A Cytomegalovirus Peptide-Specific Antibody Alters Natural Killer Cell Homeostasis and Is Shared in Several Autoimmune Diseases

• An antibody against the hCMV Pp150 protein is shared in patients with autoimmune diseases
• Anti-Pp150 recognizes CIP2A on CD56bright NK cells and induces cell death
• The percentage of circulating CD56bright NK cells is reduced in autoimmune disease patients
• CD56bright NK cell number is negatively correlated with anti-Pp150 levels

SummaryHuman cytomegalovirus (hCMV), a ubiquitous beta-herpesvirus, has been associated with several autoimmune diseases. However, the direct role of hCMV in inducing autoimmune disorders remains unclear. Here we report the identification of an autoantibody that recognizes a group of peptides with a conserved motif matching the Pp150 protein of hCMV (anti-Pp150) and is shared among patients with various autoimmune diseases. Anti-Pp150 also recognizes the single-pass membrane protein CIP2A and induces the death of CD56bright NK cells, a natural killer cell subset whose expansion is correlated with autoimmune disease. Consistent with this finding, the percentage of circulating CD56bright NK cells is reduced in patients with several autoimmune diseases and negatively correlates with anti-Pp150 concentration. CD56bright NK cell death occurs via both antibody- and complement-dependent cytotoxicity. Our findings reveal that a shared hCMV-induced autoantibody is involved in the decrease of CD56bright NK cells and may thus contribute to the onset of autoimmune disorders.

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