BAFF is a marker of hypogammaglobulinemia, neuroaxonal damage and inflammation in multiple sclerosis patients on ocrelizumab

Sep 29, 2026

Uploaded by Ben

Serum biomarker testing in multiple sclerosis is expanding, yet evidence remains limited on how disease-modifying therapy alters serum biomarker levels and how to interpret them per patient. This retrospective cohort study evaluated correlations between clinical variables and serum biomarker profiles in MS patients undergoing anti-CD20 treatment with ocrelizumab. Using the Octave MSDA panel (18 biomarkers) plus immunoglobulin longitudinal data analyzed with R, results link elevated BAFF to B-cell activation-related immunoglobulin changes and to neuroaxonal injury and inflammatory markers without recent acute activity.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Background and objectives

Methods

Results

Discussion

Introduction

Serum biomarkers and the Octave MSDA panel

Impact and rationale for anti-CD20 therapy

Methods

Study design and patient selection

Chumakova et al. Journal of Neuroinflammation (2026) 23:2 Journal of Neuroinflammation [https://doi.org/10.1186/s12974-025-03632-y](https://doi.org/10.1186/s12974-025-03632-y) RESEARCH Open Access BAFF is a marker of hypogammaglobulinemia, neuroaxonal damage and inflammation in multiple sclerosis patients on ocrelizumab Anastasia Chumakova 1*, Lauren McKay 1, Victoria Fleming 1, Michael Demetriou 1 and Michael Sy 1 Abstract Background and objectives Serum biomarker testing for multiple sclerosis has been increasing in popularity in research and clinical practice. Little evidence is available on influences of disease modifying therapy on serum biomarker levels. Interpretation of clinically available serum biomarkers in the context of each individual patient poses a greater challenge in this context. This study focuses on correlations between clinical variables and unique profile of serum biomarkers in the context of anti-CD20 treatment by ocrelizumab. Methods A cohort of multiple sclerosis patients without relapse in the last 12 months and the following 3 months who received serum biomarker testing with the Octave MSDA (Multiple Sclerosis Disease Activity) panel of 18 biomarkers between June 2023 and June 2024 was identified at the UCI Multiple Sclerosis Center. Clinical data was collected retrospectively. Data preparation, analysis and visualization were performed using R. Results A total of 118 MS patients without recent acute inflammatory activity were included (63 untreated and 55 onocrelizumab) . Longitudinal immunoglobulin data were available for 48 patients receiving ocrelizumab. Age-adjusted analyses revealed significantly elevated B-cell activating factor (BAFF) levels in the ocrelizumab group. In these patients, BAFF correlated inversely with IgG and IgA—but not IgM—levels. IgG declined over time in patients treated with ocrelizumab, with higher BAFF levels predicting lower IgG and IgA independent of treatment duration. Patients with elevated BAFF exhibited both lower baseline IgG and a more rapid IgG decline compared to those with lower BAFF. Elevated BAFF also correlated positively with markers of neuroaxonal injury, including neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP), Myelin oligodendrocyte glycoprotein (MOG), as well as with multiple pro-inflammatory biomarkers such as osteopontin (OPN), CXCL9, CXCL13, CCL20, TRAIL-R1, and CDCP1 . Discussion This study provides insight into unique biomarker profile in patients on ocrelizumab. Increased BAFF was associated with lower IgG and IgA levels, biomarkers of neuroaxonal damage and inflammation in MS patients without recent acute inflammatory activity on ocrelizumab. *Correspondence: Anastasia Chumakova [chumakoa@hs.uci.edu](chumakoa@hs.uci.edu) 1Department of Neurology, University of California, Irvine, CA, USA © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. Chumakova et al. Journal of Neuroinflammation (2026) 23:2 Introduction Serum biomarkers are increasingly integrated into both research and clinical management of multiple sclerosis (MS), offering the potential to no

FAQs

What was the study’s main goal regarding serum biomarkers in MS?

To determine how treatment-related changes, specifically anti-CD20 therapy with ocrelizumab, influence serum biomarker levels and their clinical interpretability in MS patients without recent acute inflammatory activity.

How did BAFF levels differ between ocrelizumab-treated and untreated patients?

Age-adjusted analyses showed significantly elevated BAFF levels in the ocrelizumab group.

Which biomarkers were associated with BAFF, and what patterns were observed?

BAFF correlated inversely with IgG and IgA (not IgM) and was associated positively with neuroaxonal injury markers such as sNfL and GFAP, along with multiple pro-inflammatory biomarkers including OPN, CXCL9, CXCL13, CCL20, TRAIL-R1, and CDCP1.

Sep 29, 2026

Uploaded by Ben