case_images: PMC11390570_01
case_images: Serum creatinine and B-cell counts during follow-up after kidney transplantation. Patient suffered from delayed graft function with the last hemodialysis session on day 24, warranting the first kidney biopsy (KB, day 22), which showed acute Banff IA T-cell-mediated rejection and interstitial infiltrates of monoclonal B cells. After intravenous pulses of methylprednisolone, serum creatinine (sCr) improved until day 61. However, sCr plateaued and then rose since day 100, warranting a second KB (day 128), which showed possible borderline rejection and persistent monoclonal B-cell clusters. Patient was again treated with intravenous methylprednisolone pulses. Together with the peripheral blood immunophenotyping and B-cell counts, the bone marrow biopsy at day 44 and the characterization of the interstitial monoclonal B-cell infiltrates in the first KB, the diagnosis of chronic lymphocytic leukemia was retained. Given the increase in sCr, BTKi was introduced since day 208. The transient rise in B-cell counts post-BTKi is called redistribution lymphocytosis resulting from inhibition of B-cell adhesion molecules and signaling chemokines. Despite plummeting of peripheral B-cell counts, there was no significant improvement in graft function. The third KB (day 281) showed progression of interstitial fibrosis, but no signs of rejection and almost no infiltrating monoclonal B cells. Polyclonal immunoglobulins were given at replacement doses (at day 155, 217, 313, and 407 post-transplantation) for hypogammaglobulinemia. Brown and blue lines represent sCr and B-cell counts, respectively. The hatched brown section of the graph represents time under BTKi treatment. BMB, bone marrow biopsy; BTKi, Bruton tyrosine kinase inhibitor; IVIG, intravenous immunoglobulins; KB, kidney transplant biopsy.
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case_images: PMC11390570_01_fmed-11-1451264-g001.jpg
case_images: fig1
case_images: Initial follow-up was characterized by prolonged delayed graft function (DGF) with a last hemodialysis session on postoperative day 24. sCr levels then plateaued for 10 days around 350 mumol/L without proteinuria, and progressively decreased to 218 mumol/L on day 61 (estimated glomerular filtration rate, eGFR, 19 mL/min/1.73 m2) (Figure 1). The evolution of B-cell counts and sCr after KTx is displayed in Figure 1.
case_images: Consecutive kidney allograft biopsies during follow-up after kidney transplantation. Graft biopsies were performed at different time points during follow-up and are shown after staining with Masson Trichrome Blue (MTB, 10x), Hematoxylin & Eosin (HE, 15x), and CD3 and CD5 immunohistochemistry (IHC) staining (20x and 10x, respectively). (A) First biopsy (day 22) showing intact glomeruli and 10-20% interstitial fibrosis (MTB), CD3+ T-cell infiltrates associated with tubulitis corresponding to a Banff IA acute T-cell-mediated rejection (HE, CD3 IHC), and interstitial clusters of CD5+ monoclonal B cells (HE, CD5 IHC). (B) Second biopsy (day 128, 3 months later), showing intact glomeruli and relatively stable 10-20% interstitial fibrosis (MTB), persistant mononuclear CD5+ cells clusters (HE, CD5 IHC) and small CD3+ clusters compatible with borderline rejection (HE, CD3 IHC). (C) Third biopsy (day 281, 5 months later) showing atrophic tubules and increased interstitial fibrosis 20-30% (MTB), almost no monoclonal B cells (HE, CD5 IHC) and no signs of T-cell-mediated rejection (HE, CD3 IHC).
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case_images: PMC11390570_01_fmed-11-1451264-g002.jpg
case_images: fig2
case_images: A first allograft biopsy (day 22) revealed signs of Banff IA acute T-cell-mediated rejection (TCMR, Banff adequate-t1-i1-ti1-ptc0-v0-cv0-g0-cg0-mm1-ci1-ct1-ah0-aah0-c4d0-pv0-iIFTA1), with no criteria for acute antibody-mediated rejection (Figure 2A). TCMR, (b) moderate arteriolosclerosis, and (c) focal interstitial infiltration (10-20% total surface) by CLL-like B lymphocytes (PAX5+, CD5+, CD20+, CD23+, surface IgM-; cyclin D1 negative) (Figure 2B). The interstitial infiltration had an XX profile while kidney epithelial cells were XY by interphase fluorescence in situ hybridization, showing that CLL infiltration was not donor-derived but originated from the patient. As sCr stabilized but did not decrease significantly, a third biopsy (day 281) was performed and revealed: (a) moderate interstitial fibrosis (20-30%), (b) no signs of rejection, and (c) absence of CLL-like B lymphocytes infiltration (PAX5-, CD5-, CD23-) (Figure 2C).