The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement

Filomena Monica Cavaliere; Alessandro Prezzo; Caterina Bilotta; Metello Iacobini; Isabella Quinti

doi:10.1371/journal.pone.0175961

The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement

PLoS One. 2017 Apr 19;12(4):e0175961. doi: 10.1371/journal.pone.0175961. eCollection 2017.

Authors

Filomena Monica Cavaliere¹, Alessandro Prezzo¹, Caterina Bilotta¹, Metello Iacobini², Isabella Quinti¹

Affiliations

¹ Department of Molecular Medicine, Sapienza University of Rome, Roma, Italy.
² Department of Pediatrics, Sapienza University of Rome, Roma, Italy.

Abstract

The lack of BTK in X-linked agammaglobulinemia (XLA) patients does not affect monocytes and polymorphonuclear cells (PMN) phenotype and functions. In this study, we show that XLA patients had an increased frequency of the intermediate monocytes subset and that BTK-deficient monocytes and PMN had a normal expression of receptors involved in the activation and cellular responses. We demonstrate that BTK is not required for migration, phagocytosis and the production of reactive oxygen species (ROS) following engagement of FC gamma receptors (FcγR). XLA monocytes and PMN showed an efficient calcium (Ca2+)-independent activation of oxidative burst, suggesting that oxidative burst is less dependent by Ca2+ mobilization. The phagocytosis was functional and it remained unaltered also after Ca2+ chelation, confirming the independence of phagocytosis on Ca2+ mobilization. Intravenous immunoglobulin (IVIg) infusion exerted an anti-inflammatory effect by reducing the frequency of pro-inflammatory monocytes. In monocytes, the IVIg reduce the oxidative burst and phagocytosis even if these functions remained efficient.

MeSH terms

Adult
Agammaglobulinaemia Tyrosine Kinase
Agammaglobulinemia / drug therapy*
Agammaglobulinemia / genetics
Agammaglobulinemia / immunology
Agammaglobulinemia / pathology
Calcium / metabolism
Calcium Chelating Agents / pharmacology
Case-Control Studies
Cell Movement / drug effects
Drug Administration Schedule
Gene Expression Regulation
Genetic Diseases, X-Linked / drug therapy*
Genetic Diseases, X-Linked / genetics
Genetic Diseases, X-Linked / immunology
Genetic Diseases, X-Linked / pathology
Humans
Immunoglobulins, Intravenous / therapeutic use*
Leukocytes, Mononuclear / drug effects*
Leukocytes, Mononuclear / immunology
Leukocytes, Mononuclear / pathology
Male
Middle Aged
Monocytes / drug effects*
Monocytes / immunology
Monocytes / pathology
Phagocytosis / drug effects
Phenotype
Protein-Tyrosine Kinases / deficiency*
Protein-Tyrosine Kinases / genetics
Protein-Tyrosine Kinases / immunology
Reactive Oxygen Species / immunology
Reactive Oxygen Species / metabolism
Receptors, IgG / genetics
Receptors, IgG / immunology
Respiratory Burst / drug effects
Respiratory Burst / immunology
Signal Transduction

Substances

Calcium Chelating Agents
Immunoglobulins, Intravenous
Reactive Oxygen Species
Receptors, IgG
Protein-Tyrosine Kinases
Agammaglobulinaemia Tyrosine Kinase
BTK protein, human
Calcium

Supplementary concepts

Bruton type agammaglobulinemia

Grants and funding

The authors received no specific funding for this work.