Background It has been reported that de novo donor-specific HLA antibody (dn DSA) production is associated with chronic antibody-mediated rejection (CAMR) which leads to poor outcome. However, the question of what specific amounts of dnDSA are responsible for CAMR remains to be solved. Early diagnosis before a rise in serum creatinine and/or proteinuria is observed, and is undoubtedly essential for effective treatment of CAMR. The aim of our study was to identify factors related to the development of subclinical CAMR and to evaluate the efficacy of its treatment.

Methods. We followed up on 899 renal transplants without preformed DSA. These patients were annually screened for HLA antibodies by LABScreen Mixed and DSA was identified by LABScreen single antigen beads. Among 95 DSA-positive (MFI>1000) patients, 43 without renal dysfunction who underwent renal biopsies were enrolled in this study. 18 patients (41.9%) were diagnosed with biopsy-proven subclinical CAMR. After biopsies were performed, the patients who were diagnosed subclinical CAMR underwent plasmapheresis (PP) and rituximab-based therapy,while 25 had no significant findings of CAMR. The patients who were resistant to rituximab-based treatments underwent PP and bortezomib-based therapy.

Results. Significant subclinical CAMR-related factors were younger recipients, past history of acute T cell-mediated rejection and DSA-Class II, especially DR-associated DSA. MFI values of DR-DSA were significantly higher, whereas DQ-DSA was not different between subclinical CAMR and no CAMR. Delta MFI (>50%), DSA-MFI values>3000 and positive C1q binding DSA were also significant subclinical CAMR-related factors (P<0.05). Among 18 patients treated for subclinical CAMR, 8 patients (44.4%) obtained over 50% reduction of DSA-MFI and/or improvement or no deterioration of pathological findings. In contrast, 25 patients without subclinical CAMR did not show renal dysfunction clinically. Moreover, all of 12 with re-biopsy after two years continued to demonstrate no ABMR.

Conclusions. About 40% of patients with de novo DSA demonstrated biopsy-proven subclinical CAMR, leading to progressive graft injuries. Patients with these related factors are encouraged to undergo a graft biopsy for proper evaluation, when dnDSA is detected. Further study on effective treatment for subclinical CAMR is necessary.

CITATION INFORMATION: Yamamoto T, Watarai Y, Takeda A, Okada M, Tsujita M, Hiramitsu T, Goto N, Narumi S, Morozumi K, Uchida K, Kobayashi T. De Novo Anti-HLA DSA Characteristics and Subclinical Antibody Mediated Kidney Allograft Injuries. Am J Transplant. 2016;16 (suppl 3).

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