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Class I HLA-IgM donor-specific antibodies are associated with antibody mediated rejection after renal transplantation
Philippa Dodd, Michelle Willicombe, Paul Brookes, Candice Roufosse, Eva Santos-Nunez, Dawn Goodall, Dimitrios Moutzouris, Candice Clarke, Rawya Charif, Jack Galliford, Adam McLean, David Taube
Imperial College Renal & Transplant Centre, London, UK
Pre-formed and de novo IgGdonor specific HLA antibodies (DSA) are associated with acute and chronic antibody mediated rejection (AMR) and inferior renal allograft survival. These DSAs are readily identified by single antigen bead assays. A proportion of patients with AMR have no detectable circulating IgG HLA DSAs and it is presumed that these antibodies are either absent or bound to the allograft. IgM HLA antibodies are traditionally thought to be harmless auto-antibodies and there are few studies attributing a more pathogenic role for these antibodies in renal transplantation.
We retrospectively studied 24 recipients(17male, 7female, mean age 43.7 years)transplanted between 2004-2011with histological evidence of AMR but no detectable IgG DSA. 17/24 (70.8%) recipients had evidence of either focal or diffuse C4d deposition on indicative biopsy, suggesting the presence of circulating antibody. Sera from these recipients, sampled pre and post transplantation including at the time of indicative biopsy, were screened using LABScreen® Luminex® mixed and single antigen bead assays for the presence of IgG and IgM HLA and DSA. None of the 24 patients screened positive for IgG HLA or DSA antibodies. However 17/24 (70.8%) screened positive for the presence of IgM antibodies and 12/24 (50%) were identified as having class I IgM DSA.
In this study we show that a significant proportion of patients with histological evidence of AMR and no detectable IgG HLA DSA have Class I IgM HLA DSA. These preliminary findings suggest that IgM HLA antibodies may have a significant pathogenic role in AMR, particularly in those patients who are IgG DSA negative. These findings may also have significant therapeutic implications as patients with IgG DSA negative AMR may not be plasma exchanged because traditionally no circulating antibodies have been identified for removal. If these patients have IgM DSA, they may well respond to appropriate forms of therapeutic plasma exchange.