Abstract

Aim HLA antibody identification testing has become increasingly sensitive, especially solid-phase assays using fluorescent detection. Recently, a new Luminex single antigen bead (SAB) based assay has been developed that detects HLA antibodies binding C1q, the initial complement protein. This test may help differentiate HLA antibodies with more clinical relevance than others, but the significance of C1q antibodies post-transplant (Tx) is still being determined. We have introduced C1q testing into our renal allograft antibody monitoring. Patients with donor specific antibody (DSA) also undergo C1q testing to determine DSA complement binding ability. To understand the clinical significance of C1q DSA, we determined the associations between C1q binding DSA and serum creatinine (Cr) and pathological C4d staining in a cohort of renal allograft patients. Methods DSA was detected in 72 sera by conventional Luminex SAB and C1q testing in 41 recipients (31 adult, 10 pediatric). Cr was recorded at the time of DSA testing and at the time of last follow-up. 19 adult patients had 24 biopsies at the time of C1q testing and were scored for peritubular capillary C4d immunostaining. Results At the time of DSA testing (mean 1364 days; range 7-8579), Cr did not differ between patients with or without C1q-binding DSA (1.9 ± 1.3 vs 2.1 ± 1.4; p = 0.41). Patients with DSA testing 1 year post-Tx (p = 0.29). At the time of last follow-up (mean 225d after C1q testing), Cr was significantly greater in patients with C1q DSA (2.8 ± 2.8 vs 1.4 ± 0.6; p = 0.05). In 79% of patients with C1q DSA had C4d focal or diffuse on renal biopsy compared to 60% in those without C1q DSA (Chi-Square = 9.35 p = 0.025). However, some patients with C1q DSA had minimal/no C4d, and patients without C1q DSA displayed focal or diffuse C4d. Conclusions In our renal allograft cohort, serum Cr did not different at the time of C1q DSA testing, but patients with C1q DSA had increased incidence of renal biopsy C4d and higher Cr at the time of last follow-up.

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