Clinicopathological and immunohistochemical analysis of plasma cell‐rich rejection in renal transplantation: Involvement of intratubular Th1/Th2 balance in plasma cell enrichment

Nishimura, Ayako; Masuzawa, Naoko; Nakamura, Tsukasa; Harada, S.; Nobori, Shuji; Ushigome, Hidetaka; Yoshimura, Norio; Konishi, Eiichi

doi:10.1111/nep.13273

Cited by 5 publications

(5 citation statements)

References 18 publications

(32 reference statements)

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“…The prevalence of PCRR in our study was 4% (42/1055), similar to prior research ranging from 2 to 5%. 3,5,7 The median time from renal transplantation to the episode of rejection in the last included biopsy for the entire cohort was 0.5 year (interquartile range [IQR] 0.0-2.3 years), with the median length of the follow-up period after the last included biopsy 3.0 years (IQR 0.5-7.0 years). Detailed baseline characteristics for each group are presented in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…All cases with plasma cell rich infiltrates, defined as infiltrates with more than 10% plasma cells based on a definition used in previous studies, were classified as PCRR and included. 3,7,15 Concurrent viral infections, e.g., BK nephropathy, were excluded based on immunohistochemical staining (SV40 LTAg). Inadequate biopsies as defined by the Banff classification (minimal of 7 glomeruli and one artery) and patients lacking relevant clinical data were excluded.…”

Section: Selection Of Patients and Renal Biopsiesmentioning

confidence: 99%

“…[2][3][4] In general, PCRR manifests at a later time post-transplant than TCMR, ranging from 302 days to 3.7 years post-transplant according to current literature. [3][4][5][6][7] The majority of patients with PCRR present with histopathological patterns similar to TMCR type I or II. 8 As a result, PCRR is considered a subtype of TMCR rather than a distinct entity.…”

Section: Introductionmentioning

confidence: 99%

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Clinicopathological and Molecular Characteristics of Plasma Cell Rich Rejection in Renal Transplant Biopsies

du Long,

Florquin,

Bemelman

et al. 2024

Preprint

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BackgroundPlasma cell rich rejection (PCRR) is an uncommon, ill-defined type of renal allograft rejection in the current literature considered a subtype of T cell-mediated rejection (TCMR). PCRR has poorer clinical outcome and is often refractory to classic immunosuppressive therapy. Our study analyzed clinical course, Banff lesion scores and mRNA expression of PCRR compared to (late) rejection.MethodsWe retrospectively scored and reclassified the last known biopsy of 263 renal transplant recipients, morphologically classified as rejection according to the 2019 Banff classification. mRNA expression analysis was performed using the Nanostring B-HOT panel on a subset of cases. PCRR was compared to (late) TCMR, ABMR and mixed rejection for renal function follow-up and graft survival.ResultsmRNA analysis revealed uniquely expressed genes in PCRR includingLOX,CPA3,IL4,IL17F,andMMP12. PCRR is enriched for genes related to mast cells, memory B- and T-cells and transcripts involved in NK cells and allograft fibrosis with heterogeneity in gene expression in biopsies with PCRR. PCRR might be a late event compared to late TCMR and ABMR, with a higher degree of total inflammation and fibrosis. Graft survival and renal function was similar to late TCMR and ABMR during a 5-year follow-up period after renal biopsy.ConclusionPCRR represents a distinct late-onset stage of inflammation displaying diverse gene expression patterns, with presence of mainly mast cells, NK cells and transcripts involved in renal allograft fibrosis. Clinical outcomes in patients with PCRR appeared more similar to late TCMR and ABMR.

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Section: Resultsmentioning

confidence: 99%

Section: Selection Of Patients and Renal Biopsiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinicopathological and Molecular Characteristics of Plasma Cell Rich Rejection in Renal Transplant Biopsies

du Long,

Florquin,

Bemelman

et al. 2024

Preprint

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“…However, there are several important differences between plasma cell-rich rejection and typical T cell-mediated cellular rejection [74]. Importantly, plasma cell-rich rejection is typically refractory to rejection therapy and associated with poor graft survival [75]. Although it shares a histological similarity with T cell-mediated rejection, plasma cell-rich rejection is associated with Th2 polarization and the presence of DSA [75,76].…”

Section: Major Histocompatibility Complex In Organ Transplantationmentioning

confidence: 99%

“…Importantly, plasma cell-rich rejection is typically refractory to rejection therapy and associated with poor graft survival [75]. Although it shares a histological similarity with T cell-mediated rejection, plasma cell-rich rejection is associated with Th2 polarization and the presence of DSA [75,76]. Thus, plasma cell-rich rejection is categorized as a distinctive entity.…”

Section: Major Histocompatibility Complex In Organ Transplantationmentioning

confidence: 99%

The Role of Major Histocompatibility Complex in Organ Transplantation- Donor Specific Anti-Major Histocompatibility Complex Antibodies Analysis Goes to the Next Stage -

Nakamura

Shirouzu

Nakata

et al. 2019

IJMS

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Organ transplantation has progressed with the comprehension of the major histocompatibility complex (MHC). It is true that the outcome of organ transplantation largely relies on how well rejection is managed. It is no exaggeration to say that to be well acquainted with MHC is a shortcut to control rejection. In human beings, MHC is generally recognized as human leukocyte antigens (HLA). Under the current circumstances, the number of alleles is still increasing, but the function is not completely understood. Their roles in organ transplantation are of vital importance, because mismatches of HLA alleles possibly evoke both cellular and antibody-mediated rejection. Even though the control of cellular rejection has improved by recent advances of immunosuppressants, there is no doubt that antibody-mediated rejection (AMR), which is strongly correlated with donor-specific anti-HLA antibodies (DSA), brings a poor outcome. Thus, to diagnose and treat AMR correctly is a clear proposition. In this review, we would like to focus on the detection of intra-graft DSA as a recent trend. Overall, here we will review the current knowledge regarding MHC, especially with intra-graft DSA, and future perspectives: HLA epitope matching; eplet risk stratification; predicted indirectly recognizable HLA epitopes etc. in the context of organ transplantation.

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Specific knockout of Notch2 in Treg cells significantly inhibits the growth and proliferation of head and neck squamous cell carcinoma in mice

Wei

Qiao

et al. 2023

International Immunopharmacology

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Clinicopathological and immunohistochemical analysis of plasma cell‐rich rejection in renal transplantation: Involvement of intratubular Th1/Th2 balance in plasma cell enrichment

Abstract: This study suggests that PCRR is more refractory than ATCR and there are significant differences in populations of helper T-cell subsets between them. We consider helper T-cell subset analysis valuable for developing new treatment strategies for PCRR.

Cited by 5 publications

References 18 publications

Clinicopathological and Molecular Characteristics of Plasma Cell Rich Rejection in Renal Transplant Biopsies

Clinicopathological and Molecular Characteristics of Plasma Cell Rich Rejection in Renal Transplant Biopsies

The Role of Major Histocompatibility Complex in Organ Transplantation- Donor Specific Anti-Major Histocompatibility Complex Antibodies Analysis Goes to the Next Stage -

Specific knockout of Notch2 in Treg cells significantly inhibits the growth and proliferation of head and neck squamous cell carcinoma in mice

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