Sheldon S, Yonan N A, Aziz T N, Hasleton P S, Rahman A N, Deiraniya A K, Campbell C S, Dyer P A
Transplantation Laboratory, Manchester Royal Infirmary, UK.
Transplantation. 1999 Aug 27;68(4):515-9. doi: 10.1097/00007890-199908270-00012.
We report a consecutive single center series of 261 patients who received first orthotopic heart transplants from 1986 to 1997. The 1- and 5-year graft survivals were 78 and 68%. The influence of histocompatibility was investigated by comparing graft survival and numbers of treated rejection episodes with HLA-A, -B, and -DR mismatches over different time periods.
Recipients with six mismatches for HLA-A+-B+-DR combined (13.4%) had reduced survival at 7 years (47%) when compared with other recipients (64%). In the first year of transplant, recipients with four HLA-A+-B mismatches had significantly reduced actuarial graft survival (P=0.03) with the greatest influence apparent at 6 months [0-3 mismatches (n=193) 85% versus 4 mismatches (n=68) 69%; P=0.005, OR=2.1]. For 182 recipients with functioning hearts at 1 year, the number of rejection episodes treated within this time was strongly influenced by HLA-DR mismatch [0 DR mismatch (n=15) mean 1.2 rejection episodes versus 1 DR mismatch (n=76) mean 2.7 rejection episodes versus 2 DR mismatches (n=91) mean 3.8 rejection episodes: P=0.0002]. Of these 182 transplants, recipients who had more than four treated rejection episodes during the first year had a significantly reduced 7- year survival [<5 rejection episodes (n=133) 85% versus more than four rejection episodes (n=49) 66%; P=0.02, OR=3.4], as did those with two HLA-DR mismatches [0+1 mismatch (n=91) 87% versus 2 mismatches (n=91) 70%; P<0.05, OR=2.4].
We show that graft loss in the first 6 months of transplant is significantly influenced by four HLA-A+-B mismatches. HLA-DR mismatch significantly increases the number of rejection episodes within the first year, without influencing graft survival. After 12 months both >4 rejection episodes in the first year and two HLA-DR mismatches are markers for late graft loss. We postulate that immunological graft loss in the first 6 months is dominated by the direct allorecognition pathway driven by HLA-DR mismatch. This mechanism is later lost or suppressed. Our data highlight HLA-DR mismatch as a marker for late graft loss and we show an advantage to avoiding transplanting hearts with six HLA-A+-B+-DR mismatches and to minimizing HLA-DR mismatches whenever possible.
我们报告了1986年至1997年间在单一中心连续接受首次原位心脏移植的261例患者。1年和5年移植物存活率分别为78%和68%。通过比较不同时间段内HLA - A、- B和 - DR错配情况下的移植物存活率和治疗的排斥反应发作次数，研究了组织相容性的影响。
HLA - A + - B + - DR联合错配6次的受者（13.4%）在7年时的存活率（47%）低于其他受者（64%）。在移植的第一年，HLA - A + - B错配4次的受者精算移植物存活率显著降低（P = 0.03），在6个月时影响最为明显[0 - 3次错配（n = 193）为85%，而4次错配（n = 68）为69%；P = 0.005，OR = 2.1]。对于182例术后1年心脏功能正常的受者，这段时间内治疗的排斥反应发作次数受HLA - DR错配的影响很大[0次DR错配（n = 15）平均1.2次排斥反应发作，1次DR错配（n = 76）平均2.7次排斥反应发作，2次DR错配（n = 91）平均3.8次排斥反应发作：P = 0.0002]。在这182例移植中，第一年接受超过4次治疗性排斥反应发作的受者7年存活率显著降低[<5次排斥反应发作（n = 133）为85%，超过4次排斥反应发作（n = 49）为66%；P = 0.02，OR = 3.4]，有2次HLA - DR错配的受者也是如此[0 + 1次错配（n = 91）为87%，2次错配（n = 91）为70%；P < 0.05，OR = 2.4]。
我们发现移植后前6个月的移植物丢失受4次HLA - A + - B错配的显著影响。HLA - DR错配显著增加第一年的排斥反应发作次数，但不影响移植物存活。12个月后，第一年>4次排斥反应发作和2次HLA - DR错配均是晚期移植物丢失的标志物。我们推测移植后前6个月的免疫性移植物丢失主要由HLA - DR错配驱动的直接同种异体识别途径主导。这种机制随后会丧失或受到抑制。我们的数据突出了HLA - DR错配作为晚期移植物丢失的标志物，并且我们表明避免移植HLA - A + - B + - DR错配6次的心脏以及尽可能减少HLA - DR错配具有优势。
