B Cells in Cluster or in a Scattered Pattern Do Not Correlate With Clinical Outcome of Renal Allograft Rejection

Scheepstra, Cornelis G.; Bemelman, Fréderike J.; Loos, Chris van der; Rowshani, Ajda T.; Pant, Karlijn A.M.I. van Donselaar-van der; Idu, Mirza M.; Berge, Ineke J. M. ten; Florquin, Sandrine

doi:10.1097/tp.0b013e3181860a74

Cited by 41 publications

(47 citation statements)

References 27 publications

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“…19 However, other studies showed no associations between CD20-positive cell-rich infiltrates and acute treatmentresistant rejection or unfavorable graft outcomes. 8,9,13 In the present study, CD20-positive cell-enriched infiltrates correlated with immunologic risk factors such as retransplant, higher HLA mismatch, and TCMR, but not with AMR, C4d, DSA, or the risk of graft loss. Factors such as the heterogeneity of the patient population, intensity of immunosuppression, time of post-transplant biopsy, and different methods of defining CD20-positive cells in biopsies might explain the discrepancies between these studies.…”

Section: Discussionmentioning

confidence: 74%

“…The B cells at different stages of maturation, including immature CD20-positive cells, CD38-positive plasmablasts, and CD138-positive plasma cells, are present in clusters or diffuse infiltrates in grafts during acute rejection and are functionally active. [8][9][10] In acute cellular rejection, the association between B cells, corticosteroid resistance, and poorer graft survival has been shown in some studies, [10][11][12] but these data have not been confirmed in other studies. 8,9,13 The participation of B cells in the humoral immune response also has been investigated.…”

Section: Introductionmentioning

confidence: 76%

“…[8][9][10] In acute cellular rejection, the association between B cells, corticosteroid resistance, and poorer graft survival has been shown in some studies, [10][11][12] but these data have not been confirmed in other studies. 8,9,13 The participation of B cells in the humoral immune response also has been investigated. 14,15 In kidneys undergoing rejection, strong correlations have been observed between infiltrating CD20-positive B cells, CD38-positive plasmablasts, plasma cells, circulating DSA and, to a lesser degree, C4d.…”

Section: Introductionmentioning

confidence: 76%

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Untitled

2014

Exp Clin Transplant

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Objectives: To evaluate B-cell expression patterns and association with function and survival in dysfunctional kidney allografts. Materials and Methods: There were 110 kidney transplant recipients included who had for-cause biopsies. Demographic and transplant data were collected. Immunostaining for B cells, plasma cells, and C4d was performed by the immunoperoxidase technique in paraffin-embedded samples. Circulating antihuman leukocyte antigen donorspecific antibodies were detected in a single-antigen assay at biopsy. The main outcomes were kidney graft survival and function.The patients were evaluated in 3 groups according to the Banff classification: no rejection (40 patients), T-cell-mediated rejection (50 patients), and antibody-mediated rejection (20 patients). Results: The CD138-positive plasma cell-rich infiltrates predominated in antibody-mediated rejection and were associated with stronger reactivity against panel antibodies (r = 0.41; P ≤ .001) and positive donor-specific antibodies (r = 0.32; P ≤ .006). The CD20-positive lymphocytes were associated with T-cell-mediated rejection, increased human leukocyte antigen mismatch, and frequency of retransplant. The CD138-positive cell infiltrates also were significantly greater in patients who had late than early rejection. There was no correlation between cellular CD20 and CD138 expression, and neither CD20 nor CD138 predicted worse graft function or survival. Other markers of antibodymediated rejection such as C4d and donor-specific antibodies were associated with worse graft function and survival at 4 years after transplant. In multivariate analysis, C4d was the only risk factor associated with graft loss. Conclusions: After kidney transplant, CD20-positive B-cell infiltrates were associated with T-cellmediated rejection, and CD138-positive plasma cells were associated with antibody-mediated rejection. Graft loss was associated with the presence of C4d.

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 76%

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Untitled

2014

Exp Clin Transplant

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“…1 However, these findings are controversial and not in agreement with previous reports. [8][9][10] This variance could be attributed to the use of different criteria for CD20-positive lymphocytic infiltrates, different follow-ups, and differences in study population. In our previous study (unpublished data), we found that the time of those CD20-positive recipients was longer than CD20-negative recipients without statistically significance (145.4 ± 121.2 days vs 75.4 ± 108.8 days, P = .056).…”

Section: Discussionmentioning

confidence: 99%

“…6,7 In contrast, several other reports have demonstrated that CD20 + infiltrates in renal allograft biopsies with ACR are not associated with worse graft survival. [8][9][10] Therefore, the relation between CD20 + cell infiltration and outcomes of renal allograft is controversial.…”

Section: Introductionmentioning

confidence: 99%

CD20+ B-Cell Infiltration Is Related to the Time After Transplant and Poor Prognosis of Acute Cellular Rejection in Renal Transplant

Wen

Chen²,

Cheng³

et al. 2013

Exp Clin Transplant

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Objectives: This study sought to determine the relation between CD20+ B-cell infiltration and time after transplant and outcome of acute cellular rejection in renal allografts. Materials and Methods: Fifty-five patients with acute cellular rejection were categorized into 3 groups: very early, early, and late rejection. The density of CD4 + , CD8 + , CD20 + , and CD68 + cells and HLA-DR expression were characterized and quantified using immunohistochemical staining. Histologic changes were compared between highdensity and low-density CD20 + B-cell groups. Poor prognosis factors were analyzed with Cox proportional regression. Results: Density of CD20 + cells in the very-early rejection group was lower than it was in the earlyand late-acute rejection groups (P = .03); the density of CD4 + , CD8 + , and CD68 + cells and HLA-DR expression did not differ between the groups. Mesangial matrix increase, tubular atrophy, arteriolar hyaline thickening, and tubulitis were more prevalent in the high CD20 + density group. Cox regression analysis demonstrated that HLA-DR expression on the tubules, arteriolar hyaline thickening, and CD20 + cell density were associated with an elevated risk of acute cellular rejection. Conclusions: Expansion aggregation of CD20 + B cells occurred mostly after 2 weeks. When combined with HLA-DR expression and arteriolar hyaline thickening, these influence the outcome of acute cellular rejection in renal allograft.

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