Mononuclear phagocytes in blood and cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis: Untreated and treated with anti-CD20 therapy.

BACKGROUND

Mononuclear phagocytes, including monocytes, macrophages, and microglia, play key roles in the immunopathogenesis of multiple sclerosis (MS). While anti-CD20 monoclonal antibody therapies effectively treat relapsing-remitting MS (RRMS), their secondary effects on mononuclear phagocytes remain unclear.

OBJECTIVE AND

METHODS

We analyzed blood and cerebrospinal fluid (CSF) mononuclear phagocytes in patients with RRMS treated with anti-CD20 therapy for 6 months, untreated patients, and controls. Flow cytometry was used to assess the prevalence, phenotype, and cytokine production by blood monocytes. Chitinase-1 (CHIT1) levels in CSF were measured using an enzyme-linked immunosorbent assay.

RESULTS

Blood monocyte frequencies were elevated in untreated and anti-CD20-treated RRMS patients compared with controls. CSF mononuclear phagocytes differed from blood monocytes and were classified as either CD16+ or CD16-, with CD16+ mononuclear phagocytes being enriched in all groups. However, the frequencies of CD16- mononuclear phagocytes in CSF were higher in untreated and anti-CD20-treated RRMS patients compared to controls, and the expression of CD206 and CCR2 on CD16- mononuclear phagocytes differed between untreated patients and controls. Blood monocyte cytokine production did not differ between untreated and anti-CD20-treated patients. CSF CHIT1 levels were elevated in both untreated and anti-CD20-treated patients.

CONCLUSIONS

The comparable blood and CSF mononuclear phagocyte phenotypes, along with persistently elevated CHIT1 concentrations in CSF of untreated and anti-CD20-treated patients with RRMS, suggest that residual innate immune activation is not normalized by 6 months of anti-CD20 treatment.