Alloimmune hepatitis following peripheral stem cell transplantation

Habib, Shahid; Nalesnik, Michael A.; Ahmad, Jawad; BuchBarker, Diane; Shakil, A. Obaid

doi:10.1038/sj.bmt.1705646

Cited by 14 publications

(23 citation statements)

References 10 publications

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“…The results reported in this study shed new light on the characterization of potentially severe non‐GVHD hepatitis resembling AIH that occurs after BMT. The clinical features of the five cases described here were similar to six other case reports, presenting no history of liver toxic drug absorption, patent viral infection, or histopathological findings consistent with GVHD, but with features suggestive of AIH 5‐10. BMT was well accepted by all the patients, as shown by the course of microchimerism tests during the year that followed transplantation.…”

Section: Discussionsupporting

confidence: 80%

“…Its clinical and biological findings were in accord with previous case reports. All these reports5‐10 had highlighted the role of GVHD in the pathogenic process, causing the transformation of an alloimmune process into an autoimmune reaction. In particular, the role of putative plasma membrane autoantigens in liver destruction needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Despite advances in the management of patients undergoing BMT, the risk of developing liver GVHD post‐BMT after the withdrawal of immunosuppressive treatment remains a current issue. Some studies in the literature have reported cases of BMT followed by non‐GVHD liver dysfunction with the occurrence of autoantobodies 5‐10. Advances in proteomic analysis currently provide an opportunity to better characterize and understand the pathogenesis of autoimmune diseases, including those that affect the liver,11‐13 and to identify markers for early diagnosis and follow‐up.…”

mentioning

confidence: 99%

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Immunoproteomic Analysis of Potentially Severe Non-Graft-Versus-Host Disease Hepatitis After Allogenic Bone Marrow Transplantation

et al. 2013

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The development of potentially severe non-graft-versus-host disease (GVHD) hepatitis resembling autoimmune hepatitis (AIH) has been reported after bone marrow transplantation (BMT). The aim of this study was to better characterize this form of hepatitis, particularly through the identification of autoantigens recognized by patient sera. Five patients who received an allogeneic BMT for the treatment of hematological diseases developed liver dysfunction with histological features suggestive of AIH. Before and during the onset of hepatic dysfunction, sera were tested on immunoblottings performed with cytosolic, microsomal, mitochondrial, and nuclear proteins from rat liver homogenate and resolved by two-dimensional electrophoresis. Antigenic targets were identified by mass spectrometry. During the year that followed BMT, all patients presented with GVHD. Acute hepatitis then occurred after the withdrawal, or during the tapering, of immunosuppressive therapy. At that time, no patients had a history of liver toxic drug absorption, patent viral infection, or any histopathological findings consistent with GVHD. Immunoreactive spots stained by sera collected at the time of hepatic dysfunction were more numerous and more intensely expressed than those stained by sera collected before. Considerable patient-dependent pattern heterogeneity was observed. Among the 259 spots stained exclusively by sera collected at the time of hepatitis, a total of 240 spots were identified, corresponding to 103 different proteins. Twelve of them were recognized by sera from 3 patients. Conclusions: This is the first immunological description of potentially severe non-GVHD hepatitis occurring after BMT, determined using a proteomic approach and enabling a discussion of the mechanisms that transform an alloimmune reaction into an autoimmune response. Any decision to withdraw immunosuppression after allogeneic BMT should be made with caution.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Immunoproteomic Analysis of Potentially Severe Non-Graft-Versus-Host Disease Hepatitis After Allogenic Bone Marrow Transplantation

et al. 2013

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“…We also failed to note an association with the HLA haplotypes: B8, B14, DR3, DR4, and Dw3 [22]. Habib et al [25] speculated that a multistep sequence of events may also underlie the state of antiliver reactivity that resembles AIH after HSCT. AIH is a heterogeneous disorder that can be divided into two types, depending on the presence of autoantibodies [26]: Type 1 is associated with the presence of ASMA or ANA for about 75% of patients [16]; Type 2 is associated with the presence of either anti-LKM-1 or anti-liver cytosolic-1 antibodies [19].…”

Section: Discussionmentioning

confidence: 99%

Autoimmune Complications after Hematopoietic Stem Cell Transplantation in Children with Nonmalignant Disorders

Khalil

Zaidman

Bergman

et al. 2014

The Scientific World Journal

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Background. Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for many nonmalignant disorders, such as autoimmune disorders, inborn metabolic disorders, hemoglobinopathies, and immunodeficiency disorders. Autoimmune complications (AICs) after HSCT, such as autoimmune cytopenias, autoimmune hepatitis, primary biliary cirrhosis, and autoimmune cutaneous manifestations, are still neither well defined nor characterized. Patients. Between 2000 and 2012, 92 patients (47 males, 45 females) were treated with HSCT in our hospital, 51 with congenital hemoglobinopathies, 19 with primary immunodeficiency disease, 10 with metabolic disorders, five with Fanconi anemia, three with aplastic anemia, and four with familial hemophagocytic lymphohistiocytosis. Results. Mean age at HSCT was 6.4 years (range, 0.2–32 years) and mean duration of followup after HSCT was 6.81 years (range, 1–11 years). Sixteen (17.4%) patients developed chronic GVHD and five (5.4%) showed sclerodermatous features. Five (5.4%) patients were diagnosed with scleroderma manifestations, six (6.5%) with vitiligo, six (6.5%) with autoimmune hemolytic anemia (AIHA), six (6.5%) with idiopathic thrombocytopenia, three (3.3%) with mild leucopenia, two (2.2%) with aplastic anemia, two (2.2%) (one boy, one girl) with autoimmune thyroid disease, and one (1.1%) with autoimmune hepatitis. Conclusions. It was concluded that AICs are clinically significant complications after HSCT that contribute to morbidity but not to mortality. AICs are more frequent after HSCT for metabolic disorders, and sclerodermatous GVHD is more significant in children who underwent allogeneic HSCT for hemoglobinopathies. The potential to identify risk factors for AICs could lead to less morbidity and mortality and to maintain the patient's quality of life.

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“…We summarized occasional examples of de novo autoimmune-like hepatitis following allo-SCT in which the target liver cells and effector cells are different in origin (Table 1). [2][3][4][5]8,9 Habib et al used the term 'alloimmune hepatitis' to describe this entity. The laboratory and histological findings and clinical course of our patient were very similar to these cases and she may be included in the same disease entity.…”

mentioning

confidence: 99%

Autoimmune-like hepatitis following unrelated BMT successfully treated with rituximab

Narita

Muramatsu

Takahashi

et al. 2011

Bone Marrow Transplant

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Alloimmune hepatitis following peripheral stem cell transplantation

Cited by 14 publications

References 10 publications

Immunoproteomic Analysis of Potentially Severe Non-Graft-Versus-Host Disease Hepatitis After Allogenic Bone Marrow Transplantation

Immunoproteomic Analysis of Potentially Severe Non-Graft-Versus-Host Disease Hepatitis After Allogenic Bone Marrow Transplantation

Autoimmune Complications after Hematopoietic Stem Cell Transplantation in Children with Nonmalignant Disorders

Autoimmune-like hepatitis following unrelated BMT successfully treated with rituximab

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