Leukocyte adhesion deficiency type I - a focus on oral disease in a young child

Yashodadevi, B K; Rakesh, Nagaraj; Devaraju, D; Santana, Nataraj

doi:10.4317/medoral.16.e153

Cited by 9 publications

(4 citation statements)

References 14 publications

(12 reference statements)

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“…Clinical findings, to include periodontal, are recurrent infections without pus formation, delayed umbilical cord separation, leukocytosis, skin ulcers, and severe aggressive periodontitis that may affect the primary and permanent dentition (Meyle, ; Majorana et al , ; Cox and Weathers, ; Dababneh et al , ; Notarangelo and Badolato, ; Al‐Herz et al , ; Yashoda‐Devi et al , ; Nagendran et al , ).…”

Section: Primary Immunodeficiencies (Genetic)mentioning

confidence: 99%

Periodontal and other oral manifestations of immunodeficiency diseases

2016

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The list of immunodeficiency diseases grows each year as novel disorders are discovered, classified, and sometimes reclassified due to our ever-increasing knowledge of immune system function. Although the number of patients with secondary immunodeficiencies (SIDs) greatly exceeds those with primary immunodeficiencies (PIDs), the prevalence of both appears to be on the rise probably because of scientific breakthroughs that facilitate earlier and more accurate diagnosis. Primary immunodeficiencies in adults are not as rare as once thought. Globally, the main causes of secondary immunodeficiency are HIV infection and nutritional insufficiencies. Persons with acquired immune disorders such as AIDS caused by the Human Immunodeficiency Virus (HIV) are now living long and fulfilling lives as a result of highly active antiretroviral therapy (HAART). Irrespective of whether the patient’s immune deficient state is a consequence of a genetic defect or is secondary in nature, dental and medical practitioners must be aware of the constant potential for infections and/or expressions of autoimmunity in these individuals. The purpose of this paper is to review the most common conditions resulting from primary and secondary immunodeficiency states, how they are classified, and the detrimental manifestations of these disorders on the periodontal and oral tissues.

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Section: Primary Immunodeficiencies (Genetic)mentioning

confidence: 99%

Periodontal and other oral manifestations of immunodeficiency diseases

2016

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“…Periodontitis in LAD‐I is recalcitrant to standard of care treatment and antibiotics and patients often lose their entire dentition at a very early age (teenage or young adulthood) . Significant intraoral findings also include recurrent painful oral ulcers that often impede eating . Until recently, there has not been an effective treatment for LAD‐I periodontitis.…”

Section: Defects In Neutrophil Extravasation Into Tissues: Lad‐imentioning

confidence: 99%

“…56 Significant intraoral findings also include recurrent painful oral ulcers that often impede eating. 58,59 Until recently, there has not been an effective treatment for LAD-I periodontitis. To date, only hematopoietic stem cell transplant has been reported to be curative for LAD-I-associated periodontitis.…”

Section: Leukocyte Adhesion Deficiency-i (Lad-i) and Periodontitismentioning

confidence: 99%

Primary immunodeficiencies reveal the essential role of tissue neutrophils in periodontitis

Silva

Brenchley

Moutsopoulos

2018

Immunological Reviews

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Summary Periodontitis is a common human inflammatory disease. In this condition, microbiota trigger excessive inflammation in oral mucosal tissues surrounding the dentition, resulting in destruction of tooth‐supporting structures (connective tissue and bone). While susceptibility factors for common forms of periodontitis are not clearly understood, studies in patients with single genetic defects reveal a critical role for tissue neutrophils in disease susceptibility. Indeed, various genetic defects in the development, egress from the bone marrow, chemotaxis, and extravasation are clearly linked to aggressive/severe periodontitis at an early age. Here, we provide an overview of genetic defects in neutrophil biology that are linked to periodontitis. In particular, we focus on the mechanisms underlying Leukocyte Adhesion Deficiency‐I, the prototypic Mendelian defect of impaired neutrophil extravasation and severe periodontitis.

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“…LAD1 is the consequence of mutations in the ITGB2 gene that is located on chromosome 21 (21q22.3), encodes the β2 subunit of the integrin molecule CD18 protein (Schmidt et al, 2013), and shows an autosomal recessive pattern of inheritance (Thakur et al, 2013). β2 integrins family has critical roles on leukocyte adhesion, functions in immune and inflammatory reactions such as adhesion of leukocyte to the endothelial cell, transendothelial migration, and chemotaxis (Yashoda-Devi et al, 2011). These mutations influence the function of neutrophils and lymphocytes such as proliferation, cytotoxic T lymphocyte response, and natural killer cell (NK) activity (Kuijpers et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Identification of the causative mutation in the ITGB2 gene in a LAD1 patient by whole exome sequencing

Liên

Anh

Tung

et al. 2022

Vietnam J. Biotechnol.

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Leukocyte adhesion deficiency type 1 (LAD1) is a rare congenital immunodeficiency disease. The cause of disease is determined to be the mutations in the ITGB2 gene that codes for CD18, the beta chain of beta-2 integrins, leads to decreased expression or functioning of CD18. This deficiency leads to severe impairment of leukocyte adhesion to the vascular wall and leukocyte migration to sites of infection and inflammation. LAD1 has also been associated with inhibition of interleukin-23 and interleukin-17 resulting in a hyperinflammatory and chronic inflammation. Patients with LAD1 typically present in early infancy with recurrent, life threatening infections that are frequently fatal before 2 years of age without hematopoietic stem cell transplant (HSCT). However, LAD1 is difficult to diagnose and many LAD1 patients die at a young age despite intensive antibiotic therapy. Accurate diagnosis requires detailed clinical information (delayed umbilical cord loss, severe periodontitis, delayed wound healing and sores, skin abscesses, and recurrent infection), and confirmation the absence of integrins by flow cytometric analysis. A better understanding of the molecular characteristics of this disease is needed to raise awareness and definitive diagnosis infants with LAD1. To definitive diagnosis, whole exome sequencing and Sanger sequencing were performed in an eighteen-month-old boy with severe leukocytosis, recurrent infections, delayed wound healing, and hepatosplenomegaly associated with an acquired cytomegalovirus infection. Two variants: One previously reported mutation (c.533C>T, p.Pro178Leu) and one novel variant (c.59-1G>A), in the ITGB2 gene were detected. These results can be used for definitive genetic diagnosis, genetic counseling, as well as a prenatal diagnosis in LAD1 patients.

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Leukocyte adhesion deficiency type I - a focus on oral disease in a young child

Cited by 9 publications

References 14 publications

Periodontal and other oral manifestations of immunodeficiency diseases

Periodontal and other oral manifestations of immunodeficiency diseases

Primary immunodeficiencies reveal the essential role of tissue neutrophils in periodontitis

Identification of the causative mutation in the ITGB2 gene in a LAD1 patient by whole exome sequencing

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