B cell activating factor (BAFF): Structure, functions, autoimmunity and clinical implications in Systemic Lupus Erythematosus (SLE)

Möckel, Tamara; Basta, Fabio; Weinmann‐Menke, Julia; Schwarting, Andreas

doi:10.1016/j.autrev.2020.102736

Cited by 130 publications

(74 citation statements)

References 128 publications

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“…Among the systemic autoimmune diseases, SS showed the highest serum levels of BAFF (64)(65)(66)(67)(68)(69). In mice model, the overexpression of BAFF in mice leads to hyperplasia, autoimmunity, hyperglobulinemia and splenomegaly, while the normal expression of BAFF allows B cell survival and maturation (70).…”

Section: Ss and Baff Hyperexpressionmentioning

confidence: 99%

Shared Pathogenetic Features Between Common Variable Immunodeficiency and Sjögren’s Syndrome: Clues for a Personalized Medicine

Quartuccio

Marchi²,

Longhino

et al. 2021

Front. Immunol.

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Common variable immunodeficiency disorders (CVID) are a group of rare diseases of the immune system and the most common symptomatic primary antibody deficiency in adults. The “variable” aspect of CVID refers to the approximately half of the patients who develop non-infective complications, mainly autoimmune features, in particular organ specific autoimmune diseases including thyroiditis, and cytopenias. Among these associated conditions, the incidence of lymphoma, including mucosal associated lymphoid tissue (MALT) type, is increased. Although these associated autoimmune disorders in CVID are generally attributed to Systemic Lupus Erythematosus (SLE), we propose that Sjogren’s syndrome (SS) is perhaps a better candidate for the associated disease. SS is an autoimmune disorder characterized by the lymphocytic infiltrates of lacrimal and salivary glands, leading to dryness of the eyes and mouth. Thus, it is a lymphocyte aggressive disorder, in contrast to SLE where pathology is generally attributed to auto-antibody and complement activation. Although systemic lupus erythematosus (SLE) shares these features with SS, a much higher frequency of MALT lymphoma distinguishes SS from SLE. Also, the higher frequency of germ line encoded paraproteins such as the monoclonal rheumatoid factor found in SS patients would be more consistent with the failure of B-cell VDJ switching found in CVID; and in contrast to the hypermutation that characterizes SLE autoantibodies. Thus, we suggest that SS may fit as a better “autoimmune” association with CVID. Examining the common underlying biologic mechanisms that promote lymphoid infiltration by dysregulated lymphocytes and lymphoma in CVID may provide new avenues for treatment in both the diseases. Since the diagnosis of SLE or rheumatoid arthritis is usually based on specific autoantibodies, the associated autoimmune features of CVID patients may not be recognized in the absence of autoantibodies.

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Section: Ss and Baff Hyperexpressionmentioning

confidence: 99%

Shared Pathogenetic Features Between Common Variable Immunodeficiency and Sjögren’s Syndrome: Clues for a Personalized Medicine

Quartuccio

Marchi²,

Longhino

et al. 2021

Front. Immunol.

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“…Предполагается, что это может приводить к генерации «патогенной» (аутореактивной) субпопуляции В-клеток, секретирующих аутоантитела [130]. Примечательно, что умеренное увеличение концентрации BAFF наблюдается на фоне лечения метотрексатом, АЗА и ММФ, в то время как при лечении ГХ и ГК (особенно в высоких дозах) отмечено снижение концентрации BAFF [19]. По данным W. Huang и соавт.…”

Section: комбинированная терапия белимумабом и ритуксимабомunclassified

“…Важным шагом в направлении решения этой проблемы явилась разработка препарата белимумаб (БЛМ), представляющего собой человеческие мАТ (IgG1λ) к BAFF (B cell-activating factor belonging to the TNF family). БЛМ является первым «таргетным» генно-инженерным биологическим препаратом (ГИБП), специально разработанным для лечения СКВ [15][16][17] [18][19][20][21]. BAFF относится к классу мембрано-связанных белков типа II и, подвергаясь расщеплению фурином, высвобождается с клеточных мембран, образует растворимый биологически активный BAFF-гомодимер, который является основной формой BAFF в кровяном русле.…”

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Belimumab in the treatment of systemic lupus erythematosus: 20 years of basic research, 10 years of clinical practice

Насонов

Попкова²,

Лила

2021

Naučno-praktičeskaâ revmatologiâ

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Currently, strong evidence has been obtained for the fundamental role of pathological activation of B cells in the pathogenesis of immunoinflammatory (autoimmune) rheumatic diseases (IMRD), and drugs that specifically modulate the function or cause depletion of various subpopulations of B cells and plasma cells are considered a promising direction. pharmacotherapy of these diseases. of particular interest is belimumab (BLM), a human monoclonal antibody (mAb) (IgG1λ) to BAFF (B cell-activating factor belonging to the TNF family), which is the first “targeted” biological drug specially developed for the treatment of systemic lupus erythematosus (SLE). The efficacy and safety of BLM in SLE in adults and children, including lupus nephritis, in combination therapy with rituximab, steroid-sparing effect, the ability to prevent irreversible damage to internal organs dictate the need for its wider application in clinical practice.

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“…Belimumab has been the first biologic agent approved for SLE therapy so far. Belimumab mainly acts by binding to and antagonizing soluble BAFF [101] , so that it has a rapid and harmful effect on B lymphocytes in the early developmental stage, especially naive B cells [102] . In addition, studies have found that the extrafollicular pathways are also the pathways by which BAFF affects the activation and differentiation of naive B cells.…”

Section: Belimumabmentioning

confidence: 99%

Immunopathological events surrounding IL-6 and IFN-α: A bridge for anti-lupus erythematosus drugs used to treat COVID-19

Zhou

et al. 2021

International Immunopharmacology

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B cell activating factor (BAFF): Structure, functions, autoimmunity and clinical implications in Systemic Lupus Erythematosus (SLE)

Cited by 130 publications

References 128 publications

Shared Pathogenetic Features Between Common Variable Immunodeficiency and Sjögren’s Syndrome: Clues for a Personalized Medicine

Shared Pathogenetic Features Between Common Variable Immunodeficiency and Sjögren’s Syndrome: Clues for a Personalized Medicine

Belimumab in the treatment of systemic lupus erythematosus: 20 years of basic research, 10 years of clinical practice

Immunopathological events surrounding IL-6 and IFN-α: A bridge for anti-lupus erythematosus drugs used to treat COVID-19

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