Background/Purpose: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterized by abrupt onset of obsessive-compulsive disorder (OCD) and/or food restriction with other specified neuropsychiatric symptoms.  65% of PANS patients undergo repeated episodes of flare and remission and 20% develop a chronic-static illness. In 2015, Frankovich reported monocytosis during PANS. We have followed up this observation by characterizing monocytes in active and inactive PANS.

Methods: To understand the role of monocytes in PANS, we compared the monocyte subsets in relapsing/remitting (n = 8) and chronic-static (n = 7) PANS patients with age- and sex-matched healthy controls (n = 8). We developed a novel antibody panel focused on markers likely associated with brain homing. We also profiled the circulatory dendritic cell populations in PANS patients.

Results: Human monocytes in blood can be divided into 3 subsets, the largest (~85%) being CD14⁺CD16^– “classical” monocytes. We found that CD14⁺ monocytes were increased in all PANS flare samples and reduced during remission. We found a lower frequency of CD14⁺CCR2⁺CX3CR1⁺VLA-4⁺CD166⁺ cells during PANS flare versus remission. CSF from new acute-onset PANS contained CD14⁺ monocytes with these markers, suggesting an increased extravasation of these monocytes across the BBB. These monocytes were increased in frequency in blood samples from PANS remission, suggesting they may have an immunosuppressive function. In chronic-static PANS patients, the frequency of these monocytes in the circulation was low, and they were undetectable in CSF, suggesting low production during chronic PANS patients. Incubation of healthy PBMC with plasma from PANS flare led to an increase in the expression of CCR2, CX3CR1, VLA-4, Iba1, and HLA-DR, suggesting soluble mediators drive this phenotype. Additionally, we found an increase in circulating, inflammatory monocytic DC (CD14⁺CD11c⁺CD209⁺) in PANS flare, suggesting this myeloid cell type contributes to inflammation.

Conclusion: Together, our data support a model in which myeloid cell subsets contribute to persistence and suppression of PANS brain inflammation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pediatric-acute-onset-neuropsychiatric-syndrome-pans-is-characterized-by-a-novel-subset-of-monocytes-with-markers-associated-with-crossing-the-blood-brain-barrier-bbb/