Neutrophil Migration Defects

Leukocyte Adhesion Deficiency Type 1: A Case Series and Review of the Literature

“…24 Skin and mucosal surface infections may present as indolent and necrotic lesions that can enlarge and recur, commonly leading to systemic spread of infections. 3 Infections usually appear first in the neonatal period as omphalitis and delayed umbilical detachment. 5,25 Umbilical cord complications were more frequent in patients with severe LAD, as identified in a comprehensive review performed by Novoa et al, 11 and they reported a significant correlation between lack of these complications and survival to 2 years of age.…”

“…1,2 LAD-1 severity is related to the degree of CD18 deficiency. 3 Leukocyte trafficking from circulation to tissues, as a critical response to integrins, serves as an essential dynamic process in immune surveillance and is mediated with a set of integrin molecules on leukocyte cell surfaces. 4,5 Genetic alterations in the numbers or activation of leukocyte integrins may lead to the development of LAD-1 syndromes.…”

“…[12][13][14][15] α M β 2 and α L β 2 serve as the C3b receptor in myeloid and lymphoid cells 16 and α D β 2 is restricted to macrophage subsets in mice and humans. 12,17,18 The ITGB2 gene encoding for the β 2 -integrin component CD18 1,2,11,19 is located at the long arm of chromosome 21q22.3, 3 and has >80 mutations identified so far. The severity of the clinical manifestations is directly related to the degree of CD18 deficiency, 3 with the mild-to-moderate types characterised by 2-30% CD18-expressing neutrophils and severe LAD-1 classified as <2% CD18-expressing neutrophils.…”

“…12,17,18 The ITGB2 gene encoding for the β 2 -integrin component CD18 1,2,11,19 is located at the long arm of chromosome 21q22.3, 3 and has >80 mutations identified so far. The severity of the clinical manifestations is directly related to the degree of CD18 deficiency, 3 with the mild-to-moderate types characterised by 2-30% CD18-expressing neutrophils and severe LAD-1 classified as <2% CD18-expressing neutrophils. 11,19,20 Patients with LAD-1 typically present with recurrent indolent necrotic infections of the skin and mucosal surfaces, which usually occur during the neonatal period with omphalitis and delayed separation of the umbilical cord.…”

“…11,19,20 Patients with LAD-1 typically present with recurrent indolent necrotic infections of the skin and mucosal surfaces, which usually occur during the neonatal period with omphalitis and delayed separation of the umbilical cord. 3 Additionally, failure to thrive, severe malnourishment, and delayed wound healing are common, while colitis may only occur in rare cases. 21 Many patients may develop infections before they are diagnosed with LAD-1 because many physicians are unaware of the disease.…”