A Toolkit and Framework for Optimal Laboratory Evaluation of Individuals with Suspected Primary Immunodeficiency

Knight, Vijaya; Heimall, Jennifer; Chong, Hey; Nandiwada, Sarada L.; Chen, Karin; Lawrence, Monica G.; Akha, Amir A. Sadighi; Kumánovics, Attila; Jyonouchi, Soma; Ngo, Suzanne Y.; Vinh, Donald C.; Hagin, David; Satter, Lisa R. Forbes; Marsh, Rebecca; Chiang, Samuel C.C.; Willrich, Maria Alice V.; Frazer‐Abel, Ashley; Rider, Nicholas L.

doi:10.1016/j.jaip.2021.05.004

Cited by 7 publications

(6 citation statements)

References 166 publications

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“…Due to limitation of our primers design, causal mutations within those intronic and regulatory regions may not be included in the PCR regions, and hence cannot be identified. Nevertheless, the strengths of targeted gene SS include >99% high accuracy, fast turnaround time, low cost, with fewer variants of uncertain significance and no secondary findings (3,4). Therefore, doing one round of single specific targeted gene SS remains the firsttier genetic test for patients suspected to have one of these 5 common IEI in our laboratory.…”

Section: Discussionmentioning

confidence: 99%

“…Inborn errors of immunity (IEI), previously known as primary immunodeficiency diseases (PIDD), arise from intrinsic defects in immunity, with most due to genetic mutations, and comprise over 400 diseases that could present with a diverse range of disorders including infection, autoimmunity, inflammation, malignancy, and allergy (1,2). These multitudes of disorders could present with a wide spectrum of phenotypes of varying severities, resulting in difficulty recognising and diagnosing IEI promptly and accurately, especially in resource-limited countries and regions (3).…”

Section: Introductionmentioning

confidence: 99%

“…With rapid advance in both immunological and genetic studies in IEI including newborn screening for severe combined immunodeficiency (SCID) over the last 20 years, the prognosis of patients with IEI living in resource-rich countries and regions have improved enormously due to rapid and accurate genetic diagnosis with treatment tailored to specific IEI, together with family counseling regarding recurrence risk and reproductive choices (3)(4)(5). However, for most countries and regions of Asia and Africa, many patients with suspected IEI now still do not have ready access to these diagnostic and therapeutic approaches, let alone 20 years ago, resulting in underdiagnosis of IEI and a protracted diagnostic odyssey for many families (6).…”

Section: Introductionmentioning

confidence: 99%

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Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity

et al. 2022

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To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott–Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity

et al. 2022

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“…Secondary occurs more often in adults, in the absence of a genetic predisposition, but in the context of an immunological trigger (infection, malignancy, etc). 7 Both forms are engendered by a dramatic activation of cytotoxic T cells and natural killer cells combined with macrophage activation. Such an uncontrolled immune activation syndrome can lead to a cytokine storm, which can be life-threatening.…”

Section: Discussionmentioning

confidence: 99%

Haemophagocytic lymphohistiocytosis in an adult with postacute COVID-19 syndrome

et al. 2021

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Haemophagocytic lymphohistiocytosis (HLH) causing multiorgan failure has been reported as an acute clinical presentation of COVID-19. However, the literature surrounding HLH in the context of a postacute COVID-19 syndrome is limited. This report presents a case of a life-threatening HLH occurring 6 weeks after a pauci-symptomatic COVID-19 infection in a previously healthy adult. A bone marrow aspirate confirmed the HLH and the patient was successfully treated with dexamethasone and etoposide. To our knowledge, this is the first case of HLH occurring as a postacute COVID-19 syndrome following a pauci-symptomatic initial infection.

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“…HLH has been divided into primary and secondary subtypes. Primary HLH is familial, primarily seen in children, whereas sHLH is an adult entity due to underlying infection, autoimmune disease, malignancy, or "post-allogeneic" hematopoietic stem cell transplantation (2). HLH is a life-threatening hyperinflammatory state characterized by multiorgan dysfunction, adding to the spectrum of Post-Acute COVID-19 Syndrome (PACS) (3).…”

Section: Introductionmentioning

confidence: 99%

Case Report: Secondary Hemophagocytic Lymphohistiocytosis (sHLH) and Candida auris Fungemia in Post-acute COVID-19 Syndrome: A Clinical Challenge

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a disease (COVID-19) with multisystem involvement. The world is now entering a phase of post-COVID-19 manifestations in this pandemic. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event triggered by viral infections, including SARS-CoV-2. Both Multisystem Inflammatory Syndrome-Adults (MIS-A) and Cytokine Storm Syndrome (CSS) are considered close differentials of sHLH and add to the spectrum of Post-acute COVID-19 syndrome (PACS). In this report, we presented the case of a middle-aged Asian man who was initially discharged upon recovery from severe COVID-19 infection after 17 days of hospitalization to a private institute and later came to our hospital 13 days post-discharge. Here, he was diagnosed with sHLH, occurring as an extension of CSS, with delayed presentation falling within the spectrum of PACS. The diagnosis of sHLH was made holistically with the HLH-2004 criteria. Our patient initially responded to intravenous immunoglobulin (IVIG) and dexamethasone, later complicated by disseminated Candida auris infection and had a fatal outcome. Though many cases of HLH during active COVID-19 and a few cases post COVID-19 recovery have been reported, based on H-score, which has limitations as a diagnostic tool. We report the first case report of post-COVID-19 sHLH using the HLH-2004 criteria, complicated by disseminated Candidemia, emphasizing that the care of patients with COVID-19 does not conclude at the time of hospital discharge. We highlight the importance of surveillance in the post-COVID phase for early detection of sHLH which may predispose to fatal opportunistic infections (OIs).

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A Toolkit and Framework for Optimal Laboratory Evaluation of Individuals with Suspected Primary Immunodeficiency

Cited by 7 publications

References 166 publications

Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity

Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity

Haemophagocytic lymphohistiocytosis in an adult with postacute COVID-19 syndrome

Case Report: Secondary Hemophagocytic Lymphohistiocytosis (sHLH) and Candida auris Fungemia in Post-acute COVID-19 Syndrome: A Clinical Challenge

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