Association of C1q Binding Status With De Novo HLA Antibody Clinical Features and Allograft Function in Kidney Transplantation Patients During Eight Years of Dynamic Follow-up

Transplant Proc. 2016 Jul-Aug;48(6):1944-54. doi: 10.1016/j.transproceed.2016.05.010.

Abstract

Background: C1q-binding donor-specific antibody (DSA) is detrimental to transplanted kidney function. However, the factors that affect C1q binding status are unclear.

Methods: A total of 519 samples from 129 consecutive kidney transplantation patients during 8 years of dynamic follow-up were collected for HLA antibody (Ab) screening and C1q detection.

Results: Among the detected HLA Abs, the majority were class II, and the DQ subtypes composed the highest proportion. The C1q-binding Abs were all HLA-II, and the DQ subtypes had the highest rate of C1q positivity. With a cutoff mean fluorescence intensity (MFI) value of 7349, the sensitivity and specificity of detecting C1q-binding Abs from all HLA-II Abs were 84.48% and 83.56%, respectively. Additionally, C1q is more likely to be bound by DSA than non-donor-specific antibody (NDSA). Compared with free DSA/NDSA, the MFI values of C1q-binding DSA/NDSA are more closely correlated with serum creatinine levels and reflect the effect of anti-antibody-mediated rejection treatment more sensitively.

Conclusions: HLA-II Abs (particularly DQ subtypes), high titers of Abs, and DSA are important relevant factors of C1q positivity. The MFI value of C1q-binding DSA may be a useful clinical indicator of HLA antibody-mediated graft injury before the appearance of histologically typical humoral rejection.

MeSH terms

  • Adult
  • Allografts / immunology
  • Complement C1q / immunology*
  • Female
  • Follow-Up Studies
  • Graft Rejection / immunology*
  • Graft Survival / immunology
  • HLA Antigens / immunology*
  • Humans
  • Isoantibodies / blood
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Sensitivity and Specificity
  • Tissue Donors
  • Transplantation, Homologous

Substances

  • HLA Antigens
  • Isoantibodies
  • Complement C1q