HLA-specific antibodies are associated with high-grade and persistent-recurrent lung allograft acute rejection.
BACKGROUND
The impact of HLA-specific antibodies is not well established in the acute rejection of lung allografts. Acute rejection represents the most important risk factor for the development of chronic lung allograft dysfunction.


METHODS
We analyzed the pattern of HLA antibodies before and after transplantation in 54 patients, and correlated our data with the presence and frequency of high-grade and persistent-recurrent acute rejection, during the first 18 post-operative months. The diagnosis of acute rejection was based on histologic International Society for Heart and Lung Transplantation (ISHLT)-published criteria.


RESULTS
Ten of 54 patients had a positive enzyme-linked immunoassay (ELISA) post-transplantation. In 90% of ELISA-positive patients, the presence of HLA antibodies was associated with persistent-recurrent acute rejections, compared with 34% in the ELISA-negative group (p < 0.005). There were 28 high-grade acute rejection episodes in the ELISA-positive group, compared with 36 in the ELISA-negative group (p < 0.0001). The ELISA-positive patients required a greater intensity of immunosuppressive therapy. The patients with ELISA-detected anti-HLA antibodies were at least 3-fold more likely to develop high-grade acute rejection and persistent-recurrent acute rejection, and 7-fold more likely to develop multiple episodes of persistent-recurrent acute rejection, compared with ELISA-negative patients.


CONCLUSIONS
ELISA-based screening for the development of HLA antibodies is a reliable method that can identify lung transplant recipients at increased risk for high-grade and persistent-recurrent acute rejection. Although bronchiolitis obliterans appears as a point of no return in the evolution of lung-transplanted patients, early detection of risk factors for acute rejection could indirectly decrease the incidence of bronchiolitis obliterans. These lung-transplanted patients may benefit from an altered strategy of immunosuppression.
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA.
Alin L
AL
Girnita
Kenneth R
KR
McCurry
Aldo T
AT
Iacono
Rene
R
Duquesnoy
Timothy E
TE
Corcoran
Mohamed
M
Awad
Kathy J
KJ
Spichty
Samuel A
SA
Yousem
Gilbert
G
Burckart
James H
JH
Dauber
Bartley P
BP
Griffith
Adriana
A
Zeevi
D000208:Acute Disease; D000906:Antibodies / Q000032:analysis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000032:analysis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D000906:Antibodies; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007518:Isoantibodies