Mannose-binding lectin deficiency associated with neutrophil chemotactic unresponsiveness to C5a

Rosa M. Ten, Eva M. Carmona, Dusica Babovic-Vuksanovic, Jerry A. Katzmann

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Mannose-binding lectin (MBL) plays an important role in host defense by activating the complement cascade. Objective: Three children with a history of recurrent infections since infancy were found to have MBL deficiency associated with a neutrophil chemotactic unresponsiveness specific to C5a. We have studied the genomic sequence of the C5a receptor (C5aR) in 2 of the subjects to determine whether this unresponsiveness was due to a genetic mutation or to aberrant complement activation associated with the MBL deficiency. Methods: MBL genotype analysis was performed by PCR-based methods with use of specific primers and restriction enzymes to detect the 3 previously reported mutations. Expression of C5aR was analyzed by flow cytometry. The C5aR gene was amplified from the patient's genomic DNA by PCR and sequenced by standard procedures. Results: C5aR was found to be expressed normally on the neutrophils of one of the subjects. Sequence analysis of the C5aR gene revealed a point mutation that substituted threonine at position 261 for alanine in one patient but no abnormality in the other, suggesting gene polymorphism. Treatment of 2 patients with granulocyte-colony stimulating factor corrected the neutrophil chemotactic abnormality in vitro and induced a significant clinical improvement. Conclusion: MBL deficiency can be associated with neutrophil chemotactic unresponsiveness to C5a and it is clinically manifested by recurrent and chronic infections. Treatment of these patients with granulocyte colony-stimulating factor results in normalization of neutrophil chemotaxis against C5a and significant clearing of infections.

Original languageEnglish (US)
Pages (from-to)419-424
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume104
Issue number2 I
DOIs
StatePublished - Jan 1 1999

Keywords

  • C5a
  • G-CSF
  • Mannose-binding lectin deficiency
  • Neutrophil chemotaxis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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