Indicators of rituximab responsiveness in antibody-mediated rejection after kidney transplantation

• Published in: Human immunology 2015-10, Vol.76, p.65-65
• Main Authors: Immenschuh, Stephan, Zilian, Eva, Daemmrich, Maximilian E, Gwinner, Wilfried, Becker, Jan Ulrich, Blume, Cornelia A
• Format: Article
• Language: English
• Subjects: Allergy and Immunology
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2015.07.092

Aim Treatment of patients with antibody-mediated rejection (AMR) after kidney transplantation with rituximab is ambiguous. Due to its unknown efficiency and serious side-effects, biomarkers, that are predictive for responsiveness to rituximab therapy in AMR patients, are required. Methods Twenty renal transplant patients were included in this retrospective study. Selection was based on Renal Index Biopsies, classified using Banff, where at least two AMR diagnostic criteria were positive within the three months prior to rituximab therapy. Patients were categorized into responders (R) and non-responders (NR) depending on whether they returned to dialysis within 6 months after initiation of rituximab treatment. Clinical, histopathological (Banff classification) and serological parameters were compared between both groups by t-test, Mann-Whitney-U-test or Likelihood-Ratio-Chi-square-test. Results In comparisons between the groups, the R group had a 1.5-fold higher level of estimated glomerular filtration rate (eGFR) and a 4-fold lower level of proteinuria. By contrast, there were no differences in the histological scores for chronic transplant lesions between the groups. The t- and i-scores were higher in NRs, whereas Banff-C4d-scores of peritubular capillaries were increased in the Rs. Transplant biopsies in the Rs exhibited more CD138+cell infiltrates. Serological determination of HLA antibodies showed higher positivity for HLA class II donor-specific antibodies in the R group. No significant differences in other clinical criteria were found. Conclusions Increased proteinuria, decreased graft function and a higher grade of tubulitis and inflammation in AMR are negative predictors for responsiveness to rituximab therapy. Rituximab therapy therefore should be initiated in an early phase of AMR.