Eculizumab treatment modifies the immune profile of PNH patients.

Abstract

Paroxysmal Nocturnal Haemoglobinuria (PNH) is due to pathological expansion of a stem progenitor bearing a somatic mutation of PIG-A gene involved in the biosynthesis of the glycosyl-phosphatidyl-inositol (GPI) anchor. Numerous data suggest a role for immune-mediated mechanisms in the selection/expansion of GPI-defective clone. Haemolytic anaemia in PNH is dependent on the effect of complement against GPI-defective red cells. Eculizumab, an anti-C5 monoclonal antibody, is dramatically effective in controlling haemolysis and thrombosis, in reducing fatigue and in improving quality of life of patients. However, this therapy presents new challenges that need to be properly faced. Here, we report the decrease in B, Natural Killer (NK) and regulatory T cells (Treg), an altered cytokine profile of invariant-NKT cells (NKTi) and the increasing of C-X-C chemokine receptor type 4 (CXCR4) receptor in PNH patients before the Eculizumab therapy. Treatment significantly affects some of these alterations: after Eculizumab, the number of B lymphocytes, the cytokine secretion of NKTi and CXCR4 expression on CD8 T cells became similar to healthy donors. No effects were observed on NK and Treg. The amplitude of the GPI-defective compartment remained unchanged.

• Authors: Fiorella Alfinito, Giuseppina Ruggiero, Michela Sica, Annapoorani Udhayachandran, Valentina Rubino, Roberta Della Pepa, Anna T Palatucci, Mariangela Annunziatella, Rosario Notaro, Antonio M Risitano, Giuseppe Terrazzano
• Journal: Immunobiology (Immunobiology) Vol. 217 Issue 7 Pg. 698-703 (Jul 2012) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 22206707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier GmbH. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• CXCR4 protein, human
• Cytokines
• Glycosylphosphatidylinositols
• Membrane Proteins
• Receptors, CXCR4
• phosphatidylinositol glycan-class A protein
• Complement System Proteins
• eculizumab

Topics

• Adult
• Antibodies, Monoclonal, Humanized (administration & dosage, immunology, therapeutic use)
• B-Lymphocytes (immunology, pathology)
• CD8-Positive T-Lymphocytes (immunology, pathology)
• Cell Count
• Complement System Proteins (immunology)
• Cytokines (biosynthesis, immunology)
• Erythrocytes (immunology, pathology)
• Female
• Gene Expression
• Glycosylphosphatidylinositols (genetics, immunology)
• Hemoglobinuria, Paroxysmal (drug therapy, immunology, pathology)
• Hemolysis
• Humans
• Male
• Membrane Proteins (genetics, immunology)
• Middle Aged
• Natural Killer T-Cells (immunology, pathology)
• Receptors, CXCR4 (genetics, immunology)
• T-Lymphocytes, Regulatory (immunology, pathology)