Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT

Marsh, Rebecca; Leiding, Jennifer W.; Logan, Brent R.; Griffith, Linda M.; Arnold, Danielle E.; Haddad, Élie; Falcone, Emilia Liana; Yin, Ziyan; Patel, Kadam; Arbuckle, Erin; Bleesing, Jack J.; Sullivan, Kathleen E.; Heimall, Jennifer; Burroughs, Lauri M.; Skoda-Smith, Suzanne; Chandrakasan, Shanmuganathan; Yu, Lolie C.; Oshrine, Benjamin; Cuvelier, Geoffrey D.E.; Thakar, Monica S.; Chen, Karin; Teira, Pierre; Shenoy, Shalini; Phelan, Rachel; Forbes, Lisa R.; Martinez, Caridad; Chellapandian, Deepak; Saldaña, Blachy J. Dávila; Shah, Ami J.; Weinacht, Katja G.; Joshi, Avni Y.; Boulad, Farid; Quigg, Troy C.; Dvorak, Christopher C.; Grossman, Debi; Torgerson, Troy R.; Graham, Pamela; Prasad, Vinod K.; Knutsen, Alan P.; Chong, Hey; Miller, Holly; Morena, M. Teresa de la; DeSantes, Kenneth; Cowan, Morton J.; Notarangelo, Luigi D.; Kohn, Donald B.; Stenger, Elizabeth; Pai, Sung-Yun; Routes, John M.; Puck, Jennifer M.; Kapoor, Neena; Pulsipher, Michael A.; Malech, Harry L.; Parikh, Suhag; Kang, Elizabeth M.

doi:10.1007/s10875-019-00659-8

Cited by 47 publications

(23 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reported prevalence of CGD-associated IBD (CGD-IBD) ranges from 31% [ 143 ] to 88% [ 144 ], being one of the main clinical manifestations especially in patients with p40 phox deficiency [ 145 ]. A recent report from the Primary Immune Deficiency Treatment Consortium (PIDTC) showed that HSCT is curative for CGD colitis, and importantly, that colitis itself is not a contraindication to HSCT as it does not lead to an increased risk of mortality [ 146 ].…”

Section: Gut Microbiota–host Interactions In Human Inborn Errors Omentioning

confidence: 99%

Gut Microbiota–Host Interactions in Inborn Errors of Immunity

Castagnoli

Pala

Bosticardo

et al. 2021

IJMS

View full text Add to dashboard Cite

Inborn errors of immunity (IEI) are a group of disorders that are mostly caused by genetic mutations affecting immune host defense and immune regulation. Although IEI present with a wide spectrum of clinical features, in about one third of them various degrees of gastrointestinal (GI) involvement have been described and for some IEI the GI manifestations represent the main and peculiar clinical feature. The microbiome plays critical roles in the education and function of the host’s innate and adaptive immune system, and imbalances in microbiota-immunity interactions can contribute to intestinal pathogenesis. Microbial dysbiosis combined to the impairment of immunosurveillance and immune dysfunction in IEI, may favor mucosal permeability and lead to inflammation. Here we review how immune homeostasis between commensals and the host is established in the gut, and how these mechanisms can be disrupted in the context of primary immunodeficiencies. Additionally, we highlight key aspects of the first studies on gut microbiome in patients affected by IEI and discuss how gut microbiome could be harnessed as a therapeutic approach in these diseases.

show abstract

Section: Gut Microbiota–host Interactions In Human Inborn Errors Omentioning

confidence: 99%

Gut Microbiota–Host Interactions in Inborn Errors of Immunity

Castagnoli

Pala

Bosticardo

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…[105][106][107] Another multi-center study also recently demonstrated the presence of CGD-related colitis does not appear to negatively affect survival or significantly increase the risk of GVHD. 108 The role of autoinflammation and organ dysfunction on transplant outcomes remains unclear; however, these recent publications indicate that HSCT for definitive cure may be considered for high-risk patients with reasonable outcomes.…”

Section: Long-term Management Of Cgdmentioning

confidence: 99%

<p>Geographic Variability and Pathogen-Specific Considerations in the Diagnosis and Management of Chronic Granulomatous Disease</p>

Prince¹,

Thielen²,

Williams³

et al. 2020

PHMT

View full text Add to dashboard Cite

Chronic granulomatous disease (CGD) is a rare but serious primary immunodeficiency with varying prevalence and rates of X-linked and autosomal recessive disease worldwide. Functional defects in the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex predispose patients to a relatively narrow spectrum of bacterial and fungal infections that are sometimes fastidious and often difficult to identify. When evaluating and treating patients with CGD, it is important to consider their native country of birth, climate, and living situation, which may predispose them to types of infections that are atypical to your routine practice. In addition to recurrent and often severe infections, patients with CGD and X-linked female carriers are also susceptible to developing many non-infectious complications including tissue granuloma formation and autoimmunity. The DHR-123 oxidation assay is the gold standard for making the diagnosis and it along with genetic testing can help predict the severity and prognosis in patients with CGD. Disease management focuses on prophylaxis with antibacterial, antifungal, and immunomodulatory medications, prompt identification and treatment of acute infections, and prevention of secondary granulomatous complications. While hematopoietic stem-cell transplantation is the only widely available curative treatment for patients with CGD, recent advances in gene therapy may provide a safer, more direct alternative.

show abstract

“…Older age at transplant ( P = 0·0001) and use of 9/10 HLA‐matched donors (0·01) associated with reduced survival. A trend for reduced survival was seen in patients with pre‐existing colitis ( P = 0·052), a finding at variance with experience in the U.S., where 49/145 transplanted patients with CGD had inflammatory bowel disease and survival between the groups was the same 80 . In the IEWP study, the conditioning regimen did not impact overall survival.…”

Section: Stem Cell Therapiesmentioning

confidence: 81%

“…A trend for reduced survival was seen in patients with pre-existing colitis (P = 0Á052), a finding at variance with experience in the U.S., where 49/145 transplanted patients with CGD had inflammatory bowel disease and survival between the groups was the same. 80 In the IEWP study, the conditioning regimen did not impact overall survival. The authors conclude that there was an excellent outcome after HSCT for patients with CGD, and that transplant should be firmly considered for younger patients, especially if there was a well-matched donor.…”

Section: Haematopoietic Stem Cell Transplantationmentioning

confidence: 95%

Progress in treating chronic granulomatous disease

Gennery

2020

Br J Haematol

View full text Add to dashboard Cite

Chronic granulomatous disease is a primary immunodeficiency due to a defect in one of six subunits that make up the nicotinamide adenine dinucleotide phosphate oxidase complex. The most commonly defective protein, gp91 phox , is inherited in an X-linked fashion; other defects have autosomal recessive inheritance. Bacterial and fungal infections are common presentations, although inflammatory complications are increasingly recognized as a significant cause of morbidity and are challenging to treat. Haematopoietic stem cell transplantation offers cure from the disease with improved quality of life; overall survival in the current era is around 85%, with most achieving long-term cure free of medication. More recently, gene therapy is emerging as an alternative approach. Results using gammaretroviral vectors were disappointing with genotoxicity and loss of efficacy, but preliminary results using lentiviral vectors are extremely encouraging.

show abstract

Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT

Cited by 47 publications

References 25 publications

Gut Microbiota–Host Interactions in Inborn Errors of Immunity

Gut Microbiota–Host Interactions in Inborn Errors of Immunity

<p>Geographic Variability and Pathogen-Specific Considerations in the Diagnosis and Management of Chronic Granulomatous Disease</p>

Progress in treating chronic granulomatous disease

Contact Info

Product

Resources

About