A Case of Two Adult Brothers with Wiskott-Aldrich Syndrome, One Treated with Gene Therapy and One with HLA-Identical Hematopoietic Stem Cell Transplantation

Consiglieri, Giulia; Ferrua, Francesca; Aiuti, Alessandro; Cicalese, Maria Pia

doi:10.1007/s10875-021-01157-6

Cited by 7 publications

(4 citation statements)

References 10 publications

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“…Previous studies also support dupilumab treatment of atopic dermatitis in non-STAT3-related-IEI, such as DOCK8 deficiency (40), CARD11-associated atopy with dominant interference of NF-kB signaling (CADINS) (41), Wiskott-Aldrich Syndrome (42), common variable immune deficiency (CVID) (43), TTC7A-associated combined immunodeficiency (44), and Xlinked agammaglobulinemia (45-47). Thus, indications for dupilumab use in IEI are rapidly expanding, and it should be considered a main therapeutic modality in adult patients with AD-HIES along with standard topical care.…”

Section: Discussionmentioning

confidence: 83%

Dominant-negative signal transducer and activator of transcription (STAT)3 variants in adult patients: A single center experience

et al. 2022

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BackgroundAutosomal dominant hyper-IgE syndrome (AD-HIES) caused by dominant negative (DN) variants in the signal transducer and activator of transcription 3 gene (STAT3) is characterized by recurrent Staphylococcal abscesses, severe eczema, chronic mucocutaneous candidiasis (CMC), and non-immunological facial and skeletal features.ObjectivesTo describe our experience with the diagnosis and treatment of adult patients with AD-HIES induced by DN-STAT3 variants.MethodsThe medical records of adult patients (>18 years) treated at the Allergy and Clinical Immunology Clinic of Hadassah Medical Center, Jerusalem, Israel, were retrospectively analyzed. Immune and genetic workups were used to confirm diagnosis.ResultsThree adult patients (2 males; age 29-41 years) were diagnosed with DN-STAT3 variants. All patients had non-immunological features, including coarse faces and osteopenia. Serious bacterial infections were noted in all patients, including recurrent abscesses, recurrent pneumonia, and bronchiectasis. CMC and diffuse dermatophytosis were noted in two patients. Two patients had severe atopic dermatitis refractory to topical steroids and phototherapy. Immune workup revealed elevated IgE in three patients and eosinophilia in two patients. Whole exome sequencing revealed DN-STAT3 variants (c.1166C>T; p.Thr389Ile in two patients and c.1268G>A; p. Arg423Gln in one patient). Variants were located in DNA-binding domain (DBD) and did not hamper STAT3 phosphorylation Treatment included antimicrobial prophylaxis with trimethoprim/sulfamethoxazole (n=2) and amoxycillin-clavulanic acid (n=1), and anti-fungal treatment with fluconazole (n=2) and voriconazole (n=1). Two patients who had severe atopic dermatitis, were treated with dupilumab with complete resolution of their rash. No adverse responses were noted in the dupilumab-treated patients.DiscussionDupilumab can be used safely as a biotherapy for atopic dermatitis in these patients as it can effectively alleviate eczema-related symptoms. Immunologists and dermatologists treating AD-HIES adult patients should be aware of demodicosis as a possible manifestation. DN-STAT3 variants in DBD do not hamper STAT3 phosphorylation.

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Section: Discussionmentioning

confidence: 83%

Dominant-negative signal transducer and activator of transcription (STAT)3 variants in adult patients: A single center experience

et al. 2022

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“…Skin lesions and a high titer of IgE persisted after the use of immunosuppressive treatment. Therefore, a Th2 pathogenesis has been hypothesized, and dupilumab, a monoclonal antibody that inhibits IL-4 and IL-13 signaling, was started with significant clinical benefit ( 18 ).…”

Section: Pathogenetic Mechanism and Treatment Of Ieis-a With Skin Inv...mentioning

confidence: 99%

Tailored treatments in inborn errors of immunity associated with atopy (IEIs-A) with skin involvement

et al. 2023

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Inborn errors of immunity associated with atopy (IEIs-A) are a group of inherited monogenic disorders that occur with immune dysregulation and frequent skin involvement. Several pathways are involved in the pathogenesis of these conditions, including immune system defects, alterations of skin barrier and metabolism perturbations. Current technological improvements and the higher accessibility to genetic testing, recently allowed the identification of novel molecular pathways involved in IEIs-A, also informing on potential tailored therapeutic strategies. Compared to other systemic therapy for skin diseases, biologics have the less toxic and the best tolerated profile in the setting of immune dysregulation. Here, we review IEIs-A with skin involvement focusing on the tailored therapeutic approach according to their pathogenetic mechanism.

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“…A potentially curative therapeutic option for patients with classic form is represented by allogeneic hematopoietic stem cell transplantation (HSCT) (3,4), with an estimated 3-year survival from transplantation of approximately 88% and better overall survival for patients aged <5 years (5)(6)(7). Patients lacking a matched donor may benefit from ex vivo lentiviral hematopoietic stem and progenitor cell gene therapy (HSPC-GT) (8).…”

Section: Introductionmentioning

confidence: 99%

Rare solid tumors in a patient with Wiskott–Aldrich syndrome after hematopoietic stem cell transplantation: case report and review of literature

Coppola,

Giardino,

Abate

et al. 2023

Front. Immunol.

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Background and aimsWiskott–Aldrich syndrome (WAS) is an X-linked recessive primary immunodeficiency disorder characterized by severe eczema, recurrent infections, and micro-thrombocytopenia. Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic option for patients with classic form. The risk of developing post-transplant tumors appears to be higher in patients with WAS than in other inborn errors of immunity (IEIs), but the actual incidence is not well defined, due to the scarcity of published data.MethodsHerein, we describe a 10-year-old patient diagnosed with WAS, treated with HSCT in the first year of life, who subsequently developed two rare solid tumors, kaposiform hemangioendothelioma and desmoid tumor. A review of the literature on post-HSCT tumors in WAS patients has been performed.ResultsThe patient received diagnosis of classic WAS at the age of 2 months (Zhu score = 3), confirmed by WAS gene sequencing, which detected the nonsense hemizygous c.37C>T (Arg13X) mutation. At 9 months, patient underwent HSCT from a matched unrelated donor with an adequate immune reconstitution, characterized by normal lymphocyte subpopulations and mitogen proliferation tests. Platelet count significantly increased, even though platelet count never reached reference values. A mixed chimerism was also detected, with a residual WASP− population on monocytes (27.3%). The patient developed a kaposiform hemangioendothelioma at the age of 5. A second abdominal tumor was identified, histologically classified as a desmoid tumor when he reached the age of 10 years. Both hematopoietic and solid tumors were identified in long-term WAS survivors after HSCT.ConclusionHere, we describe the case of a patient with WAS who developed two rare solid tumors after HSCT. An active surveillance program for the risk of tumors is necessary in the long-term follow-up of post-HSCT WAS patients.

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A Case of Two Adult Brothers with Wiskott-Aldrich Syndrome, One Treated with Gene Therapy and One with HLA-Identical Hematopoietic Stem Cell Transplantation

Cited by 7 publications

References 10 publications

Dominant-negative signal transducer and activator of transcription (STAT)3 variants in adult patients: A single center experience

Dominant-negative signal transducer and activator of transcription (STAT)3 variants in adult patients: A single center experience

Tailored treatments in inborn errors of immunity associated with atopy (IEIs-A) with skin involvement

Rare solid tumors in a patient with Wiskott–Aldrich syndrome after hematopoietic stem cell transplantation: case report and review of literature

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