Immunohistochemical phenotyping of the inflammatory infiltrate in de novo autoimmune hepatitis after liver transplantation in children.
We have investigated the inflammatory infiltrate in post-transplant dn-AIH, a form of late insidious graft rejection, focusing on transcription factors defining effector and T-regs, using an antigen retrieval immunohistochemical method on archived liver tissue, and compared it with ACR and classical AIH. Paraffin-embedded liver biopsies from pediatric patients with dn-AIH (n = 10), ACR (n = 10), and AIH (n = 13) were selected randomly and stained using antibodies directed to CD4, CD8, T-bet (marker of Th1 polarization), GATA-3 (marker of Th2 polarization), FOXP3 (marker for T regulatory cells), IL-17, CD56 (NK cells), and perforin. Portal and lobular lymphocytic infiltrate was assessed semi-quantitatively. Prominent CD4, CD8, and T-bet positivity were present in both the lobular and portal infiltrate of all three conditions. Overall T-bet score of lobular inflammation in the dn-AIH group was lower than in the ACR and AIH groups (p = 0.02). In contrast, most samples showed absent or minimal GATA-3 positivity. FOXP3, CD56, IL-17, and perforin staining of mild to moderate severity were present in all three groups in both the portal and lobular infiltrate. A Th1 polarization of the inflammatory infiltrate characterizes dn-AIH, but also ACR and AIH.
Department of Child Health, King's College Medical School at King's College Hospital, Denmark Hill, London, UK. nedim.hadzic@kcl.ac.uk
Nedim
N
Hadžić
Alberto
A
Quaglia
Corina
C
Cotoi
Munther J
MJ
Hussain
Nigel
N
Brown
Diego
D
Vergani
Giorgina
G
Mieli-Vergani
D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015704:CD4 Antigens / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D019693:Hepatitis, Autoimmune / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D054353:Perforin / Q000378:metabolism; D010641:Phenotype; D011183:Postoperative Complications / Q000276:immunology* / Q000473:pathology; D020825:T-Box Domain Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D000098815:T-bet Transcription Factor
D015415:Biomarkers; D015704:CD4 Antigens; D019002:CD56 Antigen; D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; D020381:Interleukin-17; C522918:NCAM1 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D054353:Perforin