ESOT 2011 Report – Gender and antibody matters

Gender differences between donor and recipient might have an impact on outcome after heart transplantation (HTx). The literature review revealed controversial results. Ingo Kaczmarek and colleagues from Munich, Germany reviewed the data of the ISHLT registry focusing on the influence of gender differences on short- and long-term outcome after HTx.

The researchers performed a registry data analysis of all adult heart transplants performed between January 1, 1980 and June 30, 2009. In contrast to other studies the data for gender differences (donor and recipient gender) were calculated with respect to survival and conditional survival (conditional to 30-day mortality). Furthermore the patients were divided into 4 subgroups: male recipients/male donors (n=40,497), male recipients/female donors (n=13,480), female recipients/male donors (n=6,436) and female recipients/female donors (n=7,420).

During the presentation the results showed67,833 hearts were analysed including 53,977 male recipients (79.6%) and 13,856 female recipients (20.4%) who received hearts from 46,933 male (69.2%) and 20,900 (30.8%) female donors.

One-year survival stratified by recipient gender and donor gender was significantly inferior in male recipients of female donor hearts (m/f: 78.95%) compared to other combinations (m/m: 83.74%; f/m: 82.94%; f/f: 81.92%; log-rank p-value <0.0001). To exclude early mortality we performed a long-term-survival analysis stratified by recipient and donor gender, conditional on survival to 30 days. The analysis revealed superior outcomes for female recipients in general with a 15-year-survival of 40.95% in female recipients of female donor hearts (f/f) and 38.58% for f/m compared to 35.97% m/m and 33.41% m/f (log-rank p-value < 0.0001).

The researchers concluded that the combination male recipient/female donor carries a higher risk for early mortality whereas other gender constellations yield similar outcomes. In the long-term follow-up female recipients reveal superior results – especially in the combination female recipient/female donor. On questioning it was concluded that the HR of 1.18 did not warrant the ceasing of female to male transplants at this time.

 

In a following presentation Markus J. Barten from Bittner Germany explained that cardiac allograft vasculopathy (CAV) after heart transplantation (HTx) is a major therapeutic challenge, occurring in more than 50% of HTx recipients in the first years after transplantation. Antibodies against human leukocyte antigens (HLA) or non-HLA antigens like major histocompatibility complex class I-related chain A (MICA), angiotensin type 1 receptor (AT1R) or endothelin receptor A (ETAR) increasingly gain in importance as modulators of allograft function and survival.

Markus J. Barten presented data where sera of 114 HTx recipients were screened post-transplantation by Luminex-technology for HLA and MICA antibodies and for antibodies against AT1R and ETAR by ELISA. For statistical analysis the gender, age, status of CAV (IVUS detection) and the number of blood transfusions was documented.

The results of the study showed that CAV was detected in n=43 recipients. There was no significant difference in gender and number of blood transfusions between recipients with or without antibodies. HTx recipients developed antibodies against HLA class I or class II to a lower extent than against non-HLA antigens (Tab.1), especially against AT1R and ETAR.

Percentage of HTx recipients with positive antibody detection and CAV-positive recipients for HLA and non-HLA antigens:

Antibody specifity	HTx recipients with positive antibody status [%] (n=114)	CAV-positive HTx recipients with positive antibody status [%] (n=43)
HLA class I	6.1 (n=7)	2.3 (n=1)
HLA class II	9.7 (n=11)	9.3 (n=4)
MICA	11.4 (n=13)	13.9 (n=6)
AT1R	33.3 (n=38)	30.2 (n=13)
ETAR	45.6 (n=52)	37.2 (n=16)

CAV appeared on average in 27.1% of recipients with antibodies against non-HLA antigens, whereas on average 5.8% of the recipients with HLA antibodies developed CAV. Recipients with non-HLA antibodies developed CAV earlier (69.1 months) than recipients without these antibodies (80.1months).

The researchers concluded that Non-HLA antibodies are connected to earlier and higher incidence of CAV after HTx. These results point out the necessity for monitoring HLA and non-HLA antibodies after HTx.

 

References:

O-230 – GENDER MATTERS – GENDER-SPECIFIC OUTCOME ANALYSIS OF 67,000 HEARTS FROM THE ISHLT REGISTRY. Ingo Kaczmarek et al. Munich, Germany

O-231 – HIGH INCIDENCE OF NON-HLA ANTIBODIES IN HEART TRANSPLANTED RECIPIENTS WITH CARDIAC ALLOGRAFT VASCULOPATHY. Markus J. Bartenet al. Leipzig and Berlin, Germany