Anti-HLA Antibodies Do Not Increase in Kidney Transplant Recipients During COVID-19 Infection

ABSTRACT

Purpose: To determine if HLA allo-antibody levels are affected by COVID-19 in renal transplanted patients and to compare the immunoglobulin class and subclass profiles as well as the epitope binding patterns of anti-HLA and anti-SARS-CoV-2 antibodies. Method(s) A cross-sectional study of 46 kidney transplant recipients diagnosed with PCR+ SARS-CoV-2 infection was conducted. Serum samples were collected at the time of infection. For 21 patients, we obtained historical anti-HLA antibody information before COVID-19. Using a single-antigen bead Luminex assay, we determined IgG, IgG1/2/3/4, IgM, and IgA antibodies against Class I and Class II HLA, as well as against five SARS-CoV-2 (Wuhan strain) protein fragments nucleocapsid, whole spike (S), spike S1, spike S2 and spike receptor binding domain (RBD). Result(s) 26/46 subjects had anti-HLA antibodies of which fourteen had donorspecific anti-HLA antibodies (DSA) compared with 45/46 had anti-SARS-CoV2 antibodies. The majority of DSA were specific to HLA-DQ (10/14), with a dominant IgG/IgG1/IgG3 subclass prevalence. Anti-SARS-CoV-2 antibodies exhibited stronger reactivity towards S and RBD and had increased IgM (38/43, 79%) and IgA (41/42, 85%) prevalence when compared to DSAs (5/14, 35% and 2/14, 14%, p<0.001).Out of 21 patients with pre-COVID-19 data available, calculated panel antibody reactivity (cPRA) levels did not change after COVID-19 in 14 cases (67%);cPRA increased in two cases (10%), both of them with allograft nephrectomy and immunosuppression discontinuation, and decreased in five patients (20%) (from 65.4+/-12.6% before COVID-19, to 29.4+/-33.6% after COVID-19) (Figure 1). Patients with DSA exhibited significantly lower anti-S IgG (9453+/-9945 vs 17975+/-12792;P=0.001), anti-RBD IgM (4464+/-3693 vs 8751+/-6468;P=0.03) and anti-nucleoprotein IgA (998+/-835 vs 5476+/-6895;P=0.001) anti-SARS-CoV2 antibody MFI values than patients without DSA. Conclusion(s) cPRA values did not increase following PCR confirmed COVID-19 diagnosis in renal transplant recipients and those subjects with pre-existing DSA had lower antibody strength directed at SARS-CoV-2 antigens. The lack of increase in alloantibody response is quite remarkable, since over 80% of the patients underwent either significant reduction or withdrawal of mycophenolate mofetil after COVID-19 diagnosis. (Figure Presented).