title: Autoantibody appearance in cytomegalovirus-infected liver transplant recipients: correlation with antigenemia.
abstract: The presence of anti-endothelial cells (AECA), smooth muscle (SMA), antinuclear (ANA) and antimitochondrial (AMA) autoantibodies, and liver/kidney microsomal antibody type 1 (LKM1) was investigated retrospectively in sera of liver transplant patients and correlated with cytomegalovirus (CMV) infection as determined by the antigenemia test and with the appearance of acute or chronic allograft rejection. Indirect immunofluorescence analysis was carried out in sequential sera from 40 liver transplant patients. Ten out of 23 antigenemia-positive and none of the antigenemia-negative patients developed serum autoantibodies (P = 0.002, Fisher's exact test). Anti-endothelial cell autoantibodies were found in nine cases and SMA in four patients. Antinuclear antibodies were detected in one otherwise autoantibody-negative patient. All but one case of autoantibody positivity were observed in the high antigenemia group (P < 0.0001, Fisher's exact test). In all but one case, autoantibodies were detected in blood during the antigenemia phase and in most cases in coincidence with or after the antigenemia peak. Even though a statistically significant correlation was not found between autoantibody production and the development of acute or chronic allograft rejection, proportionally more acute rejection cases were observed in the autoantibody-positive than in the autoantibody-negative group. It has been speculated that CMV-induced endothelial damage may be a potent antigenic stimulus, which leads to the production of anti-endothelial cells autoantibodies. Anti-endothelial cell autoantibodies may represent not only a marker of cell injury but also contribute to the progression of the inflammatory response leading to the exposure of tissue-privileged self antigens and the induction of other autoantibodies such as SMA.
authors.affiliation: Dipartimento di Medicina Clinica Specialistica e Sperimentale, Sezione di Microbiologia, University of Bologna, St. Orsola-Malpighi General Hospital, Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Varani
authors.forename: Luigi
authors.initials: L
authors.lastname: Muratori
authors.forename: Nicola
authors.initials: N
authors.lastname: De Ruvo
authors.forename: Marco
authors.initials: M
authors.lastname: Vivarelli
authors.forename: Tiziana
authors.initials: T
authors.lastname: Lazzarotto
authors.forename: Liliana
authors.initials: L
authors.lastname: Gabrielli
authors.forename: Francesco B
authors.initials: FB
authors.lastname: Bianchi
authors.forename: Roberto
authors.initials: R
authors.lastname: Bellusci
authors.forename: Maria P
authors.initials: MP
authors.lastname: Landini
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity; D002462:Cell Membrane / Q000276:immunology; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D004727:Endothelium / Q000276:immunology; D005260:Female; D006084:Graft Rejection; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood*; D014763:Viral Matrix Proteins / Q000097:blood*
chemical_list: D001323:Autoantibodies; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C087589:anti-endothelial cell antibody; C065418:cytomegalovirus matrix protein 65kDa