Boutouyrie-Dumont, Bruno (2014) A new biomarker to identify high-risk renal transplant patients. Biomarkers in Medicine, 8 (1). pp. 73-75. ISSN 1752-0363

Abstract

Summary and comments ("Research Highlights" in News and Views of the journal "Biomarkers in Medicine") on :
Complement-Binding Anti-HLA Antibodies and Kidney-Allograft Survival
Alexandre Loupy, et al.
N Engl J Med 2013;369:1215-26.

“A new Biomarker to identify high-risk renal transplant patients”

Organ transplantation has had a superb success story but there are still patients who reject their graft. It is critical to improve the a priori detection of those patients so that anti-rejection therapy is closely monitored. It was already known that anti-HLA antibodies can provoke rejection, in particular in kidney transplantation. The mechanism of rejection involves activation of the complement cascade. Anti-HLA antibodies can be characterized by their C1q (one of the complement system proteins) binding properties. Small exploratory studies were performed supporting the concept that complement binding of anti-HLA antibodies could be responsible for allograft rejection.

In this paper, the authors report the results of a large study in 1016 kidney allograft patients. The objective of the study was to assess if the presence of C1q-binding donor-specific anti-HLA antibodies after transplantation could evaluate the risk of kidney rejection.

Patients were enrolled from 2 kidney transplantation centers in Paris (France) between January 2005 and January 2011. There was also an external validation cohort of similar patients from a third center.

Acute clinical rejection was defined according to the international Banff classification criteria.
Immunosuppression protocols and treatment of rejection were similar in the 3 centers.

Graft biopsies were obtained in 845 patients, free of rejection and in 171 patients with acute clinical rejection, in the first year post-transplantation. The biopsy specimens were scored and graded following the Banff criteria.
All patients had blood samples assayed for circulating donor-specific anti-HLA antibodies. Those patients being positive for the anti-HLA antibodies were also assayed for the presence of C1q binding.

Out of the 1016 kidney transplant patients, 3 groups were identified after transplantation, based on presence or absence of anti-HLA antibodies and presence or absence of C1q binding properties : 700 had no circulating anti-HLA antibodies (anti-HLA neg group), 239 had non-complement binding anti-HLA antibodies (anti-HLA pos group) and 77 had complement-binding anti-HLA antibodies (C1q pos group).

One year after transplantation, acute rejection occurred in 171 patients : 96 were T-cell-mediated rejection (56%) and 75 were antibody-mediated rejection (44%).

T-cell mediated rejection occurred in 18% of C1q pos group (14/77), in 13% of anti-HLA pos group (30/239) and in 7% of anti-HLA neg group (52/700) (p<0.001).
Antibody-mediated rejection occurred in 48% of C1q pos group (37/77) and in 16% of anti-HLA pos group (38/239) (p<0.001).
C1q pos group had more widespread and severe histologic lesions.

The 5-year graft survival after transplantation was 54% in the C1q pos group, 93% in the anti-HLA pos group and 94% in the anti-HLA neg group (p<0.001)

The external validation group of 643 patients showed the same results.

The presence of C1q binding donor-specific anti-HLA antibodies is an independent predictor of renal allograft loss in the 5 years after transplantation. The involvement of anti-HLA antibodies in graft rejection was already known but the C1q binding detection was not sensitive enough until now. These findings might be also relevant for other transplant organs.
There might also be a therapeutic interest in finding ways of blocking the C1q activation pathway in those patients.

Item Type:	Article
Keywords:	biomarker, renal transplant
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/23632