High Mean Fluorescence Intensity Donor-Specific Anti-HLA Antibodies Associated With Chronic Rejection Postliver Transplant

Abstract

In contrast to kidney transplantation where donorspecific anti-HLA antibodies (DSA) negatively impact graft survival, correlation of DSA with clinical outcomes in patients after orthotopic liver transplantation (OLT) has not been clearly established. We hypothesized that DSA are present in patients who develop chronic rejection after OLT. Prospectively collected serial serum samples on 39 primary OLT patients with biopsy-proven chronic rejection and 39 comparator patients were blinded and analyzed for DSA using LABScreen R single antigen beads test, where a 1000 mean fluorescence value was considered positive. In study patients, the median graft survival was 15 months, 74% received ≥ one retransplant, 20% remain alive and 87% had ≥ one episode of acute rejection. This is in contrast to comparator patients where 69% remain alive, and no patient needed retransplant or experienced rejection. Thirty-six chronic rejection patients (92%) and 24 (61%) comparator patients had DSA (p = 0.003). Chronic rejection versus comparator patients had higher mean fluorescence intensity (MFI) DSA. Although a further study with larger numbers of patients is needed to identify clinically significant thresholds, there is an association of high-MFI DSA with chronic rejection after OLT.Key words: Chronic allograft rejection, donor-specific antibodies, HLA antibodies, Liver Transplantation Abbreviations: DSA, donor-specific anti-HLA antibodies; HCV, hepatitis C; MFI, mean fluoresce intensity; MELD, model for end-stage liver disease; OLT, orthotopic liver transplantation.

Prevalence, Incidence and Risk Factors for Donor-Specific Anti-HLA Antibodies in Maintenance Liver Transplant Patients

“…The prevalence of preformed DSAs and de novo DSAs was, respectively, 60% and 62% in the chronic rejection group, and 41% (p ¼ ns) and 38% (p ¼ 0.047) in patients with no rejection (18). The proportion of patients who had an MFI !10 000 was also significantly greater in patients with chronic rejection (52% vs. 13%, p < 0.0001) (18). Surprisingly, in this latter study, 61% of patients who had DSAs did not present with any rejection episodes.…”

“…In a case-controlled study, O'Leary et al (18) found DSAs in 92% of patients with chronic rejection compared to 61% in those with no history of acute or chronic rejection (p ¼ 0.003). The prevalence of preformed DSAs and de novo DSAs was, respectively, 60% and 62% in the chronic rejection group, and 41% (p ¼ ns) and 38% (p ¼ 0.047) in patients with no rejection (18).…”

“…AMR occurred in patients with de novo DSAs, though mainly in those with very low or no immunosuppression. In the study by O'Leary et al (18), 61% of patients with no rejection episodes had detectable DSAs. However, in their study, information on immunosuppressive regimens and the levels of immunosuppressants were not given for patients with chronic rejection, where DSAs occurred at a prevalence of 92% (18).…”

“…In the study by O'Leary et al (18), 61% of patients with no rejection episodes had detectable DSAs. However, in their study, information on immunosuppressive regimens and the levels of immunosuppressants were not given for patients with chronic rejection, where DSAs occurred at a prevalence of 92% (18). In an editorial, Briggs and Adams (26) wrote that it was not clear if monitoring for DSAs was needed, as their appearance might precede liver histological lesions by several years and because many patients never suffer graft dysfunction.…”

“…The difference observed between Fontana et al's (15) study and ours is probably because we used a more sensitive assay. Recently, Miyagawa-Hayashino et al (16) assessed the prevalence of DSAs among stable pediatric LT patients who had survived for >5 years: they found a prevalence of 48% at 11 years (min-max: [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] posttransplantation. This high prevalence of DSAs is probably related to the very long follow-up in this Japanese study (16).…”