Outbreaks of Dengue virus (DENV) infection and most recently Chikungunya (CHKV) and Zika virus (ZIKV) infection emerged in Latin America in 2014 and 2015. Along with these outbreaks, an increased incidence of Guillain-Barré syndrome (GBS) was observed. Although the factors associated with such increase remain unknown, it is believed these viruses play critical roles in pathogenesis of GBS.  We investigated whether patterns of specific antibody responses were associated with cases of GBS observed during and after the 2016 Zika epidemic in Colombia.

Comprehensive phage display libraries encoding all peptides from known viruses (VirScan) and arboviruses (ArboScan) were used for an unbiased screening of sera from patients with ZIKV-associated GBS (ZIKV-GBS, n= 28) and non-neurological ZIKV infection (NN-ZIKV n=30) collected during the 2016 ZIKV epidemic period, non-ZIKV-related GBS cases (n=27), 9 of them from the epidemic and 18 post-epidemic periods). Sera from DENV cases (n=10) collected previous to the outbreak of Zika in Colombia were also studied. In both ZIKV-GBS and non-ZIKV GBS cases, paired CSF/sera were also analyzed.

ZIKV-GBS cases exhibited a similar profile of anti-ZIKV peptide responses as compared with NN-ZIKV infection. Interestingly, ZIKV-GBS cases displayed a striking pattern of anti-DENV peptide antibodies as compared with NN-ZIKV and other GBS cases.  The pattern of anti-DENV antibody response targeted specifically peptides of the E protein of DENV-1 and to a lesser extent, other dengue serotypes.  We did not detect significant differences in the antibody response to other viruses previously implicated in GBS (e.g., CHIKV, EBV, CMV) between the GBS and non-GBS ZIKV-infected individuals.

Specific anti-viral responses in ZIKV-GBS cases showed an increased reactivity against peptides of the E protein of DENV, a finding that suggests such individuals had a previous DENV exposure supporting a potential pathogenic role of prior DENV infection in causing ZIKV-GBS.