Complement Fixing HLA Antibodies Predict Outcome in HLA Incompatible Renal Transplantation

C. Clarke, P. Brookes, C. Lawrence, M. Willicombe, P. Dodd, E. Santos-Nunez, J. Galliford, D. Taube

Imperial College Renal and Transplant Centre, Hammersmith Hospital, London, United Kingdom

Meeting: 2013 American Transplant Congress

Abstract number: 1

HLA incompatible [HLAi] transplantation is associated with a higher incidence of antibody mediated rejection [AMR] and Transplant Glomerulopathy [TG]. In this study, we show that HLAi patients with complement fixing donor specific antibodies [C1q+DSAbs] have a higher incidence of AMR than patients with non-complement fixing DSAbs [C1q-DSAbs].

18 HLAi patients [m3, f15, mean age 47.9±13.83 years] underwent desensitisation [DS] with plasma exchange, IVIg and monoclonal antibody induction pre transplant and Tacrolimus, MMF and a week of steroids post-transplant. All patients were FXM+ prior to DS and FXM- at operation. Rejection was diagnosed by biopsy. Stored serum samples from patients pre and post DS and at the time of rejection were retrospectively analysed with a C1q assay [One Lambda] to determine C’fixing IgG and IgM DSAbs. Death censored graft survival was 100% at 1 year and 77.8% at 5 years. 4 patients lost their grafts [3 from rejection; all had C1q+DSAbs].

10/18 (55.6%) patients had C1q+DSAbs and patients with C1q+DSAbs were significantly more likely to develop rejection compared with C1q-DSAbs patients [(fig 1) 90% vs. 25%, p=0.01].

8/11 patients who developed rejection had complement fixing antibodies at the time of their first rejection episode; 1 C1q-DSAbs patient became C1q+DSAbs at the time of rejection.

Table 1 shows that C1q+DSAbs patients had poorer allograft function and more proteinuria than C1q-DSAbs patients [p<0.001]. Peritubular capillaritis [p=0.01] and glomerulitis [p=0.01] were more common in C1q+DSAbs patients. 4 patients with C1q+DSAbs progressed to TG; no C1q-DSAbs patients developed TG.

Table 1
	Mean Creat at 12 months	Mean Creat at 24 months	Mean Creat at 36 months	Mean Urine PCR at 12 months	Mean Urine PCR at 24 months	Mean Urine PCR at 36 months
C1q+DSAbs	142 mmol/L	190 mmol/L	190 mmol/L	133	246	156
C1q-DSAbs	95 mmol/L	113 mmol/L	102 mmol/L	118	95	58

This study shows that HLAi transplant patients with C1q+DSAbs have a significantly higher incidence of rejection and graft loss; pre-screening for C1q+DSAbs identifies high risk patients.

To cite this abstract in AMA style:

Clarke C, Brookes P, Lawrence C, Willicombe M, Dodd P, Santos-Nunez E, Galliford J, Taube D. Complement Fixing HLA Antibodies Predict Outcome in HLA Incompatible Renal Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/complement-fixing-hla-antibodies-predict-outcome-in-hla-incompatible-renal-transplantation/. Accessed May 14, 2025.

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