Effect of mycophenolate mofetil regimen on peripheral blood lymphocyte subsets in kidney transplant recipients

Soto, Juan Antonio Bravo; Rosa, Rafael José Esteban de la; Luna, Juan de Dios; Morales, Sandra; Olivares, Enrique G.; Ortega, Antonio Osuna

doi:10.1016/s0041-1345(03)00364-6

Cited by 14 publications

(5 citation statements)

References 24 publications

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“…This may be due to the selective responses of immunosuppressive agents when administered as different combined therapy regimens with respect to the disease. In this regard, studies of BravoSoto et al, 16 have shown that CD19+ cells are reduces in renal allograft patients after treatment with azathioprine, prednisone and cyclosporine A 16. However in those studies CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), were also reduced in kidney transplant patients 16, whereas in our studies these cells either increased (CD3+CD4+) or remained the same (CD3(+)CD8(+)).…”

Section: Discussionmentioning

confidence: 96%

Immune Responses in Autoimmune Hepatitis: Effect of Prednisone and Azathioprine Treatment: Case Report

Bluth¹,

Kohlhoff²,

Norowitz³

et al. 2009

Int. J. Med. Sci.

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The role of the immune response in autoimmune hepatitis has not been studied before and after prednisone and azathioprine treatment. Distributions of blood lymphocytes (CD4+, CD8+, CD19+, CD23+, CD16/56+), levels of serum immunoglobulins (IgM, IgG, IgE, IgA) and cytokines (IFN-γ, IL-4, IL-12, TNFα ) were studied in a child (f/14 y/o) with autoimmune hepatitis before and after prednisone (20 mg/d) and azathioprine (50 mg/d) treatment (nephelometry, UniCAP Total IgE Fluoroenzymeimmunoassay, flow cytometry, cytokine ELISA). Patient was studied for 0-2.5 yrs; treatment was initiated 12 weeks post diagnosis. Numbers of CD4+ T cells increased (50%), while CD19+ and CD23+ cells decreased (>50%) post treatment; other lymphocyte subsets were unaffected by treatment. Serum IgG and IgE levels decreased (>50%) after treatment; serum IgM and IgA were within normal range and were not affected by treatment High levels of IFN-γ (5-23 pg/ml) were initially detected in serum, which decreased after treatment (<0.1 pg/ml). Furthermore, low levels of IL-4 (0.2 pg/mL) were detected before treatment, which were not detected after treatment (<0.1 pg/ml). In contrast, before treatment, IL-12 and TNFα were not detected in serum; however after treatment the levels of IL-12 and TNFα dramatically increased. Prednisone and azathioprine treatment decreased total serum IgG, IgE, IFN-γ and IL-4 levels, and blood CD19+ and CD23+ cells; however serum IL-12, TNFα and blood CD4+ T cells increased with treatment. Understanding immunomodulation in autoimmune hepatitis will provide better insight and mechanisms of this disease and may tailor more effective therapeutic intervention.

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Section: Discussionmentioning

confidence: 96%

Immune Responses in Autoimmune Hepatitis: Effect of Prednisone and Azathioprine Treatment: Case Report

Bluth¹,

Kohlhoff²,

Norowitz³

et al. 2009

Int. J. Med. Sci.

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“…Decreasing lymphocyte proliferation is a crucial effect of MMF administration and is concentration‐dependent . Regulating an inappropriate immune response by inhibition of T cells is important because T cells contribute to autoimmune diseases by multiple stimulatory, activation, and cytotoxic mechanisms .…”

Section: Discussionmentioning

confidence: 99%

“…However, our results suggest that a dosage ≥15 mg/kg would not be well tolerated by cats. Additionally, MMF may not have been given for a long enough time period, particularly considering that MPA has a cytostatic effect . Recent studies performed in healthy dogs suggest that MMF may need to be given for at least 2 weeks before decreased lymphocyte proliferation is observed .…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of mycophenolic acid and its effect on CD4⁺ and CD8⁺ T cells after oral administration of mycophenolate mofetil to healthy cats

Slovak

Hwang

Rivera

et al. 2019

Veterinary Internal Medicne

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Background Mycophenolate mofetil (MMF) is an immunosuppressant used in human and veterinary medicine. Little pharmacokinetic and pharmacodynamic information on MMF is available in cats. Objective To evaluate the plasma disposition of mycophenolic acid (MPA) and assess its effect on total peripheral blood mononuclear cells and CD4+/CD8+ ratios after PO administration of MMF. Animals Healthy cats (n = 10). Methods Mycophenolate mofetil was administered at a dosage of 10 mg/kg q12h (n = 3), 15 mg/kg q12h (n = 3), and 15 mg/kg q8h (n = 4) for 7 days. Concentrations of MPA and derivatives were determined using ultra‐high‐performance liquid chromatography. Flow cytometry was used to assess CD4+/CD8+ T‐cell ratios. Results All cats biotransformed MMF into MPA. Half of the cats (5/10) had adverse effects within 1 week of MMF administration. Area under the curve limit of quantification (AUC0‐LOQh) of MPA ranged from 1.27 to 2.03 hours·μg/mL and from 1.77 to 8.54 hours·μg/mL after the first and last PO dose of 10 mg/kg. The AUC0‐loqh of MPA ranged from 2.18 to 31 hours·μg/mL after the first dose of 15 mg/kg of MMF. Before the first dose of MMF, the average total number of PBMC ranged from 1.2 to 9.3 million/mL. At the last dose of MMF, the average total number of PBMC ranged from 3 to 5 million/mL. Conclusion Mycophenolic acid was detected in all cats. The dose 10 mg/kg given q12h for 1 week was tolerated (n = 3). The efficacy of MMF as an immunosuppressant and long‐term safety in cats of this dosage regimen is unknown.

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“…The dual effects of immunosuppressant drugs in organ transplant patients in general and in kidney transplant patients in particular need to be strictly controlled. Currently, the quantitative determination of calcineurin inhibitors has been carried regularly and mycophenolic acid (MPA) has been conducted at major transplant centers around the world to make a correlation between pharmacokinetics and clinical dosage (1). Although the biopsy provides a definitive diagnosis (2), the less interventional method offers an early diagnosis of transplant rejection, which is more beneficial for patients with kidney transplantation.…”

Section: Introductionmentioning

confidence: 99%

A survey on lymphocyte T CD3, CD4 and CD8 in peripheral blood of kidney transplant recipients using mycophenolic acid

Dung

et al. 2021

J Nephropathol

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Introduction: Immunological monitoring could indirectly measure the suppressive effects of the drugs and provide early guidance on necessary preventive interventions in transplant recipients. Objectives: Our goal was to determine whether mycophenolic acid (MPA) modulates peripheral blood lymphocyte T in kidney transplant recipients. Patients and Methods: We assessed T lymphocytes CD3, CD4 and CD8 in peripheral blood in 30 donors and 35 recipients one day before and 10 days after transplantation using Becton Dickinson’s direct immune fluorescent light. Results: Comparisons showed that the number of T lymphocytes CD3+, CD4+, CD8+ in peripheral blood of transplant recipients were lower than donors (TCD3 was 1690.31±503.45 versus 2280.73± 522.48; TCD4 was 549.51 ±211.72 cell/µL versus 766.37± 341.72 cell/µL and CD8 was 1134.37 ±431.07 cell/µL versus 1523.4± 349.23 cell/µL with P<0.001; P=0.001 and P= 0.0002 respectively). Additionally, post-transplantation lymphocytes TCD4 decreased in 10/35 of recipients and increased in 22/35 of recipients (P=0.036). Conclusion: The T lymphocytes CD3, CD4 and CD8 in peripheral blood should be monitored at multiple post-transplant times to make early predictions of transplant rejection during follow-up treatment.

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Effect of mycophenolate mofetil regimen on peripheral blood lymphocyte subsets in kidney transplant recipients

Cited by 14 publications

References 24 publications

Immune Responses in Autoimmune Hepatitis: Effect of Prednisone and Azathioprine Treatment: Case Report

Immune Responses in Autoimmune Hepatitis: Effect of Prednisone and Azathioprine Treatment: Case Report

Pharmacokinetics of mycophenolic acid and its effect on CD4⁺ and CD8⁺ T cells after oral administration of mycophenolate mofetil to healthy cats

A survey on lymphocyte T CD3, CD4 and CD8 in peripheral blood of kidney transplant recipients using mycophenolic acid

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Effect of mycophenolate mofetil regimen on peripheral blood lymphocyte subsets in kidney transplant recipients

Cited by 14 publications

References 24 publications

Immune Responses in Autoimmune Hepatitis: Effect of Prednisone and Azathioprine Treatment: Case Report

Immune Responses in Autoimmune Hepatitis: Effect of Prednisone and Azathioprine Treatment: Case Report

Pharmacokinetics of mycophenolic acid and its effect on CD4+ and CD8+ T cells after oral administration of mycophenolate mofetil to healthy cats

A survey on lymphocyte T CD3, CD4 and CD8 in peripheral blood of kidney transplant recipients using mycophenolic acid

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Pharmacokinetics of mycophenolic acid and its effect on CD4⁺ and CD8⁺ T cells after oral administration of mycophenolate mofetil to healthy cats