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Review
. 2025 Jan 21;219(1):uxae098.
doi: 10.1093/cei/uxae098.

The B-cells paradigm in systemic sclerosis: an update on pathophysiology and B-cell-targeted therapies

Cristina Scaletti  1 , Sara Pratesi  2 , Silvia Bellando Randone  3 , Linda Di Pietro  1 , Corrado Campochiaro  4 , Francesco Annunziato  1   2 , Marco Matucci Cerinic  4   5
Affiliations
Review

The B-cells paradigm in systemic sclerosis: an update on pathophysiology and B-cell-targeted therapies

Cristina Scaletti et al. Clin Exp Immunol. .

Abstract

Systemic sclerosis (SSc) is considered a rare autoimmune disease in which there are alterations of both the innate and adaptive immune response resulting in the production of autoantibodies. Abnormalities of the immune system compromise the normal function of blood vessels leading to a vasculopathy manifested by Raynaud's phenomenon, an early sign of SSc . As a consequence of this reactive picture, the disease can evolve leading to tissue fibrosis. Several SSc-specific autoantibodies are currently known and are associated with specific clinical manifestations and prognosis. Although the pathogenetic role of these autoantibodies is still unclear, their production by B cells and plasma cells suggests the importance of these cells in the development of SSc. This review narratively examines B-cell dysfunctions and their role in the pathogenesis of SSc and discusses B-cell-targeted therapies currently used or potentially useful for the management of end-organ complications.

Keywords: B cells; autoantibodies; autoimmunity; chimeric antigen receptor T cell.

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Conflict of interest statement

None declared.

Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
schematic figure of the mechanisms of action of anti-CD20, anti-CD19 and anti-BAFF drugs
Figure 2:
Figure 2:
immunomodulatory actions of IVIG. (IVIg) is made up of four components responsible for immunomodulation: (i) actions mediated by the F(abʹ)2 variable regions (ii), actions of Fc on Fc receptors (FcR) (iii), actions promoted by complement binding within the Fc fragment and (iv) substances other than antibodies in IVIg preparations (cytokines, cytokines receptor, sugars, stabilizing agents) can contribute, in synergy with immunoglobulins, to immunomodulate the immune response, although the mechanisms are still to be clarified
Figure 3:
Figure 3:
brief description of autologous CAR-T (A) and CAAR-T cells generation (B) and their mechanism of action after reinfusion (C and D)
Figure 4:
Figure 4:
schematic of steps of engineering techniques to obtain autologous CAR-B cells (A) and presumed mechanisms of action of the engineered B cells (B): 1–CAR-B cells could be engineered to produce specific antibodies against targeted antigens, enhancing the immune response against cancer cells or autoimmune markers, 2–CAR-B cells could present antigens more effectively to T cells, boosting the adaptive immune response, 3–CAR-B cells could be programmed to secrete immunomodulatory cytokines that modulate the immune environment, enhancing anti-tumour activity or reducing inflammation
See this image and copyright information in PMC

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