Research ArticleClinical Studies
Open Access

B-Cell and T-Cell Populations in Peripheral Blood Linked to Ocrelizumab Treatment Efficacy in Multiple Sclerosis

ECE AKBAYIR, TUGCE KIZILAY, RUZIYE EROL, DUYGU OZKAN-YASARGUN, ERDEM TUZUN, VUSLAT YILMAZ and RECAI TÜRKOGLU
In Vivo March 2025, 39 (2) 1162-1172; DOI: https://doi.org/10.21873/invivo.13920

Abstract

Background/Aim: Ocrelizumab, a CD20-targeting monoclonal antibody, is used for treatment of multiple sclerosis. The aim of this study was to explore the utility of peripheral blood cell subsets in prediction of treatment response to ocrelizumab in relapsing remitting multiple sclerosis (RRMS).

Patients and Methods: Thirty-one patients with RRMS resistant to first-line immunomodulating agents were enrolled and followed-up for 12 months under ocrelizumab treatment. Disease activity was monitored by 6-monthly assessments of Expanded Disability Status Scale and cranial-spinal magnetic resonance imaging. No evidence of disease activity (NEDA-3) status was determined, and peripheral blood mononuclear cells were immunophenotyped by flow cytometry.

Results: Peripheral blood populations of CD19+ B-cells, plasma cells and CD3+ CD20+ T-cells decreased under ocrelizumab therapy, whereas populations of switched memory B-cells, CD4+ T-cells, naïve T-cells and regulatory B-1a and CD49d+ T-cells were increased. NEDA-3 status was achieved by 19 patients, who exhibited elevated baseline populations of regulatory CD49d+ T- and B-1a-cells, reduced post-treatment (month 6 or 12) populations of switched memory B-cells, and increased post-treatment populations of naïve T-cells. Month 12 Expanded Disability Status Scale scores correlated positively with plasmablast and naïve T-cell populations.

Conclusion: Response to ocrelizumab is linked to baseline regulatory and post-treatment effector B- and T-cell subset populations. Memory B-cells appear to be a marker of treatment efficacy for ocrelizumab.

Keywords:

Introduction

Multiple sclerosis (MS) is a common autoimmune demyelinating disease of the central nervous system ultimately inducing permanent brain atrophy and neurological disability (1). Monoclonal antibodies targeting the CD20 molecule have proven effective in both relapsing remitting (RRMS) and primary progressive forms of MS through depletion of B-cells in peripheral blood and brain. The therapeutic use of ocrelizumab, a humanized monoclonal antibody targeting the CD20 molecule, has been approved in both RRMS and primary progressive forms (2).

Previous studies have shown that ocrelizumab not only suppresses effector B-cells but also modulates non-B-cell subpopulations to adopt a more tolerogenic status, and repopulates regulatory cells (3, 4). Nevertheless, around 30% of patients with RRMS under ocrelizumab treatment show disease activity through inflammatory lesions on magnetic resonance imaging (MRI), disability worsening, and relapses (5). Therefore, studies exploring the clinical and immunological variables associated with treatment efficacy of ocrelizumab are required, especially for active forms of MS.

In a previous study, we showed that ocrelizumab-treated patients with RRMS with a less than 30% reduction in baseline cerebrospinal fluid neurofilament light chain levels were more likely to show evidence of disease activity (EDA) in a 24-month follow-up period (6). In other studies, failure to exhibit reduced total peripheral blood B-cells, tumor necrosis factor-producing B-cells, plasmablasts, and CD4- and CD8-positive T-cell populations under ocrelizumab treatment were found to be associated with suboptimal response to ocrelizumab (5, 7, 8).

However, most previous determinators of ocrelizumab efficacy have been described in progressive forms of MS and only a narrow band of peripheral blood cell subsets have been investigated. In this study, to explore the mechanisms and potential immunological predictors associated with favorable response to ocrelizumab in RRMS, we investigated possible associations between peripheral blood subset populations and no evidence of disease activity (NEDA) in MS.

Patients and Methods

Patients. In this prospective study, 31 consecutive patients with RRMS (as per the revised McDonald criteria) (9), non-responding to interferon-beta and fingolimod treatment, were enrolled. Patients were selected based on not having had a relapse in the previous 4 months and not having been treated with immunosuppressive or immunomodulating agents in the previous 3 months. NEDA-3 was determined as the absence of clinical relapse, MRI evidence of disease activity and disability worsening in the 12-month follow-up period. Patients with progressive MS, coexisting autoimmune diseases, malignancy, pregnancy, history of previous ocrelizumab treatment and clinically active infections were excluded. Twelve age-/sex-matched healthy individuals were also enrolled as a control group.

Enrolled patients received ocrelizumab treatment (600 mg as an intravenous infusion every 6 months) for 12 months. All patients tolerated the treatment without serious adverse events and there were no drop-outs. Patients were evaluated at 6-monthly follow-up visits (baseline or month 0, month 6 and month 12) through neurological examination, contrast-enhanced cranial and spinal MRI, and Expanded Disability Status Scale (EDSS) assessments. The number of attacks and EDSS before ocrelizumab commencement, as well as the number of attacks, EDSS scores and MRI lesions under ocrelizumab treatment were documented (Table I). Blood samples were obtained at each follow-up visit and the month 0 blood sample was drawn before the first administration of ocrelizumab.

The study protocol was approved by the Istanbul Medical Faculty Clinical Research Ethics Committee (Protocol number: 2022/364, Reference number: E-29624016-050.99-801997) and all the participants provided their written informed consent prior to any study-related procedure. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki.

Immunophenotyping. Blood samples were collected from participants between 08:00 and 10:00 a.m. Peripheral blood mononuclear cells were isolated using Ficoll density-gradient centrifugation, then aliquoted at a density of 1×106 per cryovial in freezing media (fetal bovine serum with 10% dimethyl sulfoxide) and stored in liquid nitrogen. After thawing, cells were washed in complete medium at 1800 rpm at + 4°C for 10 minutes. The cells were then incubated with fluorescently labeled monoclonal antibodies: anti-human CD25-APC, CD45RA-fluorescein isothiocyanate (FITC), CD49d-phycoerythrin (PE)/Cyanine5, CD197 (CCR7)-PE/Cyanine5, CD19-APC (BD Biosciences, Franklin Lakes, NJ, USA), CD5-PE/Cyanine5, CD183 (CXCR3)-PE/Cyanine5, CD3-Alexa Fluor 700, and CD20-APC/Cyanine7 (BD Pharmingen, Franklin Lakes, NJ, USA); CD4-BV785, CD8-BV510, CD27-BV711, CD127-BV421, CD24-BV421, IgD-APC/Cyanine7, CD38-Alexa Fluor 700, CD138-BV510, CD196 (CCR6)-BV711, CD185 (CXCR5)-APC/Cyanine7, and CD279 PD1-BV650 (Biolegend, San Diego, CA, USA) for 20 min at room temperature in the dark. Following incubation, cells were washed with phosphate-buffered saline and analyzed using Cytek Aurora (Cytek® Biosciences, Fremont, CA, USA) instrument. Data analysis was performed using SpectroFlo 3.2.1 (Cytek® Biosciences).

View this table:
Table I.

Comparison of clinical and immunological features of patients with no evidence of disease activity-3 (NEDA-3) and evidence of disease activity-3 (EDA-3) under ocrelizumab treatment (OCR).

Statistical analysis. Multiple-group comparisons for peripheral blood immune cell subsets were conducted by analysis of variance and Tukey’s post-hoc test, whereas two-group comparisons were carried out using Mann–Whitney U-, chi-square and Student’s t-test, as required. Correlation studies were conducted with Pearson’s correlation test. Differences or associations with p<0.05 were considered as statistically significant.

Results

Impact of ocrelizumab on B-cell subset populations. Under ocrelizumab treatment, the ratio of CD19+ B-cells decreased significantly from baseline to 6 and 12 months. In contrast, CD19+ CD5+ regulatory B-1a cells exhibited a marked increase at 6 and 12 months compared to baseline and healthy controls. Furthermore, CD19+ CD27+ IgD− switched memory B-cell populations increased at 6 and 12 months relative to baseline and healthy controls. On the other hand, CD19+ CD27+ IgD+ unswitched memory B-cells, which contribute to primary immune responses, did not show significant changes. The proportion of CD19+ CD38+ CD138+ plasma cells, key players in sustained antibody secretion, were significantly suppressed at 12 months compared to healthy controls. Naive B-cells (CD19+ CD27− IgD+) significantly increased at both 6 and 12 months compared to baseline and healthy controls. No significant changes were observed in CD19+ CD38+ CD138− plasmablasts nor CD19+ CD24hi CD38hi regulatory B-cells (Figure 1).

Impact of ocrelizumab on T-cell subset populations. CD3+ CD4+ T-helper cell populations were significantly increased at 12 months, whereas CD3+ T-cell and CD3+ CD8+ cytotoxic T-cell populations remained unchanged throughout the treatment period. The effector CD3+ CD20+ and CD3+ CD4+ CXCR3+ CCR6− T helper-1 populations were significantly reduced at 12 months compared to baseline. CD3+ CD45RA+ naive T-cell populations showed trends towards increasing during the 12-month ocrelizumab treatment. This trend attained statistical significance for CD4+ and CD8+ naïve T-cells. The regulatory T-cell subsets CD3+ CD4+ CD25+ CD127− and CD3+ CD4+ CD25hi CD49d+ cells were significantly increased as compared to baseline (Figure 2).

Association between cell subsets and disease activity. Among 31 patients with RRMS, 19 (61.3%) had NEDA-3 status under 12 months of ocrelizumab treatment. NEDA-3 and EDA-3 patients showed comparable age, age at disease onset, disease duration, baseline EDSS score and total number of attack values. EDA-3 patients had a significantly higher female to male ratio. Moreover, EDA-3 patients had significantly higher final EDSS scores, new T2 lesions and attack numbers under ocrelizumab (Table I).

NEDA-3 patients had significantly higher baseline peripheral blood populations of CD3+ CD4+ CD25hi CD49d+ regulatory T-cell and CD19+ CD5+ B-1a cell subsets. EDA-3 patients showed significantly higher CD19+ CD27++ IgD− switched memory B-cell populations at 6 months. Finally, at 12 months, NEDA-3 patients showed significantly higher CD3+ CD45RA+ naïve T-cell and CD3+ CD4+ CCR7+ CD45RA+ naïve T-helper cell populations than EDA-3 patients (Table I).

Correlation analyses showed significant correlation between month 12 EDSS score and CD19+ CD38+ CD138-plasmablast (p=0.004, R=0.564) populations. Month 6 EDSS scores were negatively correlated with CD3+ CD4+ CCR7+ CD45RA+ (p=0.003, R=−0.515) and CD3+ CD8+ CCR7+ CD45RA+(p=0.003, R=−0.602) naïve T-cell populations. There were no significant correlations between clinical and immunological parameters at baseline. Likewise, no significant correlations were found between peripheral blood cell populations and number of relapses or new T2 lesions under ocrelizumab treatment.

Discussion

In this study, we identified several new effector and regulatory B and T-cell subsets that are associated with reduced treatment efficacy in patients with MS under ocrelizumab treatment. Around two-thirds of our patients achieved NEDA-3 in a 12-month follow-up period, which is slightly lower than for previously reported cohorts (5). A possible underlying reason for this discrepancy might be that, as per the national regulations, ocrelizumab is commenced in patients with RRMS unresponsive to other immunomodulating drugs. Thus, inadvertently, the patients of our cohort were relatively aged and at a relatively advanced stage of their disease course.

Failure to achieve NEDA-3 under ocrelizumab treatment has been associated with high disease activity at baseline (7). Although clinical features of our patients with NEDA-3 and EDA-3 were statistically comparable, EDA-3 patients showed trends towards exhibiting longer disease duration and higher number of attacks at baseline, in line with the literature (5).

There were no drop-outs in our study and, as expected, patients under ocrelizumab treatment showed significantly suppressed total B-cell, plasma cell and CD3+ CD20+ cell populations, indicating good patient compliance and drug efficacy. More importantly, our results emphasize once again that ocrelizumab does not cause a global decrease in all B-cell subsets but rather reorganizes B-cell subset distribution, repopulates regulatory cell subsets, and modulates B-cell regulating factors (4, 10).

An important finding of our study was the failure of ocrelizumab to suppress effector switched memory B-cell and plasmablast subsets. Failure to suppress switched memory B-cells, essential for rapid secondary immune responses, and antibody-secreting cells is well-known for its association with reduced response to treatment in autoimmune disorders (8, 11, 12). Furthermore, tumor necrosis factor-α neutralizing infliximab and B-cell activating factor atacicept worsen MS symptoms at least partially through augmentation of memory B-cell functions (12). In agreement with these views, our patients with RRMS exhibiting higher plasmablast and memory B-cell populations under ocrelizumab treatment tended to have higher EDSS scores and EDA-3 status, respectively.

Figure 1.
Figure 1.
Figure 1.

Populations (%) of peripheral blood B-cell subtypes in patients with multiple sclerosis under 0 (baseline), 6 and 12 months (Mo) of ocrelizumab treatment and in healthy controls (HC). Mean values are indicated by a horizontal bar, error bars indicate the standard deviation. p-Values obtained by analysis of variance are denoted at the upper left corner of the panel. Significantly different by pair-wise comparison at: *p<0.05, **p<0.01, ***p<0.001 and ****p<0.0001.

Another seemingly negative effect of ocrelizumab treatment was failure to enhance regulatory B-cell populations. In contrast, ocrelizumab increased the ratio of regulatory B-1a cells, which are associated with early immune responses. Patients with higher baseline B-1a populations were more likely to achieve the NEDA-3 status, implying that this B-cell subset is involved in regulation of inflammation in MS. B-1a cells have a controversial role in autoimmunity. While B-1a cells are essential for immune tolerance, they have also been implied to contribute to inflammation in several autoimmune disorders, as well as in the animal model of MS (13-16). The impact of ocrelizumab on regulatory B-cells is relatively unknown and warrants further exploration.

CD3+ and CD4+ T-cell populations were relatively increased under ocrelizumab treatment, putatively as a natural consequence of reduced B-cell populations (5, 17). Another important finding was the increase of CD4+ and CD8+ naïve T-cell populations, which may putatively be the byproduct of reduction of anti-neuronal effector T-cell populations dedicated to autoimmunity. As a matter of fact, patients with higher naïve T-cell populations showed trends towards lower EDSS scores and higher rates of NEDA-3 status. This effect of ocrelizumab might constitute an advantage over fingolimod, which reduces both naïve and effector T-cells (18).

Figure 2.
Figure 2.
Figure 2.
Figure 2.

Populations (%) of peripheral blood T-cell subtypes in patients with multiple sclerosis under 0 (baseline), 6 and 12 months (Mo) of ocrelizumab treatment and in healthy controls (HC). Mean values are indicated by a horizontal bar, error bars indicate the standard deviation. p-Values obtained by analysis of variance are denoted at the upper left corner of the panel. Significantly different by pair-wise comparison at: *p<0.05, **p<0.01 and ***p<0.001.

Reduction of T-cells under ocrelizumab treatment has often been attributed to the suppression of CD20+ T-cells (3). Alternatively, B-cells stimulate auto-reactive T-cells through pro-inflammatory cytokine production and antigen presentation in brain parenchyma and meningeal follicles (12). Reduction of B-cells under ocrelizumab treatment might contribute to reduced B-cell-dependent T-cell proliferation and subsequently reduced autoreactive T-cell populations (19, 20).

Regulatory T-cell subsets were repopulated under ocrelizumab treatment especially at month 12, as reported (4, 21). Additionally, NEDA-3 patients exhibited significantly higher baseline CD49d+ regulatory T-cell populations than EDA-3 patients. Anti-inflammatory cytokines, such as interleukin-10 and transforming growth factor β produced by these regulatory cells might contribute to suppression of inflammation and disease severity in MS (22, 23).

Conclusion

Our findings indicate that ocrelizumab selectively modulates B- and T-cell subsets involved in both early and long-term immune responses, suggesting an impact on lymphocyte maturation and memory cell formation, which may have implications for adaptive immunity. NEDA-3 status and reduced disease activity under ocrelizumab are generally associated with increased baseline populations of regulatory B and T-cells and reduced post-treatment populations of effector B and T-cells. Failure to suppress switched memory B-cell populations appears to be a hazard for treatment efficacy of ocrelizumab in MS.

Footnotes

  • Authors’ Contributions

    Conceptualization: ET, RT and VY. Data curation: EA and VY. Formal analysis: EA and ET. Funding acquisition: RT and EA. Investigation: TK and RE. Methodology: EA and VY. Project administration: ET, RT and VY. Resources: EA and DÖY. Software: EA and DÖY. Supervision: ET, RT and VY. Validation: EA, RE and TK. Visualization: EA and VY. Writing – original draft: ET and EA. Writing - review and editing: ET and VY. All Authors have read and agreed to the published version of the manuscript.

  • Conflicts of Interest

    The Authors declare that they have no competing interests related to the study.

  • Funding

    This study was supported the Scientific Research Projects Coordination Unit of Istanbul University, Istanbul/Turkey (TDK-2023-40013, DPT-2019 K12–149071) and the Turkish Scientific and Technical Research Council (123S095).

  • Received November 25, 2024.
  • Revision received December 12, 2024.
  • Accepted December 13, 2024.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

References

  1. ↵
    1. Filippi M,
    2. Bar-Or A,
    3. Piehl F,
    4. Preziosa P,
    5. Solari A,
    6. Vukusic S,
    7. Rocca MA
    : Multiple sclerosis. Nat Rev Dis Primers 4(1): 43, 2018. DOI: 10.1038/s41572-018-0041-4
    OpenUrlCrossRefPubMed
  2. ↵
    1. Faissner S,
    2. Gold R
    : Progressive multiple sclerosis: latest therapeutic developments and future directions. Ther Adv Neurol Disord 12: 1756286419878323, 2019. DOI: 10.1177/1756286419878323
    OpenUrlCrossRefPubMed
  3. ↵
    1. Fernández-Velasco JI,
    2. Kuhle J,
    3. Monreal E,
    4. Meca-Lallana V,
    5. Meca-Lallana J,
    6. Izquierdo G,
    7. Gascón-Giménez F,
    8. Sainz de la Maza S,
    9. Walo-Delgado PE,
    10. Maceski A,
    11. Rodríguez-Martín E,
    12. Roldán E,
    13. Villarrubia N,
    14. Saiz A,
    15. Blanco Y,
    16. Sánchez P,
    17. Carreón-Guarnizo E,
    18. Aladro Y,
    19. Brieva L,
    20. Íñiguez C,
    21. González-Suárez I,
    22. Rodríguez de Antonio LA,
    23. Masjuan J,
    24. Costa-Frossard L,
    25. Villar LM
    : Effect of ocrelizumab in blood leukocytes of patients with primary progressive MS. Neurol Neuroimmunol Neuroinflamm 8(2): e940, 2021. DOI: 10.1212/NXI.0000000000000940
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Rodriguez-Mogeda C,
    2. van Lierop ZYGJ,
    3. van der Pol SMA,
    4. Coenen L,
    5. Hogenboom L,
    6. Kamermans A,
    7. Rodriguez E,
    8. van Horssen J,
    9. van Kempen ZLE,
    10. Uitdehaag BMJ,
    11. Teunissen CE,
    12. Witte ME,
    13. Killestein J,
    14. de Vries HE
    : Extended interval dosing of ocrelizumab modifies the repopulation of B cells without altering the clinical efficacy in multiple sclerosis. J Neuroinflammation 20(1): 215, 2023. DOI: 10.1186/s12974-023-02900-z
    OpenUrlCrossRefPubMed
  5. ↵
    1. Cellerino M,
    2. Boffa G,
    3. Lapucci C,
    4. Tazza F,
    5. Sbragia E,
    6. Mancuso E,
    7. Bruschi N,
    8. Minguzzi S,
    9. Ivaldi F,
    10. Poirè I,
    11. Laroni A,
    12. Mancardi G,
    13. Capello E,
    14. Uccelli A,
    15. Novi G,
    16. Inglese M
    : Predictors of ocrelizumab effectiveness in patients with multiple sclerosis. Neurotherapeutics 18(4): 2579-2588, 2021. DOI: 10.1007/s13311-021-01104-8
    OpenUrlCrossRefPubMed
  6. ↵
    1. Kızılay T,
    2. Akbayir E,
    3. Erol R,
    4. Demir AS,
    5. Özkan Yaşargün D,
    6. Yilmaz V,
    7. Tuzun E,
    8. Turkoglu R
    : Altered cerebrospinal fluid neurofilament light chain but not neurogranin levels are associated with response to ocrelizumab treatment in relapsing-remitting multiple sclerosis: a preliminary study. Eur Neurol 87(4): 203-210, 2024. DOI: 10.1159/000539376
    OpenUrlCrossRefPubMed
  7. ↵
    1. Fernández-Velasco JI,
    2. Monreal E,
    3. Kuhle J,
    4. Meca-Lallana V,
    5. Meca-Lallana J,
    6. Izquierdo G,
    7. Oreja-Guevara C,
    8. Gascón-Giménez F,
    9. Sainz de la Maza S,
    10. Walo-Delgado PE,
    11. Lapuente-Suanzes P,
    12. Maceski A,
    13. Rodríguez-Martín E,
    14. Roldán E,
    15. Villarrubia N,
    16. Saiz A,
    17. Blanco Y,
    18. Diaz-Pérez C,
    19. Valero-López G,
    20. Diaz-Diaz J,
    21. Aladro Y,
    22. Brieva L,
    23. Íñiguez C,
    24. González-Suárez I,
    25. Rodríguez de Antonio LA,
    26. García-Domínguez JM,
    27. Sabin J,
    28. Llufriu S,
    29. Masjuan J,
    30. Costa-Frossard L,
    31. Villar LM
    : Baseline inflammatory status reveals dichotomic immune mechanisms involved in primary-progressive multiple sclerosis pathology. Front Immunol 13: 842354, 2022. DOI: 10.3389/fimmu.2022.842354
    OpenUrlCrossRefPubMed
  8. ↵
    1. Boziki M,
    2. Bakirtzis C,
    3. Sintila SA,
    4. Kesidou E,
    5. Gounari E,
    6. Ioakimidou A,
    7. Tsavdaridou V,
    8. Skoura L,
    9. Fylaktou A,
    10. Nikolaidou V,
    11. Stangou M,
    12. Nikolaidis I,
    13. Giantzi V,
    14. Karafoulidou E,
    15. Theotokis P,
    16. Grigoriadis N
    : Ocrelizumab in patients with active primary progressive multiple sclerosis: clinical outcomes and immune markers of treatment response. Cells 11(12): 1959, 2022. DOI: 10.3390/cells11121959
    OpenUrlCrossRef
  9. ↵
    1. Thompson AJ,
    2. Banwell BL,
    3. Barkhof F,
    4. Carroll WM,
    5. Coetzee T,
    6. Comi G,
    7. Correale J,
    8. Fazekas F,
    9. Filippi M,
    10. Freedman MS,
    11. Fujihara K,
    12. Galetta SL,
    13. Hartung HP,
    14. Kappos L,
    15. Lublin FD,
    16. Marrie RA,
    17. Miller AE,
    18. Miller DH,
    19. Montalban X,
    20. Mowry EM,
    21. Sorensen PS,
    22. Tintoré M,
    23. Traboulsee AL,
    24. Trojano M,
    25. Uitdehaag BMJ,
    26. Vukusic S,
    27. Waubant E,
    28. Weinshenker BG,
    29. Reingold SC,
    30. Cohen JA
    : Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 17(2): 162-173, 2018. DOI: 10.1016/S1474-4422(17)30470-2
    OpenUrlCrossRefPubMed
  10. ↵
    1. Ho S,
    2. Oswald E,
    3. Wong HK,
    4. Vural A,
    5. Yilmaz V,
    6. Tüzün E,
    7. Türkoğlu R,
    8. Straub T,
    9. Meinl I,
    10. Thaler F,
    11. Kümpfel T,
    12. Meinl E,
    13. Mader S
    : Ocrelizumab treatment modulates B-cell regulating factors in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 10(2): e200083, 2023. DOI: 10.1212/NXI.0000000000200083
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Shah K,
    2. Leandro M,
    3. Cragg M,
    4. Kollert F,
    5. Schuler F,
    6. Klein C,
    7. Reddy V
    : Disrupting B and T-cell collaboration in autoimmune disease: T-cell engagers versus CAR T-cell therapy? Clin Exp Immunol 217(1): 15-30, 2024. DOI: 10.1093/cei/uxae031
    OpenUrlCrossRefPubMed
  12. ↵
    1. Baker D,
    2. Marta M,
    3. Pryce G,
    4. Giovannoni G,
    5. Schmierer K
    : Memory B cells are major targets for effective immunotherapy in relapsing multiple sclerosis. EBioMedicine 16: 41-50, 2017. DOI: 10.1016/j.ebiom.2017.01.042
    OpenUrlCrossRefPubMed
  13. ↵
    1. Choi JK,
    2. Yu CR,
    3. Bing SJ,
    4. Jittayasothorn Y,
    5. Mattapallil MJ,
    6. Kang M,
    7. Park SB,
    8. Lee HS,
    9. Dong L,
    10. Shi G,
    11. Caspi RR,
    12. Egwuagu CE
    : IL-27-producing B-1a cells suppress neuroinflammation and CNS autoimmune diseases. Proc Natl Acad Sci USA 118(47): e2109548118, 2021. DOI: 10.1073/pnas.2109548118
    OpenUrlAbstract/FREE Full Text
    1. Ma Q,
    2. Didonna A
    : The novel multiple sclerosis susceptibility gene ATXN1 regulates B cell receptor signaling in B-1a cells. Mol Brain 14(1): 19, 2021. DOI: 10.1186/s13041-020-00715-0
    OpenUrlCrossRefPubMed
    1. Miles K,
    2. Simpson J,
    3. Brown S,
    4. Cowan G,
    5. Gray D,
    6. Gray M
    : Immune tolerance to apoptotic self is mediated primarily by regulatory B1a cells. Front Immunol 8: 1952, 2018. DOI: 10.3389/fimmu.2017.01952
    OpenUrlCrossRefPubMed
  16. ↵
    1. Deng J,
    2. Wang X,
    3. Chen Q,
    4. Sun X,
    5. Xiao F,
    6. Ko KH,
    7. Zhang M,
    8. Lu L
    : B1a cells play a pathogenic role in the development of autoimmune arthritis. Oncotarget 7(15): 19299-19311, 2016. DOI: 10.18632/oncotarget.8244
    OpenUrlCrossRefPubMed
  17. ↵
    1. Lapucci C,
    2. Frau J,
    3. Cocco E,
    4. Coghe G,
    5. Petracca M,
    6. Lanzillo R,
    7. Brescia Morra V,
    8. Nicoletti CG,
    9. Landi D,
    10. Marfia G,
    11. Vercellino M,
    12. Cavalla P,
    13. Bianco A,
    14. Mirabella M,
    15. Torri Clerici V,
    16. Tomas E,
    17. Ferrò MT,
    18. Grossi P,
    19. Nozzolillo A,
    20. Moiola L,
    21. Zaffaroni M,
    22. Ronzoni M,
    23. Pinardi F,
    24. Novi G,
    25. Cellerino M,
    26. Uccelli A,
    27. Inglese M
    : Ocrelizumab in MS patients with persistence of disease activity after alemtuzumab: A multi-center Italian study. Mult Scler 30(9): 1151-1162, 2024. DOI: 10.1177/13524585241266509
    OpenUrlCrossRefPubMed
  18. ↵
    1. Grützke B,
    2. Hucke S,
    3. Gross CC,
    4. Herold MV,
    5. Posevitz-Fejfar A,
    6. Wildemann BT,
    7. Kieseier BC,
    8. Dehmel T,
    9. Wiendl H,
    10. Klotz L
    : Fingolimod treatment promotes regulatory phenotype and function of B cells. Ann Clin Transl Neurol 2(2): 119-130, 2015. DOI: 10.1002/acn3.155
    OpenUrlCrossRefPubMed
  19. ↵
    1. Holloman JP,
    2. Axtell RC,
    3. Monson NL,
    4. Wu GF
    : The role of B cells in primary progressive multiple sclerosis. Front Neurol 12: 680581, 2021. DOI: 10.3389/fneur.2021.680581
    OpenUrlCrossRef
  20. ↵
    1. Feige J,
    2. Moser T,
    3. Akgün K,
    4. Schwenker K,
    5. Hitzl W,
    6. Haschke-Becher E,
    7. Ziemssen T,
    8. Sellner J
    : Repeated iv anti-CD20 treatment in multiple sclerosis: Long-term effects on peripheral immune cell subsets. Ann Clin Transl Neurol 11(2): 450-465, 2024. DOI: 10.1002/acn3.51965
    OpenUrlCrossRefPubMed
  21. ↵
    1. Howlett-Prieto Q,
    2. Feng X,
    3. Kramer JF,
    4. Kramer KJ,
    5. Houston TW,
    6. Reder AT
    : Anti-CD20 therapy corrects a CD8 regulatory T cell deficit in multiple sclerosis. Mult Scler 27(14): 2170-2179, 2021. DOI: 10.1177/13524585211003301
    OpenUrlCrossRefPubMed
  22. ↵
    1. Karaaslan Z,
    2. Kahraman ÖT,
    3. Şanlı E,
    4. Ergen HA,
    5. Ulusoy C,
    6. Bilgiç B,
    7. Yılmaz V,
    8. Tüzün E,
    9. Hanağası HA,
    10. Küçükali Cİ
    : Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients. Sci Rep 11(1): 2316, 2021. DOI: 10.1038/s41598-021-81961-7
    OpenUrlCrossRef
  23. ↵
    1. Kraczyk B,
    2. Remus R,
    3. Hardt C
    : CD49d− Treg cells with high suppressive capacity are remarkably less efficient on activated CD45RA− than on naive CD45RA+ Teff cells. Cell Physiol Biochem 34(2): 346-355, 2014. DOI: 10.1159/000363004
    OpenUrlCrossRefPubMed
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Reprints and Permissions
B-Cell and T-Cell Populations in Peripheral Blood Linked to Ocrelizumab Treatment Efficacy in Multiple Sclerosis
ECE AKBAYIR, TUGCE KIZILAY, RUZIYE EROL, DUYGU OZKAN-YASARGUN, ERDEM TUZUN, VUSLAT YILMAZ, RECAI TÜRKOGLU
In Vivo Mar 2025, 39 (2) 1162-1172; DOI: 10.21873/invivo.13920
Twitter logo Facebook logo Mendeley logo

Jump to section

Keywords