Disease activity in chronic inflammatory demyelinating polyneuropathy: association between circulating B-cell subsets, cytokine levels, and clinical outcomes

• Published in: Clinical and experimental immunology Vol. 215; no. 1; pp. 65 - 78
• Main Authors: Ozdag Acarli, Ayse Nur, Tuzun, Erdem, Sanli, Elif, Koral, Gizem, Akbayir, Ece, Cakar, Arman, Sirin, Nermin Gorkem, Soysal, Aysun, Aysal, Fikret, Durmus, Hacer, Parman, Yesim, Yilmaz, Vuslat
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 09.01.2024
• Subjects: B-Lymphocyte Subsets - metabolism; Cytokines - genetics; Humans; Inflammation/Inflammatory Disease; Interleukin-10 - genetics; Interleukin-6 - genetics; Leukocytes, Mononuclear - metabolism; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating - diagnosis; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating - genetics; B cell; chronic inflammatory demyelinating polyneuropathy; miRNA; cytokines; epidermal nerve fibers; skin biopsy
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1093/cei/uxad103

Chronic inflammatory demyelinating polyneuropathy (CIDP), a common and treatable autoimmune neuropathy, is frequently misdiagnosed. The aim of this study is 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. Twenty-three typical, 16 multifocal and five 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 the distal leg. We detected a 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 the 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). Altered B-cell homeostasis and IL10 and TNFA gene expression levels imply chronic antigen exposure and overactivity in the humoral immune system, and seem to be a common pathological pathway in both typical CIDP and CIDP variants.