The identification of low-level antibodies by single antigen bead methodology has brought advancements in risk evaluation of kidney transplants recipients. However, the use of the mean fluorescence intensity values (MFIs) to quantify antibodies and to guide therapy is not enough. Here we evaluated the function and activity of donor-specific antibodies (DSA) sequentially after transplantation to determine the characteristics of those DSA that show higher prediction values for ABMR. We prospectively monitored thirty DSA positive kidney allograft recipients at multiple time points up to 5 years after transplantation. Then we retrospectively tested DSA positive sera to identify IgG subclass composition and its ability to bind complement and evaluate the positive and negative prediction (PPV; NPV) value of each DSA characteristic towards ABMR. A mean value of 8.8 post-transplant sera were tested per patient, completing a 4.5 years mean follow-up. During the post-transplant evolution, we observed changes in antibody subclass profile, MFI values and C1q-binding over time. The DSA characteristics associated with higher PPV were: DSA of both class I and and II (PPV=33.3%; NPV=97.3%); MFI greater than 6000 (PPV=50.0%; NPV=97.3%); DSA with C1q-binding (PPV=47.6%; NPV=99.0%); and presence of 4 IgG subclasses (PPV=57.1%; NPV=94.2%). We further evaluated the diagnostic value of the use of all DSA characteristics information together to the prediction of ABMR, which showed an increase in PPV of 85.7% and a NPV of 98.0%. In conclusion, subclass identification and C1q-binding testing provide additional information for ABMR prediction and helps to describe the sequence of events in the evolution of the antibody response. Moreover, the combined use of all information of DSA characteristics improves ABMR diagnosis, showing a possible relationship of high MFIs, C1q-binding and the presence of 4 subclasses with ABMR.

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