Spinal fluid antibodies against multiple sclerosis candidate bacteria in demyelinating disease

Eckman, E.; Laman, J.; Fischer, K.; Lopansri, B.; Martins, T.; Hill, H.; Kriesel, J. D.

A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases (DD). Selection of the anti-microbial ELISA assays was guided by previous RNA sequencing studies that established a multiple sclerosis (MS) microbial candidate list. Microbial antigens included on the ELISA panel were derived from Akkermansia muciniphila, Atopobium vaginae, Bacteroides fragilis, Lactobacillus paracasei, Odoribacter splanchnicus, Pseudomonas aeruginosa, Cutibacterium (Propionibacterium) acnes, Fusobacterium necrophorum, Porphyromonas gingivalis, and Streptococcus mutans. Spinal fluid responses from patients with demyelinating diseases (DD, N=14) were compared to those with other neurological diseases (OND, N=8), and non-MS (Control, N=13) control patients. Commercial positive and negative control CSF specimens were run with each assay. ELISA Index values were derived for each specimen against each of the 10 bacterial antigen preparations. Intrathecal production of anti-microbial antibodies was assessed by comparing CSF and comparably diluted serum. CSF reactivity was significantly higher in the DD group compared to the controls against Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Four of the 11 tested DD group subjects had elevated antibody indexes against at least one of the 10 bacterial antigens, suggesting intrathecal production of anti-bacterial antibodies. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes may contribute to demyelination in some patients.