Food allergies can persist after myeloablative hematopoietic stem cell transplantation in dedicator of cytokinesis 8–deficient patients

Happel, Corinne S.; Stone, Kelly D.; Freeman, Alexandra F.; Shah, Nirali N.; Wang, Angela Yee-Moon; Lyons, Jonathan J.; Guerrerio, Pamela A.; Hickstein, Dennis D.; Su, Helen C.

doi:10.1016/j.jaci.2015.11.017

Cited by 32 publications

(28 citation statements)

References 12 publications

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“…Additionally, because autoimmunity is rare in DIDS patients, not enough of those patients have been transplanted to determine whether autoimmunity can also be cured. However, food allergies remain a significant problem for many patients, an observation that has been replicated in a larger retrospective review of transplanted DIDS patients . Because donor chimerism in the bone marrow, as compared to peripheral blood, can be incomplete, It is likely that the conditioning regimens used do not fully eliminate long‐lived plasma cells that continue to produce food allergen‐specific IgE after transplant.…”

Section: Transplantationmentioning

confidence: 92%

“…However, food allergies remain a significant problem for many patients, an observation that has been replicated in a larger retrospective review of transplanted DIDS patients . Because donor chimerism in the bone marrow, as compared to peripheral blood, can be incomplete, It is likely that the conditioning regimens used do not fully eliminate long‐lived plasma cells that continue to produce food allergen‐specific IgE after transplant. However, since total IgE gradually decreases after transplant, food allergen‐specific IgE might also gradually decrease so that these food allergies could eventually resolve.…”

Section: Transplantationmentioning

confidence: 92%

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Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome

Jing

Angelus

et al. 2018

Immunological Reviews

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Summary: DOCK8 immunodeficiency syndrome (DIDS) is a progressive combined immunodeficiency that can be distinguished from other combined immunodeficiencies or hyperimmunoglobulinemia E syndromes in featuring 1) profound susceptibility to virus infections of the skin, with associated skin cancers, and 2) severe food allergies. The DOCK8 locus has many repetitive sequence elements that predispose to the generation of large germline deletions as well as recombination-mediated somatic DNA repair. Residual DOCK8 protein contributes to the variable disease phenotype. The severe virus infections of the skin, and probably also VZV-associated vasculopathy, reflect an important function of DOCK8, which is normally required to maintain lymphocyte shape integrity as the cells migrate through dense tissues. Loss of DOCK8 also causes immune deficits through other mechanisms including a milder generalized cell survival defect and skewing of T helper cell subsets. Recent work has uncovered roles for DOCK8 in dendritic cell responses that can also help explain the virus susceptibility, as well as in regulatory T cells that might help explain autoimmunity in a minority of patients. Fortunately, hematopoietic stem cell transplantation cures the eczema and infection susceptibility of DIDS, but not necessarily the other disease manifestations including food allergies.

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Section: Transplantationmentioning

confidence: 92%

Section: Transplantationmentioning

confidence: 92%

Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome

Jing

Angelus

et al. 2018

Immunological Reviews

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“…Improvements in both infections and atopy have been described post-transplant. IgE levels decline post-transplant, and in some patients is accompanied by resolution of food allergies, while in others food allergies may persist [42,45,46]. A recent review of 11 patients who received allogeneic HSCT showed that even in the setting of significant pre-transplant morbidity, survival post-transplant was high (91%), and associated with improvement in both atopic and infectious complications [42].…”

Section: Diagnosis and Management Of Dock8 Deficiencymentioning

confidence: 99%

DOCK8 deficiency: Insights into pathophysiology, clinical features and management

Biggs

Keleş

Chatila

2017

Clinical Immunology

144

119

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Dedicator of Cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency that exemplifies the broad clinical features of primary immunodeficiencies (PIDs), extending beyond recurrent infections to include atopy, autoimmunity and cancer. It is caused by loss of function mutations in DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes that regulates the actin cytoskeleton. Additional roles of DOCK8 have also emerged, including regulating MyD88-dependent Toll-like receptor signaling and the activation of the transcription factor STAT3. DOCK8 deficiency impairs immune cell migration, function and survival, and it impacts both innate and adaptive immune responses. Clinically, DOCK8 deficiency is characterized by allergic inflammation as well as susceptibility towards infections, autoimmunity and malignancy. This review details the pathophysiology, clinical features and management of DOCK8 deficiency. It also surveys the recently discovered combined immunodeficiency due to DOCK2 deficiency, highlighting in the process the emerging spectrum of PIDs resulting from DOCK protein family abnormalities.

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“…HSCT also cures the eczematous dermatitis, as well as food allergies in some but not all patients (26-29, 33, 34). Whether HSCT also cures the autoimmune complications and reduces the risk of cancers are as yet undetermined.…”

Section: Clinical Progression Of Disease and Its Treatmentmentioning

confidence: 99%

Recent Advances in DOCK8 Immunodeficiency Syndrome

Zhang

Jing

2016

J Clin Immunol

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Since the discovery of the genetic basis of DOCK8 immunodeficiency syndrome (DIDS) in 2009, several hundred patients worldwide have been reported, validating and extending the initial clinical descriptions. Importantly, the beneficial role of hematopoietic stem cell transplantation for this disease has emerged, providing impetus for improved diagnosis. Additionally, several groups have further elucidated the biological functions of DOCK8 in the immune system that help explain disease pathogenesis. Here, we summarize these recent developments.

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Food allergies can persist after myeloablative hematopoietic stem cell transplantation in dedicator of cytokinesis 8–deficient patients

Cited by 32 publications

References 12 publications

Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome

Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome

DOCK8 deficiency: Insights into pathophysiology, clinical features and management

Recent Advances in DOCK8 Immunodeficiency Syndrome

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