Autoimmune Neutropenia of Infancy with Multiple Brain Abscesses during the Course of Human Herpesvirus-6 Infection

Tokushima-Imayoshi, Miyoko; Onoue, T.; Matsuo, Muneaki; Yoshida, Nobuyuki; Sato, Takashi; Kobayashi, Masao; Hamasaki, Yuhei; Ishii, Eiichi

doi:10.1532/ijh97.06064

Cited by 4 publications

(2 citation statements)

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“…The virus could also induce aberrant expression of histocompatibility molecules thereby promoting the presentation of auto-antigens. Notably, HHV-6 has the ability to trigger all the above mentioned mechanisms and in the recent years, several reports have suggested a potential role of HHV-6 in autoimmunity [21], [24], [43], [44], [45], [46], [47]. Overall, our study indicates that HHV-6 infection might be an important factor in HT development.…”

Section: Discussionsupporting

confidence: 63%

Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis

et al. 2012

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Hashimoto's thyroiditis (HT) is the most common of all thyroid diseases and is characterized by abundant lymphocyte infiltrate and thyroid impairment, caused by various cell- and antibody-mediated immune processes. Viral infections have been suggested as possible environmental triggers, but conclusive data are not available. We analyzed the presence and transcriptional state of human herpesvirus 6 (HHV-6) in thyroid fine needle aspirates (FNA) and peripheral blood mononuclear cells (PBMCs) from 34 HT patients and 28 controls, showing that HHV-6 DNA prevalence (82% vs. 10%, p≤0.001) and viral load were significantly increased in FNA from HT patients, and thyrocytes from HT FNA displayed a 100-fold higher HHV-6 DNA load compared to infiltrating lymphocytes. In addition, while HHV-6 was strictly latent in positive samples from controls, a low grade acute infection was detected in HT samples. HHV-6 variant characterization was carried out in 10 HT FNA samples, determining that all specimens harbored HHV-6 Variant A.The tropism of HHV-6 for thyroid cells was verified by infection of Nthy-ori3-1, a thyroid follicular epithelial cell line, showing that thyrocytes are permissive to HHV-6 replication, which induces de novo expression of HLA class II antigens. Furthermore, HHV-6-infected Nthy-ori3-1 cells become targets for NK-mediated killing, NK cells from HT patients show a significantly more efficient killing of HHV-6 infected thyroid cells than healthy controls, and HT patients have increased T-cell responses to HHV-6 U94 protein, associated to viral latency. These observations suggest a potential role for HHV-6 (possibly variant A) in the development or triggering of HT.

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Section: Discussionsupporting

confidence: 63%

Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis

et al. 2012

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“…To the best of our knowledge, adult-onset AIN associated with HHV-6 infection has not been reported in the literature. Two reports described patients up to 12 months of age with HHV-6 infection manifested as transient erythroblastopenia and multiple brain abscesses ( 8 , 9 ). Our patient presented with severe agranulocytosis and recent exposure to medications that could cause the insult.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune Neutropenia Associated With HHV-6 Virus Infection: A Case Report

et al. 2022

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BackgroundAutoimmune neutropenia (AIN) is divided into primary and secondary forms. The former is more prevalent in children and is usually a self-limiting disease. Secondary AIN is more common in adults and often occurs in the setting of another autoimmune disorder or secondary to infections, malignancies or medications. Several viral and bacterial pathogens were described to trigger AIN. Here we report a case of AIN in an adult woman associated with human herpesvirus-6 (HHV-6) infection.Case PresentationWe report a case of AIN in an adult woman associated with HHV-6 infection. The patient presented to the emergency department with fever and painful genital ulcers. Upon arrival, her laboratory workup demonstrated severe neutropenia and elevated inflammatory markers. She was hospitalized and underwent a thorough infectious, hematological, autoimmune and inflammatory workup. Malignancy was also excluded using an advanced whole body radiological scan. Serological tests confirmed the presence of both acute and chronic types of HHV-6 antibodies, at very high titers. Polymerase chain reaction demonstrated a numerous copies of the virus in the patient’s blood. Specific immunofluorescence test confirmed the diagnosis of autoimmune neutropenia.ConclusionSecondary AIN is a rare disease that may affect all range of ages. The adult type is a challenging disorder that has different etiologies and may be triggered by a variable infectious pathogen. The finding of HHV-6 as a possible culprit pathogen may warrant physicians into widening the evaluation and include HHV-6 in the analysis.

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HHV-6-Associated Neurological Disease in Children: Epidemiologic, Clinical, Diagnostic, and Treatment Considerations

Eliassen

Hemond

Santoro

2020

Pediatric Neurology

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Autoimmune Neutropenia of Infancy with Multiple Brain Abscesses during the Course of Human Herpesvirus-6 Infection

Cited by 4 publications

References 10 publications

Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis

Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis

Autoimmune Neutropenia Associated With HHV-6 Virus Infection: A Case Report

HHV-6-Associated Neurological Disease in Children: Epidemiologic, Clinical, Diagnostic, and Treatment Considerations

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