Cyclosporine microemulsion- and mycophenolate mofetil-related lymphoid aggregates are not associated with acute rejection.
BACKGROUND
Microemulsion cyclosporine, mycophenolate mofetil, and prednisone have become a common immunosuppressive protocol in renal transplantation. We identified lymphocytic infiltrates in transplant fine-needle aspirates and core biopsies from patients on this regimen without acute rejection clinically or by standardized morphological criteria and investigated this inflammatory response.


METHODS
Twenty-eight aspirates from 21 patients were included and assessed in the standard fashion. Nine core biopsies showing interstitial lymphocytic infiltration were evaluated with antibodies against CD3, CD4, CD8, CD20, CD30, CD56, KP1, and epithelial membrane antigen (EMA). Aspirates and biopsies were assessed for tubular cell major histocompatibility complex (MHC) class II antigen and for gamma-interferon (gamma-IFN), interleukin-4 (IL-4), and IL-10 mRNAs by reverse transcription-polymerase chain reaction.


RESULTS
Fifteen aspirates showed immune activation solely due to mature lymphocytes and monocytes; 13 had no immune activation. All aspirates were negative for MHC class II antigens. Of 6 activated aspirates assessed for gamma-IFN mRNA, 5 were negative. All 21 patients had similar clinical characteristics and recovered renal function without rejection treatment. The core biopsies had lymphocytes in 5-30% of the interstitium. The cells were 70-85% CD3+, with 50-85% CD4+, 3-10% KP1+, and rare cells CD56+. No T-cell activation was present (EMA- and CD30-). Seven biopsies were assessed and were negative for gamma-IFN mRNA; only one biopsy had weakly positive MHC class II staining. Two activated aspirates were negative for IL-4 and IL-10 mRNA, while three biopsies each contained IL-4 and IL-10 mRNAs.


CONCLUSIONS
Inactive interstitial lymphoid infiltrates are frequent in patients on this drug regimen and should not be interpreted as acute rejection, particularly in aspirate samples. These lymphocytes may play a role in long-term allograft acceptance.
Nast
C C
CC
Department of Pathology, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
Moudgil
A
A
Zuo
X J
XJ
Wilkinson
A
A
Danovitch
G M
GM
Jordan
S C
SC
D015703:Antigens, CD / Q000032:analysis; D001706:Biopsy; D001707:Biopsy, Needle; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004655:Emulsions; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018396:Mucin-1 / Q000032:analysis; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D015703:Antigens, CD; D004655:Emulsions; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D018396:Mucin-1; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D016572:Cyclosporine; D009173:Mycophenolic Acid