The Impact of Donor-Recipient Human Leukocyte Antigen Matching on Bronchiolitis Obliterans-Free Survival Among Lung Transplant Recipients With Connective Tissue Diseases.

The development of connective tissue disease-associated lung diseases (CTD-LD) occurs in association with specific human leukocyte antigens (HLA). For CTD-LD patients who require lung transplant, it is unknown whether utilization of donor organs expressing these same HLA impacts posttransplant outcomes. Using the Scientific Registry of Transplant Recipients, we assessed whether CTD-LD lung transplant recipients in the United States have worse bronchiolitis obliterans (BOS)-free survival based on the degree of donor HLA matching. This included overall degree of donor-recipient HLA matching, donor-recipient matching at DR loci, and recipient matching with specific donor HLA antigens associated with the development of pulmonary disease in their condition. Among 1413 patients with CTD-ILD, highly HLA-matched donor-recipients did not have worse adjusted survival (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.58-1.51, p = 0.77). Recipients who were fully matched at HLA DR did not have worse survival (HR = 0.82, 95% CI = 0.56-1.19, p = 0.29). Finally, among individual CTD-LD, including rheumatoid arthritis, systemic sclerosis, the idiopathic inflammatory myopathies, and systemic lupus erythematous, transplant with a donor expressing HLA antigens associated with lung manifestations in these conditions was not associated with worse BOS-free survival. Among transplant recipients with CTD-LD, HLA donor-recipient matching, including at the DR loci, does not result in worse BOS-free survival. Based on these findings, there is no reason to treat these as unacceptable antigens when considering donor offers for CTD-LD candidates.

Courtwright AM ，Diamond JM ，Sandorfi N ，Goldberg HJ ... -  《-》

The impact of HLA-DR mismatch status on retransplant-free survival and bronchiolitis obliterans syndrome‒free survival among sensitized lung transplant recipients.

Donor‒recipient HLA-DR locus matching may be protective against bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. It is unknown whether this benefit is more significant among sensitized (calculated panel reactive antibodies (CPRAs) of >0%) and highly sensitized (CPRAs of ≥80%) recipients who may be at a higher risk for BOS. This was a retrospective cohort study of adults in the Scientific Registry of Transplant Recipients who underwent lung transplantation between May 5, 2005 and May 31, 2019. Retransplant-free survival and BOS-free survival were compared among recipients with 0 vs ≥1 DR mismatches, grouped according to sensitization. Among all 20,355 included recipients, 0 DR mismatch status was associated with improved retransplant-free survival (hazard ratio [HR] = 0.83, 95% CI = 0.74-0.93, p = 0.002) and BOS-free survival (HR = 0.86, 95% CI = 0.77-0.96, p = 0.007). Among sensitized recipients, 0 DR mismatch status was also associated with improved retransplant-free survival (HR = 0.79, 95% CI = 0.65-0.97, p = 0.02) and BOS-free survival (HR = 0.82, 95% CI = 0.67-1.00, p = 0.04). There was however no difference in retransplant-free or BOS-free survival between sensitized and non-sensitized recipients with 0 DR mismatches. Among highly sensitized recipients, 0 DR mismatch status was not associated with retransplant-free or BOS-free survival. Among sensitized and highly sensitized recipients, 0 DR mismatch status was not associated with reduced use of plasmapheresis or reduced biopsy-proven, treated acute cellular rejection compared with non-sensitized recipients. HLA-DR matching is associated with a similar improvement in retransplant-free and BOS-free survival among non-sensitized and sensitized lung transplant recipients. DR matching does not confer a more substantial retransplant-free or BOS-free survival benefit to highly sensitized recipients than to non-sensitized recipients.

Courtwright AM ，Kamoun M ，Kearns J ，Diamond JM ，Golberg HJ ... -  《-》

Development of an antibody specific to major histocompatibility antigens detectable by flow cytometry after lung transplant is associated with bronchiolitis obliterans syndrome.

Palmer SM ，Davis RD ，Hadjiliadis D ，Hertz MI ，Howell DN ，Ward FE ，Savik K ，Reinsmoen NL ... -  《-》

Effect of human leukocyte antigen-C and -DQ matching on pediatric heart transplant graft survival.

A higher degree of human leukocyte antigen (HLA) matching at the A, B, and DR loci has been associated with improved long-term survival after pediatric heart transplantation in multiple International Society for Heart and Lung Transplantation registry reports. The aim of this study was to investigate the association of HLA matching at the C and DQ loci with pediatric graft survival. The United Network of Organ Sharing database was queried for isolated heart transplants that occurred from 1988 to 2012 with a recipient age of 17 or younger and at least 1 postoperative follow-up encounter. When HLA matching at the C or DQ loci were analyzed, only transplants with complete typing of donor and recipient at the respective loci were included. Transplants were divided into patients with at least 1 match at the C locus (C-match) vs no match (C-no), and at least 1 match at the DQ (DQ-match) locus vs no match (DQ-no). Primary outcome was graft loss. Univariate analysis was performed with the log-rank test. Cox regression analysis was performed with the following patient factors included in the model: recipient age, ischemic time; recipient on ventilator, extracorporeal membrane oxygenation, ventricular assist device, or inotropes at transplant; recipient serum bilirubin and creatinine closest to transplant, ratio of donor weight to recipient weight, underlying cardiac diagnosis, crossmatch results, transplant year, and HLA matching at the A, B, and DR loci. Complete typing at the C locus occurred in 2,429 of 4,731 transplants (51%), and complete typing at the DQ locus occurred in 3,498 of 4,731 transplants (74%). Patient factors were similar in C-match and C-no, except for year of transplant (median year, 2007 [interquartile range, 1997-2010] vs year 2005 [interquartile range, 1996-2009], respectively; p = 0.03) and the degree of HLA matching at the A, B, and DR loci (high level of HLA matching in 11.9% vs 3%, respectively; p < 0.01). Matching at the C locus was not associated with a decreased risk of graft loss (median graft survival: 13.1 years [95% confidence interval {CI}, 11.5-14.8] in C-no vs 15.1 years [95% CI, 13.5-16.6) in C-match, p = 0.44 log-rank; hazard ratio, 0.93; 95% CI, 0.76-1.15; p = 0.52). DQ-match did not differ from DQ-no in any of the analyzed patient factors, except DQ-match was more likely to have high degree of matching at the A, B, and DR loci vs DQ-no (9.8% vs 3.2%, p < 0.01). Matching at the DQ locus was not associated with decreased risk of graft loss (median graft survival: DQ-no, 13.1 years [95% CI, 11.7-14.6) vs DQ-match, 13.0 years [95% CI, 11.4-14.6], p = 0.80, log-rank; hazard ratio, 0.95; 95% CI, 0.81-1.1; p = 0.51. Complete typing at the C locus of both donor and recipient occurs less often then typing at the DQ locus. A higher degree of donor-recipient HLA matching at the C locus or the DQ locus appears not to confer any graft survival advantage.

Butts RJ ，Savage AJ ，Nietert PJ ，Kavarana M ，Moussa O ，Burnette AL ，Atz AM ... -  《-》

De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation.

Bronchiolitis obliterans syndrome (BOS) is the major cause of late graft failure after lung transplantation. The objective was to determine whether de novo donor human leukocyte antigen (HLA)-specific antibodies (DSA) are associated with the development of BOS or patient survival. Data were analyzed from 188 lung transplant recipients with a follow-up period up to 8 years. HLA antibody monitoring was performed at 3-month intervals post-transplant at routine outpatient clinic attendances and during the investigation of any acute deterioration. HLA antibody data were available for 148 patients; 66 (45%) had produced HLA antibodies after transplant, of which 38 (26%) were DSA and 28 (19%) non-donor-specific HLA antibodies. De novo DSA was associated with development of BOS Stage 1 (BOS1; hazard ratio [HR] = 2.302, p = 0.0015), BOS2 (HR = 3.627, p < 0.0001) and BOS3 (HR = 5.736, p < 0.0001). De novo persistent DSA correlated strongly with shorter time to onset of BOS3 (HR = 6.506, p = 0.0001). There was a significant reduction in patient survival associated with de novo DSA (HR = 1.886, p = 0.047). In multivariable analyses, de novo DSA was an independent predictor for development of all stages of BOS as well as an independent predictor of poor patient survival. De novo DSA is a major risk factor for progression to BOS and shorter patient survival. Treatments to remove antibodies or limit antibody-mediated damage could be considered when DSA are first detected. However, a randomized, controlled trial of treatment options would enable a clearer understanding of the benefits, if any, of antibody-removal therapies.

Safavi S ，Robinson DR ，Soresi S ，Carby M ，Smith JD ... -  《-》