B Cell Deficiency Attenuates Transplant Glomerulopathy in a Rat Model of Chronic Active Antibody-mediated Rejection

AbstractThe B cell activating factor BAFF has gained importance in the context of kidney transplantation due to its role in B cell survival. Studies have shown that BAFF correlates with an increased incidence of antibody-mediated rejection and the development of donor-specific antibodies. In this study, we analyzed a defined cohort of kidney transplant recipients who were treated with standardized immunosuppressive regimens according to their immunological risk profile. The aim was to add BAFF as an awareness marker in the course after transplantation to consider patient’s individual immunological risk profile. Included patients were transplanted between 2016 and 2018. Baseline data, graft function, the occurrence of rejection episodes, signs of microvascular infiltration, and DSA kinetics were recorded over 3 years. BAFF levels were determined 14 d, 3 and 12 months post transplantation. Although no difference in graft function could be observed, medium-risk patients showed a clear dynamic in their BAFF levels with low levels shortly after transplantation and an increase in values of 123% over the course of 1 year. Patients with high BAFF values were more susceptible to rejection, especially antibody-mediated rejection and displayed intensified microvascular inflammation; the combination of high BAFF + DSA puts patients at risk. The changing BAFF kinetics of the medium risk group as well as the increased occurrence of rejections at high BAFF values enables BAFF to be seen as an awareness factor. To compensate the changing immunological risk, a switch from a weaker induction therapy to an intensified maintenance therapy is required.

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Comparison of Pediatric Patients with Pure Antibody-mediated Rejection (AMR) and Recipients with both AMR and Vascular Rejection in the Development of Interstitial Fibrosis and Transplant Glomerulopathy

Transplantation Journal ◽

10.1097/01.tp.0000520366.53452.88 ◽

2017 ◽

Vol 101 ◽

pp. S44

Author(s):

B. Handan Ozdemir ◽

Esra Baskin ◽

F. Nurhan Ozdemir ◽

Gökhan Moray ◽

Mehmet Haberal

Keyword(s):

Pediatric Patients ◽

Interstitial Fibrosis ◽

Vascular Rejection ◽

Antibody Mediated Rejection ◽

Transplant Glomerulopathy

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Identification of 22 novel BTK gene variants in B cell deficiency with hypogammaglobulinemia

Clinical Immunology ◽

10.1016/j.clim.2021.108788 ◽

2021 ◽

pp. 108788

Author(s):

Monica T. Kraft ◽

Regan Pyle ◽

Xiangyang Dong ◽

John B. Hagan ◽

Elizabeth Varga ◽

...

Keyword(s):

B Cell ◽

Gene Variants ◽

B Cell Deficiency

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B-cell Deficiency: A De Novo IKZF1 Patient and Review of the Literature

Journal of Investigational Allergology and Clinical Immunology ◽

10.18176/jiaci.0207 ◽

2018 ◽

Vol 28 (1) ◽

pp. 53-56 ◽

Cited By ~ 6

Author(s):

QY Chen ◽

XC Wang ◽

WJ Wang ◽

QH Zhou ◽

DR Liu ◽

...

Keyword(s):

B Cell ◽

De Novo ◽

Review Of The Literature ◽

B Cell Deficiency

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B Cell Activating Factor, Renal Allograft Antibody-Mediated Rejection, and Long-Term Outcome

Journal of Immunology Research ◽

10.1155/2018/5251801 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Haiyan Xu ◽

Xiaozhou He ◽

Renfang Xu

Keyword(s):

B Cell ◽

Renal Allograft ◽

Delayed Diagnosis ◽

Clinical Manifestations ◽

Direct Proof ◽

Term Outcome ◽

Long Term Outcome ◽

Antibody Mediated Rejection ◽

B Cell Activating Factor

Antibody-mediated rejection (ABMR) of renal allograft lacks typical phenotypes and clinical manifestations, always resulting in delayed diagnosis and treatment. It has been considered to be an elemental factor influencing the improvement of the long-term outcome of renal allograft. The B cell activating factor (BAFF) signal plays a fundamental function in the process of antibody-mediated immune response. Data from recipients and the nonhuman primate ABMR model suggest that the BAFF signal participates in the ABMR of renal allograft, while there are objections. The challenges in the diagnosis of ABMR, different study population, and details of research may explain the discrepancy. Large quantities of dynamic, credible data of BAFF ligands and their association with renal allograft pathological characteristics would constitute a direct proof of the role of BAFF in the progression of renal allograft ABMR.

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A study of the imbalance in B cell-expressed nucleoside triphosphate diphosphohydrolase 1-induced ADP degradation in graft injury during acute antibody-mediated rejection

Transplant Immunology ◽

10.1016/j.trim.2012.07.004 ◽

2012 ◽

Vol 27 (4) ◽

pp. 175-178 ◽

Cited By ~ 2

Author(s):

Yong Zhang ◽

Yamei Wang ◽

Huantao Zong ◽

Chenchen Yang

Keyword(s):

B Cell ◽

Nucleoside Triphosphate ◽

Nucleoside Triphosphate Diphosphohydrolase ◽

Antibody Mediated Rejection

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Short-Term Immunopathological Changes Associated with Pulse Steroids/IVIG/Rituximab Therapy in Late Kidney Allograft Antibody Mediated Rejection

Kidney360 ◽

10.34067/kid.0001082019 ◽

2020 ◽

Vol 1 (5) ◽

pp. 389-398

Author(s):

Kenna R. Degner ◽

Nancy A. Wilson ◽

Shannon R. Reese ◽

Sandesh Parajuli ◽

Fahad Aziz ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

Regulatory T Cells ◽

B Cell ◽

Cd8 T Cells ◽

Hla Class I ◽

B Cell Depletion ◽

Short Term ◽

Antibody Mediated Rejection ◽

Pulse Steroids

BackgroundB cell depletion is a common treatment of antibody-mediated rejection (ABMR). We sought to determine the specific immunopathologic effects of this therapeutic approach in kidney transplantation.MethodsThis was a prospective observational study of recipients of kidney transplants diagnosed with late ABMR (>3 months after transplant). Patients received treatment with pulse steroids, IVIG, and rituximab. Donor-specific HLA antibodies (DSA), kidney allograft pathology, renal function, immune cell phenotypes, and 47 circulating cytokines were assessed at baseline and at 3 months.ResultsWe enrolled 23 patients in this study between April 2015 and March 2019. The majority of patients were male (74%) and white (78%) with an average age of 45.6±13.8 years. ABMR was diagnosed at 6.8±5.9 years (4 months to 25 years) post-transplant. Treatment was associated with a significant decline in circulating HLA class I (P=0.003) and class II DSA (P=0.002) and peritubular capillaritis (ptc; P=0.04) compared to baseline. Serum creatinine, BUN, eGFR, and proteinuria (UPC) remained stable. Circulating B cells were depleted to barely detectable levels (P≤0.001), whereas BAFF (P=0.0001), APRIL (P<0.001), and IL-10 (P=0.02) levels increased significantly post-treatment. Notably, there was a significant rise in circulating CD4+ (P=0.02) and CD8+ T cells (P=0.003). We also noted a significant correlation between circulating cytotoxic CD8+ T cells and BAFF (P=0.05), regulatory T cells and IL-10 (P=0.002), and regulatory T cells and HLA class I DSA (P=0.005).ConclusionsShort-term pulse steroids/IVIG/rituximab therapy was associated with inhibition of ABMR (DSA and ptc), stabilization of kidney function, and increased regulatory B cell and T cell survival cytokines. Additional studies are needed to understand the implications of B cell depletion on the crosstalk between T cells and B cells, and humoral components that regulate ABMR.

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