Intravenous (IV) anti-D and IV immunoglobulin achieve acute platelet increases by different mechanisms: modulation of cytokine and platelet responses to IV anti-D by FcgammaRIIa and FcgammaRIIIa polymorphisms.

Abstract

Intravenous (IV) anti-D and IV immunoglobulin (IVIG) slow the Fcgamma receptor (FcgammaR)-mediated destruction of antibody-coated platelets in patients with immune thrombocytopenic purpura (ITP). This pilot study explored the mechanism of these immunoglobulin preparations by measuring interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), IL-6 and tumour necrosis factor alpha (TNFalpha), before and after infusion and by assessing the effect of FcgammaRIIa and FcgammaRIIIa polymorphisms on both cytokine and haematologic responses to anti-D. Following IVIG, only IL-10 was increased at 2 h and MCP-1 on day 7 (P < 0.05). In contrast, 2 h after anti-D infusion, plasma levels of all four cytokines were increased (P < 0.01); five of six patients with the highest MCP-1, IL-6 and TNFalpha levels had chills. Higher IL-10 levels correlated with platelet increases at 24 h and haemoglobin decreases at day 7 (P < 0.025). Patients with the FcgammaRIIa-131HH genotype had significantly higher MCP-1, IL-6 and TNFalpha levels. Patients with the FcgammaRIIIa-158VF genotype had higher platelet increments at day 7 (P < 0.05). Soluble CD16 (sCD16) was increased 2 h after IV anti-D; day 7 levels correlated with day 7 haemoglobin decreases (P < 0.01). In conclusion, the relationship of FcgammaRIIa and FcgammaRIIIa polymorphisms with both cytokine levels and platelet increments implicated these receptors in responses to anti-D and supported different mechanisms of FcgammaR interaction to those seen with IVIG.

• Authors: Nichola Cooper, Nancy M Heddle, Masja Haas, Marion E Reid, Martin L Lesser, Howard B Fleit, B M R Woloski, James B Bussel
• Journal: British journal of haematology (Br J Haematol) Vol. 124 Issue 4 Pg. 511-8 (Feb 2004) ISSN: 0007-1048 [Print] England
• PMID: 14984503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Cytokines
• Fc gamma receptor IIA
• Glucocorticoids
• Immunoglobulins, Intravenous
• Isoantibodies
• RHO(D) antibody
• Receptors, IgG
• Rh-Hr Blood-Group System
• Rho(D) Immune Globulin
• Prednisone

Topics

• Adolescent
• Adult
• Antigens, CD (genetics)
• Blood Platelets (immunology)
• Cytokines (biosynthesis)
• Female
• Glucocorticoids (therapeutic use)
• Humans
• Immunoglobulins, Intravenous (therapeutic use)
• Isoantibodies (adverse effects, therapeutic use)
• Male
• Middle Aged
• Phenotype
• Pilot Projects
• Platelet Count
• Polymorphism, Genetic
• Prednisone (therapeutic use)
• Purpura, Thrombocytopenic, Idiopathic (blood, immunology, therapy)
• Receptors, IgG (genetics)
• Rh-Hr Blood-Group System (blood)
• Rho(D) Immune Globulin