Clinical and Osteopetrosis-Like Radiological Findings in Patients with Leukocyte Adhesion Deficiency Type III.
Journal of clinical immunology, cilt.43, sa.6, ss.1250-1258, 2023 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 43 Sayı: 6
- Basım Tarihi: 2023
- Doi Numarası: 10.1007/s10875-023-01479-7
- Dergi Adı: Journal of clinical immunology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
- Sayfa Sayıları: ss.1250-1258
- Anahtar Kelimeler: KINDLIN3, FERMT3, osteopetrosis, bleeding diathesis, JMML, MDS, JUVENILE MYELOMONOCYTIC LEUKEMIA, STEM-CELL TRANSPLANTATION, LAD-III, INTEGRIN, MUTATION, KINDLIN-3, DEFECTS, GENE, ACTIVATION, DIAGNOSIS
- Bursa Uludağ Üniversitesi Adresli: Evet
Özet
BackgroundLeukocyte and platelet integrin function defects are present in leukocyte adhesion deficiency type III (LAD-III) due to mutations in FERMT3. Additionally, osteoclast/osteoblast dysfunction develops in LAD-III.AimTo discuss the distinguishing clinical, radiological, and laboratory features of LAD-III.MethodsThis study included the clinical, radiological, and laboratory characteristics of twelve LAD-III patients.ResultsThe male/female ratio was 8/4. The parental consanguinity ratio was 100%. Half of the patients had a family history of patients with similar findings. The median age at presentation and diagnosis was 18 (1-60) days and 6 (1-20) months, respectively. The median leukocyte count on admission was 43,150 (30,900-75,700)/mu L. The absolute eosinophil count was tested in 8/12 patients, and eosinophilia was found in 6/8 (75%). All patients had a history of sepsis. Other severe infections were pneumonia (66.6%), omphalitis (25%), osteomyelitis (16.6%), gingivitis/periodontitis (16%), chorioretinitis (8.3%), otitis media (8.3%), diarrhea (8.3%), and palpebral conjunctiva infection (8.3%). Four patients (33.3%) received hematopoietic stem cell transplantation (HSCT) from HLA-matched-related donors, and one deceased after HSCT. At initial presentation, 4 (33.3%) patients were diagnosed with other hematologic disorders, three patients (P5, P7, and P8) with juvenile myelomonocytic leukemia (JMML), and one (P2) with myelodysplastic syndrome (MDS).ConclusionIn LAD-III, leukocytosis, eosinophilia, and bone marrow findings may mimic pathologies such as JMML and MDS. In addition to non-purulent infection susceptibility, patients with LAD-III exhibit Glanzmann-type bleeding disorder. In LAD-III, absent integrin activation due to kindlin-3 deficiency disrupts osteoclast actin cytoskeleton organization. This results in defective bone resorption and osteopetrosis-like radiological changes. These are distinctive features compared to other LAD types.