Immune Monitoring of Patients With Primary Immune Regulation Disorders Unravels Higher Frequencies of Follicular T Cells With Different Profiles That Associate With Alterations in B Cell Subsets

Caldirola, María Soledad; Martinez, María Paula; Bezrodnik, Liliana; Zwirner, Norberto Walter; Gaillard, María Isabel

doi:10.3389/fimmu.2020.576724

Cited by 11 publications

(1 citation statement)

References 96 publications

(109 reference statements)

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“…Variations in the extent of immune cell compartment imbalance in CVID may enhance the progression of ILD due to mechanisms that remain unclear. T cells from CVID patients demonstrate increased frequencies of activated, memory, and effector populations with a lack of naïve and regulatory T cell subsets (112). The enhanced state of T cell activation and effector function in CVID may further contribute to the B cell hyperplasia observed in CVID ILD due to a lack of T cell-mediated regulation of B cell activity in addition to upregulation of non-canonical NF-kB signaling in B cells as a result of more widespread stimulation of CD40 through CD40L expressed on activated T cells (113,114).…”

Section: The Potential Contribution Of Baff To Cvid Ildmentioning

confidence: 99%

B Cell Dysregulation in Common Variable Immunodeficiency Interstitial Lung Disease

et al. 2021

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Common variable immunodeficiency (CVID) is the most frequently diagnosed primary antibody deficiency. About half of CVID patients develop chronic non-infectious complications thought to be due to intrinsic immune dysregulation, including autoimmunity, gastrointestinal disease, and interstitial lung disease (ILD). Multiple studies have found ILD to be a significant cause of morbidity and mortality in CVID. Yet, the precise mechanisms underlying this complication in CVID are poorly understood. CVID ILD is marked by profound pulmonary infiltration of both T and B cells as well as granulomatous inflammation in many cases. B cell depletive therapy, whether done as a monotherapy or in combination with another immunosuppressive agent, has become a standard of therapy for CVID ILD. However, CVID is a heterogeneous disorder, as is its lung pathology, and the precise patients that would benefit from B cell depletive therapy, when it should administered, and how long it should be repeated all remain gaps in our knowledge. Moreover, some have ILD recurrence after B cell depletive therapy and the relative importance of B cell biology remains incompletely defined. Developmental and functional abnormalities of B cell compartments observed in CVID ILD and related conditions suggest that imbalance of B cell signaling networks may promote lung disease. Included within these potential mechanisms of disease is B cell activating factor (BAFF), a cytokine that is upregulated by the interferon gamma (IFN-γ):STAT1 signaling axis to potently influence B cell activation and survival. B cell responses to BAFF are shaped by the divergent effects and expression patterns of its three receptors: BAFF receptor (BAFF-R), transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA). Moreover, soluble forms of BAFF-R, TACI, and BCMA exist and may further influence the pathogenesis of ILD. Continued efforts to understand how dysregulated B cell biology promotes ILD development and progression will help close the gap in our understanding of how to best diagnose, define, and manage ILD in CVID.

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Section: The Potential Contribution Of Baff To Cvid Ildmentioning

confidence: 99%