Variable CD18 expression in a 22‐year‐old female with leukocyte adhesion deficiency I: Clinical case and literature review
Анастасія БондаренкоOksana BoyarchukInga SakovichEkaterina PolyakovaAlexander A. MigasAleksandra N. KupchinskayaAleksandra OpalińskaAdam ReichL.A. VolianskaAnna HilfanovaFedir LapiyЛ.И. ЧернышоваAlla VolokhaDariia V. OsypchukMikhail BelevtsevТ. В. ШманLyudmila V. KukharenkoMikhail V. GoltsevTatsiana G. DubouskayaAndrei HancharouWeizhen JiSaquib A. LakhaniC. LucasOlga AleinikovaSvetlana O. Sharapova
4
Citation
30
Reference
10
Related Paper
Citation Trend
Abstract:
Partial leukocyte adhesion deficiency type 1 (LAD-1) deficiency is extremely rare condition with milder infectious manifestation and immune system imbalance leads to increased risks of autoinflammatory complications, such as pyoderma gangrenosum, that can be triggered by trauma or pregnancy. In patients with spice-site ITGB2 variants, partial expression can occur due to different β2 integrin isophorms expression.Keywords:
Leukocyte adhesion deficiency
Expression (computer science)
Bovine leukocyte adhesion deficiency (BLAD) is an autosomal recessive disease caused by A-->G mutation in the CD18 gene. The disease is characterized by greatly reduced expression of the heterodimeric beta2 integrin adhesion molecules on leukocytes, resulting in multiple defects in leukocyte function and significant deficits on performance traits in Holstein cattle. In this study, primers were designed to amplify the CD18 gene fragment and BLAD was detected by PCR-SSCP in a simple, highly accurate and high throughput manner. Results were confirmed by DNA sequencing. This study provides a more reliable and useful method for extensive screening of BLAD and also offers a theoretical basis for molecular diagnosis in Holstein calves.
Leukocyte adhesion deficiency
Single-strand conformation polymorphism
Holstein Cattle
Cite
Citations (0)
Bovine leukocyte adhesion deficiency(BLAD) is a newly discovered autosomal recessive genetic disease in recent years caused by A→G mutation in the CD18 gene.The disease is characterized by greatly reduced expression of the hetero dimeric β2 integrin adhesion molecules on leukocytes resulting in multiple defects in leukocyte function and significant deficits on performance traits in Holstein cattle.The main features of sick cattle is immunity reduction,susceptibility to diseases and affecting production performance.This review focus on the progress of test methods of BLAD.
Leukocyte adhesion deficiency
Cite
Citations (0)
Bovine leukocyte adhesion deficiency (BLAD) was identified in a two-month-old Holstein heifer calf using DNA-polymerase chain reaction analysis of the affected calf and other clinical parameters. Neutrophil integrin expression (CD18, CD11a, CD11c), aggregation, and transendothelial migration were studied in vitro. Neutrophils were isolated from the affected calf and from normal, healthy, age-matched control Holstein calves. Neutrophils isolated from the affected BLAD calf had decreased expression of leukocyte integrins on their cell surface, decreased ability to aggregate in response to chemotactic stimuli, and decreased ability to migrate across bovine endothelial cell monolayers in vitro. Transendothelial migration of neutrophils from normal calves was reduced to levels comparable to the BLAD neutrophils by treatment with an anti-CD18 monoclonal antibody (MAb 60.3). Peripheral-blood lymphocytes from the BLAD calf also expressed negligible levels of leukocyte integrins, similar to their neutrophil counterparts. Our experimental findings in vitro correlate well with the clinical observations of decreased leukocyte trafficking and diminished host defense in leukocyte adhesion-deficient animals. The syndrome of BLAD may be a suitable model for one of the human leukocyte adhesion deficiency disorders.
CD11a
Leukocyte adhesion deficiency
CD11c
Cite
Citations (15)
Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, autosomal recessive inherited immunodeficiency disease characterized by recurrent severe bacterial infection, impaired pus formation, poor wound healing, associated with the mutation in the CD18 gene responsible for the ability of the leucocytes to migrate from the blood stream towards the site of inflammation. Correct and early diagnosis of LAD-1 is vital to the success of treatment and prevention of aggressive infections. The purpose of this study was to collect the clinical findings of the disease and to identify the genetic entity.CD18 expression in the peripheral blood leukocytes from the patient, his parents and normal control was measured with flow cytometry. The entire coding regions of the CD18 gene were screened with direct sequencing genomic DNA.CD18 expression level on this patient's leukocyte surface was significantly decreased, with normal level in control group, his father and mother. Gene analysis revealed that this patient had a homozygous c.899A > T missense mutation in exon 8 of CD18 gene, causing the substitution of Asp to Val at the 300 amino acid. His parents were both heterozygous carriers while no such mutation was found in 50 normal controls.This study disclosed a novel point mutation Asp 300 Val located in a highly conserved region (HCR) of CD18 and confirmed the heterogeneity of the mutations causing LAD-1, indicating it was quite beneficial to establish correct and early diagnosis in children with severe LAD-1.
Leukocyte adhesion deficiency
Cite
Citations (10)
Two calves (5 and 9 months old) affected with pneumonia and gingivitis were also diagnosed as having bovine leukocyte adhesion deficiency (BLAD). The gene of leukocyte adhesion molecule CD18 in these BLAD calves and their dams (carrier) were examined by means of polymerase chain reaction (PCR) and digestion of restriction endonuclease. The splicing in mRNA coded CD18 reported in human LAD was not recognized in BLAD on the basis of the results of PCR amplification. The region including the portion of point mutation, which corresponded to the region reported in the human patient, was amplified by PCR, and the PCR product was then digested with TaqI. An obvious difference was recognized in the pattern of digestion among healthy calves, BLAD calves and their dams. In BLAD, therefore, the point mutation reported in human patients was strongly suggested. Moreover it may be a method able to be used in detecting the carrier.
Leukocyte adhesion deficiency
TaqI
Cite
Citations (23)
To identify cellular promoters in a self-inactivating (SIN) lentiviral vector that might be beneficial in treating children with leukocyte adhesion deficiency type 1 (LAD-1), we tested lentiviral vectors with human CD11 and CD18 leukocyte integrin proximal promoter elements directing expression of canine CD18 in animals with canine LAD (CLAD). Lentiviral vectors with either the human CD11b (637 bp) proximal promoter or the human CD18 (1,060 bp) proximal promoter resulted in the highest percentages of CD18+ CLAD CD34+ cells in vitro. Subsequently, two CLAD dogs were infused with autologous CD34+ cells transduced with the hCD11b (637 bp)-cCD18 vector, and two CLAD dogs were infused with autologous CD34+ cells transduced with the hCD18 (1,060 bp)-cCD18 vector. Each dog received a nonmyeloablative dose of 200 cGy total body irradiation (TBI) before the infusion of transduced cells. The two CLAD dogs treated with the hCD18 (1,060 bp)-cCD18 vector, and one of the two dogs treated with the hCD11b (637 bp)-cCD18 vector, had reversal of the CLAD phenotype. These studies using endogenous leukocyte integrin proximal promoters represent an important step in the development of gene therapy for children with LAD-1. To identify cellular promoters in a self-inactivating (SIN) lentiviral vector that might be beneficial in treating children with leukocyte adhesion deficiency type 1 (LAD-1), we tested lentiviral vectors with human CD11 and CD18 leukocyte integrin proximal promoter elements directing expression of canine CD18 in animals with canine LAD (CLAD). Lentiviral vectors with either the human CD11b (637 bp) proximal promoter or the human CD18 (1,060 bp) proximal promoter resulted in the highest percentages of CD18+ CLAD CD34+ cells in vitro. Subsequently, two CLAD dogs were infused with autologous CD34+ cells transduced with the hCD11b (637 bp)-cCD18 vector, and two CLAD dogs were infused with autologous CD34+ cells transduced with the hCD18 (1,060 bp)-cCD18 vector. Each dog received a nonmyeloablative dose of 200 cGy total body irradiation (TBI) before the infusion of transduced cells. The two CLAD dogs treated with the hCD18 (1,060 bp)-cCD18 vector, and one of the two dogs treated with the hCD11b (637 bp)-cCD18 vector, had reversal of the CLAD phenotype. These studies using endogenous leukocyte integrin proximal promoters represent an important step in the development of gene therapy for children with LAD-1.
Leukocyte adhesion deficiency
Cite
Citations (30)
Two Holstein heifers with persistent and recurrent infections including ulcerative gingivitis, periodontitis, pneumonia, loss of teeth and stunted growth associated with marked neutrophilia were evaluated clinically and for neutrophil function, CD18 expression on neutrophils and CD18 genotype analysis by DNA-polymerase chain reaction (PCR) test. Adherence to nylon fibers and phagocytic activity of neutrophils from affected animals were significantly (p < 0.05) impaired as compared with those of controls. Neutrophils from affected heifers had decreased chemiluminescent (CL) responses when stimulated with opsonized zymosan, compared with those of controls. In contrast, neutrophils from affected heifers produced increased CL responses when stimulated with latex beads and phorbol myristate acetate compared with those of controls. The clinical findings, functional leukocyte abnormalities, deficiency in expression of CD18 on neutrophils, and the D128G mutation detected by DNA-PCR testing of affected heifers demonstrated that these heifers have bovine leukocyte adhesion deficiency (BLAD). Although both animals were confirmed to be homozygotes for BLAD by DNA-PCR test, they had differences in clinical, hematological and neutrophil functional characteristics.
Leukocyte adhesion deficiency
Neutrophilia
Zymosan
Neutrophil Extracellular Traps
Leukocytosis
Cite
Citations (29)
Leukocyte adhesion deficiency
CD11a
Cite
Citations (19)
Bovine leukocyte adhesion deficiency (BLAD) is autosomal recessive disease. The pathogeny of BLAD is genic mutation of CD18-integrins on the leukocyte. In order to know the carrier and occurrence of bovine leukocyte adhesion deficiency (BLAD) among cows age from one to six years old in China, 1,000 cows were investigated by means of amplifying a CD18 gene fragment via reverse transcriptase-PCR followed by restriction digestion with Taq I. Results showed that 19 cows were BLAD carriers, indicating that the BLAD carrier rate was 1.9 percent. In addition, one cow was found to have BLAD.
Leukocyte adhesion deficiency
Cite
Citations (5)
Leukocyte adhesion deficiency
CD11c
CD11a
Polymorphonuclear leukocyte
Cite
Citations (18)