title: Participation of functionally active plasma cells in acute rejection and response to therapy in renal allografts.
abstract: Acute rejection (AR) includes T-cell-mediated and antibody-mediated rejection. The inflammatory infiltrate comprised not only T cells but also varying amounts of B cells (CD20(+)) and plasma cells (CD138(+)). The latter are associated with poor clinical outcomes, but their functional status is not clear. The phosphorylation of the S6 ribosomal protein (p-S6RP) is present in cells that are metabolically active, thus identifying functionally active antibody-secreting plasma cells. This study was designed to evaluate the clinical significance of functionally active p-S6RP plasma cells in AR in renal allografts. Renal allografts with biopsy evidence of AR during 2006-2009 were included. Immunohistochemistry staining for CD20, CD138, and p-S6RP was performed on paraffin-embedded slides and scaled as 0-6. The response to antirejection treatment was assessed by the serum creatinine ratio (CrR) at rejection episode (time 0) and following treatment (4 and 12 weeks). Patients with lower scores (0-2) were compared with a higher scored group (3-6). The T-test was conducted using statistical significance of p<0.05. A total of 28 patients (40.7 ± 14.3 year; M:F=15:13) were diagnosed with acute T-cell-mediated rejection (I and II). The p-S6RP staining in the high-score group had a significantly higher CrR (p<0.05) than the low-score group at the time of biopsy, 4 and 12 weeks following treatment. There was no significant difference in the CrR between groups for CD20 or CD138 staining. Functional antibody-secreting p-S6RP plasma cells are actively participating in AR and associated with poor response to treatment in renal allografts.
authors.affiliation: 1 Division of Nephrology, Department of Internal Medicine, Wayne State University , Detroit, Michigan.
authors.forename: Zeenat Yousuf
authors.initials: ZY
authors.lastname: Bhat
authors.forename: David G
authors.initials: DG
authors.lastname: Bostwick
authors.forename: Deloar
authors.initials: D
authors.lastname: Hossain
authors.forename: Xu
authors.initials: X
authors.lastname: Zeng
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000378:metabolism*; D053668:Syndecan-1 / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D018951:Antigens, CD20; D053668:Syndecan-1