CIRCULATING IMMUNE COMPLEXES IN IMMUNE THROMBOCYTOPENIC PURPURA (ITP)

1982 ◽  
Vol 52 (4) ◽  
pp. 679-680 ◽  
Author(s):  
M. G. Ercilla ◽  
L. Borche ◽  
J. Vives ◽  
R. Castillo ◽  
A. Gelabert ◽  
...  
Keyword(s):  
Immune Complexes ◽  
Immune Thrombocytopenic Purpura ◽  
Circulating Immune Complexes ◽  
Thrombocytopenic Purpura

MECHANISMS OF IMMUNOLOGIC THROMBOCYTOPENIA IN INDIVIDUALS AT RISK FOR AIDS

1987 ◽  
Author(s):  
S Karpatkin
Keyword(s):  
Platelet Count ◽  
Immune Complex ◽  
Immune Complexes ◽  
Inverse Correlation ◽  
Circulating Immune Complexes ◽  
Response To Treatment ◽  
Thrombocytopenic Purpura ◽  
Atp Level ◽  
Healthy Control ◽  
Platelet Antibody

HIV-seropositive homosexuals, narcotic addicts and hemophiliacs develop a new syndrome of immunologic thrombocytopenic purpura (ITP) which is clinically indistinguishable from classic autoimmune thrombocytopenic purpura (ATP) with respect to increased megakaryocytes in the bone marrow, peripheral destruction of antibody-coated platelets, negative serology for SLE, response to treatment with prednisone and/or splenectomy. However, their platelet immunologic profiles are different.Homosexuals appear to have an immune complex-mediated mechanism: markedly elevated platelet-bound IgG and C3C4 (3.8 and 4.2-fold greater than classic ATP, respectively), elevated circulating immune complexes (3-fold greater than classic ATP), anti-F(ab')2 antibodies and absence of 7S anti-platelet IgG. There is no inverse correlation between platelet count and platelet-bound IgG or platelet-elutable anti-platelet antibody as in classic ATP.Hemophiliacs appear to have an autoimmune 7S IgG-mediated mechanism similar to classic ATP: inverse relationship betweem platelet count and platelet-bound IgG, r = 0.84, p less than 0.001, 26 df, anti-platelet reactive 7S IgG which reacts by its F(ab')2 domain, (reactive at 60-130 ug/ml compared to control IgG), platelet-elutable anti-platelet antibody. However, these patients also have elevated circulating immune complexes (2.4-fold classic ATP level) and markedly elevated platelet-bound IgG and C3C4 (3.4 and 1.2-fold classic ATP level, respectively). Anti-HIV antibody correlated with circulating immune complexes, r = 0.833, p less than 0.001.Narcotic addicts appear to have a mixture of both mechanisms (immune complex as well as autoimmune 7S IgG): markedly elevated platelet-bound IgG and C3C4 (2.6 and 2.4-fold classic ATP level, respectively), elevated circulating immune complexes (7.3-fold classic ATP level), anti-F(ab')2 antibodies, absence of an inverse correlation between platelet count and platelet-bound IgG. However, these patients do have specific 7S IgG anti-platelet antibody, which reacts by its F(ab')2 domain.F(ab')2antibodies were of the IgG class and correlated with circulating immune complex level. They react with autologous, homologous patient and healthy control F(ab')2 fragments. Some anti-F(ab')2 antibodies have broad reactivity, others are more limited. Some immune complexes were shown to contain HIV antibody. It is postulated that the immune complex platelet deposition noted with homosexual and narcotic addict thrombocytopenia may in part be due to HIV antibody complexes, some of which may exist as anti-antibody complexes.

scholarly journals Role of leuCAM integrins and complement in platelet-monocyte rosette formation induced by immune complexes of human immunodeficiency virus- type 1-immune thrombocytopenic purpura patients

Blood ◽  
1993 ◽  
Vol 81 (9) ◽  
pp. 2375-2380
Author(s):  
K Hymes ◽  
M Nardi ◽  
A Leaf ◽  
S Karpatkin
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Immune Complexes ◽  
Immune Thrombocytopenic Purpura ◽  
Rosette Formation ◽  
U937 Cells ◽  
Thrombocytopenic Purpura ◽  
Immunodeficiency Virus ◽  
Hiv 1

Patients with human immunodeficiency virus-type 1-immune thrombocytopenic purpura (HIV-1-ITP) have elevated polyethylene glycol (PEG)-precipitable immune complexes (ICs) composed of IgG, IgM, and complement that are threefold to sevenfold higher than in healthy control subjects. These complexes contain anti-F (ab')2 as well as anti- idiotype antibodies versus anti-HIV-1gp120. Because anti-F (ab')2 and anti-idiotype antibodies correlate with thrombocytopenia (r = .83 [J Clin Invest 77:1756, 1986] and r = .90 [J Clin Invest 89:356, 1992], respectively) we studied the binding of ICs to platelets and monocytes as well as their role in platelet-monocyte rosette formation. ICs bind to platelets in a saturation-dependent manner (optimum at 10 micrograms/mL; 0.5% of serum conc). Binding to platelets could not be inhibited with platelet saturating concentrations of aggregated IgG or with monoclonal antibody (MoAb) IV.3 versus FcR gamma II. Platelet binding could be inhibited with Fab anti-C3, anti-Clq, or anti-C4 by 57%, 40%, and 46% respectively, not with control Fab (P < .001). Monocytes from HIV-1-ITP patients form rosettes with normal platelets 16.8 +/- 5.2 rosettes/100 monocytes compared with 4.8 +/- 0.8 control monocytes plus normal platelets (P = .009). Gel-washed HIV-1-ITP platelets formed 19 +/- 2.0 rosettes with U937 cells compared to 6.3 +/- 1.0 for normal platelets (P = 0.001). Arming of U937 cells with HIV-1- ITP ICs (5 micrograms/mL) formed 36.7 +/- 2.5 rosettes compared with 10.6 +/- 1.2 for control ICs (P < .01). Rosetting of armed U937 cells could be inhibited with MoAbs versus the alpha chains of CD11a (LFA-1), 11b (Mac-1), or 11c (p150,95) by 67%, 70%, and 61%, respectively (P < .007), whereas binding of ICs to U937 cells was unaffected. Isotype- matched control as well as MoAbs versus antigens on U937 cells (CD13, CD33) or the anti-FcR gamma II receptor had no effect. However, Fab fragments of polyclonal anti-C3 inhibited rosette formation by 78% (P < .01); control Fab had no effect. Thus, platelet-monocyte rosette formation is not Fc dependent. It is complement receptor dependent and requires the cooperation of all three leuCAM integrins.

Variable Results With Plasma Exchange In Thrombotic Thrombocytopenic Purpura

1981 ◽  
Author(s):  
Toby L Simon
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Immune Complexes ◽  
Raji Cell ◽  
Disease Onset ◽  
Circulating Immune Complexes ◽  
Cardiac Complications ◽  
Thrombocytopenic Purpura ◽  
The Third ◽  
Fresh Frozen

The clinical efficacy of plasma exchange with fresh frozen single donor plasma in thrombotic thrombocytopenic purpura (TTP) was evaluated. Six patients with the classical findings of TTP, had plasmapheresis using the Haemonetics Model 30. Treatments were initiated daily. Two to three liters total exchanges were done; 1-1½ liters fresh frozen plasma were infused with each exchange. In five of the six cases, therapy was begun immediately after diagnosis. Steroids and antiplatelet agents were also used. Five of the patients were comatose when treatment was begun; the sixth had neurological symptoms of memory loss and aphasia with severe hemolytic anemia and thrombocytopenia. Circulating immune complex measurements were performed in all patients prior to treatment using the Clq and Raji cell assays.Three patients (2 in coma) responded to therapy. The two comatose patients required more than four daily treatments before beginning to respond (followed by four and six alternate day treatments, respectively). The third patient went into remission after four daily treatments. Three patients in coma died, two deteriorating after the first plasma exchange. The third, treated after a delay due to severe cardiac complications, subsequently died.The three responding patients were younger than the three who died. The two in coma who responded to therapy had a longer course of symptoms (suggesting disease onset prior to onset of coma) than the three who died. Circulating immune complexes by the Clq assay were negative in all six patients. The Raji cell assay was positive in one patient.Even severely ill comatose patients with TTP respond to plasma exchange, but aggressive, persistent therapy may be required before response is seen. More fulminant disease with rapid onset may fail to respond. Circulating immune complexes do not appear to mediate the disease process.

scholarly journals Role of leuCAM integrins and complement in platelet-monocyte rosette formation induced by immune complexes of human immunodeficiency virus- type 1-immune thrombocytopenic purpura patients

Blood ◽  
1993 ◽  
Vol 81 (9) ◽  
pp. 2375-2380 ◽  
Author(s):  
K Hymes ◽  
M Nardi ◽  
A Leaf ◽  
S Karpatkin
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Immune Complexes ◽  
Immune Thrombocytopenic Purpura ◽  
Rosette Formation ◽  
U937 Cells ◽  
Thrombocytopenic Purpura ◽  
Immunodeficiency Virus ◽  
Hiv 1

Abstract Patients with human immunodeficiency virus-type 1-immune thrombocytopenic purpura (HIV-1-ITP) have elevated polyethylene glycol (PEG)-precipitable immune complexes (ICs) composed of IgG, IgM, and complement that are threefold to sevenfold higher than in healthy control subjects. These complexes contain anti-F (ab')2 as well as anti- idiotype antibodies versus anti-HIV-1gp120. Because anti-F (ab')2 and anti-idiotype antibodies correlate with thrombocytopenia (r = .83 [J Clin Invest 77:1756, 1986] and r = .90 [J Clin Invest 89:356, 1992], respectively) we studied the binding of ICs to platelets and monocytes as well as their role in platelet-monocyte rosette formation. ICs bind to platelets in a saturation-dependent manner (optimum at 10 micrograms/mL; 0.5% of serum conc). Binding to platelets could not be inhibited with platelet saturating concentrations of aggregated IgG or with monoclonal antibody (MoAb) IV.3 versus FcR gamma II. Platelet binding could be inhibited with Fab anti-C3, anti-Clq, or anti-C4 by 57%, 40%, and 46% respectively, not with control Fab (P < .001). Monocytes from HIV-1-ITP patients form rosettes with normal platelets 16.8 +/- 5.2 rosettes/100 monocytes compared with 4.8 +/- 0.8 control monocytes plus normal platelets (P = .009). Gel-washed HIV-1-ITP platelets formed 19 +/- 2.0 rosettes with U937 cells compared to 6.3 +/- 1.0 for normal platelets (P = 0.001). Arming of U937 cells with HIV-1- ITP ICs (5 micrograms/mL) formed 36.7 +/- 2.5 rosettes compared with 10.6 +/- 1.2 for control ICs (P < .01). Rosetting of armed U937 cells could be inhibited with MoAbs versus the alpha chains of CD11a (LFA-1), 11b (Mac-1), or 11c (p150,95) by 67%, 70%, and 61%, respectively (P < .007), whereas binding of ICs to U937 cells was unaffected. Isotype- matched control as well as MoAbs versus antigens on U937 cells (CD13, CD33) or the anti-FcR gamma II receptor had no effect. However, Fab fragments of polyclonal anti-C3 inhibited rosette formation by 78% (P < .01); control Fab had no effect. Thus, platelet-monocyte rosette formation is not Fc dependent. It is complement receptor dependent and requires the cooperation of all three leuCAM integrins.

Platelet Antibodies and Circulating Immune Complexes in Thrombocytopenic Purpura

1979 ◽  
Author(s):  
J.L. Wautier ◽  
H. Kadeva ◽  
M.P. Wautier ◽  
B. Boizard ◽  
J.P. Caen
Keyword(s):  
Platelet Count ◽  
Immune Complexes ◽  
Circulating Immune Complexes ◽  
Normal Range ◽  
Thrombocytopenic Purpura ◽  
Platelet Antibodies ◽  
High Level

Forty five patients with thrombocytopenia (Platelet count below 105/ul) have been studied. Platelet associated IgG (Plat IgG) was determined by the method of Dixon et al (Normal range 38 ± 16 × 10-16g). Circulating immune complexes were detected by the [3H] Clq precipitation and the PEG precipitation techniques.The sera were also tested for their thrombo-agglutinating activity (Aggl.). The results were:The [3H] Clq test and the PEG test were significantly more frequently positive in patients with high level of Plat IgG.The thramboagglutination seems to be independant of the level of Plat IgG. It could be correlated with the presence of circulating immune complexes in the serum.

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