Abstract: Background: The improvement in the definition of serum anti-HLA antibodies (HLA-Abs) profiles after Luminex-assay implementation in transplant patients follow-up is clear. This success has permitted the development of hypersensitized-recipient allocation and donor-paired exchange programs improving the access to transplantation. However, non-HLA Abs have been described in transplanted patients but their effect in hypersensitized transplanted recipients is unclear. Methods: Twenty-seven HLA hypersensitized patients awaiting for kidney transplantation (KT) were studied and 11 of them were followed after KT. The HLA Abs profile was confirmed in serum by Single Antigen Luminex assay and panel reactive of antigens >98% was achieved in all patients. Subsequently, the ability to fix complement by C1q test was also assessed. Serum non-HLA Abs before and 1 month after transplantation were measured in the 11 hypersensitized recipients. Results: 95.2% of the hypersensitized on waiting list had concomitant serum anti-HLA and non-HLA Abs. The more frequent specificity in non-HLA Abs were found against Glutathione S-transferase theta-1 (GSST-1) (in 62%) and C-terminal fragment of perlecan (LG3) (in 52%). Four out of 11 transplanted patients presented early antibody-mediated rejection (ABMR) confirmed by biopsy and had serum anti-LG3 antibodies, two of them with concomitant anti-anti-angiotensin II type I receptor. Only one patient developed de novo-donor specific HLA antibodies. Conclusions: The incidence of non-HLA antibodies in patients in the waiting list is largely underestimated. The concomitance anti-HLA and non-HLA Abs in hypersensitized patients is very common and the detection of non-HLA Abs in this population could allow to identify patients with an increased risk of humoral rejection.

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