Analysis of specificity of anti-human leukocyte antigen antibodies in kidney recipients in reference to clinical outcome.
BACKGROUND
Anti-human leukocyte antigens antibodies (HLA) are not always the main cause of graft injury but can be a marker of immune response to the graft. The aim of this study was to analyze anti-HLA specificities with the use of the most sensitive detection method (Luminex) in reference to clinical condition.


METHODS
Sera of 65 kidney recipients (n = 443) were screened with the use of the mixed LABScreen kit, and, for 47 recipients, sera with maximal normalized background ratio (NBG) were subjected to specificity testing. NBG, numbers of specificities, donor-specific antibodies (DSA), and normalized mean fluorescence index (nMFI) of DSA and maximal anti-HLA were analyzed in reference to clinical (acute rejection [AR] diagnosis, immunosuppression), histopathological (C4d staining, chronic allograft nephropathy, AR type), and laboratory parameters (creatinine).


RESULTS
We observed 1 to 51 specificities, class I DSA in 26.7%, class II in 10%, and estimated DQ-DSA in 63.3% of tested patients. Patients with AR and humoral AR had significantly higher NBG, number of anti-HLA class I, DQ and DQ-DSA types, and more frequently had anti-HLA and class II DSA-positive sera (P < .052). C4d staining was associated with higher anti-HLA class I (P = .053) and class I DSA (P = .002) type numbers, and maximal anti-HLA nMFI (P = .036) and was more frequent in AR (P = .048) and class II DSA positive patients (P = .046). Patients with chronic allograft nephropathy showed higher DQ-DSA-nMFI (P = .036). DQ-DSA-nMFI and maximal anti-HLA-nMFI correlated with creatinine increase (Spearman range [SR] = 0.64, SR = 0.41). Together with NBG, maximal class I and class II anti-HLA-nMFI correlated with the number of transplantation and maximal panel-reactive antibodies ratio (SR = 0.19-0.40).


CONCLUSIONS
Anti-HLA detection allows for humoral AR diagnosis but also for identification of patients with risk of any rejection. However, clear rules of anti-HLA interpretation and studies on their clinical impact are needed.
Department of Microbiology and Immunology, Pomeranian Medical University, Szczecin, Poland. Electronic address: monikan@wp.pl.
M
M
Nowosiad-Magda
Department of Nephrology, Transplantology and Internal Diseases, Pomeranian Medical University, Szczecin, Poland.
M
M
Myślak
Department of Microbiology and Immunology, Pomeranian Medical University, Szczecin, Poland.
P
P
Roszkowska
Department of Microbiology and Immunology, Pomeranian Medical University, Szczecin, Poland.
Z
Z
Borowiec-Chłopek
Departament of Pathology, Pomeranian Medical University, Szczecin, Poland.
E
E
Urasińska
Department of Nephrology, Transplantology and Internal Diseases, Pomeranian Medical University, Szczecin, Poland.
J
J
Różański
Department of Nephrology, Transplantology and Internal Diseases, Pomeranian Medical University, Szczecin, Poland.
L
L
Domański
Department of Nephrology, Transplantology and Internal Diseases, Pomeranian Medical University, Szczecin, Poland.
K
K
Ciechanowski
Department of Microbiology and Immunology, Pomeranian Medical University, Szczecin, Poland.
S
S
Giedrys-Kalemba
D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D066027:Transplant Recipients; D016896:Treatment Outcome; D055815:Young Adult
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II