Mycophenolate Mofetil Treatment Research Articles

Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment.

Osteoporosis can arise in systemic lupus erythematosus (SLE) patients secondary to medication and/or chronic inflammation. To analyze if patients with SLE have phenotypically-impaired osteoclastogenesis, we differentiated ex vivo monocytes from 72 SLE patients and 15 healthy individuals into osteoclasts followed by TRAP staining and counting. We identified a subgroup of SLE patients (45%) with a significantly impaired osteoclast differentiation, relative to the other SLE patients or healthy individuals (OR 11.2; 95% CI 1.4–89.9). A review of medication indicated that patients with osteoclast counts equal to healthy donors were significantly more likely to be treated with mycophenolate mofetil (MMF) compared to patients with impaired osteoclastogenesis. We analyzed expression of RANKL and the MMF target genes IMPDH1 and IMPDH2 in osteoclasts by qPCR, but detected no difference. Since MMF might influence interferon-α (IFNα) and -γ (IFNγ) we measured serum IFNα and IFNγ levels. Patients with very low osteoclast counts also had comparably higher IFNα serum levels than patients with normal osteoclast counts. We conclude that in vitro osteoclastogenesis is impaired in a subgroup of SLE patients. This correlates inversely with MMF treatment and high IFNα serum levels. Further observational study will be required to determine whether this translates into a clinically meaningful effect.

WITHDRAWN: Natural Killer Cell Activating Receptor NKG2D Is Involved in the Immunosuppressant Effect of Mycophenolate Mofetil and Infection of Hepatitis B Virus

In this study we investigated whether mycophenolate mofetil (MMF), a new immunosuppressant, and its metabolite mycophenolic acid (MPA) influence the activity of liver resident natural killer (NK) cells, resulting in increased susceptibility to hepatitis B virus (HBV) infection. We isolated the hepatic NK cells of C57BL/6 and C57BL/6JTgN (A1b1HBV) 44Bri) transgenic mice administered MMF in the presence or absence of interleukin (IL)-15, or incubated isolated hepatic NK cells in the presence or absence of MPA and used RT-PCR, immunolabeling to assess the expression of NK receptors Ly49A, NKG2A and NKG2D, and cytokine ELISA and [(3)H]-TdR-release assay to assess the activation and cytotoxic capacity of NK cells. After treatment of MMF in the presence or absence of IL-15, HBsAg titer was also measured in C57BL/6JTgN (A1b1HBV) 44Bri) transgenic mice. After both MPA and MMF treatments, NK cytotoxicity was reduced, NKG2D and Ly49A expression was down-regulated, but NKG2A was up-regulated. Down-regulation of NKG2D could be ameliorated by IL-15, and in HBV-transgenic mice, MMF treatment impaired NK cell activity, but did not influence virus replication, whereas IL-15 treatment depressed HBsAg titer. MPA and MMF mediate down-regulation of NKG2D in vitro and vivo, restricting the cytotoxic capacity of NK cells. Regulation of NKG2D may be important in the effect of immunosuppressant on NK cell activity and involved in HBV infection.

Circadian variation in hepatic toxicity of the immunosuppressive agent “Mycophenolate Mofetil” in rats

Immunosuppressive drugs may have varying toxicity or efficacy depending on the administration time. This study investigates whether the liver toxicity of the mycophenolate mofetil (MMF) varies according to the circadian dosing-time in rats. 300 mg/kg of MMF was injected by intraperitonal route to different groups of animals at four different circadian stages (1, 7, 13, and 19 h after light onset, HALO). Biochemical variable (transaminase, alkaline phosphatase) and histopathological examinations on liver section were performed. The results obtained showed that MMF treatment induced hepato-toxicity depending on the circadian time. A severe toxicity in the liver was observed when the drug was injected at 7 HALO. The data obtained indicate that the maximum of hepato-toxicity is observed when MMF was injected in the middle of the light-rest span of rats which is physiologically analogous to the end of the activity of the diurnal phase in human patients.

The Diagnosis and Treatment of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a prevalence of 36.7/100 000 in Germany and a female/male ratio of 4:1. The clinical course is variable, with a broad spectrum of organ manifestations; lupus nephritis develops in about half of all patients. This review is based on a selective search of PubMed and the Cochrane Library, including current guidelines and expert recommendations. Assessment of clinical symptoms, laboratory findings, and optional biopsy results are the basis for early diagnosis of SLE. All patients should be treated with antimalarials as soon as the diagnosis is confirmed. In particular, hydroxychloroquine is associated with a higher rate of remission, fewer relapses, and reduced damage in the course of the disease, even in lupus nephritis. High-dose glucocorticoids should be given only when acutely indicated; immunosuppressives such as azathioprine, methotrexate, or mycophenolate mofetil may be administered to reduce glucocorticoids, according to the EULAR recommendations. Belimumab was recently approved as add-on therapy in autoantibody-positive SLE patients with high disease activity unresponsive to standard treatment. Short-term induction pulse therapy with low-dose intravenous cyclophosphamide, as well as continued mycophenolate mofetil treatment are advances in lupus nephritis. The long-term prognosis for SLE has improved markedly in recent decades because of earlier diagnosis and optimized treatment. Further research and randomized controlled trials are needed for the development of specifically targeted therapies.

Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial mesenchymal transition in rats.

Recent studies in animal models have revealed that mycophenolate mofetil (MMF) has certain protective effects against experimental diabetic nephropathy. The present study therefore aimed to investigate the hypothesis that diabetic nephropathy may be ameliorated by mycophenolate mofetil and benazepril treatment alone or in combination, and identify the potential underlying mechanisms in a rat model. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin. Rats were subsequently treated with benazepril, MMF or a combination of the two drugs, and blood glucose, normalized kidney weight, urine protein and serum creatinine were determined. The pathological changes in renal tissue were also observed. In addition, indices of epithelial mesenchymal transition, including α-smooth muscle actin (α-SMA) and transforming growth factor (TGF)-β1 expression, were examined. Normalized kidney weight, urine protein and serum creatinine levels were significantly improved in the diabetic rats treated with benazepril or mycophenolate mofetil, compared with those of rats in the untreated diabetic group. Pathological changes in the kidney were detected concurrently with increasing kidney weight and urinary albumin excretion, with a similar trend in variation among groups. In addition, the expression of epithelial mesenchymal transition indices, including α-SMA and TGF-β1, in the renal tubule interstitium were significantly decreased in the benazepril- and MMF-treated groups compared with those of the diabetic group. As expected, the aforementioned indices were markedly lower in the benazepril and MMF combined treatment group than those in the single medication groups. These data suggested that MMF may have a protective role in diabetic nephropathy, and that the underlying mechanism may be partially dependent upon the suppression of the epithelial mesenchymal transition. Furthermore, the combination of benazepril and MMF conferred enhanced efficacy over monotherapies in the treatment of diabetic nephropathy.

Incidence of Late Acute Rejection in Living Donor Liver Transplant Patients, Risk Factors, and the Role of Immunosuppressive Drugs

IntroductionLate acute rejection (LAR) is a clinical manifestation that occurs 6 months after liver transplantation, shows histopathologic features different from those of acute rejection, and is the cause of a high prevalence of morbidity and mortality. MethodsIn this study, hospital records of 211 living donor liver transplantation (LDLT) patients who underwent surgery in our clinic between June 2000 and February 2014 were reviewed retrospectively. The patients were ≥18 years old and were followed for ≥6 months. ResultsOf the 211 patients, 21 (9.9%; 16 males, 5 females) developed LAR. The mean age of the patients was 46 years (range, 33–58). The mean follow-up period was 61.2 months (range, 6–152) and the median time to development of LAR was 26.4 months (range, 7–77). In our study, patients who received cyclosporine and mycophenolate mofetil (MMF) treatment developed more LAR than did patients who received tacrolimus and MMF therapy (P = .05). In addition, the incidence of LAR in patients who underwent LDLT was significantly greater in the ABO-matched groups than in the ABO identical group (P = .028). ConclusionsDevelopment of LAR and serious complications related to it can be avoided if liver transplant recipients are followed regularly and closely in outpatient clinics after transplantation.

Natural Killer Cell Activating Receptor NKG2D Is Involved in the Immunosuppressive Effects of Mycophenolate Mofetil and Hepatitis B Virus Infection

The purpose of this study is to investigate whether mycophenolate mofetil (MMF), a new immunosuppressant, and its metabolite mycophenolic acid (MPA) affect the activity of liver resident natural killer (NK) cells, resulting in increased susceptibility to hepatitis B virus (HBv) infection. Hepatic NK cells were isolated from C57BL/6 and C57BL/ 6JTgN (A1b1HBV) 44Bri transgenic mice treated with MMF in the presence or absence of IL-15. After incubation of isolated hepatic NK cells in the presence or absence of MPA, reverse transcription polymerase chain reaction and immunolabeling were used to assess the expression of NK receptors Ly49A, NKG2A and NKG2D. In addition, cytokine enzyme-linked immunosorbent assay and [3H]-TdR-release assay were carried out to assess NK cell activation and cytotoxic capacity. After treatment with MMF in the presence or absence of IL-15, HBsAg titers were measured in C57BL/6JTgN (A1b1HBV) 44Bri transgenic mice. Treatment with either MPA or MMF resulted in reduced NK cell cytotoxicity, downregulated NKG2D and Ly49A expression and upregulated NKG2A. Interestingly, NKG2D downregulation was ameliorated by IL-15. In HBV-transgenic mice, MMF treatment impaired NK cell activity but did not affect virus replication, whereas IL-15 treatment reduced HBsAg titers. MPA and MMF mediate NKG2D downregulation both in vitro and in vivo, reducing the cytotoxic capacity of NK cells. These findings indicate that NKG2D regulation may be important in the immunosuppressive effect NK cells and involved in HBV infection.

Mycophenolate mofetil therapy for steroid-resistant IgA nephropathy with the nephrotic syndrome in children.

BackgroundImmunoglobulin A nephropathy (IgAN) presents as nephrotic syndrome (NS) relatively rarely, and the current treatment experience of IgAN patients with NS is mostly with adults. The objective of our study was to investigate the efficacy of corticosteroids and mycophenolate mofetil (MMF) in treating childhood immunoglobulin A nephropathy (IgAN) with nephrotic syndrome.MethodsA total of 58 children (39 boys and 19 girls) diagnosed with nephrotic syndrome and primary IgAN were enrolled in the study. All the patients were administered prednisone 2 mg/kg per day for 8 weeks. Steroid-resistant patients were treated with the combined use of MMF (dose of 20 ~ 30 mg/kg per day) and prednisone for 6–12 months. The prednisone dose was reduced stepwise during the combined treatment.ResultsOf the 58 children, 14 were steroid-sensitive (M, S, and T variants of the Oxford classification were 0 in most children), and 44 cases who presented serious pathological damage to the kidney were steroid-resistant. The estimated glomerular filtration rate (eGFR) of the steroid-resistant children (86.69 ± 26.85 ml/min/1.73 m2) was significantly lower (P < 0.05) than that of the steroid-sensitive children (106.89 ± 26.94 ml/min/1.73 m2). After 4 months of combined MMF treatment in 33 steroid-resistant children, complete remission of proteinuria was found in 21 cases, partial remission of proteinuria in 6 cases, and no response was found in 6 cases. Except for the T variant, other variants of the Oxford classification, including M, E, and S morphological variables, was not significantly different among patients complete remission, those with partial remission, and those with no response. The eGFR of children with complete remission of proteinuria (100.04 ± 18.47 ml/min/1.73 m2), that of those with partial remission (92.24 ± 27.63 ml/min/1.73 m2), and that of those with no response (72.17 ± 27.55 ml/min/1.73 m2) were significantly different (P < 0.05).ConclusionCorticosteroid therapy showed satisfactory efficacy in IgAN children with nephrotic syndrome and slight pathological damage. The effect of MMF was good for steroid-resistant IgAN children, but poor for those with tubular atrophy/interstitial fibrosis and renal function impairment.

Mycophenolate Mofetil Ameliorates Diabetic Nephropathy in db/db Mice.

Chronic low-grade inflammation is an important factor in the pathogenesis of diabetic complication. Mycophenolate mofetil (MMF) has an anti-inflammatory effect, inhibiting lymphocyte proliferation. Previous studies showed attenuation of diabetic nephropathy with MMF, but the underlying mechanisms were unclear. This study aimed to identify the effect of MMF on diabetic nephropathy and investigate its action mechanisms in type 2 diabetic mice model. Eight-week-old db/db and control mice (db/m mice) received vehicle or MMF at a dose of 30 mg/kg/day for 12 weeks. MMF-treated diabetic mice showed decreased albuminuria, attenuated mesangial expansion, and profibrotic mRNA expressions despite the high glucose level. The number of infiltrated CD4+ and CD8+ T cells in the kidney was significantly decreased in MMF-treated db/db mice and it resulted in attenuating elevated intrarenal TNF-α and IL-17. The renal chemokines expression and macrophages infiltration were also attenuated by MMF treatment. The decreased expression of glomerular nephrin and WT1 was recovered with MMF treatment. MMF prevented the progression of diabetic nephropathy in db/db mice independent of glycemic control. These results suggest that the effects of MMF in diabetic nephropathy are mediated by CD4+ T cell regulation and related cytokines.

Successful treatment by mycophenolate mofetil in a patient with focal segmental glomerulosclerosis associated with posterior reversible encephalopathy syndrome.

It has been reported that cyclosporine A (CsA) treatment may be associated with posterior reversible encephalopathy syndrome. We report a 16-year-old man who exhibited nephrotic syndrome and posterior reversible encephalopathy syndrome. Intensive antihypertensive therapy restored him to consciousness. Renal biopsy revealed that he suffered from focal segmental glomerulosclerosis. Although he was treated with prednisolone and low-density lipoprotein apheresis therapy, his proteinuria remained at high level. Then, mycophenolate mofetil (MMF) with less influence on vessel endothelium compared with CsA and tacrolimus was administered. Soon after, he reached remission of nephrotic syndrome without recurrence of posterior reversible encephalopathy syndrome. This is the first case that a young patient of focal segmental glomerulosclerosis with posterior reversible encephalopathy syndrome achieved a complete remission by MMF treatment without recurrence of posterior reversible encephalopathy syndrome. MMF may be effective for young patients of focal segmental glomerulosclerosis especially with clinical condition of vascular endothelial damage such as posterior reversible encephalopathy syndrome.

Effects of mycophenolate mofetil on kidney function and phosphorylation status of renal proteins in Alport COL4A3-deficient mice.

BackgroundWe investigated the effects of mycophenolate mofetil (MMF) on kidney function and on protein phosphorylation in a mouse model for the human Alport syndrome.MethodsCOL4A3-deficient (COL4A3−/−) mice were randomly allocated to receive a placebo (PLC COL4A3−/−) or MMF treatment (MMF COL4A3−/−). Wild type mice (WT) were used as controls. Changes in serum creatinine, total protein and blood urea nitrogen (BUN), concentrations of mycophenolic acid (MPA) and its glucuronide metabolite (MPAG), serum protein electrophoresis, urine dipstick chemistry and sediment were measured. Changes in the phosphorylation status of renal proteins and histology were analyzed.ResultsMMF influenced kidney function and protein phosphorylation. Serum creatinine and BUN were lower in MMF treated compared to PLC treated COL4A3−/− mice. Serum albumin and alpha-1 globulins were significantly decreased while serum creatinine, alpha-2 globulins, urine dipstick protein, leukocyte esterase, hemoglobin and red blood cells were all increased in both COL4A3−/− groups compared to WT. Differential 2DE-gel analysis identified six phosphorylated kidney protein spots that were significantly altered by MMF.ConclusionsThese data suggest that the MMF treatment in this murine model moderately improved kidney function and reversed the phosphorylation status of six renal phosphoprotein spots to that seen in WT mice.Electronic supplementary materialThe online version of this article (doi:10.1186/s12953-014-0056-z) contains supplementary material, which is available to authorized users.

Efficacy and safety of mycophenolate mofetil treatment in IgA nephropathy: a systematic review.

BackgroundIgA nephropathy is the most common primary glomerular disease worldwide and also the most frequent cause of kidney failure. Mycophenolate mofetil (MMF) is a selective immunosuppressant widely used in many autoimmune diseases. However, the benefits and risks of MMF for the treatment of IgA nephropathy remain uncertain.MethodsA systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to assess the efficacy and safety of MMF in IgA nephropathy patients, using the statistical software Review Manager 5.1.ResultsEight RCTs involving 357 patients were identified and included in this review. Overall, no statistical difference was found in the therapeutic effect of MMF treatment compared with other therapies. MMF had no significant effects on reducing proteinuria or protecting renal function. However, subgroup analysis indicated that relatively short-term therapy (<18 months) might be beneficial in IgA nephropathy patients while longer term MMF use conferred no advantage. There was also no statistical difference between MMF and control groups in the incidence of side effects. When compared with other immunosuppressants, MMF was considered superior to cyclophosphamide in terms of better therapeutic effects and fewer adverse reactions, but no difference was found between MMF and leflunomide.ConclusionsOur current evidence indicates that a relatively short course of MMF may be beneficial in treating IgA nephropathy. However, high-quality RCTs with large sample size as well as a well-designed study to evaluate the long-term effects of MMF are needed to further evaluate the efficacy and safety of MMF in this disease.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2369-15-193) contains supplementary material, which is available to authorized users.

Conversion of Th17 into IL-17A(neg) regulatory T cells: a novel mechanism in prolonged allograft survival promoted by mesenchymal stem cell-supported minimized immunosuppressive therapy.

The ultimate goal in transplantation medicine is the promotion of operational tolerance. Although Th cells of the Th17 type have been predominantly associated with rejection of allogeneic solid organ grafts, regulatory T (T(reg)) cells appear to foster operational tolerance. Induced T(reg) and Th17 cells have a higher lineage plasticity than has been recognized thus far. We found that when mesenchymal stem cells (MSCs) were used to induce long-term acceptance of allogeneic heart grafts in mice, the induction of T(reg) cells was preceded by development of a CD11b(hi)Gr1(int) myeloid-derived immunosuppressive cell-mediated Th17 response. Substantial suppression of Foxp3(+) T(reg) cell generation from retinoic acid receptor-related orphan receptor γ(-/-) T cells by MSCs revealed that retinoic acid receptor-related orphan receptor γ is a common factor in the differentiation of T(reg) and Th17 cells. Immunosuppressant mycophenolate mofetil treatment of enriched IL-17A(+) cells from MSC-primed allograft mouse recipients resulted in a reduction of IL-17A production and an increase in the Foxp3(+) T(reg) cell fraction. Furthermore, identification of IL-17A(+) Foxp3(+) double-positive and ex-IL-17-producing IL-17A(neg)Foxp3(+) T cells strongly argues for direct conversion of Th17 cells into T(reg) cells as the underlying mechanism of immune regulation in MSC-mediated allograft survival. The Th17 into T(reg) conversion identified in this study constitutes an important immunological mechanism by which MSC-induced myeloid-derived immunosuppressive cells mediate operational transplant tolerance. The possibility to create T(reg) cell-regulated operational tolerance in the absence of complete immune suppression provides strong clinical implications for cell therapy-assisted minimization protocols.

P237 A Review Of The Steroid Sparing Impact Of Mycophenolate Mofetil In The Severe Asthma Population At The North West Lung Centre, University Hospital South Manchester

Objectives To determine whether Mycophenolate mofetil (MMF) is an effective steroid sparing agent in a single centre cohort of severe asthma patients. Background MMF is a powerful inhibitor of purine and pyrimidine synthesis via the de novo pathway, upon which lymphocyte production is dependent. It is currently licensed for use in transplant rejection prophylaxis. Other immunosuppressant therapies have been used off licence in difficult-to-treat asthma patients under specialist supervision in an effort to reduce corticosteroid use. MMF is currently a third line immunosuppressant after methotrexate and azathioprine at the North West Lung Centre. Methods A retrospective data analysis was performed including all patients under specialist asthma care at UHSM that were previously or currently treated with MMF. Annualised average daily steroid dose was calculated from the available data in patient case notes. This was calculated for 12 months prior to commencing any immunosuppressant therapy and during MMF treatment. Exacerbation and hospital admission rates were also recorded. Results A total of 34 patients were identified as being on MMF for severe asthma for at least 8 weeks. 11 did not tolerate MMF or had no response and subsequently stopped. The primary analysis was carried out on 23 patients and a secondary post hoc analysis was performed on all patients who had been on treatment for a minimumof 6 months at the time of the study (N=12). The average yearly steroid sparing impact of MMF was 5.9 mg per day, (p 6 months (Δ 3.9 p = 0.20). There was no statistically significant reduction in admission or exacerbation rates. Conclusion MMF has shown a small steroid sparing effect in this retrospective analysis, although the effect appeared less positive in the sub-group of those analysed after being on treatment for at least 6 months further analysis of the potential benefits of MMF in this patient population is required.

Hypertensive renal injury is associated with gene variation affecting immune signaling.

The spontaneously hypertensive rat (SHR) strain exists in lines that contrast strongly in susceptibility to renal injury in hypertension. These inbred lines share common ancestry, and only 13% of their genomes arise from different ancestors. We used next gen sequencing to detect natural allelic variation in 5 genes of the immunoreceptor signaling pathway (IgH, Dok3, Src, Syk, and JunD) that arise from different ancestors in the injury-prone SHR-A3 and the resistant SHR-B2 lines. We created an intercross between these lines, and in the F2 progeny, we observed that the inheritance of haplotype blocks containing the SHR-A3 alleles of these 5 genes correlated with increased albuminuria and histological measures of renal injury. To test whether accumulated genetic variation in this pathway may create a therapeutic target in hypertensive renal injury, rats of both lines were treated with the immunosuppressant mycophenolate mofetil (MMF). MMF reduced proteinuria (albumin to creatinine ratio) from 6.6 to 1.2 mg/mg (P<0.001) in SHR-A3. Glomerular injury scores were reduced in MMF-treated SHR-A3 from 1.6 to 1.4 (P<0.002). Tubulo-interstitial injury was reduced in MMF-treated SHR-A3 from 2.62 to 2.0 (P=0.001). MMF treatment also reduced renal fibrosis in SHR-A3 (3.9 versus 2.0; P<0.001). Polygenic susceptibility to renal injury in hypertension arises in association with genetic variation in genes that participate in immune responses and is dramatically improved by reduction of immune system activity.

Mycophenolate mofetil in the treatment of neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disorder of the central nervous system. Recently, various immunosuppressant medications were introduced as therapeutic options for preventing relapse of NMOSD. However, our understanding of the effectiveness of mycophenolate mofetil (MMF) in treating patients with NMOSD is based on only a small number of studies. To evaluate the efficacy and safety of MMF treatment in patients with NMOSD. A 3-center retrospective review of our experiences, examining results from 59 patients with NMOSD (24 with neuromyelitis optica and 35 with a limited form of the disease) who were treated with MMF (1000-2000 mg/d). Patients' annualized relapse rate, disability as measured by the Expanded Disability Status Scale, and experience of adverse effects due to MMF were assessed. Of the 59 patients, 1 with NMOSD who had to discontinue MMF use in the first month due to a rash was excluded. The remaining 58 patients were included in the drug-efficacy analysis. The median post-MMF annualized relapse rate was significantly lower than the pre-MMF annualized relapse rate (0.0 vs 1.5; P < .001). The Expanded Disability Status Scale scores also significantly decreased after MMF treatment (3.0 vs 2.5; P = .005). Thirty-five patients (60%) were relapse free, and Expanded Disability Status Scale scores were stabilized or improved in 53 patients (91%). Fourteen patients discontinued MMF treatment owing to ongoing relapse (10 patients), rash (1 patient), pregnancy (1 patient), and financial problems (2 patients), but MMF was generally well tolerated. In this observational study, MMF treatment induced reduction of relapse frequency, stabilized or improved disability, and was well tolerated in patients with NMOSD.

Mycophenolate mofetil and cyclophosphamide treatment suppress inflammation intensity in experimental model of autoimmune uveitis

AbstractPurpose The research in experimental models of autoimmune uveitis helps to find new therapeutical strategies. The aim of this study is to compare the effect of cyclophosphamide (CPA), mycophenolate mofetil (MMF) and golimumab on inflammation intensity in mice model of experimental autoimmune uveitis (EAU).Methods EAU was induced in C57BL/6 mice by subcutaneous application of IRBP (interphotoreceptor retinoid binding protein) in complete Freund’s adjuvant and pertussis toxin. CPA was injected intraperitoneally in a single dose of 100 mg/kg, MMF intraperitoneally daily in a dose of 30 and 50 mg/kg, golimumab subcutaneously weekly in a dose of 70 mg/kg. Mice with EAU without treatment and group with EAU with sham treatment served as controls. Histological grading of uveitis at day 35 post induction of EAU was used.Results The comparison of intensity of inflammation in group of treated and untreated mice shows that MMF significantly suppressed the inflammation (p˂0,05). The absolute suppression of inflammation by CPA (p˂0,0001) was shown. On the contrary, golimumab enhanced the ocular inflammation.Conclusion In this study, we have confirmed the efficacy of CPA and MMF in treatment of posterior uveitis, which supports its use in human medicine. This project was supported by grant IGA MZ NT/14017‐3/2013 and SVV‐266505/2013.

Two-year experience with mycophenolate mofetil in patients with scleroderma lung disease: a case series.

To assess the effect of mycophenolate mofetil (MMF) on pulmonary functions in patients with systemic sclerosis-associated lung disease (SSc-ILD) who experienced an inadequate response to first line cyclophosphamide (CYC) therapy. Twelve consecutive SSc-ILD patients who received MMF due to inadequate response to CYC as a first line agent, were retrospectively reviewed. Over the course of 2 years, pulmonary function tests (PFT) and high-resolution computed tomography (HRCT) scans were performed. Following initial baseline tests, PFTs were continued at a frequency of every 6 months and HRCT scans were performed every 12 months. After MMF treatment, values of forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) improved in three (25%) and two (16.6%) patients, respectively. It is also noted that the evaluation of serial HCRT scans showed no change in 54.5% of patients. Our case series suggested that PFT and imaging scores seemed to be stabilized by MMF in SSc-ILD patients who were inadequate responders to CYC.

Mycophenolate mofetil therapy in the management of inflammatory bowel disease — A retrospective case series and review

Background and aimsThe role of mycophenolate mofetil (MMF) as an immunomodulatory drug in managing inflammatory bowel disease (IBD) is yet to be fully defined. We reviewed our experience of MMF in treating patients with IBD. MethodsRetrospective analysis was performed on all patients treated with MMF for inflammatory bowel disease between 2003 and 2011. Remission was assessed by reviewing clinical, endoscopic and laboratory indices. ResultsWe identified 36 patients, 23 male (64%), median age 46years (range 19–75). Nineteen patients had Crohn's disease, 16 with ulcerative colitis (UC), and one with indeterminate colitis. 33 patients (92%) had previously received azathioprine; 32 of whom discontinued this due to side-effects. 26 patients (72%) were concurrently taking oral corticosteroids. Median length of MMF treatment observed was 21.5months (IQR 9.7–31.6). At 8weeks, 29 patients (81%) had either achieved or maintained remission. After 6months, 19 of 33 patients (58%) were in sustained steroid-free remission. At the end of the observation period, 29 patients (81%) remained on MMF. 13 patients (36% of original treatment group; UC/IBDU 8, Crohn's 5) maintained steroid free remission. Median time in remission was 21.4months (IQR 11.0–30.0). Drug side-effects were experienced by 7 patients (19%), managed by dose reduction in 5 patients, with discontinuation in 2 (6%). ConclusionsMycophenolate mofetil may represent a promising treatment for inducing and maintaining remission in IBD patients intolerant of thiopurines. It may be of more value and relevance in ulcerative colitis, since less alternative proven therapies are available.

A8.38 MMF treatment differentially regulates immune responses to vaccination by PNEUMOVAX but not prevnar in MRL/LPR mice

Background and ObjectivesInfections are a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) treated with immunosuppressive therapy. Mycophenolate mofetil (MMF) blocks the proliferation of activated...