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Fulltext Variable outcome in infantile-onset inflammatory bowel disease in an Asian cohort

Lee WS, Ng RT, Chan KW, Lau YL

World J Gastroenterol, 2016 Dec 28;22(48):10653-10662.
PMID: 28082818 DOI: 10.3748/wjg.v22.i48.10653

AIM: Infantile-onset inflammatory bowel disease (IO-IBD) with the onset of disease before 12 mo of age, is a different disease entity from childhood IBD. We aimed to describe the clinical features, outcome and role of mutation in interleukin-10 (IL-10) and interleukin-10 receptors (IL-10R) in Asian children with IO-IBD.
METHODS: All cases of IO-IBD, defined as onset of disease before 12 mo of age, seen at University Malaya Medical Center, Malaysia were reviewed. We performed mutational analysis for IL10 and IL10R genes in patients with presenting clinical features of Crohn's disease (CD).
RESULTS: Six [13%; CD = 3, ulcerative colitis (UC) = 2, IBD-unclassified (IBD-U) = 1] of the 48 children (CD = 25; UC = 23) with IBD have IO-IBD. At final review [median (range) duration of follow-up: 6.5 (3.0-20) years], three patients were in remission without immunosuppression [one each for post-colostomy (IBD-U), after standard immunosuppression (CD), and after total colectomy (UC)]. Three patients were on immunosuppression: one (UC) was in remission while two (both CD) had persistent disease. As compared with later-onset disease, IO-IBD were more likely to present with bloody diarrhea (100% vs 55%, P = 0.039) but were similar in terms of an associated autoimmune liver disease (0% vs 19%, P = 0.31), requiring biologics therapy (50% vs 36%, P = 0.40), surgery (50% vs 29%, P = 0.27), or achieving remission (50% vs 64%, P = 0.40). No mutations in either IL10 or IL10R in the three patients with CD and the only patient with IBD-U were identified.
CONCLUSION: The clinical features of IO-IBD in this Asian cohort of children who were negative for IL-10 or IL-10R mutations were variable. As compared to childhood IBD with onset of disease after 12 mo of age, IO-IBD achieved remission at a similar rate.

Matched MeSH terms: Immunosuppression
Treatment of immunosuppressed chronic hepatitis B patients

Lau GK

Med J Malaysia, 2005 Jul;60 Suppl B:57-62.
PMID: 16108175
Matched MeSH terms: Immunosuppression*
Post transplant lymphoproliferative disorder: a case series and review of literature

Cader RA, Mohd R, Gafor HA, Kong NC

EXCLI J, 2013;12:144-9.
PMID: 26417223

Post-transplant lymphoproliferative disorder (PTLD) is a recognized complication exclusive to solid organ transplant recipients and carries a high mortality. We retrospectively reviewed records of all renal transplant recipients under follow up at our institution over the last seven years (2005-2011). We reviewed the patient characteristics, immunosuppression regimen and risk factors for the development of PTLD and its outcomes in our transplant cohort. Four out of 63 patients were diagnosed with PTLD. PTLD was incidentally diagnosed on a transplant biopsy that was performed for an unexplained rise in serum creatinine in three patients. The fourth patient presented with left submandibular lymphadenopathy. Majority presented within 18 months of renal transplantation. After the diagnosis of PTLD on graft biopsy, all patients were fully investigated and two patients had systemic involvement. In the patients with systemic involvement, reduction of immunosuppression and anti B cell therapy with Rituximab was used with good success. The patient with submandibular lymphadenopathy received chemotherapy in addition to reduction of immunosuppression. Three PTLD cases were polyclonal and diagnosed early whereas the fourth case was monoclonal. PTLD can sometimes be incidentally diagnosed on an allograft biopsy performed for rejection. The incidence of PTLD in our centre is higher than reports from other centres but our outcome is good if recognised and treated early.

Matched MeSH terms: Immunosuppression
Hepatitis in renal transplant recipients with and without donor-specific blood transfusion

Morad Z, Suleiman AB, Kong CT

Transplant Proc, 1989 Feb;21(1 Pt 2):1825-6.
PMID: 2652593
Matched MeSH terms: Immunosuppression
Renal transplantation in Malaysia

Fan KS, Lim TO, Morad Z, Suleiman AB, Lei CC, Khairullah A

Transplant Proc, 1995 Feb;27(1):1466-8.
PMID: 7878944
Matched MeSH terms: Immunosuppression/methods
Fulltext Ectopic ACTH syndrome - Experience with Etomidate

Tong CV, Hussein Z

J ASEAN Fed Endocr Soc, 2017;32(1):54-56.
PMID: 33442086 DOI: 10.15605/jafes.032.01.10

For ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), when surgery is not feasible, or in cases of severe biochemical disturbances, immunosuppression or mental instability, medical therapy with agents such as etomidate is indicated. We present our experience in using etomidate for a 41-year old female with EAS secondary to a malignant mediastinal paraganglioma. We were able to demonstrate that etomidate can be used effectively to control severe hypercortisolism in a lower dose than previously described.

Matched MeSH terms: Immunosuppression
Fulltext Fatal infections in older patients with inflammatory bowel disease on anti-tumor necrosis factor therapy

Lee WS, Azmi N, Ng RT, Ong SY, Ponnampalavanar SS, Mahadeva S, et al.

Intest Res, 2017 Oct;15(4):524-528.
PMID: 29142521 DOI: 10.5217/ir.2017.15.4.524

Anti-tumor necrosis factor (anti-TNF) is highly effective in inflammatory bowel disease (IBD); however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years). All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia). All 3 patients died within 1 year from the onset of the infection(s). We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD.

Matched MeSH terms: Immunosuppression
Early infection with Marek's disease virus can jeopardize protection conferred by laryngotracheitis vaccines: a method to study MDV-induced immunosuppression

Faiz NM, Cortes AL, Guy JS, Fletcher OJ, West M, Montiel E, et al.

Avian Pathol, 2016 Dec;45(6):606-615.
PMID: 27207594

Marek's disease virus (MDV) is a herpesvirus that induces lymphomas and immunosuppression in chickens. MDV-induced immunosuppression (MDV-IS) is divided into two phases: early-MDV-IS occurring mainly in chickens lacking maternal antibodies (MAb) against MDV and associated with lymphoid organ atrophy; and late-MDV-IS occurring once MDV enters latency and during tumour development. Our objectives were to document the impact of late-MDV-IS on commercial poultry (meat-type chickens bearing MAb against MDV and that were vaccinated or unvaccinated against MD) and to optimize a model to study late-MDV-IS under laboratory conditions. The impact of late-MDV-IS was evaluated by assessing the effect of early infection (day of age) with a very virulent plus MDV (vv+MDV) on the efficacy of chicken-embryo-origin (CEO) infectious laryngotracheitis (ILT) virus vaccine against ILT challenge. The CEO ILT vaccine was administered in water at 14 days of age and ILT virus (ILTV) challenge was done intratracheally at 30 days of age. Development of ILT was monitored by daily evaluation of clinical signs, development of gross and histological lesions in trachea, and quantification of ILTV transcripts in trachea. Infection with vv+MDV strain 648A resulted in total abrogation of protection conferred by the CEO vaccine against ILTV challenge even in chickens vaccinated at 1 day of age with either HVT, HVT+SB-1, or CVI988. Chickens exposed to vv+MDV prior to vaccination with CEO ILTV vaccine had similar (P

Matched MeSH terms: Immunosuppression
Phytosterols isolated from Clinacanthus nutans induce immunosuppressive activity in murine cells

Le CF, Kailaivasan TH, Chow SC, Abdullah Z, Ling SK, Fang CM

Int Immunopharmacol, 2017 Mar;44:203-210.
PMID: 28119186 DOI: 10.1016/j.intimp.2017.01.013

Clinacanthus nutans (Burm. f.) Lindau is a traditional medicinal plant belonging to the Acanthaceae family. Its therapeutic potentials have been increasingly documented particularly the antiviral activity against Herpes Simplex Virus (HSV), anti-cancer, anti-oxidant, anti-inflammatory and immunomodulatory activities. However, majority of these studies used crude or fractionated extracts and not much is known about individual compounds from these extracts and their biological activities. In the present study, we have isolated four compounds (CN1, CN2, CN3 and CN4) from the hexane fractions of C. nutans leaves. Using NMR spectroscopic analysis, these compounds were identified to be shaftoside (CN1), stigmasterol (CN2), β-sitosterol (CN3) and a triterpenoid lupeol (CN4). To determine the immunosuppressive potential of these compounds, their effects on mitogens induced T and B lymphocyte proliferation and the secretion of helper T cell cytokines were examined. Among the four compounds, stigmasterol (CN2) and β-sitosterol (CN3) were shown to readily inhibit T cell proliferation mediated by Concanavalin A (ConA). However, only β-sitosterol (CN3) and not stigmasterol (CN2) blocks the secretion of T helper 2 (Th2) cytokines (IL-4 and IL-10). Both compounds have no effect on the secretion of Th1 cytokines (IL-2 and IFN-γ), suggesting that β-sitosterol treatment selectively suppresses Th2 activity and promotes a Th1 bias. CN3 was also found to significantly reduce the proliferation of both T helper cells (CD4(+)CD25(+)) and cytotoxic T cells (CD8(+)CD25(+)) following T cell activation induced by ConA. These results suggested that phytosterols isolated from C. nutans possess immunomodulatory effects with potential development as immunotherapeutics.

Matched MeSH terms: Immunosuppression
Immunomodulatory effect of Noni fruit and its isolates: insights into cell-mediated immune response and inhibition of LPS-induced THP-1 macrophage inflammation

Ezzat MI, Hassan M, Abdelhalim MA, El-Desoky AM, Mohamed SO, Ezzat SM

Food Funct, 2021 Mar 18.
PMID: 33734250 DOI: 10.1039/d0fo03402a

Morinda citrifolia L. is a plant of the family Rubiaceae and is known as Indian mulberry or Noni in India. It is a perennial herb native to Southeast Asia and has been used over the years as a food supplement and medicinal plant. Noni fruits are reported to possess anticancer, fungicidal, antiviral and antiarthritic effects. The objective of our study is the screening of the immunomodulatory activity of the total extract, fractions, and isolated compounds of Noni fruits to identify their bioactive compounds. To achieve our goal, an ethanol extract (EE) was prepared from Noni fruits. Fractionation and purification of the EE were accomplished. The cell-mediated immune (CMI) response in prednisolone-induced immunosuppression rats was evaluated. The toxicity of the EE, fractions and isolated compounds on the differentiated THP-1 macrophage was assessed using the MTT viability assay. Moreover, the inflammation-related immune responses in lipopolysaccharide (LPS)-induced THP-1 macrophage activation were evaluated. Fractionation of the EE gave three fractions, dichloromethane (DCMF), water (WF) and methanol (MF). Purification of DCMF yielded stigmast-7-ene-3-ol (M1), 28-hydroxy-3β-acetoxy-9-dehydrogramisterol (M2), 3β-acetoxy-taraxast-20(30)-ene-21-ol (M3), 22-dehydroclerosterol (M4) and 22-dehydroclerosterol-3-O-β-d-glucopyranoside (M5), while purification of MF yielded quercetin (M6), hesperidin (M7), naringin (M9) and gallic acid (M8). The results revealed that DCMF elicited an increase in paw edema to the extent of 35.8%. All the tested samples had no cytotoxic effect on THP-1 macrophages. Co-treatment of the LPS-induced macrophages with DCMF, M2, M3, and M6 decreased the production of TNF-α, IL-1β, and IL-6/IL-10. The expression of iNOS, COX-2, and NF-κB decreased to 0.14 ± 0.02, 0.15 ± 0.02, and 0.17 ± 0.03, respectively, after co-treatment with LPS and DCMF. M2 attenuated the expression of iNOS and NF-κB to 0.18 ± 0.03 and 0.17 ± 0.03, respectively. Additionally, M3 attenuated the expression of iNOS to 0.18 ± 0.03, and after co-treatment with M6 and LPS, the expression of COX-2 and NF-κB was down-regulated to 0.2 ± 0.03. Our study proves the immunomodulatory effect of Noni fruits and specifies for the first time the compounds responsible for their activity.

Matched MeSH terms: Immunosuppression
An unusual rash and end-stage renal failure

Tan HJ, Eadington D

Hosp Med, 2001 Mar;62(3):176-7.
PMID: 11291470
Matched MeSH terms: Immunosuppression
Fulltext PIP4Ks impact on PI3K, FOXP3, and UHRF1 signaling and modulate human regulatory T cell proliferation and immunosuppressive activity

Poli A, Abdul-Hamid S, Zaurito AE, Campagnoli F, Bevilacqua V, Sheth B, et al.

Proc Natl Acad Sci U S A, 2021 08 03;118(31).
PMID: 34312224 DOI: 10.1073/pnas.2010053118

Regulatory T cells (Tregs) play fundamental roles in maintaining peripheral tolerance to prevent autoimmunity and limit legitimate immune responses, a feature hijacked in tumor microenvironments in which the recruitment of Tregs often extinguishes immune surveillance through suppression of T-effector cell signaling and tumor cell killing. The pharmacological tuning of Treg activity without impacting on T conventional (Tconv) cell activity would likely be beneficial in the treatment of various human pathologies. PIP4K2A, 2B, and 2C constitute a family of lipid kinases that phosphorylate PtdIns5P to PtdIns(4,5)P 2 They are involved in stress signaling, act as synthetic lethal targets in p53-null tumors, and in mice, the loss of PIP4K2C leads to late onset hyperinflammation. Accordingly, a human single nucleotide polymorphism (SNP) near the PIP4K2C gene is linked with susceptibility to autoimmune diseases. How PIP4Ks impact on human T cell signaling is not known. Using ex vivo human primary T cells, we found that PIP4K activity is required for Treg cell signaling and immunosuppressive activity. Genetic and pharmacological inhibition of PIP4K in Tregs reduces signaling through the PI3K, mTORC1/S6, and MAPK pathways, impairs cell proliferation, and increases activation-induced cell death while sparing Tconv. PIP4K and PI3K signaling regulate the expression of the Treg master transcriptional activator FOXP3 and the epigenetic signaling protein Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1). Our studies suggest that the pharmacological inhibition of PIP4K can reprogram human Treg identity while leaving Tconv cell signaling and T-helper differentiation to largely intact potentially enhancing overall immunological activity.

Matched MeSH terms: Immunosuppression
The immunosuppressive effects of human bone marrow-derived mesenchymal stem cells target T cell proliferation but not its effector function

Ramasamy R, Tong CK, Seow HF, Vidyadaran S, Dazzi F

Cell Immunol, 2008 Feb;251(2):131-6.
PMID: 18502411 DOI: 10.1016/j.cellimm.2008.04.009

Mesenchymal stem cells (MSC) are non-haematopoietic stem cells that are capable of differentiating into tissues of mesodermal origin. MSC play an important role in supporting the development of fetal and adult haematopoiesis. More recently, MSC have also been found to exhibit inhibitory effect on T cell responses. However, there is little information on the mechanism of this immunosuppression and our study addresses this issue by targeting T cell functions at various level of immune responses. We have generated MSC from human adult bone marrow (BM) and investigated their immunoregulatory function at different phases of T cell responses. MSC showed the ability to inhibit mitogen (CD3/CD28 microbeads)-activated T cell proliferation in a dose-dependent manner. In order to evaluate the specificity of this immunosuppression, the proliferation of CD4(+) and CD8(+) cells were measured. MSC equally inhibit CD4(+) and CD8(+) subpopulations of T cells in response to PHA stimulation. However, the antiproliferative effect of MSC is not due to the inhibition of T cell activation. The expression of early activation markers of T cells, namely CD25 and CD69 were not significantly altered by MSC at 24, 48 and 72h. Furthermore, the immunosuppressive effect of MSC mainly targets T cell proliferation rather than their effector function since cytotoxicity of T cells is not affected. This work demonstrates that the immunosuppressive effect of MSC is exclusively a consequence of an anti-proliferative activity, which targets T cells of different subpopulations. For this reason, they have the potential to be exploited in the control of unwanted immune responses such as graft versus host disease (GVHD) and autoimmunity.

Matched MeSH terms: Immunosuppression
Fulltext Asymptomatic Lymphocytic Interstitial Pneumonia with Extensive HRCT Changes Preceding Sjogren's Syndrome

Baharuddin H, Hanafiah M, Aflah SSS, Zim MAM, Ch'Ng SS

Case Rep Pulmonol, 2021;2021:6693031.
PMID: 33505755 DOI: 10.1155/2021/6693031

Lymphocytic interstitial pneumonia (LIP) is a rare condition, commonly associated with Sjogren's syndrome (SS). We report a 53-year-old woman with an incidental finding of an abnormal chest radiograph. LIP was diagnosed based on high-resolution computed tomography and lung biopsy, but treatment was not initiated. Six years later, she developed cough and dyspnoea, associated with dry eyes, dry mouth, and arthralgia. While being investigated for the respiratory symptoms, she developed cutaneous vasculitis and was treated with 1 mg/kg prednisolone, which resulted in the improvement of her respiratory symptoms. Physical examination revealed fine bibasal crepitations, active vasculitic skin lesions, and a positive Schirmer's test. Investigations revealed a restrictive pattern in the pulmonary function test, stable LIP pattern in HRCT, and positive anti-Ro antibodies. She was treated with prednisolone and azathioprine for 18 months, and within this time, she was hospitalised for flare of LIP, as well as respiratory tract infection on three occasions. During the third flare, when she also developed cutaneous vasculitis, she agreed for prednisolone but refused other second-line agents. To date, she remained well with the maintenance of prednisolone 2.5 mg monotherapy for more than one year. The lessons from this case are (i) patients with LIP can be asymptomatic, (ii) LIP can precede symptoms of SS, and (iii) treatment decision for asymptomatic patients with abnormal imaging or patients with mild severity should be weighed between the risk of immunosuppression and risk of active disease.

Matched MeSH terms: Immunosuppression
Impact of low disease activity, remission, and complete remission on flares following tapering of corticosteroids and immunosuppressive therapy in patients with systemic lupus erythematous: a multinational cohort study

Cho J, Shen L, Huq M, Kandane-Rathnayake R, Golder V, Louthrenoo W, et al.

Lancet Rheumatol, 2023 Oct;5(10):e584-e593.
PMID: 38251484 DOI: 10.1016/S2665-9913(23)00209-6

BACKGROUND: Targets of treatment for systemic lupus erythematosus (SLE) include the Lupus Low Disease Activity State (LLDAS), remission, and complete remission. Whether treatment can be tapered after attaining these targets and whether tapering is safer in patients in complete remission compared with LLDAS are unknown. We aimed to assess the odds of disease flares after treatment tapering in stable disease, versus continuing the same therapy. We also aimed to examine whether tapering in complete remission resulted in fewer flares or longer time to flare compared with tapering in LLDAS or remission.
METHODS: This multinational cohort study was conducted at 25 sites across 13 Asia-Pacific countries. We included adult patients aged 18 years or older with stable SLE who were receiving routine clinical care, had two or more visits and had attained stable disease at one or more visits. We categorised stable disease into: LLDAS (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] score ≤4, Physician Global Assessment [PGA] ≤1, and prednisolone ≤7·5 mg/day); Definitions of Remission in SLE (DORIS) remission (clinical SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day); or complete remission on therapy (SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day). Stable disease categories were mutually exclusive. Tapering was defined as any decrease in dose of corticosteroids or immunosuppressive therapy (mycophenolate mofetil, calcineurin inhibitors, azathioprine, leflunomide, or methotrexate). Using multivariable generalised estimating equations, we compared flares (SELENA-SLEDAI Flare Index) at the subsequent visit after drug tapering. We used generalised estimating equations and Cox proportional hazard models to compare tapering attempts that had begun in LLDAS, remission, and complete remission.
FINDINGS: Between May 1, 2013, and Dec 31, 2020, 4106 patients were recruited to the cohort, 3002 (73·1%) of whom were included in our analysis. 2769 (92·2%) participants were female, 233 (7·8%) were male, and 2636 (88·1%) of 2993 with ethnicity data available were Asian. The median age was 39·5 years (IQR 29·0-50·0). There were 14 808 patient visits for patients in LLDAS, or remission or complete remission, of which 13 140 (88·7%) entered the final multivariable model after excluding missing data. Among the 9863 visits at which patients continued the same therapy, 1121 (11·4%) flared at the next visit, of which 221 (19·7%) were severe flares. Of the 3277 visits at which a patient received a tapering of therapy, 557 (17·0%) flared at the next visit, of which 120 (21·5%) were severe flares. Tapering was associated with higher odds of flare compared with continuing the same therapy (odds ratio [OR] 1·24 [95% CI 1·10-1·39]; p=0·0005). Of 2095 continuous tapering attempts, 860 (41·1%) were initiated in LLDAS, 596 (28·4%) in remission, and 639 (30·5%) in complete remission. Tapering initiated in LLDAS (OR 1·37 [95% CI 1·03-1·81]; p=0·029) or remission (1·45 [1·08-1·94]; p=0·013) had higher odds of flare in 1 year compared with complete remission. Tapering in LLDAS (hazard ratio 1·24 [95% CI 1·04-1·48]; p=0·016) or remission (1·30 [1·08-1·56]; p=0·0054) had a significantly shorter time to first flare than tapering initiated in complete remission. Attaining sustained LLDAS, remission, or complete remission for at least 6 months just before the time of taper was associated with lower odds of flare at next visit, flares in 1 year, and longer time to flare.
INTERPRETATION: Tapering of corticosteroids or immunosuppressive therapy in patients with stable SLE was associated with excess flares. Our findings suggest that drug tapering should be carefully considered, weighing the risks and benefits, and is best exercised in complete (clinical and serological) remission and after maintaining stable disease for at least 6 months.
FUNDING: AstraZeneca, BMS, Eli Lily, Janssen, Merck Serono, GSK, and UCB.

Matched MeSH terms: Immunosuppression
Fulltext Disease risk analysis in sea turtles: A baseline study to inform conservation efforts

Mashkour N, Jones K, Kophamel S, Hipolito T, Ahasan S, Walker G, et al.

PLoS One, 2020;15(10):e0230760.
PMID: 33095793 DOI: 10.1371/journal.pone.0230760

The impact of a range of different threats has resulted in the listing of six out of seven sea turtle species on the IUCN Red List of endangered species. Disease risk analysis (DRA) tools are designed to provide objective, repeatable and documented assessment of the disease risks for a population and measures to reduce these risks through management options. To the best of our knowledge, DRAs have not previously been published for sea turtles, although disease is reported to contribute to sea turtle population decline. Here, a comprehensive list of health hazards is provided for all seven species of sea turtles. The possible risk these hazards pose to the health of sea turtles were assessed and "One Health" aspects of interacting with sea turtles were also investigated. The risk assessment was undertaken in collaboration with more than 30 experts in the field including veterinarians, microbiologists, social scientists, epidemiologists and stakeholders, in the form of two international workshops and one local workshop. The general finding of the DRA was the distinct lack of knowledge regarding a link between the presence of pathogens and diseases manifestation in sea turtles. A higher rate of disease in immunocompromised individuals was repeatedly reported and a possible link between immunosuppression and environmental contaminants as a result of anthropogenic influences was suggested. Society based conservation initiatives and as a result the cultural and social aspect of interacting with sea turtles appeared to need more attention and research. A risk management workshop was carried out to acquire the insights of local policy makers about management options for the risks relevant to Queensland and the options were evaluated considering their feasibility and effectiveness. The sea turtle DRA presented here, is a structured guide for future risk assessments to be used in specific scenarios such as translocation and head-starting programs.

Matched MeSH terms: Immunosuppression

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