Foxp3 staining in BK virus allograft nephropathy and comparison with acute cellular rejection.
BACKGROUND
Foxp3(+)CD4(+)CD25(+) regulatory T cells are involved in maintaining immunologic self-tolerance. These cells have been investigated in acute cellular rejection (ACR) of renal allografts. In this retrospective pathological study, we evaluated Foxp3(+) immunostaining in BK virus nephropathy (BKVN). In some circumstances, BKVN may be difficult to distinguish histologically from ACR.


METHODS
Sequential sections were made of 30 allograft core biopsies and stained for hematorylin and eosin (H&E), C4d, cytomegalovirus (all negative), SV40, CD3, CD20, and Foxp3. Twelve biopsies were from diagnosed BKVN cases, 12 were from diagnosed ACR cases, and six showed neither BKVN nor ACR (controls). The 100x field of maximum cellular inflammation was located and marked on the H&E stain. The same area on the CD3, CD20, and Foxp3 slides was marked. Staining lymphocytes were counted under 400x magnification. Degree of BKVN was assessed according to the Drachenberg scale; degree of ACR was assessed by the Banff criteria.


RESULTS
The range of Foxp3(+) staining (cells/mm(2)) was much larger in BKVN (0-270) compared to ACR (0-35). The mean difference did not reach statistical significance owing to a large degree of overlap between the two groups. In BKVN, the Foxp3(+) infiltrate correlated with the degree of CD3(+) infiltrate (P = .012), and median Foxp3(+) infiltrate increased with Drachenberg grade of BKVN. CD3(+) cell levels were not significantly different in BKVN versus ACR.


CONCLUSIONS
BKVN cases with high levels of Foxp3(+) graft infiltrates may be manifesting an immune response different from that of ACR. Positive Foxp3 correlation with Drachenberg grade suggests a down-regulatory response.
Miller
D C
DC
University of Southern California Keck School of Medicine, LA County Hospital, Room 6610, 1200 N. State Street, Los Angeles, CA 90033, USA.
Qazi
Y
Y
Smogorzewski
M
M
Azen
C G
CG
Shah
T
T
Koss
M N
MN
D018951:Antigens, CD20 / Q000032:analysis; D001739:BK Virus / Q000302:isolation & purification*; D001706:Biopsy; D017252:CD3 Complex / Q000032:analysis; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006084:Graft Rejection / Q000473:pathology* / Q000821:virology; D006801:Humans; D015994:Incidence; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology; D018655:Lymphocyte Count; D027601:Polyomavirus Infections / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D011183:Postoperative Complications / Q000453:epidemiology / Q000473:pathology / Q000821:virology; D012189:Retrospective Studies; D013539:Simian virus 40 / Q000302:isolation & purification
D018951:Antigens, CD20; D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors