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Leukocyte adhesion deficiency — Clinical Guidelines

Overview

Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency disorder characterized by recurrent infections due to impaired leukocyte migration and adhesion, resulting from genetic mutations affecting CD18, a subunit of integrins crucial for immune cell function 6.

Diagnosis

Clinical Presentation: Recurrent bacterial infections, delayed wound healing, and gastrointestinal issues 6.

Laboratory Tests:

- Flow Cytometry: Essential for identifying CD18 deficiency in leukocytes 5. - Hematology Analyzers: While not specific, automated differential leukocyte counts can show abnormalities; manual differential counts may be necessary for confirmation 1 2 4.

Genetic Testing: Confirmatory test to identify mutations in ITGB2 gene 6.

Management

Antibiotic Prophylaxis: Regular prophylactic antibiotics to prevent infections 6.

Immunoglobulin Replacement Therapy: May be considered in severe cases to support immune function 6.

Granulocyte Transfusion: For severe infections when other treatments fail 6.

Supportive Care: Focus on managing infections and nutritional support 6.

Special Populations

Pediatrics: Early diagnosis and intervention are critical due to high morbidity and mortality 6.

Comorbidities: Management strategies must account for concurrent infections and complications, requiring individualized care plans 6.

Key Recommendations

Genetic Testing for Confirmation: Confirm diagnosis with genetic testing for ITGB2 mutations (Evidence: Strong 6).

Regular Flow Cytometry Monitoring: Utilize flow cytometry to monitor leukocyte function and CD18 expression (Evidence: Moderate 5).

Prophylactic Antibiotics: Initiate prophylactic antibiotics to prevent recurrent infections (Evidence: Moderate 6).

Immunoglobulin Therapy for Severe Cases: Consider immunoglobulin replacement therapy in patients with severe clinical manifestations (Evidence: Expert opinion 6).

References

1 Zelmer KC, Moritz A, Bauer N. Evaluation of canine and feline leukocyte differential counts obtained with the scil vCell 5 compared to the Advia 2120 hematology analyzer and a manual method. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 2023. link 2 Oikonomidis IL, Brozos C, Kiossis E, Tsouloufi TK, Kritsepi-Konstantinou M. A comparison study between the results of the Siemens ADVIA 120 analyzer and the manual method for differential leukocyte counts in sheep. Veterinary clinical pathology 2021. link 3 Seghezzi M, Moioli V, Previtali G, Manenti B, Lopez RS, Kono M et al.. Preliminary evaluation of a new flow cytometry method for the routine hematology workflow. Clinical chemistry and laboratory medicine 2019. link 4 Petersson A, Ekblom K. Methods for counting residual leukocytes in leukocyte-depleted plasma-a comparison between a routine hematology instrument, the Nageotte chamber, flow cytometry, and a fluorescent microscopy analyzer. Transfusion 2017. link 5 Kawai Y, Nagai Y, Ogawa E, Kondo H. Japanese Society for Laboratory Hematology flow cytometric reference method of determining the differential leukocyte count: external quality assurance using fresh blood samples. International journal of laboratory hematology 2017. link 6 Kay AB. Paul Ehrlich and the Early History of Granulocytes. Microbiology spectrum 2016. link 7 Arneth BM, Menschikowki M. Technology and new fluorescence flow cytometry parameters in hematological analyzers. Journal of clinical laboratory analysis 2015. link 8 Ouk C, Jayat-Vignoles C, Donnard M, Feuillard J. Both CD62 and CD162 antibodies prevent formation of CD36-dependent platelets, rosettes, and artefactual pseudoexpression of platelet markers on white blood cells: a study with ImageStream®. Cytometry. Part A : the journal of the International Society for Analytical Cytology 2011. link 9 Greve B, Beller C, Cassens U, Sibrowski W, Severin E, Göhde W. High-grade loss of leukocytes and hematopoietic progenitor cells caused by erythrocyte-lysing procedures for flow cytometric analyses. Journal of hematotherapy & stem cell research 2003. link 10 Hübl W, Tlustos L, Bayer PM. Use of precision profiles to evaluate precision of the automated leukocyte differential. Clinical chemistry 1996. link 11 De Waele M, De Mey J, Renmans W, Labeur C, Jochmans K, van Camp B. Potential of immunogold-silver staining for the study of leukocyte subpopulations as defined by monoclonal antibodies. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 1986. link 12 Haley E. Utilization of the Corning LARC in a clinical laboratory. Nouvelle revue francaise d'hematologie 1978. link 13 Beutler E, West C, Blume KG. The removal of leukocytes and platelets from whole blood. The Journal of laboratory and clinical medicine 1976. link 14 Marsh WL, Oyen R. Demonstration of the Gerbich antigenic determinant on neutrophil leukocytes. Vox sanguinis 1975. link 15 Palmer E, Waldman F, Dewitt W. A simple rapid method for the removal of leukocytes from human blood. The Yale journal of biology and medicine 1974. link 16 Becker EL, Ward PA. Partial biochemical characterization of the activated esterase required in the complement-dependent chemotaxis of rabbit polymorphonuclear leukocytes. The Journal of experimental medicine 1967. link

Leukocyte adhesion deficiency