Case Report: DOCK8 Deficiency Without Hyper-IgE in a Child With a Large Deletion

Venegas-Montoya, Edna; Staines‐Boone, Aidé Tamara; Sánchez‐Sánchez, Luz María; García-Campos, Jorge Alberto; Córdova-Gurrola, Rubén Antonio; Salazar-Galvez, Yuridia; Muzquiz‐Zermeño, David; González-Serrano, María Edith; Reyes, Saúl

doi:10.3389/fped.2021.635322

Cited by 8 publications

(8 citation statements)

References 25 publications

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“…The hallmark humoral alteration of DOCK8-Def is high serum IgE levels; nonetheless, some pathogenic variants with normal IgE levels have been reported; the multicenter series coordinated by ESID described three cases with normal IgE levels. We found just one case with normal IgE levels previously reported by Venegas-Montoya et al 8 Skin involvement is key to suspecting DOCK8-Def since it is usually the first clinical feature and the most frequent reason for referral to specialized centers. In contrast to other IEIs characterized by eczema, DOCK8-Def patients typically do not exhibit congenital dermatological disease; instead, the condition tends to manifest in early childhood, usually before the age of two.…”

Section: Discussionsupporting

confidence: 53%

“…In contrast to other IEIs characterized by eczema, DOCK8‐Def patients typically do not exhibit congenital dermatological disease; instead, the condition tends to manifest in early childhood, usually before the age of two 9 . It has traditionally been described as a hard‐to‐control atopic dermatitis 8,10,11 . Nevertheless, our findings indicate that the condition diverges from the typical sites affected by atopic dermatitis.…”

Section: Discussionmentioning

confidence: 55%

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Clinical, immunological, and genetic description of a Mexican cohort of patients with DOCK8 deficiency

Liquidano‐Perez,

Maza‐Ramos,

Perez Arias

et al. 2024

Pediatric Allergy Immunology

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PurposeWe aimed to describe the clinical, immunological, and genetic features of patients with DOCK8 deficiency (DOCK8‐Def) in a tertiary care center for children.MethodsRetrospective chart review of patients' clinical, immunological, and genetic characteristics with DOCK8‐Def. Genetic analysis was performed with targeted‐ or whole‐exome sequencing; we also assessed DOCK8 protein expression and a lymphoproliferation assay and analyzed survival by the Kaplan–Meier method.ResultsWe described 11 patients from 8 unrelated kindreds. The median age at symptoms' onset was 10 months (range 1–54 months). The median follow‐up time was 53.4 months (4.8–118.8). All patients presented eczema and recurrent sinopulmonary and cutaneous infections. Besides those symptoms, the most frequent manifestations were bronchiectases (8/11), food allergies (6/11), and severe infections (6/11). Infrequent characteristics were detection of CMV in bronchial lavage, C. parvum‐driven sclerosing cholangitis, Takayasu vasculitis, neurological syndromes, pulmonary tuberculosis, and lymphomatoid granulomatosis.ConclusionDOCK8‐Def has a broad spectrum of manifestations, including allergy, autoimmunity, inflammation, infection, and cancer. The hallmark of this inborn error of immunity is IEI‐associated eczema with eosinophilia and increased IgE. Here, we report six new mutations causing human DOCK8 deficiency and symptoms previously unrecognized to occur in DOCK8‐Def. Therefore, an early diagnosis of DOCK8‐Def is essential to facilitate an adequate treatment such as HSCT.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 55%

Clinical, immunological, and genetic description of a Mexican cohort of patients with DOCK8 deficiency

Liquidano‐Perez,

Maza‐Ramos,

Perez Arias

et al. 2024

Pediatric Allergy Immunology

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“…This demonstrates the importance of CTL and NK cells in controlling viral infections and killing cancer cells via immune synapses 112, 113 . It should be noted there are some reports of DOCK8‐deficient patients without hyper‐IgE 114 and there is an observed association between DOCK8 deficiency and a novel variant of combined immunodeficiency, 115 suggesting DOCK8 deficiency should be reclassified as a distinct entity to HIES with a poorer prognosis.…”

Section: Hyper Ige Syndromementioning

confidence: 89%

Malignancy‐associated immune responses: Lessons from human inborn errors of immunity

Aliyath,

Eni‐Olotu,

Donaldson

et al. 2023

Immunology

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It is widely understood that cancer is a significant cause of morbidity and mortality worldwide. Despite numerous available treatments, prognosis for many remains poor, thus, the development of novel therapies remains essential. Given the incredible success of many immunotherapies in this field, the important contribution of the immune system to the control, and elimination, of malignancy is clear. While many immunotherapies target higher‐order pathways, for example, through promoting T‐cell activation via immune checkpoint blockade, the potential to target specific immunological pathways is largely not well researched. Precisely understanding how immunity can be tailored to respond to specific challenges is an exciting idea with great potential, and may trigger the development of new therapies for cancer. Inborn Errors of Immunity (IEI) are a group of rare congenital disorders caused by gene mutations that result in immune dysregulation. This heterogeneous group, spanning widespread, multisystem immunopathology to specific immune cell defects, primarily manifest in immunodeficiency symptoms. Thus, these patients are particularly susceptible to life‐threatening infection, autoimmunity and malignancy, making IEI an especially complex group of diseases. While precise mechanisms of IEI‐induced malignancy have not yet been fully elucidated, analysis of these conditions can highlight the importance of particular genes, and downstream immune responses, in carcinogenesis and may help inform mechanisms which can be utilised in novel immunotherapies. In this review, we examine the links between IEIs and cancer, establishing potential connections between immune dysfunction and malignancy and suggesting roles for specific immunological mechanisms involved in preventing carcinogenesis, thus, guiding essential future research focused on cancer immunotherapy and providing valuable insight into the workings of the immune system in both health and disease.

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“…It affects both the innate and adaptive compartments of the immune system. Affected individuals present with chronic eczema, recurrent sinopulmonary infections, and have an increased predisposition to malignancies [7].…”

Section: Discussionmentioning

confidence: 99%

Clinical and molecular profile of 17 patients with DOCK8 deficiency: A single-centre experience from Southern India

Janardhanan

Ranganath

Mohite

et al. 2023

Preprint

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Introduction DOCK8 deficiency is the most common cause of autosomal recessive Hyper IgE syndrome (AR-HIES). The clinical spectrum is wide resulting in combined immunodeficiency, atopy, autoimmunity, and malignancies. Objectives To study the clinical and molecular profile of 17 patients with DOCK8 deficiency. Methods Three hundred sixty patients with various Inborn errors of Immunity (IEIs) were diagnosed in the Pediatric Immunology Unit of our hospital during the study period of February 2017 to April 2023. Based on the clinical and immunological phenotype, DOCK8 deficiency was suspected in 21 patients. Genetic studies confirmed DOCK8 deficiency in 17 patients and their profile was analysed in detail. Results Seventeen patients from 14 kindreds were diagnosed with DOCK8 deficiency. Thirteen of these families (92%) reported consanguinity. Our cohort had eight male and nine females. The mean age at onset of symptoms and diagnosis was seven months and 5.8 years respectively. Eczema was noted in 16 patients. Mucocutaneous manifestations included oromucosal hyperpigmentation(n=6), scalp seborrhoea(n=2), alopecia(n=1) and perianal tag(n=1). The spectrum of infections included pneumonia(n=11), diarrhea (n=5), otitis media (n=4), mucocutaneous candidiasis(n=3),meningoencephalitis(n=2), and cutaneous viral infections (n=3). Two patients had developed bronchiectasis. Autoimmune manifestations were noted in four patients and included autoimmune haemolytic anaemia (n=2) and vasculitis (n=2). Single exonic deletions(n=10) in DOCK8 gene were the most common mutations observed and 13 of these were novel. Twelve patients were on monthly intravenous immunoglobulin therapy at the time of writing this paper. Three patients underwent hematopoietic stem cell transplants elsewhere, two of whom succumbed to post-transplant complications and one is doing well. Overall, eight patients died during the study period, while nine patients continue to remain on follow-up. Conclusion We present one of the largest single-centre experiences on DOCK8 deficiency from India. A significant delay in the diagnosis contributed to poor outcome in our cohort.

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Case Report: DOCK8 Deficiency Without Hyper-IgE in a Child With a Large Deletion

Cited by 8 publications

References 25 publications

Clinical, immunological, and genetic description of a Mexican cohort of patients with DOCK8 deficiency

Clinical, immunological, and genetic description of a Mexican cohort of patients with DOCK8 deficiency

Malignancy‐associated immune responses: Lessons from human inborn errors of immunity

Clinical and molecular profile of 17 patients with DOCK8 deficiency: A single-centre experience from Southern India

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