With great interest we read the recently published article “Advanced Tertiary Lymphoid Tissues in Protocol Biopsies Are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients” by Lee et al.1 This is the first study investigating the prevalence and clinical relevance of tertiary lymphoid tissues (TLTs) in protocol biopsies in a large cohort of 214 patients with stable renal allograft function.
Although this study shows interesting results about the presence of advanced TLTs in relation to progressive graft dysfunction, we have some remarks regarding the subgroup of ABO-incompatible patients of which most received a single dose of rituximab pretransplantation. According to their results, T cell dominant TLTs were detected in this subgroup, harboring far fewer B cells than TLTs in aged kidneys and kidneys with CKD based on immunofluorescence staining with CD3 and CD20. Firstly, for the reader it is unclear what the authors mean with “aged kidneys and kidneys with chronic kidney disease.” Secondly, we believe staining for intragraft B cells using only anti-CD20 antibody proposes difficulties in interpreting the results of their study. Besides depleting CD20+ B cells, it is known from the treatment of B cell non-Hodgkin lymphomas that rituximab leads to loss of expression of CD20 on B cells,2 causing false negative results. Therefore, staining with anti-CD20 antibody is not the preferred method to detect intragraft B cells. A more informative assessment would be to look for the expression of alternative B cell lineage markers, e.g., CD79a or PAX-5 as used in a previous study to detect intragraft B cells in patients treated with rituximab.3
Results on phenotypic characterization of TLTs in patients who underwent an ABO-incompatible transplantation treated with rituximab in this study based on staining with CD20 alone should be interpreted with caution and we advise using anti-CD79a antibody as an additional B cell marker to confirm the low number of intragraft B cells.
Disclosures
J. Kers reports consultancy with Alentis Therapeutics and Center for Human Drug Research in Leiden. All remaining authors have nothing to disclose.
Funding
None.
Footnotes
Published online ahead of print. Publication date available at www.jasn.org.
See related reply, “Authors’ Reply: Advanced Tertiary Lymphoid Tissues in Protocol Biopsies in Kidney Transplant Recipients: Addressing Additional Methods To Detect Intragraft B Cells,” on pages 868–869, and original article “Advanced Tertiary Lymphoid Tissues in Protocol Biopsies Are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients,” in Vol. 33, Iss. 1, on pages 186–200.
References
- 1.Lee YH, Sato Y, Saito M, Fukuma S, Saito M, Yamamoto S, et al. : Advanced tertiary lymphoid tissues in protocol biopsies are associated with progressive graft dysfunction in kidney transplant recipients. J Am Soc Nephrol 33: 186–200, 2022 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Foran JM, Norton AJ, Micallef IN, Taussig DC, Amess JA, Rohatiner AZ, et al. : Loss of CD20 expression following treatment with rituximab (chimeric monoclonal anti-CD20): A retrospective cohort analysis. Br J Haematol 114: 881–883, 2001 [DOI] [PubMed] [Google Scholar]
- 3.van den Hoogen MW, Steenbergen EJ, Baas MC, Florquin S, Hilbrands LB: Absence of intragraft B cells in rejection biopsies after rituximab induction therapy: Consequences for clinical outcome. Transplant Direct 3: e143, 2017 [DOI] [PMC free article] [PubMed] [Google Scholar]
