Disease Activity in Chronic Inflammatory Demyelinating Polyneuropathy: Association Between Circulating B Cell Subsets, Cytokine Levels and Clinical Outcomes
Ayse Nur Ozdag Acarli, Erdem Tuzun, Elif Sanli, Gizem Koral, Ece Akbayir, Arman Cakar, Nermin Gorkem Sirin, Aysun Soysal, Fikret Aysal, Hacer Durmus, Yesim Parman, Vuslat Yilmaz- Immunology
- Immunology and Allergy
Abstract
Objective
To evaluate the relationship between immunological markers and clinical outcome measures in a mixed cohort of patients with typical CIDP and CIDP variants at different disease stages.
Methods
Twenty-three typical, 16 multifocal and 5 distal CIDP patients were included. Twenty-five sex and age-matched healthy controls and 12 patients with Charcot-Marie-Tooth type 1A (CMT1A) disease served as controls. Peripheral B-cell populations were analyzed by flow cytometry. IL6, IL10, TNFA mRNA and mir-21, mir-146a and mir-155-5p expression levels were evaluated by real-time polymerase chain reaction in Peripheral blood mononuclear cells (PBMC) and/or skin biopsy specimens. Results were then assessed for a possible association with clinical disability scores and intraepidermal nerve fiber densities (IENFD) in distal leg.
Results
We detected significant reduction in naive B-cells (p≤0.001), plasma cells (p≤0.001) and regulatory B-cells (p<0.05), and an elevation in switched memory B-cells (p≤0.001) in CIDP compared to healthy controls. CMT1A and CIDP patients had comparable B-cell subset distribution. CIDP cases had significantly higher TNFA and IL10 gene expression levels in PBMC compared to healthy controls (p<0.05 and p≤0.01, respectively). IENFDs in distal leg showed a moderate negative correlation with switched memory B-cell ratios (r=-0.51, p<0.05) and a moderate positive correlation with plasma cell ratios (r=0.46, p<0.05). INCAT sum scores showed a moderate positive correlation with IL6 gene expression levels in PBMC (r=0.54, p<0.05).
Discussion
Altered B-cell homeostasis and IL10 and TNFA gene expression levels imply chronic antigen exposure and overactivity in humoral immune system, and seem to be a common pathological pathway in both typical CIDP and CIDP variants.