, as measured by HAI titers. Waterfall plot depicts linear regression coefficients for gated immune populations, selected by elastic net regularisation. Colour scheme refers to B, T or innate parent cell population with B cell gates in blue, T cell gates in red and innate cell gates in green. * denote populations gated with functional markers.