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.
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.
Division of Hematology/Oncology, Department of Pediatrics, New York Presbyterian Hospital - Weill Medical College of Cornell University, New York, NY 10021, USA. nicholacooper@yahoo.com
Nichola
N
Cooper
Nancy M
NM
Heddle
Masja
M
Haas
Marion E
ME
Reid
Martin L
ML
Lesser
Howard B
HB
Fleit
B M R
BM
Woloski
James B
JB
Bussel
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D001792:Blood Platelets / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007518:Isoantibodies / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010865:Pilot Projects; D010976:Platelet Count; D011110:Polymorphism, Genetic; D011241:Prednisone / Q000627:therapeutic use; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000276:immunology / Q000628:therapy*; D017452:Receptors, IgG / Q000235:genetics; D012204:Rh-Hr Blood-Group System / Q000097:blood; D018029:Rho(D) Immune Globulin
D015703:Antigens, CD; D016207:Cytokines; C080568:Fc gamma receptor IIA; D005938:Glucocorticoids; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; C061961:RHO(D) antibody; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; D011241:Prednisone