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A new perspective on therapies involving B-cell depletion in autoimmune diseases

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Abstract

It has been rediscovered in the last fifteen years that B-cells play an active role in autoimmune etiology rather than just being spectators. The clinical success of B-cell depletion therapies (BCDTs) has contributed to this. BCDTs, including those that target CD20, CD19, and BAFF, were first developed to eradicate malignant B-cells. These days, they treat autoimmune conditions like multiple sclerosis and systemic lupus erythematosus. Particular surprises have resulted from the use of BCDTs in autoimmune diseases. For example, even in cases where BCDT is used to treat the condition, its effects on antibody-secreting plasma cells and antibody levels are restricted, even though these cells are regarded to play a detrimental pathogenic role in autoimmune diseases. In this Review, we provide an update on our knowledge of the biology of B-cells, examine the outcomes of clinical studies employing BCDT for autoimmune reasons, talk about potential explanations for the drug’s mode of action, and make predictions about future approaches to targeting B-cells other than depletion.

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No datasets were generated or analysed during the current study.

Abbreviations

BCDTs:

B-cell depletion therapies

RA:

Rheumatoid arthritis

SLE:

Systemic lupus erythematosus

MS:

Multiple sclerosis

APCs:

Antigen-presenting cells

ADCC:

Antibody-dependent cell-mediated cytotoxicity

CDC:

Complement-dependent cytotoxicity

B-reg:

Regulatory B-cells

LLPCs:

Long-lived plasma cells

NK:

Natural killer cells

NMOSD:

Neuromyelitis optica spectrum disorder

AQP4:

Aquaporin 4

CAR:

Chimeric antigen receptor

DMARDs:

Disease-modifying antirheumatic drugs

BAFF:

B-cell-activating factor

IL:

Interleukin

CNS:

Central nervous system

MOG:

Myelin oligodendrocyte glycoprotein

TNF-α:

Tumor necrosis factor-alpha

BBB:

Blood–brain barrier

TLS:

Tertiary lymphoid structure

ITP:

Immune thrombocytopenic purpura

HBV:

Hepatitis B virus

TB:

Tuberculosis

PJP:

Pneumocystis jirovecii pneumonia

UTIs:

Urinary tract infections

VZV:

Varicella-zoster virus

ADAs:

Anti-drug antibodies

LT3:

Lymphotoxin 3

GM-CSF:

Granulocyte macrophage colony-stimulating factor

Ig:

Immunoglobulin

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Acknowledgements

The authors would like to thank the Deanship of Shaqra University, Shaqra 15526, Saudi Arabia, for supporting this work.

Funding

This study is supported via funding from Shaqra University, Shaqra 15526, Saudi Arabia.

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Authors and Affiliations

  1. Al Al-Bayt University, Al-Mafraq, Jordan

    Sulieman Ibraheem Shelash Al-Hawary

  2. Medical Laboratory Techniques Department, Al-Maarif University College, Anbar, Iraq

    Saade Abdalkareem Jasim

  3. Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, 11942, Al-Kharj, Saudi Arabia

    Ahmed Hjazi

  4. College of Medicine, Shaqra University, 15526, Shaqra, Saudi Arabia

    Himayat Ullah

  5. Department of Biotechnology and Genetics, Jain (Deemed-to-Be) University, Bengaluru, Karnataka, 560069, India

    Pooja Bansal

  6. Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, 303012, India

    Pooja Bansal

  7. Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India

    Mahamedha Deorari

  8. Tashkent Institute of Irrigation and Agricultural Mechanization Engineers National Research University, Tashkent, Uzbekistan

    I. B. Sapaev

  9. Scientific Researcher, Western Caspian University, Baku, Azerbaijan

    I. B. Sapaev

  10. Department of Medical Laboratories Technology, Al-Nisour University College, Baghdad, Iraq

    Ahmed Ali Ami

  11. Scientific Research Center, Al-Ayen University, Thi-Qar, 64001, Iraq

    Karrar Hatif Mohmmed

  12. College of Pharmacy, The Islamic University, Najaf, Iraq

    Munther Kadhim Abosaoda

  13. College of Pharmacy, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq

    Munther Kadhim Abosaoda

  14. College of Pharmacy, The Islamic University of Babylon, Hillah, Iraq

    Munther Kadhim Abosaoda

Authors
  1. Sulieman Ibraheem Shelash Al-Hawary
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  2. Saade Abdalkareem Jasim
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  3. Ahmed Hjazi
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  4. Himayat Ullah
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  5. Pooja Bansal
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  6. Mahamedha Deorari
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  7. I. B. Sapaev
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  8. Ahmed Ali Ami
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  9. Karrar Hatif Mohmmed
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  10. Munther Kadhim Abosaoda
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Contributions

S.I.S.A-H, S.A.J, A.H, P.B, M.D, I.B.S, A.A.A, KHM, and M.K.A: Conceptualization, Writing -original draft, Writing—Review & Editing. H.U: Conceptualization, Supervision. All authors reviewed the manuscript.

Corresponding author

Correspondence to Himayat Ullah.

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Al-Hawary, S.I.S., Jasim, S.A., Hjazi, A. et al. A new perspective on therapies involving B-cell depletion in autoimmune diseases. Mol Biol Rep 51, 629 (2024). https://doi.org/10.1007/s11033-024-09575-6

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