*Purpose: To identify HLA-DQ de novo donor-specific antibodies (dnDSA) characteristics associated with acute humoral rejection (ABMR) and response to treatment.

*Methods: We performed a retrospective analysis of all patients who underwent a kidney (n=33) and pancreas after kidney (n=1) transplant and developed anti-HLA-DQ dnDSA between 12/14 and 6/19 at our center. Antigen level or molecular HLA typing was available for all donors and patients. No patient had detectable DSA pre-transplant.

*Results: Of the 34 patients with HLA-DQ dnDSA, 31 patients had biopsy data. 21 patients (68%) had biopsy proven ABMR (Group 1) and 10 (32%) had ABMR negative biopsies (Group 2). The two groups were equivalent in demographic characteristics. The concurrent presence of Class I and Class II DSA vs Class II DSA alone were similar between groups: (Gr1 v Gr2: 48% v 40% and 52% v 60% respectively) as was the number of HLA-DQ mismatches (p=0.18) and onset of DSA (<1yr vs >1yr p=0.17). However, more Gr1 vs Gr2 patients had acute kidney injury (n=8 vs n=0 p=0.02) and received treatment (90% vs 50% p=0.01). Despite therapy, the trend was that more patients in Gr1 than Gr2 developed worsening renal function (n=9 vs n=1 p=0.06) and graft failure (n=5 vs n=0 p=0.09). Anti-HLA-DQ dnDSA MFI levels were reassessed in 28 patients (19 Gr1, 8 Gr2, 1 no bx data). For Gr1 patients, only 26% cleared HLA-DQ alloantibodies. In contrast, HLA-DQ alloantibodies resolved in 50% of Gr2 patients. Irrespective of treatment or the presence of ABMR, 73% of all HLA-DQ dnDSA with MFI <10,000 cleared whereas only 6% with MFI >10,000 resolved (p<0.01).

*Conclusions: Our data demonstrates that the presence of anti-HLA-DQ dnDSA does not invariably correlate with ABMR or early graft loss. Anti-HLA-DQ dnDSA in the absence of ABMR are likely to be of lower MFI level, less likely to lead to early graft loss and more likely to resolve with therapy. Therefore, our results support the benefit of routine anti-HLA-DQ dnDSA monitoring and early treatment in the goal of preventing late onset ABMR and graft loss.

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