To study the role of the antibody response to HSV1, and profile the antibody-mediated innate immunity functions that will track periphHSV, HE and postHE-AE. 

Herpes simplex virus 1 (HSV1) establishes lifelong latency in trigeminal ganglia and can reactivate causing peripheral manifestations (periphHSV; e.g. recurrent cold sore), or encephalitis (HE). HE can be complicated by autoimmune encephalitis associated with neuronal cell-surface antibodies (postHE-AE). The role of the immune system in controlling HSV1 reactivation and the mechanisms of HSV1-triggered autoimmunity remain unclear.

We profiled HSV1-specific antibody functions in serum of patients with periphHSV or HE (with or without postHE-AE) examining Antibody-Dependent Cellular Phagocytosis (ADCP), Neurotrophil Phagocytosis (ADNP), Complement Deposition (ADCD) and Cellular (NK-cells) Cytotoxicity (ADCC).

We included 22 patients with HE from a longitudinal cohort (Spanish study; samples available at encephalitis onset, day 21, and day 90), and 12 patients with periphHSV from a transversal cohort (sample obtained ≥3 months after the last recurrence). At disease onset, HE showed a clearly different HSV1-specific antibody profile compared with periphHSV: titers were lower (including total IgG, IgG1 and IgG4, but not IgG2, IgG3, IgM and IgA) and significantly less functional (p<0.05) in mediating ADCP, ADNP, and ADCD, but not ADCC. During recovery from HE (day 21 and 90), antibody titers and functions improved but did not reach the level of periphHSV patients. In patients with HE, we did not observe significant differences in terms of titers, Ig classes or functions between those who developed postHE-AE (n=9) and those who did not (n=13).

HSV1-antibody responses and functions are impaired in patients with HE compared with those with periphHSV, suggesting that humoral immunity plays a crucial role in controlling virus spread to (or reactivation within) the brain. These responses do not seem to correlate with development of neuronal autoimmunity.