scholarly journals Alloimmune neonatal neutropenia due to an antibody to the neutrophil Fc- gamma receptor III with maternal deficiency of CD16 antigen

Blood ◽  
1991 ◽  
Vol 77 (7) ◽  
pp. 1572-1580 ◽  
Author(s):  
DF Stroncek ◽  
KM Skubitz ◽  
LB Plachta ◽  
RA Shankar ◽  
ME Clay ◽  
...  
Keyword(s):  
Healthy Person ◽  
Maternal Serum ◽  
Maternal Antibody ◽  
Fc Gamma Receptor ◽  
Glycosyl Phosphatidylinositol ◽  
Gamma Receptor ◽  
Rabbit Polyclonal Antibody ◽  
Specific Antigens ◽  
Neonatal Neutropenia ◽  
Cd16 Antigen

Abstract Antibodies to the neutrophil-specific antigens NA1 and NA2 are associated with alloimmune neonatal neutropenia (ANN), autoimmune neutropenia of childhood, and acute pulmonary transfusion reactions. These antigens have been found to be located on the neutrophil Fc-gamma receptor III (FcRIII). The mother of a child with ANN was found to lack both NA antigens and to produce an antibody that reacted with all normal neutrophils tested. We used maternal antibody and a CD16 monoclonal antibody (MoAb) that has specificity for FcRIII to immunoblot and immunoprecipitate neutrophil membranes of various NA phenotypes. Both antibodies immunoblotted an approximately 40- to 70-Kd glycoprotein (GP) on NA1, NA2-positive membrane, an approximately 40- to 55-Kd GP on NA1-homozygous membranes, and an approximately 55- to 70- Kd GP on NA2-homozygous membranes. Both antibodies also immunoprecipitated a 50- to 80-Kd GP from NA1, NA2-positive cells, a 50- to 60-Kd GP from NA1-homozygous cells, and a 55- to 80-Kd GP from NA2- homozygous cells. To further examine the specificity of the maternal antibody, sequential immunoprecipitation studies were performed using maternal antisera and a CD16 MoAb. After extracts of 125I surface- labeled neutrophils were precleared with maternal serum, CD16 MoAbs no longer immunoprecipitated any GP. Neither the CD16 MoAb nor a rabbit polyclonal antibody specific for FcRIII detected any GP in maternal neutrophil membranes by immunoblotting. Neutrophil FcRIII is a glycosyl- phosphatidylinositol anchored membrane GP as is decay accelerating factor and both are absent from neutrophils of patients with paroxysmal nocturnal hemoglobinuria (PNH). Maternal neutrophil membranes were probed with antibody specific for DAF and an 80-Kd GP was detected. This woman also has had no clinical evidence of PNH. These studies provide further evidence that the NA1 and NA2 antigens are on FcRIII and identify a healthy person whose neutrophils lack not only the neutrophil specific antigens NA1 and NA2 but multiple other epitopes of FcRIII and, therefore, likely lack FcRIII entirely.

Alloimmune neonatal neutropenia due to an antibody to the neutrophil Fc- gamma receptor III with maternal deficiency of CD16 antigen

Blood ◽  
1991 ◽  
Vol 77 (7) ◽  
pp. 1572-1580 ◽  
Author(s):  
DF Stroncek ◽  
KM Skubitz ◽  
LB Plachta ◽  
RA Shankar ◽  
ME Clay ◽  
...  
Keyword(s):  
Healthy Person ◽  
Maternal Serum ◽  
Maternal Antibody ◽  
Fc Gamma Receptor ◽  
Glycosyl Phosphatidylinositol ◽  
Gamma Receptor ◽  
Rabbit Polyclonal Antibody ◽  
Specific Antigens ◽  
Neonatal Neutropenia ◽  
Cd16 Antigen

Antibodies to the neutrophil-specific antigens NA1 and NA2 are associated with alloimmune neonatal neutropenia (ANN), autoimmune neutropenia of childhood, and acute pulmonary transfusion reactions. These antigens have been found to be located on the neutrophil Fc-gamma receptor III (FcRIII). The mother of a child with ANN was found to lack both NA antigens and to produce an antibody that reacted with all normal neutrophils tested. We used maternal antibody and a CD16 monoclonal antibody (MoAb) that has specificity for FcRIII to immunoblot and immunoprecipitate neutrophil membranes of various NA phenotypes. Both antibodies immunoblotted an approximately 40- to 70-Kd glycoprotein (GP) on NA1, NA2-positive membrane, an approximately 40- to 55-Kd GP on NA1-homozygous membranes, and an approximately 55- to 70- Kd GP on NA2-homozygous membranes. Both antibodies also immunoprecipitated a 50- to 80-Kd GP from NA1, NA2-positive cells, a 50- to 60-Kd GP from NA1-homozygous cells, and a 55- to 80-Kd GP from NA2- homozygous cells. To further examine the specificity of the maternal antibody, sequential immunoprecipitation studies were performed using maternal antisera and a CD16 MoAb. After extracts of 125I surface- labeled neutrophils were precleared with maternal serum, CD16 MoAbs no longer immunoprecipitated any GP. Neither the CD16 MoAb nor a rabbit polyclonal antibody specific for FcRIII detected any GP in maternal neutrophil membranes by immunoblotting. Neutrophil FcRIII is a glycosyl- phosphatidylinositol anchored membrane GP as is decay accelerating factor and both are absent from neutrophils of patients with paroxysmal nocturnal hemoglobinuria (PNH). Maternal neutrophil membranes were probed with antibody specific for DAF and an 80-Kd GP was detected. This woman also has had no clinical evidence of PNH. These studies provide further evidence that the NA1 and NA2 antigens are on FcRIII and identify a healthy person whose neutrophils lack not only the neutrophil specific antigens NA1 and NA2 but multiple other epitopes of FcRIII and, therefore, likely lack FcRIII entirely.

scholarly journals A Case of Neonatal Neutropenia Due to Anti-Fc Gamma Receptor IIIb Isoantibodies Treated with Recombinant Human Granulocyte Colony Stimulating Factor

2009 ◽  
Vol 2009 ◽  
pp. 1-4 ◽  
Author(s):  
Maja Tomicic ◽  
Mirta Starcevic ◽  
Vanja Zach ◽  
Jasna Bingulac-Popovic ◽  
Zeljka Hundric-Haspl
Keyword(s):  
Clinical Status ◽  
Severe Neutropenia ◽  
Therapy Discontinuation ◽  
Fc Gamma Receptor ◽  
Granulocyte Count ◽  
Transient Nature ◽  
Gamma Receptor ◽  
Specific Antigens ◽  
Neonatal Neutropenia ◽  
Stimulating Factor

Alloimmunization to granulocyte-specific antigens can occur during pregnancy. Maternal antibodies of IgG class can cross the placenta to result in alloimmune neonatal neutropenia. Antibodies to human neutrophil antigens anti-HNA-1a, HNA-1b, and HNA-2a have been most commonly reported to cause alloimmune neonatal neutropenia. Isoantibodies to Fc gamma RIIIb (CD16) if mother is a HNA-null phenotype are rarely involved in neonatal neutropenia. We report on a case of severe neutropenia (440 neutrophils/μL) due to anti-Fc gamma RIIIb (CD16) isoimmunization. On day 14 severe omphalitis developed, which was treated for 7 days by an antibiotic (ceftriaxone in a dose of 80 mg/kg/d) according to umbilical swab finding. Omphalitis persisted for 10 days in spite of antibiotic therapy and only resolved upon the introduction of rhG-CSF therapy. Therapy with rh-GCSF proved efficient and led to neutrophil count increase to 1970/μL and cure of omphalitis. However, therapeutic effect on granulocyte count was of transient nature, as granulocyte count fell to 760 n/μL on day 4 of therapy discontinuation. Neutropenia persisted for 2 months. The newborn was discharged from the hospital on day 26 with normal clinical status with clinical and laboratory control examinations at 2-week intervals. No additional infections were observed during the course of neutropenia.

scholarly journals Prominent Indomethacin-Induced Enteropathy in Fcgriib Defi-cient lupus Mice: An Impact of Macrophage Responses and Immune Deposition in Gut

2021 ◽  
Vol 22 (3) ◽  
pp. 1377
Author(s):  
Thansita Bhunyakarnjanarat ◽  
Kanyarat Udompornpitak ◽  
Wilasinee Saisorn ◽  
Bhumdhanin Chantraprapawat ◽  
Peerapat Visitchanakun ◽  
...  
Keyword(s):  
Cytokine Production ◽  
High Dose ◽  
Flux Analysis ◽  
Wild Type ◽  
Fc Gamma Receptor ◽  
Serum Cytokines ◽  
Extracellular Flux ◽  
Gamma Receptor ◽  
Gut Leakage ◽  
Gastrointestinal Permeability

A high dose of NSAIDs, a common analgesic, might induce lupus activity through several NSAIDs adverse effects including gastrointestinal permeability defect (gut leakage) and endotoxemia. Indomethacin (25 mg/day) was orally administered for 7 days in 24-wk-old Fc gamma receptor IIb deficient (FcgRIIb-/-) mice, an asymptomatic lupus model (increased anti-dsDNA without lupus nephritis), and age-matched wild-type (WT) mice. Severity of indomethacin-induced enteropathy in FcgRIIb-/- mice was higher than WT mice as demonstrated by survival analysis, intestinal injury (histology, immune-deposition, and intestinal cytokines), gut leakage (FITC-dextran assay and endotoxemia), serum cytokines, and lupus characteristics (anti-dsDNA, renal injury, and proteinuria). Prominent responses of FcgRIIb-/- macrophages toward lipopolysaccharide (LPS) compared to WT cells due to the expression of only activating-FcgRs without inhibitory-FcgRIIb were demonstrated. Extracellular flux analysis indicated the greater mitochondria activity (increased respiratory capacity and respiratory reserve) in FcgRIIb-/- macrophages with a concordant decrease in glycolysis activity when compared to WT cells. In conclusion, gut leakage-induced endotoxemia is more severe in indomethacin-administered FcgRIIb-/- mice than WT, possibly due to the enhanced indomethacin toxicity from lupus-induced intestinal immune-deposition. Due to a lack of inhibitory-FcgRIIb expression, mitochondrial function, and cytokine production of FcgRIIb-/- macrophages were more prominent than WT cells. Hence, lupus disease-activation from NSAIDs-enteropathy-induced gut leakage is possible.

scholarly journals Murine autoimmune hemolytic anemia resulting from Fc gamma receptor- mediated erythrophagocytosis: protection by erythropoietin but not by interleukin-3, and aggravation by granulocyte-macrophage colony- stimulating factor

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2960-2964 ◽  
Author(s):  
T Berney ◽  
T Shibata ◽  
R Merino ◽  
Y Chicheportiche ◽  
V Kindler ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Colony Stimulating Factor ◽  
Fc Gamma Receptor ◽  
Interleukin 3 ◽  
Gamma Receptor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract We have evaluated the therapeutic activity of recombinant erythropoietin (rEpo), in comparison with recombinant interleukin-3 (rIL-3) and granulocyte-macrophage colony-stimulating factor (rGM-CSF), on a lethal form of acute anemia resulting from Fc gamma receptor- mediated erythrophagocytosis after a single injection (500 micrograms) of a monoclonal anti-mouse red blood cell (MRBC) autoantibody. Continuous perfusion of rEpo before the administration of anti-MRBC monoclonal antibody completely protected animals from death due to anemia with a rapid recovery, while no protection was obtained by rIL-3 perfusion. In contrast, rGM-CSF perfusion markedly accelerated the progression of anemia and the mortality rate. This was found to result from an enhancement of erythrophagocytosis by Kupffer cells and by polymorphonuclear leukocytes that massively infiltrated the livers. Even after the injection of a sublethal dose (100 micrograms) of anti- MRBC monoclonal antibody, rGM-CSF-perfused mice died of a severe form of acute anemia. Furthermore, we have shown that rEpo was able to treat efficiently a spontaneous form of autoimmune hemolytic anemia in a majority of anemic NZB mice, whereas rGM-CSF markedly aggravated anemia. This may be of clinical importance, because GM-CSF administration could exhibit an adverse effect in some autoimmune diseases that involve autoimmune anemia.

scholarly journals Fc-Gamma Receptor Polymorphisms Predispose Patients to Infectious Complications After Liver Transplantation

2015 ◽  
Vol 16 (2) ◽  
pp. 625-633 ◽  
Author(s):  
S. Shimizu ◽  
Y. Tanaka ◽  
H. Tazawa ◽  
S. Verma ◽  
T. Onoe ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Infectious Complications ◽  
Fc Gamma Receptor ◽  
Gamma Receptor
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