Case report: Myocarditis in congenital STAT1 gain-of function

Staels, Frederik; Roosens, Willem; Giovannozzi, Simone; Moens, Leen; Bogaert, Jan; Iglesias-Herrero, Cecilia; Gijsbers, Rik; Bossuyt, Xavier; Frans, Glynis; Liston, Adrian; Humblet-Baron, Stéphanie; Meyts, Isabelle; Aelst, Lucas Van; Schrijvers, R.

doi:10.3389/fimmu.2023.1095595

Cited by 3 publications

(2 citation statements)

References 23 publications

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“… Recurrent tinea capitis infections; Bronchiectasis; Hypothyroidism 23 2020 STAT1 male data missing Candida spp. Bronchiectasis; Diffuse myocarditis 24 2022 CARD9 female 5 years old <10Y (2Y) Candida spp. Meningoencephalitis 25 2023 CARD9 female 1.5 years old <10Y (3Y) C. albicans Candida meningitis 26 2019 IL-12R female after birth <10Y (3Y) Candida spp.…”

Section: Discussionmentioning

confidence: 99%

Chinese Chronic Mucocutaneous Candidiasis: A Case Report Series

Qian,

Zhang,

Shi

et al. 2024

IDR

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Chronic Mucocutaneous Candidiasis (CMC) is a rare immunodeficiency disease characterized by chronic or recurrent superficial Candida infections on the skin, nail, and mucous membranes. Here, we present four Chinese patients with CMC who manifested oral mucosal leukoplakia and nail thickening during early childhood, all displaying fissured tongue lines. The causative pathogens isolated from their oral mucosa and nails were identified as C. albicans and C. parapsilosis through morphology and molecular sequencing. Notably, among the four patients, one presented with vitiligo, while another had hypothyroidism. We have also conducted a review of reported cases of CMC in China and worldwide over the last five years, highlighting potential approaches for diagnosis and treatment. The current molecular evidence in the literature suggests potential for the development of early diagnosis methods, such as screening genetic variables on STAT1 and STAT3 . Additionally, potential treatment avenues, including gene-targeted analogues and GM-CSF analogues, could be explored in conjunction with traditional antifungal therapy.

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Section: Discussionmentioning

confidence: 99%

Chinese Chronic Mucocutaneous Candidiasis: A Case Report Series

Qian,

Zhang,

Shi

et al. 2024

IDR

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“…Exposure to pharmacological agents such as antipsychotic agents, cytotoxic drugs, salicylates, and vaccines as well as immune checkpoint inhibitor (ICI) treatment may predispose to myocarditis [10]. Although most patients recover from myocarditis, MEFV mutations in familial mediterranean fever (FMF) or STAT1 gain-offunction mutations, for example, may contribute to myocardial injury due to aberrant host immunity [11][12][13][14][15]. However, genetic and biological mechanisms of autoinflammatory myocarditis remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Germline HAVCR2/TIM-3 Checkpoint Inhibitor Receptor Deficiency in Recurrent Autoinflammatory Myocarditis

Pernaa,

Vakkuri,

Arvonen

et al. 2024

J Clin Immunol

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Myocarditis can be caused by viral infection, drug reaction or general inflammatory condition. To provide understanding on inflammatory myocarditis, we describe clinical, genetic, and immunological properties of a young male patient who suffered from recurrent myocarditis episodes since the age of four years. Electrocardiography, troponin I/T, echocardiography, myocardial magnetic resonance imaging and histological findings were consistent with recurrent myocarditis episodes. Homozygous c.245 A > G p.Tyr82Cys pathogenic variant in Hepatitis A Virus Cellular Receptor 2 (HAVCR2) gene encoding T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) receptor was found. Peripheral blood mononuclear cells were collected when the patient was asymptomatic; CD4+ and CD8+ T lymphoblasts, CD56+ natural killer cells and CD14+ monocytes were negative for surface TIM-3 expression. In vitro, TLR4 mediated interleukin-1β (IL-1β) response was high after LPS/ATP stimulation. Clinical symptoms responded to IL-1 receptor antagonist anakinra. TIM-3 p.Tyr82Cys CD4+ and CD8+ T cell proliferation in vitro was unrestrained. Findings on IL-2, interferon gamma, regulatory T cells, signal transducer and activator of transcription (STAT) 1, 3 and 4 phosphorylation, and PD-1 and LAG-3 checkpoint inhibitor receptor analyses were comparable to controls. We conclude that TIM-3 deficiency due to homozygous HAVCR2 c.245 A > G p.Tyr82Cys pathogenic variant in the patient described here is associated with autoinflammatory symptoms limited to early onset recurrent febrile myocarditis. Excessive IL-1β production and defective regulation of T cell proliferation may contribute to this clinical condition responsive to anakinra treatment.

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