Researcher:
Yüksel, Muhammed

Profile Picture
ORCID

Job Title

Researcher

First Name

Muhammed

Last Name

Yüksel

Name

Name Variants

Yüksel, Muhammed

Email Address

Birth Date

Filters

2020 - 202310

Advanced Search

Filter by

Settings

Researcher Of Publications: search.filters.isAuthorOfPublication.fe6e9c91-ca1f-4635-ba59-8f9df9f2cc56

Search Results

Now showing 1 - 10 of 10
  • Placeholder
    PublicationMetadata only
    Telemedicine in monitoring pediatric LT patients before and during COVID-19 pandemic
    (Wiley, 2022) N/A; N/A; Musaoğlu, Miraç Nur; Yüksel, Muhammed; Mizikoğlu, Özlem; Arıkan, Çiğdem; PhD Student; Researcher; Other; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; N/A; School of Medicine; School of Medicine; N/A; N/A; N/A; 240198
    Background: the delivery of healthcare services by telemedicine decreases costs of traveling for patients, is less time-consuming, and most importantly permits the connection between highly skilled specialists and patients. However, whether the use of telemedicine (text messaging) for LT patients was affected by the COVID-19 pandemic is unknown. Methods: We collected data (following consent from patients and parents) from 57 patients (33 male/24 female) with a median age of 47 (IQR: 9-91) months, whom we followed up with text messaging between September 2019 and September 2020, spanning the 6 months prior to COVID-19 and during this period. Results: in total, 723 text message mediated consultations occurred during this period, henceforth simply referred to as "messages." Three hundred and twenty-eight (45%) messages occurred during the 6 months up to the start of the pandemic. Following the COVID-19 outbreak, the number of messages increased to 395 (55%). the three most common reasons of messaging were post-liver-LT follow-up messages (n = 215/723, 29.7%), consultations for drug use (n = 157/723, 21.7%), and medication prescriptions (n = 113/723, 15.6%). Protocol biopsy discussions (n = 33/723, 4.6%) and fever (n = 27/723, 3.7%) were among others (vaccination, rash, diarrhea, cough, fatigue, Acne). During the COVID-19 outbreak, only post-LT follow-up messages increased significantly to 132/395 (33%) from 83/328 (25%) (p-value: .02). Conclusions: We found that the pandemic resulted in an increase in the total number of text message mediated consultations and specifically for the use of post-LT follow-up. Messaging was effective for post-LT follow-ups and all patients were at least satisfied.
  • Placeholder
    PublicationMetadata only
    What is hot and new in basic and translational science in liver transplantation in 2022? report of the basic and translational research committee of the international liver transplantation society
    (Lippincott Williams and Wilkins (LWW), 2022) Bhat, Mamatha; Dondossola, Daniele; Varghese, Rhea; Czigany, Zoltan; Emamaullee, Juliet; Ghinolfi, Davide; Al-Adra, David; Bonaccorsi-Riani, Eliano; Pang, Li; Boteon, Yuri L.; Brüggenwirth, Isabel; Pavan-Guimaraes, Juliana; Ho, Cheng-Maw; Zarrinpar, Ali; Abdelrahim, Maen; Barbas, Andrew S.; Mas, Valeria; Selzner, Markus; Martins, Paulo N; N/A; Yüksel, Muhammed; Researcher; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A
    N/A
  • Placeholder
    PublicationMetadata only
    Standard immunosuppressive treatment reduces regulatory B cells in children with autoimmune liver disease
    (Frontiers, 2023) Polat, Esra; N/A; Yüksel, Muhammed; Nazmi, Farinaz; Alwardat, Dima; Akgül, Sebahat Usta; Akyıldız, Murat; Arıkan, Çiğdem; Researcher; PhD Student; Researcher; Doctor; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Koç University Transplant Immunology Research Centre of Excellence (TIREX) Inaugurated; N/A; Graduate School of Health Sciences; N/A; N/A; School of Medicine; School of Medicine; Koç University Hospital; Koç University Hospital; N/A; Koç University Hospital; Koç University Hospital; Koç University Hospital; N/A; N/A; N/A; N/A; 123080; 240198
    Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease caused by a perturbed immune system. The scarcity of short- and long-term immune monitoring of AIH hampered us to comprehend the interaction between immunosuppressive medication and immune homeostasis. Methods and Patients: We recruited children with AIH at the time of diagnosis and at the 1st, 3rd, 6th, 12th, 18th, and 24th months of immunosuppression (IS). We also enrolled children with AIH being on IS for >2 years. Children with drug-induced liver injury (DILI), and those receiving tacrolimus after liver transplantation (LT), were enrolled as disease/IS control subjects. Healthy children (HC) were also recruited. Peripheral blood mononuclear cells (PBMCs) were isolated from all participants. Healthy liver tissue from adult donors and from livers without inflammation were obtained from children with hepatoblastoma. By using flow cytometry, we performed multi-parametric immune profiling of PBMCs and intrahepatic lymphocytes. Additionally, after IS with prednisolone, tacrolimus, rapamycin, or 6-mercaptopurine, we carried out an in vitro cytokine stimulation assay. Finally, a Lifecodes SSO typing kit was used to type HLA-DRB1 and Luminex was used to analyze the results. Results: Untreated AIH patients had lower total CD8 T-cell frequencies than HC, but these cells were more naïve. While the percentage of naïve regulatory T cells (Tregs) (CD4+FOXP3lowCD45RA+) and regulatory B cells (Bregs, CD20+CD24+CD38+) was similar, AIH patients had fewer activated Tregs (CD4+FOXP3highCD45RA-) compared to HC. Mucosal-associated-invariant-T-cells (MAIT) were also lower in these patients. Following the initiation of IS, the immune profiles demonstrated fluctuations. Bregs frequency decreased substantially at 1 month and did not recover anymore. Additionally, the frequency of intrahepatic Bregs in treated AIH patients was lower, compared to control livers, DILI, and LT patients. Following in vitro IS drugs incubation, only the frequency of IL-10-producing total B-cells increased with tacrolimus and 6MP. Lastly, 70% of AIH patients possessed HLA-DR11, whereas HLA-DR03/DR07/DR13 was present in only some patients. Conclusion: HLA-DR11 was prominent in our AIH cohort. Activated Tregs and MAIT cell frequencies were lower before IS. Importantly, we discovered a previously unrecognized and long-lasting Bregs scarcity in AIH patients after IS. Tacrolimus and 6MP increased IL-10+ B-cells in vitro.
  • Placeholder
    PublicationMetadata only
    Examining the hepatic immune system in children with liver disease with fine needle aspiration
    (Lippincott Williams & Wilkins, 2022) N/A; N/A; N/A; N/A; N/A; N/A; N/A; Yüksel, Muhammed; Demirbaş, Burak; Mizikoğlu, Özlem; Tütüncü, Yıldız; Kanmaz, Turan; Oğuzkurt, Levent; Arıkan, Çiğdem; Researcher; Doctor; Researcher; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A; N/A; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; N/A; N/A; N/A; 239430; 275799; 13559; 240198
    Objectives: Liver biopsy is the standard in diagnosing liver diseases. Yet, it provides little space to perform comprehensive immune profiling of the liver. Hence, we explored whether fine needle aspirates (FNAs) could be used to elucidate the hepatic immunity in children. Methods: We enrolled 74 children undergoing diagnostic (n = 17) or protocol biopsy (n = 57) following liver transplantation (LT). Matched blood and FNAs were obtained. Additionally, explant liver tissue was collected from children (n = 14) undergoing LT. Immune cells were isolated from peripheral blood, FNAs and explanted livers. Immune-phenotypical profiling was done by flow cytometry. Results: Biopsied patients (58% female) were at a median age of 46 months (interquartile range [IQR]: 12–118) and LT patients (71% female) were 48 months (IQR: 21–134, P = 0.78) old. CD69+, a hallmark of tissue-resident immune cells was expressed in 1.3% of CD3+ T cells from blood being higher in FNA (20%) and tissue (49%, P < 0.001). CD4+ T-cell frequencies in tissue (13%) and FNAs (20%) were lower compared to blood (35%, P < 0.001) whereas CD8+ T cells in tissue (33.5%) and FNA (32%) were higher than in blood (25%, P < 0.01). Mucosal associated invariant T cells were enriched in liver tissue (8.8%) and in the FNA (4.4%) compared to blood (1.7%, P < 0.001). Whereas the percentage of total Tregs (CD4+CD25+FOXP3+CD127low/−) decreased, the proportion of activated Tregs (CD4+CD45RA-FOXP3high) increased in FNA and explant. Breg (CD19+CD20+CD24highCD38high) frequencies were similar in all groups. Conclusion: FNA is a practical method to sample the liver immune system collecting even small cell subsets such as regulatory T/B cells.
  • Placeholder
    PublicationMetadata only
    Course of vitamin D levels before and after liver transplantation in pediatric patients
    (Wiley, 2021) N/A; N/A; N/A; N/A; N/A; N/A; Yüksel, Muhammed; Demir, Barış; Mızıkoğlu, Özlem; Akyıldız, Murat; Baygül, Arzu Eden; Arıkan, Çiğdem; Researcher; Doctor; Researcher; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A; N/A; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; N/A; N/A; N/A; 123080; 272290; 240198
    Background: 25-hydroxy VD insufficiency is known in children undergoing LT but the serial post-transplant VD course and supplementation modalities in the peri-transplant period are lacking. We aimed to determine the pre-VD status and the post-transplant VD status course following VD supplementation and to elucidate its relationship with post-transplant outcome parameters such as infection and survival. Methods: Pre- and post-VD levels were monitored in parallel with interventions to adjust VD levels in LT patients. VD status was categorized as circulating levels <30–21 ng/ml (insufficiency), 20–10 ng/ml (deficiency), and <10 ng/ml (severe deficiency). Patients received stoss (300000IU) VD3 within the pretransplant period if serum levels were <20 ng/ml. Results: 135 transplanted children were included. The age at LT was 22 months (IQR: 8–60). The pretransplant median VD level was 14 ng/ml. Despite stoss dose, post-transplant median VD level was 1.8 ng/ml (day one), 4 ng/ml (week one), 19 ng/ml (month one), 33 ng/ml (month three), 38 ng/ml (months 6–12), and 40 ng/ml (month 24). After 6 months, VD status reached >30 ng/ml in 98% of patients. Only at pre-LT, higher infection rate (18.7%) in the severe VD deficiency group was observed compared to the VD deficiency group (2.9%, p = .04). Survival was not affected by serum VD levels. Conclusion: VD levels fell substantially after LT but are rectifiable by stoss dose, which was well tolerated. Only the infection rate was associated with the VD status.
  • Thumbnail Image
    PublicationOpen Access
    A novel insight into the pathophysiology of autoimmune hepatitis: an immune activator mutation in the FLT3 receptor
    (Kare Yayıncılık, 2021) Armutlu, Ayşe; Yüksel, Muhammed; Nazmi, Farinaz; Arıkan, Çiğdem; Teaching Faculty; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Koç University Hospital; 133567; N/A; N/A; 240198
    Autoimmune hepatitis (AIH) is a chronic progressive autoimmune liver disease characterized by hypergammaglobulinemia, interface hepatitis, a female preponderance, and the presence of autoantibodies in most patients. The presence of HLA-DR3/DR4 and functional impairment in regulatory T cells are associated with AIH. However, AIH is a multifactorial complex disease. This report is a description of a case of seronegative AIH in a girl with chronic hepatitis, a high immunoglobulin E (IgE) level, perforating nodular dermatitis, and sheer eosinophilia. To re-evaluate the diagnosis, whole exon sequencing was performed. It was determined that the patient had ancestral haplotype A1-B8-DR3, which is associated with autoimmunity. Importantly, it was also noted that an undocumented point mutation (Ala627Thr) of the FMS-like tyrosine 3 kinase (FLT3) receptor was present. This FLT3 receptor gain-of-function mutation is associated with the activation of the mechanistic target of rapamycin (mTOR), and dendritic cell activation. In addition, a loss-of-function mutation in the melanocortin-3 receptor gene, which inhibits interleukin 4, was detected. The constellation of these immune deregulatory factors may have propagated auto-aggression of the liver, causing chronic hepatitis with AIH features. The findings of seronegativity with eosinophilia and a high IgE level led us to hypothesize that the pathognomonic mechanism in this case was unlike that of classic AIH pathophysiology. Since mTOR is constitutively activated, mTOR inhibitors may be a useful option to treat AIH and dermatitis.
  • Thumbnail Image
    PublicationOpen Access
    Immune monitoring of a child with autoimmune hepatitis and type 1 diabetes during COVID-19 infection
    (Lippincott Williams and Wilkins (LWW), 2020) Yüksel, Muhammed; Aktürk, Hacer; Arıkan, Çiğdem; Researcher; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Koç University Hospital; N/A; N/A; 240198
    Immunocompromised patients may be at increased risk to develop COVID-19 during the 2019 β-coronavirus infection. We present the unique opportunity we had to monitor the liver, IL-6 and immune cell course before, during and after COVID-19 in a boy with autoimmune hepatitis (AIH) and type 1 diabetes (T1D). CD4+and CD8+T cells frequencies decreased because of prednisolone, followed by a plateauing increase whereas CD19+CD20+B cell increased strongly and was unaffected by COVID-19 infection. Moreover, the percentage of activated CD8+T cells expressing HLA-DR (CD8+HLA-DR+) increased during COVID-19 and subsided after its clearance. Total regulatory T cells (Tregs: CD4+CD25+CD127lowFOXP3+) remained stable. Although activated Tregs (CD4+CD45RA-FOXP3high) strongly increased upon prednisolone, it decreased afterwards. Furthermore, regulatory B cells (Bregs: CD19+CD20+CD24highCD38high) declined sharply owing to prednisolone. Serum IL-6 remained undetectable at all times. We demonstrated for the first time immune monitoring in a child with AIH and T1D before, during and after COVID-19. We hypothesize that continuing with low level of prednisolone without azathioprine may have abrogated activated Tregs, Bregs and IL-6 production and therefore permitting the activation of CD8+T cells, clearing the virus.
  • Thumbnail Image
    PublicationOpen Access
    A single-center report of COVID-19 disease course and management in liver transplanted pediatric patients
    (Wiley, 2021) Yüksel, Muhammed; Aktürk, Hacer; Mızıkoğlu, Özlem; Toroslu, Ertuğ; Arıkan, Çiğdem; Researcher; Faculty Member; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Koç University Hospital; N/A; N/A; N/A; N/A; 240198
    Background: in 2019, SARS-CoV-2 causing COVID-19 emerged. Severe COVID-19 symptoms may evolve by virtue of hyperactivation of the immune system. Equally, immunocompromised patients may be at increased risk to develop COVID-19. However, treatment guidelines for children following liver transplantation are elusive. Methods: as a liver transplantation center, we diagnosed and followed up 10 children (male/female: 8/2) with a median age of 8.5 years (IQR: 5.2-11.0), with COVID-19 post-liver transplant between March 2019 and December 2020. COVID-19 diagnosis was based on PCR test and or florid X-ray findings compatible with COVID-19 in the absence of other cause. We retrospectively collected clinical and laboratory data from electronic patient records following written consent from patients/parents. Results: nine patients were diagnosed as definitive (PCR positive) with one patient being diagnosed as probable COVID-19. Seven patients recovered without any support whereas three were admitted for non-invasive oxygenation. Lymphopenia and/or high levels of serum IL-6 were detected in four patients. Six patients mounted anti-SARS-CoV-2 antibodies at median 30 days (IQR: 26.5-119.0) following COVID-19 diagnosis. Antibiotic therapy, favipiravir, anakinra, and IVIG were used as treatment in 4,1,1 and 2 patients, respectively. Furthermore, we kept the tacrolimus with or without everolimus but stopped MMF in 2 patients. Importantly, liver allograft function was retained in all patients. Conclusions: we found that being immunocompromised did not affect disease severity nor survival. Stopping MMF yet continuing with tacrolimus was an apt treatment modality in these patients.
  • Thumbnail Image
    PublicationOpen Access
    Human leukocyte antigen (HLA) profile predicts severity of autoimmune liver disease in children of European ancestry
    (Wiley, 2021) Ma, Yun; Su, Haibin; Longhi, Maria Serena; McPhail, Mark J.; Wang, Pengyun; Bansal, Sanjay; Wong, Guan-Wee; Graham, Jonathon; Yang, Li; Thompson, Richard J.; Doherty, Derek G.; Hadzic, Nedim; Zen, Yoh; Quaglia, Alberto; Heneghan, Michael A.; Samyn, Marianne; Vergani, Diego; Mieli-Vergani, Giorgina; Yüksel, Muhammed; Researcher; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM)
    Background and aims: genetic predisposition to autoimmune hepatitis (AIH) in adults is associated with possession of human leukocyte antigen (HLA) class I (A*01, B*08) and class II (DRB1*03, -04, -07, or -13) alleles, depending on geographic region. Juvenile autoimmune liver disease (AILD) comprises AIH-1, AIH-2, and autoimmune sclerosing cholangitis (ASC), which are phenotypically different from their adult counterparts. We aimed to define the relationship between HLA profile and disease course, severity, and outcome in juvenile AILD. Approach and results: we studied 236 children of European ancestry (152 female [64%], median age 11.15 years, range 0.8-17), including 100 with AIH-1, 59 with AIH-2, and 77 with ASC. The follow-up period was from 1977 to June 2019 (median 14.5 years). Class I and II HLA genotyping was performed using PCR/sequence-specific primers. HLA B*08, -DRB1*03, and the A1-B8-DR3 haplotype impart predisposition to all three forms of AILD. Homozygosity for DRB1*03 represented the strongest risk factor (8.8). HLA DRB1*04, which independently confers susceptibility to AIH in adults, was infrequent in AIH-1 and ASC, suggesting protection; and DRB1*15 (DR15) was protective against all forms of AILD. Distinct HLA class II alleles predispose to the different subgroups of juvenile AILD: DRB1*03 to AIH-1, DRB1*13 to ASC, and DRB1*07 to AIH-2. Possession of homozygous DRB1*03 or of DRB1*13 is associated with fibrosis at disease onset, and possession of these two genes in addition to DRB1*07 is associated with a more severe disease in all three subgroups. Conclusions: unique HLA profiles are seen in each subgroup of juvenile AILD. HLA genotype might be useful in predicting responsiveness to immunosuppressive treatment and course.
  • Thumbnail Image
    PublicationOpen Access
    Aberrant hepatic trafficking of gut-derived T cells is not specific to primary sclerosing cholangitis
    (Wiley, 2022) Graham, Jonathon J.; Mukherjee, Sujit; Mateos, Rebeca Sanabria; Si, Tengfei; Huang, Zhenlin; Huang, Xiahong; Abu Arqoub, Hadil; Patel, Vishal; McPhail, Mark; Zen, Yoh; Heaton, Nigel; Longhi, Maria Serena; Heneghan, Michael A.; Liberal, Rodrigo; Vergani, Diego; Mieli-Vergani, Giorgina; Ma, Yun; Hayee, Bu'Hussain; Yüksel, Muhammed; Researcher; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM)
    Background and aims: the ""gut homing"" hypothesis suggests the pathogenesis of primary sclerosing cholangitis (PSC) is driven by aberrant hepatic expression of gut adhesion molecules and subsequent recruitment of gut-derived T cells to the liver. However, inconsistencies lie within this theory including an absence of investigations and comparisons with other chronic liver diseases (CLD). Here, we examine ""the gut homing theory"" in patients with PSC with associated inflammatory bowel disease (PSC-IBD) and across multiple inflammatory liver diseases. Approach and results: expression of MAdCAM-1, CCL25, and E-Cadherin were assessed histologically and using RT-PCR on explanted liver tissue from patients with CLD undergoing OLT and in normal liver. Liver mononuclear cells were isolated from explanted tissue samples and the expression of gut homing integrins and cytokines on hepatic infiltrating gut-derived T cells was assessed using flow cytometry. Hepatic expression of MAdCAM-1, CCL25 and E-Cadherin was up-regulated in all CLDs compared with normal liver. There were no differences between disease groups. Frequencies of alpha 4 beta 7, alpha E beta 7, CCR9, and GPR15 expressing hepatic T cells was increased in PSC-IBD, but also in CLD controls, compared with normal liver. beta 7 expressing hepatic T cells displayed an increased inflammatory phenotype compared with beta 7 negative cells, although this inflammatory cytokine profile was present in both the inflamed and normal liver. Conclusions: these findings refute the widely accepted ""gut homing"" hypothesis as the primary driver of PSC and indicate that aberrant hepatic recruitment of gut-derived T cells is not unique to PSC, but is a panetiological feature of CLD.