Oral and Genital Ulceration

Kwong, Pearl; O'Marcaigh, Aengus; Howard, R. G.; Cowan, Morton J.; Frieden, Ilona J.

doi:10.1001/archderm.135.8.927

Cited by 28 publications

(3 citation statements)

References 8 publications

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“…The subset of SCID found in in these Athabascan-speaking Native Americans is due to an autosomal recessive nonsense Artemis mutation in exon 8, which causes a truncation of the 692 aa protein at the 192nd aa ( 6 ). As expected, these patients suffer from the early onset of serious infections due to their lack of an adaptive immune system ( 10 ). Thus, the biomedical importance of Artemis is substantial.…”

Section: Introductionmentioning

confidence: 62%

Structure-Specific nuclease activities of Artemis and the Artemis: DNA-PKcs complex

Chang

Lieber

2016

Nucleic Acids Res

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Artemis is a vertebrate nuclease with both endo- and exonuclease activities that acts on a wide range of nucleic acid substrates. It is the main nuclease in the non-homologous DNA end-joining pathway (NHEJ). Not only is Artemis important for the repair of DNA double-strand breaks (DSBs) in NHEJ, it is essential in opening the DNA hairpin intermediates that are formed during V(D)J recombination. Thus, humans with Artemis deficiencies do not have T- or B-lymphocytes and are diagnosed with severe combined immunodeficiency (SCID). While Artemis is the only vertebrate nuclease capable of opening DNA hairpins, it has also been found to act on other DNA substrates that share common structural features. Here, we discuss the key structural features that all Artemis DNA substrates have in common, thus providing a basis for understanding how this structure-specific nuclease recognizes its DNA targets.

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Section: Introductionmentioning

confidence: 62%

Structure-Specific nuclease activities of Artemis and the Artemis: DNA-PKcs complex

Chang

Lieber

2016

Nucleic Acids Res

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“…Although no family history of SCID was recorded before the NBS result, upon review 2 distant cousins had succumbed to SCID, one with complications following attempted HCT and the other with an infection before HCT could be performed. Physical examination at 4 weeks was normal except for an oral ulcer, a previously described non-infectious characteristic of SCID-A [19]. At 2 months she received a haploidentical, CD34 selected, T cell depleted peripheral HCT from her mother without pre-conditioning, followed by a stem cell boost at 7 months.…”

Section: Resultsmentioning

confidence: 96%

Successful newborn screening for SCID in the Navajo Nation

Kwan

Song

et al. 2015

Clinical Immunology

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Newborn screening (NBS) for severe combined immunodeficiency (SCID) identifies affected infants before the onset of life-threatening infections, permitting optimal treatment. Navajo Native Americans have a founder mutation in the DNA repair enzyme Artemis, resulting in frequent Artemis SCID (SCID-A). A pilot study at 2 Navajo hospitals assessed the feasibility of SCID NBS in this population. Dried blood spots from 1,800 infants were assayed by PCR for T-cell receptor excision circles (TRECs), a biomarker for naïve T cells. Starting in February 2012, TREC testing transitioned to standard care throughout the Navajo Area Indian Health Service, and a total of 7,900 infants were screened through July 2014. One infant had low TRECs and was diagnosed with non-SCID T lymphopenia, while 4 had undetectable TRECs due to SCID-A, all of whom were referred for hematopoietic cell transplantation. This report establishes the incidence of SCID-A and demonstrates effectiveness of TREC NBS in the Navajo.

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“…SNM1C/Artemis gene mutation is rare in Europe, < 1/ 500 000 births, but its incidence is much higher in the Athabascanspeaking, Navajo and Apache Native Americans involving 1/2000 births (49). First cases of severe combined immunodeficiency were reported in Athabascan-speaking American Indian Children, who presented B-cells and T-cells deficiency associated with oral and/or genital ulceration (50). Clinical presentations were also characterized by hypogammaglobulinemia and poor antibody response ( inflammation, lymphoproliferative diseases and lymphoma malignancies with later clinical manifestations, in childhood or adulthood (37,53,58,60).…”

Section: Snm1c/artemis Mutation In Humansmentioning

confidence: 99%

Could β-Lactam Antibiotics Block Humoral Immunity?

et al. 2021

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It has been reported that treatment with β-lactam antibiotics induces leukopenia and candidemia, worsens the clinical response to anticancer immunotherapy and decreases immune response to vaccination. β-lactamases can cleave β-lactam antibiotics by blocking their activity. Two distincts superfamilies of β-lactamases are described, the serine β-lactamases and the zinc ion dependent metallo-β-lactamases. In human, 18 metallo-β-lactamases encoding genes (hMBLs) have been identified. While the physiological role of most of them remains unknown, it is well established that the SNM1A, B and C proteins are involved in DNA repair. The SNM1C/Artemis protein is precisely associated in the V(D)J segments rearrangement, that leads to immunoglobulin (Ig) and T-cell receptor variable regions, which have a crucial role in the immune response. Thus in humans, SNM1C/Artemis mutation is associated with severe combined immunodeficiency characterized by hypogammaglobulinemia deficient cellular immunity and opportunistic infections. While catalytic site of hMBLs and especially that of the SNM1 family is highly conserved, in vitro studies showed that some β-lactam antibiotics, and precisely third generation of cephalosporin and ampicillin, inhibit the metallo-β-lactamase proteins SNM1A & B and the SNM1C/Artemis protein complex. By analogy, the question arises as to whether β-lactam antibiotics can block the SNM1C/Artemis protein in humans inducing transient immunodeficiency. We reviewed here the literature data supporting this hypothesis based on in silico, in vitro and in vivo evidences. Understanding the impact of β-lactam antibiotics on the immune cell will offer new therapeutic clues and new clinical approaches in oncology, immunology, and infectious diseases.

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Oral and Genital Ulceration

Cited by 28 publications

References 8 publications

Structure-Specific nuclease activities of Artemis and the Artemis: DNA-PKcs complex

Structure-Specific nuclease activities of Artemis and the Artemis: DNA-PKcs complex

Successful newborn screening for SCID in the Navajo Nation

Could β-Lactam Antibiotics Block Humoral Immunity?

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