The role of APRIL - A proliferation inducing ligand - In autoimmune diseases and expectations from its targeting

Baert, Laurie; Manfroi, Benoît; Casez, Olivier; Stürm, Nathalie; Huard, Bertrand

doi:10.1016/j.jaut.2018.10.016

Cited by 41 publications

(41 citation statements)

References 149 publications

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“…In keeping with compensatory roles for BAFF and APRIL in plasma cell survival, a specific antibody to APRIL only modestly decreased autoantibody titers in aged NZB/W mice without affecting overall survival. 19,119 Consistent with these results, long-term TACI-Ig treatment reduced splenic and bone marrow plasma cells in NZB/W mice, resulting in reduced anti-dsDNA titers and protection from proteinuria. 118…”

Section: Is There a Difference Between Targeting Baff Or April Alonsupporting

confidence: 61%

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BAFF inhibition in SLE—Is tolerance restored?

Jackson

Davidson

2019

Immunological Reviews

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The B cell activating factor (BAFF) inhibitor, belimumab, is the first biologic drug approved for the treatment of SLE, and exhibits modest, but durable, efficacy in decreasing disease flares and organ damage. BAFF and its homolog APRIL are TNF‐like cytokines that support the survival and differentiation of B cells at distinct developmental stages. BAFF is a crucial survival factor for transitional and mature B cells that acts as rheostat for the maturation of low‐affinity autoreactive cells. In addition, BAFF augments innate B cell responses via complex interactions with the B cell receptor (BCR) and Toll like receptor (TLR) pathways. In this manner, BAFF impacts autoreactive B cell activation via extrafollicular pathways and fine tunes affinity selection within germinal centers (GC). Finally, BAFF and APRIL support plasma cell survival, with differential impacts on IgM‐ and IgG‐producing populations. Therapeutically, BAFF and combined BAFF/APRIL inhibition delays disease onset in diverse murine lupus strains, although responsiveness to BAFF inhibition is model dependent, in keeping with heterogeneity in clinical responses to belimumab treatment in humans. In this review, we discuss the mechanisms whereby BAFF/APRIL signals promote autoreactive B cell activation, discuss whether altered selection accounts for therapeutic benefits of BAFF inhibition, and address whether new insights into BAFF/APRIL family complexity can be exploited to improve human lupus treatments.

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Section: Is There a Difference Between Targeting Baff Or April Alonsupporting

confidence: 61%

“…19 APRIL is cleaved within the Golgi apparatus and does not usually appear on the cell membrane. 19 APRIL is cleaved within the Golgi apparatus and does not usually appear on the cell membrane.…”

Section: Aprilmentioning

confidence: 99%

BAFF inhibition in SLE—Is tolerance restored?

Jackson

Davidson

2019

Immunological Reviews

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“…We believe that a better understanding of effector mechanisms will suggest new approaches for treatment in an individualized manner. 64,197 Conflict of Interest G.M.H. has been a study investigator for PBC and PSC trials within the last five years sponsored by Cymabay, Falk Pharma, FF Pharma, Genfit, Genkyotek, Gilead, GSK, Intercept Pharma, Johnson and Johnson, NGM Bio, Novartis, and Shire.…”

Section: Pathogenetic Overview and Conclusionmentioning

confidence: 99%

The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review

et al. 2019

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Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune destruction of small to medium size intrahepatic bile ducts. The etiology of PBC remains unknown and pathogenesis features immune-mediated biliary injury, alongside the consequences of chronic cholestasis. PBC is strongly associated with the loss of immune tolerance against mitochondrial antigens and the subsequent presence of an articulated immunologic response that involves both humoral and cellular responses. Both environmental factors and genetic variants increase PBC susceptibility. Biliary epithelial cells have often been considered a passive target of the immune attack in PBC; however, cholangiocyte dedifferentiation, senescence, stress, and deoxyribonucleic acid damage have been recognized to play an active role in the pathogenesis of PBC. This review highlights and discusses the most relevant pathogenetic mechanisms in PBC, focusing on the key factors that lead to the onset of cholestasis and immune activation.

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“…B-cell activating factor (BAFF; BLyS; TALL-1) and APRIL (a proliferation-inducing ligand) are two homologous members of the tumor necrosis factor (TNF) superfamily [ 6 , 7 ] that have received much recent attention for their roles in the pathology of lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases [ 8 , 9 ]. There also is evidence that the production of both of these cytokines in the bone marrow microenvironment plays a key role in the viability and proliferation of myeloma cells [ 10 ].…”

Section: The Baff/april/bcma Axismentioning

confidence: 99%

B-Cell Maturation Antigen (BCMA) as a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma

Abramson

2020

IJMS

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During the past two decades there has been a major shift in the choice of agents to treat multiple myeloma, whether newly diagnosed or in the relapsed/refractory stage. The introduction of new drug classes, such as proteasome inhibitors, immunomodulators, and anti-CD38 and anti-SLAMF7 monoclonal antibodies, coupled with autologous stem cell transplantation, has approximately doubled the disease’s five-year survival rate. However, this positive news is tempered by the realization that these measures are not curative and patients eventually relapse and/or become resistant to the drug’s effects. Thus, there is a need to discover newer myeloma-driving molecular markers and develop innovative drugs designed to precisely regulate the actions of such putative targets. B cell maturation antigen (BCMA), which is found almost exclusively on the surfaces of malignant plasma cells to the exclusion of other cell types, including their normal counterparts, has emerged as a specific target of interest in this regard. Immunotherapeutic agents have been at the forefront of research designed to block BCMA activity. These agents encompass monoclonal antibodies, such as the drug conjugate belantamab mafodotin; bispecific T-cell engager strategies exemplified by AMG 420; and chimeric antigen receptor (CAR) T-cell therapeutics that include idecabtagene vicleucel (bb2121) and JNJ-68284528.

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The role of APRIL - A proliferation inducing ligand - In autoimmune diseases and expectations from its targeting

Cited by 41 publications

References 149 publications

BAFF inhibition in SLE—Is tolerance restored?

BAFF inhibition in SLE—Is tolerance restored?

The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review

B-Cell Maturation Antigen (BCMA) as a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma

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