Skip to main content

Advertisement

SpringerLink
Log in

Successful adjunctive immunoglobulin treatment in patients affected by leukocyte adhesion deficiency type 1 (LAD-1)

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Two patients with a severe leukocyte adhesion deficiency type 1 (LAD-1) phenotype were analyzed by flow cytometry and functional assays to demonstrate the improper adhesive and phagocytic responses of their leukocytes. A single homozygous defect that involves a missense mutation (c.817G>A) that encodes for a G273R substitution in CD18 was identified in both patients. The adhesion and phagocytosis assays demonstrated the inability of patients’ leukocytes to perform these functions. Expression of the LFA-1 (CD11a/CD18) on the co-transfected HEK 293 cells with the mutated form of CD18 was not detected. Finally, both patients have been treated with immunoglobulin as an adjunctive therapy with positive results. We propose that intravenous immunoglobulin treatment is safe and efficacious in LAD-1 patients before hematopoietic stem cell transplantation and helpful in controlling severe infections. Subcutaneous immunoglobulin appeared to help wound healing in refractory ulcers in these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Gelfand EW, Ochs HD, Shearer WT. Controversies in IgG replacement therapy in patients with antibody deficiency diseases. J Allergy Clin Immunol. 2013;131(4):1001–5.

    Article  CAS  PubMed  Google Scholar 

  2. Maarschalk-Ellerbroek LJ, Hoepelman IM, Ellerbroek PM. Immunoglobulin treatment in primary antibody deficiency. Int J Antimicrob Agents. 2011;37(5):396–404.

    Article  CAS  PubMed  Google Scholar 

  3. Garcia JM, Espanol T, Gurbindo MD, Casas CC. Update on the treatment of primary immunodeficiencies. Allergol Immunopathol (Madr). 2007;35(5):184–92.

    Article  CAS  Google Scholar 

  4. Li L, Jin YY, Cao RM, Chen TX. A novel point mutation in CD18 causing leukocyte adhesion deficiency in a Chinese patient. Chin Med J (Engl). 2010;123(10):1278–82.

    CAS  Google Scholar 

  5. Etzioni A. Defects in the leukocyte adhesion cascade. Clin Rev Allergy Immunol. 2010;38(1):54–60.

    Article  CAS  PubMed  Google Scholar 

  6. Campbell ID, Humphries MJ. Integrin structure, activation, and interactions. Cold Spring Harb Perspect Biol. 2011;3(3):a004994.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Luo BH, Carman CV, Springer TA. Structural basis of integrin regulation and signaling. Annu Rev Immunol. 2007;25:619–47.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Tan SM. The leucocyte beta2 (CD18) integrins: the structure, functional regulation and signalling properties. Biosci Rep. 2012;32(3):241–69.

    Article  CAS  PubMed  Google Scholar 

  9. van de Vijver E, Maddalena A, Sanal O, Holland SM, Uzel G, Madkaikar M, et al. Hematologically important mutations: leukocyte adhesion deficiency (first update). Blood Cells Mol Dis. 2012;48(1):53–61.

    Article  PubMed  Google Scholar 

  10. Hogg N, Patzak I, Willenbrock F. The insider’s guide to leukocyte integrin signalling and function. Nat Rev Immunol. 2011;11(6):416–26.

    Article  CAS  PubMed  Google Scholar 

  11. Etzioni A. Genetic etiologies of leukocyte adhesion defects. Curr Opin Immunol. 2009;21(5):481–6.

    Article  CAS  PubMed  Google Scholar 

  12. Mellouli F, Ksouri H, Barbouche R, Maamer M, Hamed LB, Hmida S, et al. Successful treatment of Fusarium solani ecthyma gangrenosum in a patient affected by leukocyte adhesion deficiency type 1 with granulocytes transfusions. BMC Dermatol. 2010;10:10.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Etzioni A. Leukocyte adhesion deficiencies: molecular basis, clinical findings, and therapeutic options. Adv Exp Med Biol. 2007;601:51–60.

    Article  PubMed  Google Scholar 

  14. Hogg N, Stewart MP, Scarth SL, Newton R, Shaw JM, Law SK, et al. A novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins Mac-1 and LFA-1. J Clin Invest. 1999;103(1):97–106.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Roos D, Law SK. Hematologically important mutations: leukocyte adhesion deficiency. Blood Cells Mol Dis. 2001;27(6):1000–4.

    Article  CAS  PubMed  Google Scholar 

  16. Maravillas-Montero JL, Gillespie PG, Patino-Lopez G, Shaw S, Santos-Argumedo L. Myosin 1c Participates in B Cell cytoskeleton rearrangements, is recruited to the immunologic synapse, and contributes to antigen presentation. J Immunol. 2011;187(6):3053-63.

  17. Theodoridis AA, Eich C, Figdor CG, Steinkasserer A. Infection of dendritic cells with herpes simplex virus type 1 induces rapid degradation of CYTIP, thereby modulating adhesion and migration. Blood. 2011;118(1):107–15.

    Article  CAS  PubMed  Google Scholar 

  18. Qasim W, Cavazzana-Calvo M, Davies EG, Davis J, Duval M, Eames G, et al. Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency. Pediatrics. 2009;123(3):836–40.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Zhou MJ, Brown EJ. CR3 (Mac-1, alpha M beta 2, CD11b/CD18) and Fc gamma RIII cooperate in generation of a neutrophil respiratory burst: requirement for Fc gamma RIII and tyrosine phosphorylation. J Cell Biol. 1994;125(6):1407–16.

    Article  CAS  PubMed  Google Scholar 

  20. Nord KM, Pappert AS, Grossman ME. Pyoderma gangrenosum-like lesions in leukocyte adhesion deficiency I treated with intravenous immunoglobulin. Pediatr Dermatol. 2011;28(2):156–61.

    Article  PubMed  Google Scholar 

  21. Lin JH, Wang KY, Kraft S, Roberts RL. Resolution of warts in association with subcutaneous immunoglobulin in immune deficiency. Pediatr Dermatol. 2009;26(2):155–8.

    Article  PubMed  Google Scholar 

  22. Nishio N, Ito S, Suzuki H, Isobe K. Antibodies to wounded tissue enhance cutaneous wound healing. Immunology. 2009;128(3):369–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Lai A, Hosseini-Tabatabaei A, Hartwell R, Rahmani-Neishaboor E, Kilani RT, Ghahary A. Topical application of aminopeptidase N-neutralizing antibody accelerates wound closure. Mol Cell Biochem. 2013;372(1–2):95–100.

    Article  CAS  PubMed  Google Scholar 

  24. Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science. 1998;282(5388):490–3.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank to Dr. Héctor Romero-Ramírez and M.Sc. Víctor H. Rosales-García for their help at different stages of this work. Supported by Instituto de Ciencia y Tecnología del Distrito Federal (ICyTDF) (Grant PICSA12-157) and Consejo Nacional de Ciencia y Tecnología (CONACyT) (Grant 153733 awarded to L.S.A.). J.L.M.M. and N.R.A. were supported by doctoral scholarships 203768 and 456878 from CONACyT. L.B.R was the recipient of a doctoral (176353) and postdoctoral (CVU 44813) scholarship from CONACyT.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Departamento de Inmunología Clínica, Instituto Nacional de Pediatría, CP 04530, Mexico City, Mexico

    Marco Yamazaki-Nakashimada, Francisco Rivas-Larrauri & Selma Scheffler-Mendoza

  2. Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida IPN 2508, CP 07360, Mexico City, D.F., Mexico

    José L. Maravillas-Montero, Laura Berrón-Ruiz, Orestes López-Ortega, Noé Ramírez-Alejo, Ernesto Acevedo-Ochoa & Leopoldo Santos-Argumedo

  3. Red de Apoyo a la Investigación, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”-Coordinación de la Investigación Científica, Universidad Nacional Autónoma de México, CP 14000, Mexico City, Mexico

    José L. Maravillas-Montero

  4. Unidad de Investigación en Inmunodeficiencias, Instituto Nacional de Pediatría, CP 04530, Mexico City, Mexico

    Laura Berrón-Ruiz, Lizbeth Blancas-Galicia & Selma Scheffler-Mendoza

  5. Hospital del Niño y el Adolescente Morelense, CP 62765, Cuernavaca, Morelos, Mexico

    Beatriz Llamas-Guillén

  6. Departamento Oncología, Unidad de Trasplantes de Células Madre Hematopoyéticas, Instituto Nacional de Pediatría, CP 04530, Mexico City, Mexico

    Alberto Olaya-Vargas

Authors
  1. Marco Yamazaki-Nakashimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. José L. Maravillas-Montero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laura Berrón-Ruiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Orestes López-Ortega
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Noé Ramírez-Alejo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ernesto Acevedo-Ochoa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Francisco Rivas-Larrauri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Beatriz Llamas-Guillén
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lizbeth Blancas-Galicia
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Selma Scheffler-Mendoza
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Alberto Olaya-Vargas
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Leopoldo Santos-Argumedo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leopoldo Santos-Argumedo.

Additional information

Marco Yamazaki-Nakashimada and José L. Maravillas-Montero have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamazaki-Nakashimada, M., Maravillas-Montero, J.L., Berrón-Ruiz, L. et al. Successful adjunctive immunoglobulin treatment in patients affected by leukocyte adhesion deficiency type 1 (LAD-1). Immunol Res 61, 260–268 (2015). https://doi.org/10.1007/s12026-014-8619-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-014-8619-8

Keywords

Search

Navigation