Variable CD18 expression in a 22‐year‐old female with leukocyte adhesion deficiency I: Clinical case and literature review

Abstract

Key Clinical MessagePartial 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.AbstractLAD‐1, OMIM ID #116920 is a rare, autosomal recessive disorder that results from mutations in the ITGB2 gene that encodes the CD18 β2 integrin subunit. According to the CD18 expression, LAD‐1 is categorized as severe (<2%), moderate (2%–30%), or mild (>30%). Here, we describe a 22‐year‐old female, who presented with inflammatory skin disease and oral cavity, as well as respiratory tract infections during the first year of life. LAD‐1 was diagnosed at the age of 2 years by low expression of CD18 (1%). Whole‐exome sequencing identified homozygous c. 59‐10C>A variant in the ITGB2 gene. Despite severe phenotype, the patient survived to adulthood without hematopoietic stem cell transplantation and became pregnant at the age of 20 years, with pregnancy complicated by a pyoderma gangrenosum‐like lesion. During her life, CD18 expression increased from 1% to 9%; at 22 years of age, 5% of neutrophils and 9% of lymphocytes were CD18+. All CD18+‐lymphocytes were predominantly memory/effector cytotoxic T cells. However, revertant mosaicism was not being established suggesting that CD18 expression variability may be mediated by other mechanisms such as different β2 integrin isophorms expression.

Flow cytometric analysis of immune cell populations in the bronchial and mesenteric lymph nodes of the dromedary camel

“…In the present study, lymph node lymphocytes showed lower CD44 expression compared to lymphocytes from peripheral blood, indicating a higher frequency of naïve lymphocytes in the lymph nodes. This was also supported by the lower expression of the cell adhesion molecule CD18 on lymph node compared to blood lymphocytes ( 36 ). The presence of naïve T cells in lymphoid and mucosal tissues has been described previously with the evidence that these cells are blood-derived cells that supply the draining lymph nodes with cells that can be rapidly sampled by local antigen-presenting cells ( 4 , 37 ).…”

Sweet syndrome associated with moderate leukocyte adhesion deficiency type I: a case report and review of the literature

“…Although these patients can survive into adulthood, some may develop overwhelming infections later in life. The average lifespan of patients with the less severe form of LAD-I is approximately 40 years old and as such can experience frequent skin infections and disabling, recurrent skin ulcerations, inflammatory periodontal disease with bone loss and/or inflammatory bowel disease ( 9 , 12 ).…”

“…Sweet syndrome has been described in association with common variable immunodeficiency (CVID) and chronic granulomatous disease (CGD), but not LAD-I ( 19 – 25 ). Pyoderma gangrenosum (PG), another non-infectious neutrophilic dermatosis, has also been described as a comorbidity of IEI, including LAD-I ( 3 , 6 , 11 , 12 , 26 ). All neutrophilic dermatoses occurring in pediatric patients should incite clinicians to examine patients for evidence of involvement of other organs and other general disorders ( 27 ).…”