scholarly journals Lactose drives Enterococcus expansion to promote graft-versus-host disease

Science ◽  
2019 ◽  
Vol 366 (6469) ◽  
pp. 1143-1149 ◽  
Author(s):  
C. K. Stein-Thoeringer ◽  
K. B. Nichols ◽  
A. Lazrak ◽  
M. D. Docampo ◽  
A. E. Slingerland ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Microbial Communities ◽  
Graft Versus Host Disease ◽  
Inflammatory Disease ◽  
Hematopoietic Cell Transplantation ◽  
Commensal Bacterium ◽  
Host Disease ◽  
Graft Versus Host ◽  
Systemic Inflammatory Disease ◽  
High Incidence

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.

Immune Mediated Cerebellar Ataxia: An Unknown Manifestation of Graft-versus-Host Disease

2018 ◽  
Vol 141 (1) ◽  
pp. 19-22
Author(s):  
Liat Shargian-Alon ◽  
Pia Raanani ◽  
Uri Rozovski ◽  
Tali Siegal ◽  
Shlomit Yust-Katz ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Cerebellar Atrophy ◽  
Acid Decarboxylase ◽  
High Dose ◽  
Host Disease ◽  
Graft Versus Host ◽  
Aged Woman

Neurologic complications of allogeneic hematopoietic cell transplantation (allo-HCT) include infections, cerebrovascular events, therapy-induced neurotoxicity, recurrent malignancies, and neurologic manifestations of graft-versus-host disease (GVHD). Anti-glutamic acid decarboxylase (GAD) antibody-associated cerebellar ataxia is a well-established disorder of autoimmune origin, but there are no reports in the literature of its occurrence following allo-HCT. We describe a middle-aged woman with chronic GVHD after allo-HCT who presented with a rapidly progressive cerebellar syndrome. Thorough investigation revealed only cerebellar atrophy on brain imaging and positive anti-GAD65 antibodies in serum and cerebrospinal fluid suggesting the diagnosis of anti-GAD antibody-associated cerebellar ataxia. Despite prompt treatment with high-dose corticosteroids, intravenous immunoglobulins, and rituximab, the patient’s condition rapidly deteriorated, and she died 4 months later. This case suggests that anti-GAD antibody-associated cerebellar ataxia may be a rare manifestation of chronic GVHD.

scholarly journals Interfering With Inflammation: Heterogeneous Effects of Interferons in Graft-Versus-Host Disease of the Gastrointestinal Tract and Inflammatory Bowel Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Eileen Haring ◽  
Robert Zeiser ◽  
Petya Apostolova
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gastrointestinal Tract ◽  
Graft Versus Host Disease ◽  
Bowel Disease ◽  
Intestinal Barrier Function ◽  
Type I ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Inflammatory Bowel

The intestine can be the target of several immunologically mediated diseases, including graft-versus-host disease (GVHD) and inflammatory bowel disease (IBD). GVHD is a life-threatening complication that occurs after allogeneic hematopoietic stem cell transplantation. Involvement of the gastrointestinal tract is associated with a particularly high mortality. GVHD development starts with the recognition of allo-antigens in the recipient by the donor immune system, which elicits immune-mediated damage of otherwise healthy tissues. IBD describes a group of immunologically mediated chronic inflammatory diseases of the intestine. Several aspects, including genetic predisposition and immune dysregulation, are responsible for the development of IBD, with Crohn’s disease and ulcerative colitis being the two most common variants. GVHD and IBD share multiple key features of their onset and development, including intestinal tissue damage and loss of intestinal barrier function. A further common feature in the pathophysiology of both diseases is the involvement of cytokines such as type I and II interferons (IFNs), amongst others. IFNs are a family of protein mediators produced as a part of the inflammatory response, typically to pathogens or malignant cells. Diverse, and partially paradoxical, effects have been described for IFNs in GVHD and IBD. This review summarizes current knowledge on the role of type I, II and III IFNs, including basic concepts and controversies about their functions in the context of GVHD and IBD. In addition, therapeutic options, research developments and remaining open questions are addressed.

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