SO056THE CLINICAL AND IMMUNOLOGICAL IMPACT OF LOW DOSE RITUXIMAB IN CLINICAL NEPHROLOGY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sunu Alex
Keyword(s):  
B Cells ◽  
B Cell ◽  
Low Dose ◽  
Cost Effective ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cell Percentage ◽  
Steroid Dependent ◽  
One Year

Abstract Background and Aims Currently, the dose of rituximab used in nephrology practice is mostly extrapolated from the dose used in lymphoproliferative disorders. It is possible that a lesser dose may suffice when treating a non-neoplastic disorder. We conducted this study to study the clinical response and CD19 B cell suppression with a single dose of 100mg rituximab in nephrology practice Method This was a single center prospective study of role of 100mg rituximab as initial dose in steroid dependent (SDNS), frequently relapsing nephrotic syndrome (FRNS), idiopathic membranous nephropathy (MN) and high immunologic risk kidney transplantation with subsequent doses based on CD19 B cell reconstitution. Results Following 100mg rituximab in 42 patients, CD19 B cell percentage decreased from 16.3+7.6 to 0.3±0.3, 1.9±1.7 and 4.0±4.5 by 30, 90 and 180 days respectively. At 30th day, 40(95.2%) had CD19 B cell count <1%. Of the 30 patients with SDNS and FRNS followed up for one year, 29(96.7%) went into remission at day 30. Remission was sustained in 23(76.6%) at day 180 and 21(70%) at 1 year. There was significant decrease [P <0.001] in the dose of steroids needed to maintain remission at 180 days following rituximab (0.27±0.02mg/Kg to 0.02±0.00mg/Kg). Of the five patients with MN, four patients achieved remission by 6 months. Remission was sustained in three patients by 1 year. Of the 7 kidney transplant recipients, 2 had antibody mediated rejections though CD19 B cells were suppressed even at one year. Conclusion Low dose of 100 mg rituximab is sufficient to deplete CD19 B cells for up to 90days and is effective in inducing remission in SDNS and FRNS and MN. Targeting subsequent doses depending on CD19 B cell reconstitution may prevent relapses, limit toxicity and be cost effective.

scholarly journals Clinical Response and Pattern of B cell Suppression with Single Low Dose Rituximab in Nephrology

Kidney360 ◽  
2020 ◽  
Vol 1 (5) ◽  
pp. 359-367
Author(s):  
Jacob George ◽  
Sunu Alex ◽  
E.T. Arun Thomas ◽  
Noble Gracious ◽  
Nalanda S. Vineetha ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
B Cells ◽  
B Cell ◽  
Clinical Response ◽  
Low Dose ◽  
Clinical Status ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cell Percentage ◽  
Steroid Dependent

BackgroundThere is no consensus regarding dose and frequency of rituximab in nephrology with extrapolation of doses used in treating lymphoproliferative disorders. There are no guidelines on targeting initial and subsequent doses on the basis of CD19+ B cells.MethodsInitially, 100 mg rituximab was given to 42 adults with steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS), idiopathic membranous nephropathy (MN), and high-immunologic-risk kidney transplantation. Absolute and percentage levels of CD19 B cells and clinical status were assessed at baseline, days 30, 90, and 180, and at 1 year. Subsequent doses of rituximab were on the basis of CD19 B cell reconstitution and clinical response.ResultsCD19 B cell percentage decreased from 16.3 ± 7.6 to 0.3 ± 0.3 (P≤0.001), 1.9 ± 1.7 (P≤0.001), and 4.0 ± 4.5 (P=0.005) by 30, 90, and 180 days, respectively. Suppression of CD19 B cell count below 1% at days 30, 90, and 180 was seen in 40 of 42 (95.2%), 18 of 42 (42.9%), and 7 of 42 (16.7%) patients, respectively. Of 30 with SDNS and FRNS followed up for 1 year, 29 (96.7%) went into remission at day 30. Remission was sustained in 23 (76.6%) at day 180 and 21 (70%) at 1 year. There was a significant decrease (P<0.001) in the dose of steroids needed to maintain remission at 180 days after rituximab (0.27 ± 0.02 mg/kg to 0.02 ± 0.00 mg/kg). CD19 B cell percentage at 90 days correlated with relapse (P=0.001; odds ratio 1.42; 95% confidence interval, 1.25 to 2.57). Eighteen (60%) required an additional dose. Of five with MN, four achieved remission by 6 months, which was sustained in three by 1 year. Of the seven kidney transplant recipients, two had antibody-mediated rejections, although CD19 B cells were suppressed even at 1 year.ConclusionsLow-dose rituximab induces sustained depletion of CD19 B cells for up to 90 days. Its role in preventing relapses in SDNS, FRNS, MN, and rejection needs further study.

scholarly journals FP865SUCCESSFUL COST EFFECTIVE PREVENTION OF CYTOMEGALOVIRUS DISEASE IN KIDNEY TRANSPLANT RECIPIENTS USING LOW DOSE VALGANCICLOVIR

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii366-iii366
Author(s):  
Medhat Halim ◽  
Torki Alotaibi ◽  
Osama Gheith ◽  
Hany Adel ◽  
Ahmed Mosaad ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Low Dose ◽  
Cost Effective ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cytomegalovirus Disease ◽  
Effective Prevention

scholarly journals MP687SUCCESSFUL COST EFFECTIVE PREVENTION OF CYTOMEGALOVIRUS DISEASE IN KIDNEY TRANSPLANT RECIPIENTS USING LOW DOSE VALGANCICLOVIR

2016 ◽  
Vol 31 (suppl_1) ◽  
pp. i568-i568
Author(s):  
Osama Gheith ◽  
Torki Al Otaibi ◽  
Medhat A Halim ◽  
Hany Mansour ◽  
Hany Mansour ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Low Dose ◽  
Cost Effective ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cytomegalovirus Disease ◽  
Effective Prevention

scholarly journals Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients

2021 ◽  
Vol 6 (60) ◽  
pp. eabj1031
Author(s):  
Hector Rincon-Arevalo ◽  
Mira Choi ◽  
Ana-Luisa Stefanski ◽  
Fabian Halleck ◽  
Ulrike Weber ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Kidney Transplant ◽  
Absolute Number ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Dialysis Patients ◽  
Cell Responses ◽  
Increased Risk ◽  
Switch Memory

Patients with kidney failure are at increased risk for SARS-CoV-2 infection making effective vaccinations a critical need. It is not known how well mRNA vaccines induce B and plasma cell responses in dialysis patients (DP) or kidney transplant recipients (KTR) compared to healthy controls (HC). We studied humoral and B cell responses of 35 HC, 44 DP and 40 KTR. Markedly impaired anti-BNT162b2 responses were identified among KTR and DP compared to HC. In DP, the response was delayed (3-4 weeks after boost) and reduced with anti-S1 IgG and IgA positivity in 70.5% and 68.2%, respectively. In contrast, KTR did not develop IgG responses except one patient who had a prior unrecognized infection and developed anti-S1 IgG. The majority of antigen-specific B cells (RBD+) were identified in the plasmablast or post-switch memory B cell compartments in HC, whereas RBD+ B cells were enriched among pre-switch and naïve B cells from DP and KTR. The frequency and absolute number of antigen-specific circulating plasmablasts in the cohort correlated with the Ig response, a characteristic not reported for other vaccinations. In conclusion, these data indicated that immunosuppression resulted in impaired protective immunity after mRNA vaccination, including Ig induction with corresponding generation of plasmablasts and memory B cells. Thus, there is an urgent need to improve vaccination protocols in patients after kidney transplantation or on chronic dialysis.

P1709THE ROLE OF CXCL9 AND CXCL13 IN PREDICTION OF POSTTRANSPLANT INFECTION IN KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yangjuan Bai ◽  
Lin Yan ◽  
Yi Li ◽  
Yamei Li ◽  
Xianding Wang ◽  
...  
Keyword(s):  
Serum Level ◽  
Infectious Diseases ◽  
Kidney Transplant ◽  
Kidney Diseases ◽  
Interferon Γ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Suspension Array ◽  
One Year

Abstract Background and Aims Chemokines are deeply involved in the process of inflammatory and immune responses. Interferon-γ-inducible chemokines C-X-C motif chemokine 9 and 10 (CXCL9 and CXCL10) are significantly associated with Th1 cells and monocytes and rise rapidly during early episode of renal allograft rejection and various infectious diseases. CXCL13 is one of the most potent B cells and T follicular helper (Tfh) cells chemoattractants when acts through its cognate receptor CXCR5. Recent work of CXCL13 indicated a critical immune regulatory role in both multiple infectious diseases and kidney transplantation. Additionally, C-C motif chemokine 2 (CCL2) is shown to be is critical for chronic kidney diseases. The aim of this study was to identify the predictive role of serum CXCL9, CXCL10, CXCL13 or CCL2 on kidney posttransplant infection. Method 95 kidney transplant recipients (KTRs) were enrolled in this study. 31 recipients experienced at least once infection episodes within the first posttransplant 12 months and 64 KTRs did not experience any infection episode during the follow-up period. Serum CXCL9, CXCL10, CXCL13 and CCL2 at the time points of pre-transplantation and post-transplant 30 days (POD 30) were analyzed with Bio-Plex® suspension array system. Results It was found that serum level of POD 30 CXCL9 and POD 30 CXCL13 was associated with infection within one year after transplantation (P=0.021, P=0.002, respectively, shown in Figure 1). The serum level of CXCL9 and CXCL13 before surgery, the serum level of CCL2 and CXCL10 before and after surgery were not associated with infection within posttransplant one year (P&gt;0.05, shown in Figure 1). The combination of POD 30 CXCL9 plus POD 30 CXCL13 provided the best results with AUC of 0.721 (95%CI, 0.591-0.852), sensitivity of 71.4% and specificity of 68.5% at the optimal cut-off value of 52.72 pg/ml (shown in Figure 2). Conclusion Chemokines CXCL9 and CXCL13 as important chemokines could be used to predict the occurrence of infection within posttransplant one year in kidney transplant recipients.

P1740KINETICS OF B-CELL SUBSETS RECONSTITUTION FOLLOWING RITUXIMAB TREATMENT IN ABO-INCOMPATIBLE KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yamei Li ◽  
Yunying Shi ◽  
Tao Lin ◽  
Xianding Wang ◽  
Lin Yan ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Kidney Transplant ◽  
Cell Population ◽  
Immune Cell ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Antibody Mediated Rejection ◽  
B Cell Subsets

Abstract Background and Aims With the application of B-cell-depleting agent rituximab, plasmapheresis and powerful immunosuppression, ABO-incompatible kidney transplant recipients (ABOi-KT) have successfully overcome the ABO antibody barrier. As an important immune cell population, B cells are not only involved in antibody-mediated rejection, but also have been reported to have different immunoregulatory effects due to the existence of distinct B cell subsets. Therefore, comprehensively understanding the reconstitution of B-cell subsets in ABOi-KTRs is crucial to know the immune status that may be related to the subsequent complications. Method Fresh whole blood were collected from 22 ABOi-KTRs and 22 ABO-compatible recipients (ABOc-KTRs) at 0, 1week, 2 weeks ,1month, 3months, and 6 months post-transplantation between October 2018 and May 2019. In addition, pre-desensitization samples were also collected from ABOi-KTRs. B cell subsets including total, naïve, memory, plasma, plasma blast and regulatory B cells were determined by flow cytometry. Results The percentages of B cells in ABOi group remained extremely low and significantly lower than ABOc group through the first 6 months after rituximab treatment (Fig. A). Similar trends were observed in total memory and switched memory B cells whose frequencies increased within first 2 weeks, then decreased thereafter. Meanwhile, the significant differences between ABOi and ABOc groups disappeared at 6 months (Fig. B-D). In addition, plasma and plasma blast B cells increased 2 weeks after transplantation and were significantly higher in ABOi group compared to ABOc group (Fig. E, G), while Naïve B cells started to elevate 1 month after transplantation in ABOi-KTRs and significantly higher proportions were found in ABOc group through the entire 6 months (Fig. F). No obvious difference was observed between ABOi and ABOc groups regarding unswitched memory and regulatory B cell percentages (Fig. C, H). Conclusion Our preliminary results indicated that B-cell depletion therapy applied in ABOi-KTRs not only significantly reduced the number of B cells, but also changed the composition of B cell subsets in the remaining B cell population. Whether such alteration would be clinical significance requires further follow-up.

scholarly journals Induction of Donor-Specific Immune Tolerance with Clinical MIC Cell Infusion — a Phase I Study (TOL-1)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4539-4539
Author(s):  
Christian Morath ◽  
Anita Schmitt ◽  
Christian Kleist ◽  
Volker Daniel ◽  
Gerhard Opelz ◽  
...  
Keyword(s):  
Body Weight ◽  
B Cells ◽  
Immunosuppressive Therapy ◽  
Kidney Transplant ◽  
Cyclosporine A ◽  
Low Dose ◽  
Immunosuppressive Drugs ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Donor Pbmcs

Abstract Background: After transplantation of solid organs like allogeneic kidneys, the administration of immunosuppressive drugs such as cyclosporine A (CSA) and steroids is mandatory. This regimen exerts toxicity to the graft and makes transplant recipients prone to opportunistic infections. Replacement of the immunosuppressive drugs by a transfusion of tolerogenic cells might overcome these noxious side effects. Mitomycin-induced cells (MICs) are donor-derived monocytes that gain immunosuppressive properties after incubation with the proliferation inhibitor mitomycin C and have a myeloid-derived suppressor cell (MDSC) character. Materials and methods: Peripheral blood mononuclear cells (PBMCs) were harvested from living kidney donors by leukapheresis and MIC cells were manufactured under Good Manufacturing Practice (GMP) conditions in the clean room of our University Hospital. Kidney transplant recipients received either 1.5x10E6 MIC cells per kg body weight on day -2 (N=3, group A) or 1.5x10E8 MIC cells per kg body weight on day -2 (N=3, group B) or on day -7 (N=4, group C) before living donor kidney transplantation. Patients received immunosuppressive therapy with cyclosporine a (CSA), enteric coated mycophenolate sodium (EC-MPS) and corticosteroids. The primary outcome was measured by the frequency of adverse events (AEs) on post-transplant day 30 with a follow-up until post-transplant day 360 for all patients. Results: Clinically, all kidney transplant recipients showed a median serum creatinine of 1.4 mg/dL at day 30 and remained stable with a median creatinine of 1.48 mg/dL at day 180 without significant proteinuria (median 10 g/mol creatinine at day 180) and without rejection episode. In total 72 AEs were observed including three severe AEs which were not associated with the MIC cell transfusion. Besides two infectious complications, no positive cross match results, no de novo donor-specific antibodies or rejection episodes were recorded. In group C, a reduction of immunosuppressive therapy was effective in the observational phase with low-dose CSA and low-dose EC-MPS. Immunologically, CD19+ B cells increased up to a median of 300/µL until day 30, followed by a decrease to a median of 35/µL at day 180 in group C. Notably, CD19+CD24highCD38high regulatory B cells were significantly increased from a median of 2% on day 30 to a median of 20% on day 180. The plasma IL-10/TNF-α ratio increased from a median of 0.05 before cell therapy to a median of 0.11 at day 180. Moreover, recipient lymphocytes showed no or only minimal reactivity against irradiated donor PBMCs, while reactivity against 3rd party healthy donor PBMCs in vitro was not impaired. Additionally, the quality assessment demonstrated that MIC cells have the capability to induce tolerogenic dendritic cells (tDCs) by down-regulating the costimulatory molecules CD80 and CD86, and the maturation molecule CD83, while up-regulating the immunosuppressive molecule CD103. MIC-induced tDCs showed the capacity to inhibit donor specific allo-reactive CD4 and CD8 T cell proliferation. Conclusion: A stable function was observed in all transplant recipients receiving the MIC cells product without any allograft injury or rejection episodes even under reduction of conventional therapy with immunosuppressive drugs. MIC cells constitute a novel tool for immunotherapy with a high potential in transplantation medicine. Disclosures No relevant conflicts of interest to declare.

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