Citrulline Level Is a Potent Indicator of Acute Rejection in the Long Term Following Pediatric Intestinal/Multivisceral Transplantation

Hibi, Taizo; Nishida, Seigo; García, Jennifer; Tryphonopoulos, Panagiotis; Tekin, Akin; Selvaggi, Gennaro; Weppler, D.; Levi, David; Ruiz, Phillip; Tzakis, Andreas G.

doi:10.1111/j.1600-6143.2012.04155.x

Cited by 36 publications

(23 citation statements)

References 39 publications

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“…7 Serum citrulline has also been considered, however, it has not been shown to predict asymptomatic rejection and also has significant variability between patients. 8 Immune cell function assay (Cylex ImmuKnow – Viracor IBT Laboratories) has been investigated, and while it may be used as an adjunctive diagnostic tool, it cannot replace endoscopy with biopsy. 9 Finally, the newly FDA-apporved Pleximmune™ test (Plexision, Pittsburgh, PA) is designed to predict the risk of acute cellular rejection after pediatric liver or intestine transplantation, but has yet to be utilized in a large multi-center study.…”

Section: Discussionmentioning

confidence: 99%

Endoscopy Following Pediatric Intestinal Transplant

Yeh

Ngo

Wozniak

et al. 2015

J. pediatr. gastroenterol. nutr.

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Objectives Biopsies remain the gold standard in the diagnosis of intestinal transplant (ITx) rejection, and gastrointestinal endoscopy plays a pivotal role in patient management. Herein, we describe a single center 23 year endoscopic experience in pediatric ITx recipients. Methods A retrospective review of endoscopy and pathology reports of all ITx recipients <18 years old transplanted between 1991 and 2013 was performed with the aim of describing the procedural indications, findings, and complications. Results A total of 1770 endoscopic procedures within 1014 sessions were performed. Combination EGD and ileoscopy was the most common procedure (36%). Increased stool output (35%) and surveillance endoscopy (32%) were the most common indications. 162 episodes of biopsy proven rejection were diagnosed. First episode of rejection occurred at a median of 1 month post-ITx. 45% of histology-proven rejection had normal appearing endoscopies. The rate of procedural complications including but not limited to bleeding and perforation was 1.8%. Conclusions Endoscopy with biopsy plays a significant role in the care of ITx recipients. Multiple procedures are required for graft surveillance, diagnosis of rejection, subsequent treatment, and follow-up of therapy. The gross endoscopic appearance, particularly in mild to moderate acute cellular rejection, does not correlate well with histology. Complex anatomy, complication rates which are higher than non-ITx pediatric endoscopy cases, and timely histologic interpretation by experienced pathologists are reasons that these procedures should be performed at centers accustomed to caring for ITx recipients. The field would benefit from the development of a noninvasive biomarker to reliably and efficiently detect rejection.

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Section: Discussionmentioning

confidence: 99%

Endoscopy Following Pediatric Intestinal Transplant

Yeh

Ngo

Wozniak

et al. 2015

J. pediatr. gastroenterol. nutr.

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“…Studies on visual surveillance of intestinal allografts via endoscopic evaluation have concluded that biopsy is mandatory for detecting early, treatable rejection even though visual inspection of grafts is able to detect severe rejection [71]. Serum citrulline and fecal calprotectin have recently emerged as potential reliable noninvasive indicators of acute rejection [72,73]. Furthermore, gut microbiota, proteomics and metabolomics such as pro-inflammatory mediator leukotriene E 4 , vitamins-B 2 , B 5 , B 6 and taurocholate may be able to identify bioprofiles associated with intestinal rejection [74,75].…”

Section: Intestinal Failurementioning

confidence: 99%

Current status of intestinal and multivisceral transplantation

Bharadwaj

Tandon

Gohel

et al. 2017

Gastroenterol. Rep.

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Clinical-nutritional autonomy is the ultimate goal of patients with intestinal failure (IF). Traditionally, patients with IF have been relegated to lifelong parenteral nutrition (PN) once surgical and medical rehabilitation attempts at intestinal adaptation have failed. Over the past two decades, however, outcome improvements in intestinal transplantation have added another dimension to the therapeutic armamentarium in the field of gut rehabilitation. This has become possible through relentless efforts in the standardization of surgical techniques, advancements in immunosuppressive therapies and induction protocols and improvement in postoperative patient care. Four types of intestinal transplants include isolated small bowel transplant, liver-small bowel transplant, multivisceral transplant and modified multivisceral transplant. Current guidelines restrict intestinal transplantation to patients who have had significant complications from PN including liver failure and repeated infections. From an experimental stage to the currently established therapeutic modality for patients with advanced IF, outcome improvements have also been possible due to the introduction of tacrolimus in the early 1990s. Studies have shown that intestinal transplant is cost-effective within 1–3 years of graft survival compared with PN. Improved survival and quality of life as well as resumption of an oral diet should enable intestinal transplantation to be an important option for patients with IF in addition to continued rehabilitation. Future research should focus on detecting biomarkers of early rejection, enhanced immunosuppression protocols, improved postoperative care and early referral to transplant centers.

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“…В то же время разработка систем надежных пока-зателей по результатам исследования крови продол-жается [39][40][41][42][43][44], так как кровь в клиническом плане наиболее доступная и насыщенная информацион-ная среда, а индустрия современной диагностики имеет практически неограниченные возможности, так как позволяют определить в крови концентра-цию практически любой значимой молекулы [41].…”

Section: диагностика доминирующего стереотипа иммунного реагироваunclassified

“…Идеальным вариантом такого маркера может служить недав-но показанная в эксперименте связь концентрации цитрулина в крови и острого или хронического отторжения при интестинальной и мультивисце-ральной пересадке органов [43]. Установлена кри-тическая концентрация цитрулина для острого (10 мкМ/л) и для хронического (20 мкМ/л) отторжения.…”

Section: маркеры метаболизма в трансплантатеunclassified

Individual Stability of Stereotypes of Immune Reacting and Modern Possibilities of Their Diagnostic in Organ Transplantation (Immune-Physiological Analysis of a Problem)

Onischenko¹,

Artamonov²,

Крашенинников³

et al. 2014

Russian Journal of Transplantology and Artificial Organs

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Лаборатория биотехнологии стволовых клеток (зав. -проф. Н.А. Онищенко) ФГБУ «ФНЦ трансплантологии и искусственных органов им. академика В.И. Шумакова» Министерства здравоохранения РФ (директор -академик РАМН, проф. С.В. Готье), Москва, Российская Федерация Авторы обосновывают варианты иммунного реагирования организма при трансплантации органов сущес-твованием индивидуальных специфических программ реагирования на аллоантигены, которые, исполь-зуя естественные активационные и тормозные механизмы, формируют различную степень устойчивости двух физиологических стереотипов «поведения иммунной системы» -эффекторного и толерогенного. Для идентификации индивидуального доминирующего стереотипа иммунного реагирования реципиента на трансплантат и прогнозирования изменений иммунного гомеостаза в организме авторы предлагают использовать показатели реактивности иммунной системы -консервативность и пластичность, которые могут быть выявлены подбором соответствующих биомаркеров. В настоящее время широко использует-ся система маркеров, характеризующих воспалительные реакции (инфекции/воспаления), для выявле-ния отторжения и сопутствующих осложнений. Для прогнозирования индивидуального доминирующего стереотипа реагирования при иммунологически спокойном течении посттрансплантационного периода авторы предлагают изучать систему информационно значимых клеточных маркеров адаптивного имму-нитета и использовать их для формирования комплексных информативных иммуно-клеточных диагнос-тических модулей.Ключевые слова: стереотипы иммунного ответа, трансплантация органов, биомаркеры. The authors prove variants of immune reacting of an human organism in organ transplantation by existence of individual specifi c programs of reacting on alloantigens which, using natural activatory and inhibitory mechanisms, form various degree of stability of two physiological stereotypes of "behavior of immune system" -effectoric and tolerogenic. For identifi cation of an individual predominant stereotype of recipient immune reacting on a graft and for forecasting changes of an immunological homeostasis in a human organism, authors suggest to use indexes of reactance of immune system -conservatism and plasticity which can be taped by selection of the conforming biomarkers. Now the system of markers characterizing infl ammatory reactions (infections/ infl ammation) for recognition organ rejection and related complications, is widely used. For forecasting of an individual dominant stereotype of reacting in immunologically quiet post-transplant follow-up authors suggest to study a system of informative cellular markers of adaptive immunity and to use them for a formation of complex informative diagnostic immuno-cellular modules. INDIVIDUAL STABILITY OF STEREOTYPES OF IMMUNE REACTING AND MODERN POSSIBILITIES OF THEIR DIAGNOSTIC IN ORGAN TRANSPLANTATION (IMMUNE-PHYSIOLOGICAL ANALYSIS OF A PROBLEM)

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Citrulline Level Is a Potent Indicator of Acute Rejection in the Long Term Following Pediatric Intestinal/Multivisceral Transplantation

Abstract: Citrulline has been advocated as a marker for acute cellular rejection (ACR) in intestinal transplantation

Cited by 36 publications

References 39 publications

Endoscopy Following Pediatric Intestinal Transplant

Endoscopy Following Pediatric Intestinal Transplant

Current status of intestinal and multivisceral transplantation

Individual Stability of Stereotypes of Immune Reacting and Modern Possibilities of Their Diagnostic in Organ Transplantation (Immune-Physiological Analysis of a Problem)

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