This patient presents with leukocyte adhesion deficiency type 1 (LAD-1) in which neutrophilia is observed on peripheral blood smear (Figure D) due to the inability of neutrophils to exit the bloodstream.
LAD-1 is an autosomal recessive immunodeficiency causing phagocytic dysfunction. It is caused by a defect in the LFA-1 integrin protein on phagocytes which prevents their adherence and migration out of blood vessels. It presents with recurrent bacterial infections, absent pus formation, poor wound healing, and delayed separation of the umbilical cord. Neutrophilia will be observed on the peripheral blood smear due to the inability of phagocytes to exit circulation.
Guan et al. identify specific mutations causing LAD-1. Specifically, they examine 18 missense mutations, 14 of which fail to support the surface expression of the ß2 integrins. They state that integrins with ß2 mutations fail to bind ligands, possibly due to the failure of certain segments to form an a-helical structure.
Yamazaki-Nakashimada et al. describe two case reports of successful treatment of infections in patients with LAD-1 without requiring hematopoietic stem cell transplantation. Intravenous immunoglobulin was used as a treatment modality in both patients with successful results, leading the investigators to propose that intravenous immunoglobulin treatment is safe and efficacious in controlling severe infections in LAD-1 patients before hematopoietic stem cell transplantation.
Figures are described in the incorrect answer choice explanations below.
Answer 1: Figure A demonstrates a normal peripheral blood smear. In LAD, the peripheral blood smear would demonstrate neutrophilia.
Answer 2: Figure B demonstrates giant granules in neutrophils as is observed in Chediak-Higashi syndrome.
Answer 3: Figure C demonstrates thrombocytopenia as is observed in Wiskott-Aldrich syndrome
Answer 5: Figure E demonstrates a negative nitroblue tetrazolium (NBT) test which is observed in chronic granulomatous disease.
Guan S, Tan SM, Li Y, Torres J, Uzel G, Xiang L, Law SK. Characterization of single amino acid substitutions in the ß2 integrin subunit of patients with leukocyte adhesion deficiency (LAD)-1. Blood Cells Mol Dis. 2015 Feb;54(2):177-82. doi: 10.1016/j.bcmd.2014.11.005. Epub 2014 Nov 28. PubMed PMID: .
PMID:25514840 (Link to Abstract)
Yamazaki-Nakashimada M, Maravillas-Montero JL, Berrón-Ruiz L, López-Ortega O, Ramírez-Alejo N, Acevedo-Ochoa E, Rivas-Larrauri F, Llamas-Guillén B, Blancas-Galicia L, Scheffler-Mendoza S, Olaya-Vargas A, Santos-Argumedo L. Successful adjunctive immunoglobulin treatment in patients affected by leukocyte adhesion deficiency type 1 (LAD-1). Immunol Res. 2014 Dec 21. [Epub ahead of print] PubMed PMID:
PMID:25527966 (Link to Abstract)