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Adaptive immune cell responses as therapeutic targets in antibody-mediated organ rejection.

ABSTRACT: Humoral alloimmunity of organ transplant recipient to donor can lead to antibody-mediated rejection (ABMR), causing thousands of organ transplants to fail each year worldwide. However, the mechanisms of adaptive immune cell responses at the basis of humoral alloimmunity have not been entirely understood. In this review, we discuss how recent investigations have uncovered the key contributions of T follicular helper (T_FH) and B cells and their coordinated actions in driving donor-specific antibody generation and immune progression towards ABMR. We show how recognition of the role of T_FH-B cell interactions may allow the elaboration of improved clinical strategies for immune monitoring and the identification of novel therapeutic targets to tackle ABMR that will ultimately improve organ transplant survival.

SUBMITTER: Louis K

PROVIDER: S-EPMC8882148 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Adaptive immune cell responses as therapeutic targets in antibody-mediated organ rejection.

Louis Kevin K Macedo Camila C Lefaucheur Carmen C Metes Diana D

Trends in molecular medicine 20220129 3

Humoral alloimmunity of organ transplant recipient to donor can lead to antibody-mediated rejection (ABMR), causing thousands of organ transplants to fail each year worldwide. However, the mechanisms of adaptive immune cell responses at the basis of humoral alloimmunity have not been entirely understood. In this review, we discuss how recent investigations have uncovered the key contributions of T follicular helper (T<sub>FH)</sub> and B cells and their coordinated actions in driving donor-speci ...[more]

PMID: 35093288

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Project description:Background and objectivesActive antibody-mediated rejection is the main cause of kidney transplant loss, sharing with SLE the alloimmune response and the systemic activation of the IFN-α pathway. IgE-mediated immune response plays a key role in the development of SLE nephritis and is associated with IFN-α secretion. The aim of our study was to investigate IgE-mediated immune response in antibody-mediated rejection.Design, setting, participants, & measurementsThis was a cross-sectional study of 56 biopsy-proven antibody-mediated rejection study participants, 80 recipients with normal graft function/histology (control), 16 study participants with interstitial fibrosis/tubular atrophy, and six participants with SLE. We evaluated graft IgE deposition, tryptase (a mast cell marker), and CD203 (a specific marker of activated basophils) by immunofluorescence/confocal microscopy. In addition, we measured serum concentration of human myxovirus resistance protein 1, an IFN-α-induced protein, and anti-HLA IgE.ResultsWe observed a significantly higher IgE deposition in tubules and glomeruli in antibody-mediated rejection (1766±79 pixels) and SLE (1495±43 pixels) compared with interstitial fibrosis/tubular atrophy (582±122 pixels) and control (253±50 pixels). Patients with antibody-mediated rejection, but not control patients and patients with interstitial fibrosis/tubular atrophy, presented circulating anti-HLA IgE antibodies, although with a low mean fluorescence intensity. In addition, immunofluorescence revealed the presence of both mast cells and activated basophils in antibody-mediated rejection but not in control and interstitial fibrosis/tubular atrophy. The concentration of circulating basophils was significantly higher in antibody-mediated rejection compared with control and interstitial fibrosis/tubular atrophy. MxA serum levels were significantly higher in antibody-mediated rejection compared with control and correlated with the extent of IgE deposition.ConclusionsOur data suggest that IgE deposition and the subsequent recruitment of basophils and mast cells within the kidney transplant might play a role in antibody-mediated rejection.

Dataset Information

Adaptive immune cell responses as therapeutic targets in antibody-mediated organ rejection.

Publications

Adaptive immune cell responses as therapeutic targets in antibody-mediated organ rejection.

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