Mycophenolic acid and intravenous immunoglobulin exert an additive effect on cell proliferation and apoptosis in the mixed lymphocyte reaction

Sharma, Kavita G.; Radha, Raju; Pao, Andy; Amet, Nurmamet; Baden, Lara; Jordan, Stanley C.; Toyoda, Mieko

doi:10.1016/j.trim.2010.04.009

Cited by 8 publications

(8 citation statements)

References 38 publications

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“…As PHA has been shown to cause cell death on its own; induction of apoptosis might have been a consequence of a synergistic action of MPA and PHA [ 63 ]. Lack of a consistent increase in lymphocyte apoptosis was also previously reported and could have been explained by the design of our study [ 9 , 10 , 57 , 58 , 62 , 64 ]. Quéméneur et al observed that MPA induces cell apoptosis through S-phase arrest only in lymphocytes which were in the cell cycle prior to drug treatment [ 65 ].…”

Section: Discussionsupporting

confidence: 43%

In Vitro Influence of Mycophenolic Acid on Selected Parameters of Stimulated Peripheral Canine Lymphocytes

et al. 2016

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Mycophenolic acid (MPA) is an active metabolite of mycophenolate mofetil, a new immunosuppressive drug effective in the treatment of canine autoimmune diseases. The impact of MPA on immunity is ambiguous and its influence on the canine immune system is unknown. The aim of the study was to determine markers of changes in stimulated peripheral canine lymphocytes after treatment with MPA in vitro. Twenty nine healthy dogs were studied. Phenotypic and functional analysis of lymphocytes was performed on peripheral blood mononuclear cells cultured with mitogens and different MPA concentrations– 1 μM (10−3 mol/m3), 10 μM or 100 μM. Apoptotic cells were detected by Annexin V and 7-aminoactinomycin D (7-AAD). The expression of antigens (CD3, CD4, CD8, CD21, CD25, forkhead box P3 [FoxP3] and proliferating cell nuclear antigen [PCNA]) was assessed with monoclonal antibodies. The proliferation indices were analyzed in carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled cells. All analyses were performed using flow cytometry. The influence of MPA on apoptosis was dependent on the mechanism of cell activation and MPA concentration. MPA caused a decrease in the expression of lymphocyte surface antigens, CD3, CD8 and CD25. Its impact on the expression of CD4 and CD21 was negligible. Its negative influence on the expression of FoxP3 was dependent on cell stimulation. MPA inhibited lymphocyte proliferation. In conclusion, MPA inhibited the activity of stimulated canine lymphocytes by blocking lymphocyte activation and proliferation. The influence of MPA on the development of immune tolerance–expansion of Treg cells and lymphocyte apoptosis–was ambiguous and was dependent on the mechanism of cellular activation. The concentration that MPA reaches in the blood may lead to inhibition of the functions of the canine immune system. The applied panel of markers can be used for evaluation of the effects of immunosuppressive compounds in the dog.

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Section: Discussionsupporting

confidence: 43%

In Vitro Influence of Mycophenolic Acid on Selected Parameters of Stimulated Peripheral Canine Lymphocytes

et al. 2016

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“…Sharma et al . 118 examined the effects of in vitro treatment of cells with IVIG and/or mycophenolic acid (MPA), a common immunosuppressive agent in desensitization protocols, on cell proliferation in a two-way mixed lymphocyte reaction. They found that both drugs, individually, suppressed cell proliferation and when used together, acted synergistically to amplify the effect.…”

Section: Mechanisms: Desensitization For Hla Antibodymentioning

confidence: 99%

“…In vitro experiments performed by Tha-In et al (117) showed that IVIG activated regulatory T cells (Treg) and increased their ability to suppress proliferation of allogeneic T cells. Sharma et al (118) examined the effects of in vitro treatment of cells with IVIG and/or mycophenolic acid (MPA), a common immunosuppressive agent in desensitization protocols, on cell proliferation in a two-way mixed lymphocyte reaction. They found that both drugs, individually, suppressed cell proliferation and when used together, acted synergistically to amplify the effect.…”

Section: Mechanisms: Desensitization For Hla Antibodymentioning

confidence: 99%

Desensitization for solid organ and hematopoietic stem cell transplantation

Zachary

Leffell

2014

Immunological Reviews

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Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft.

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“…In addition, both immunosuppressive agents decreased the production of IgM in the stimulation environment, which is consistent with previous studies. 29,30 Other studies also have shown that a decrease in donor-specific antibodies strongly correlates with successful treatment of antibody-mediated rejection. 8,31,32 Our results suggest that bortezomib and MPA can inhibit B-cell antibody secretion.…”

Section: Discussionmentioning

confidence: 99%

Effect of Mycophenolic Acid and Bortezomib on Purified Human B Cells: An In Vitro Study of Long-Term Functionally Stable MICA-Sensitized Renal Recipients

Wen²,

Wang³

et al. 2013

Exp Clin Transplant

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Mycophenolic acid and intravenous immunoglobulin exert an additive effect on cell proliferation and apoptosis in the mixed lymphocyte reaction

Cited by 8 publications

References 38 publications

In Vitro Influence of Mycophenolic Acid on Selected Parameters of Stimulated Peripheral Canine Lymphocytes

In Vitro Influence of Mycophenolic Acid on Selected Parameters of Stimulated Peripheral Canine Lymphocytes

Desensitization for solid organ and hematopoietic stem cell transplantation

Effect of Mycophenolic Acid and Bortezomib on Purified Human B Cells: An In Vitro Study of Long-Term Functionally Stable MICA-Sensitized Renal Recipients

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