Trial reportJournal of translational medicine2017
B cell repertoires in HLA-sensitized kidney transplant candidates undergoing desensitization therapy.
Trial report in Journal of translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- B-cell receptor profiling before and after IVIG monotherapy in newly diagnosed idiopathic inflammatory myopathies.Rheumatology (Oxford, England) · 2023Article
- Clinical application of immune repertoire sequencing in solid organ transplant.Frontiers in immunology · 2023Review
- Advances of the experimental models of idiopathic membranous nephropathy (Review).Molecular medicine reports · 2020Review
- Pre-existing Alloreactive T and B Cells and Their Possible Relevance for Pre-transplant Risk Estimation in Kidney Transplant Recipients.Frontiers in medicine · 2020Review
- Characterizing pre-transplant and post-transplant kidney rejection risk by B cell immune repertoire sequencing.Nature communications · 2019Article
- Composition and diversity analysis of the B-cell receptor immunoglobulin heavy chain complementarity-determining region 3 repertoire in patients with acute rejection after kidney transplantation using high-throughput sequencing.Experimental and therapeutic medicine · 2019Article
- IVIg-induced plasmablasts in patients with Guillain-Barré syndrome.Annals of clinical and translational neurology · 2019Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
backgroundKidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy.
methodsWe developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels. Responders to desensitization had a decrease of 5% points or greater in cumulated calculated panel reactive antibody (cPRA) levels, and non-responders had no decrease in cPRA.
resultsDominant B cell clones were not observed in highly sensitized candidates, suggesting that the B cells responsible for sensitization are either not present in peripheral blood or present at comparable levels to other circulating B cells. Candidates that responded to desensitization therapy had pre-treatment repertoires composed of a larger fraction of class-switched (IgG and IgA) isotypes compared to non-responding candidates. After B cell depleting therapy, the proportion of switched isotypes increased and the mutation frequencies of the remaining non-switched isotypes (IgM and IgD) increased in both responders and non-responders, perhaps representing a shift in the repertoire towards memory B cells or plasmablasts. Conversely, after transplantation, non-switched isotypes with fewer mutations increased, suggesting a shift in the repertoire towards naïve B cells.
conclusionsRelative abundance of different B cell isotypes is strongly perturbed by desensitization therapy and transplantation, potentially reflecting changes in the relative abundance of memory and naïve B cell compartments. Candidates that responded to therapy experienced similar changes to those that did not respond. Further studies are required to understand differences between these two groups of highly sensitized kidney transplant candidates.
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