MECHANISMS OF IMMUNOLOGIC THROMBOCYTOPENIA IN INDIVIDUALS AT RISK FOR AIDS

1987 ◽  
Author(s):  
S Karpatkin

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.

1979 ◽  
Author(s):  
J.L. Wautier ◽  
H. Kadeva ◽  
M.P. Wautier ◽  
B. Boizard ◽  
J.P. Caen

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.


1979 ◽  
Author(s):  
J Wautier ◽  
H Kadeva ◽  
M Wautier ◽  
B Boizard ◽  
J Caen

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 x 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 thromboagglutination seems to be independant of the level of Plat IgG. It could be correlated with the presence of circulating immune complexes in the serum.


2021 ◽  
Vol 9 (4) ◽  
pp. 712
Author(s):  
Cristina Cacheiro-Llaguno ◽  
Nuria Parody ◽  
Marta R. Escutia ◽  
Jerónimo Carnés

During canine visceral leishmaniasis (CanL), due to Leishmania infantum (L. infantum), uncontrolled infection leads to a strong humoral immune response. As a consequence of the production of high antibody levels and the prolonged presence of parasite antigens, circulating immune complexes (CIC) are formed, which can be deposited in certain organs and tissues, inducing vasculitis, uveitis, dermatitis and especially glomerulonephritis and renal failure. A method to detect CIC and quantify their levels in serum samples from dogs infected with L. infantum has been recently described. It allowed demonstration of a correlation between CIC levels and disease severity. Thus, CIC measurement may be useful for diagnosis, assessment of disease progression and monitoring response to treatment. This is an interesting finding, considering that there remains an urgent need for identification of novel biomarkers to achieve a correct diagnosis and for optimal disease staging of dogs suffering from Leishmania infection. The objective of the present review is to shed light on the role of CIC in CanL, as well as to highlight their potential use not only as diagnostic and prognostic biomarkers but also as a valuable tool in vaccine development and new immunotherapy strategies to prevent or control disease outcome.


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

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3288-3288 ◽  
Author(s):  
Robert Makar ◽  
Olga S. Zhukov ◽  
Mervyn A. Sahud ◽  
David J. Kuter

Abstract Abstract 3288 INTRODUCTION: Thrombopoietin (TPO) is the major regulator of platelet production. In prior clinical studies, thrombopoietin levels have been shown to vary inversely with circulating platelet mass and with the rate of platelet production. Thus, TPO levels may help distinguish between the various disorders of thrombocytopenia. In addition, the introduction of TPO agonists has created an interest in predicting the response of patients to these agents. Determining TPO levels may help predict such treatment responses. METHODS: Sera from 121 patients with a history of abnormal platelet counts were tested using a novel, commercially available ELISA assay that measures TPO levels. The TPO assay detected TPO levels as low as 7 pg/mL and was linear for levels up to 2000 pg/mL. The coefficient of variation ranged from 27% near the lower limit of detection to 9% at a TPO concentration of 669 pg/mL. The reference range for TPO was established in serum samples from 118 apparently healthy individuals (58 males and 60 females) and was 7–99 pg/mL. The Wilcoxon test was used to compare continuous variables and the Fisher's exact test was used to compare categorical variables. RESULTS: The patient population included 40 patients with a consumptive thrombocytopenia (38 with primary or secondary immune thrombocytopenic purpura (ITP), 2 with thrombotic thrombocytopenic purpura), 34 patients with myeloproliferative disorders (23 with essential thrombocytosis, 9 with polycythemia vera, 2 with an ill-defined myeloproliferative disorder), and 47 patients with hypoproliferative thrombocytopenia (29 with chemotherapy-related thrombocytopenia, 19 with primary or secondary bone marrow failure syndromes). Among the 38 patients with ITP, 11 were taking TPO agonists (9 on romiplostim, 2 on eltrombopag), 19 were taking immunomodulatory agents (16 on steroids alone or in combination with other therapies, 2 on azathioprine, 1 on danazol), and 12 were off ITP-specific therapy when the TPO level was measured. 9 out of 38 (24%) patients with ITP had undergone splenectomy and/or been previously treated with rituximab. The median serum TPO level in patients with consumptive thrombocytopenia was 64.5 pg/mL (interquartile range, 48.5–97.5 pg/mL) and the corresponding median platelet count was 68,000/μL (interquartile range, 27,000–144,500) (Figure). While patients with myeloproliferative disorders had similar TPO levels [median 87.0 pg/mL (38.0–125.5)], their platelet counts were significantly higher than those of patients with consumptive thrombocytopenia [median 549,500/mL (431,250–693,000] (P <0.0001). Contrastingly, comparable platelet counts [median 61,000/μL (31,000–118,000)] were observed among patients with hypoproliferative thrombocytopenia, but serum TPO levels were significantly higher than those of patients with consumptive thrombocytopenia [844 pg/mL (409.5–1551.5), P <0.0001]. Among 22 evaluable patients meeting diagnostic criteria for primary or secondary ITP who had taken a TPO agonist for at least 1 month, serum TPO levels appeared to predict responsiveness to the drug. A clinical response to a TPO agonist was defined as achieving a platelet count ≥50,000/μL after starting the drug and maintaining it at or above that count in ≥50% of subsequent complete blood counts from initiation until discontinuation of the drug, loss to follow-up, or 6 months had passed, whichever was longest, without the need for recurrent rescue therapy. Whereas 14 out of 16 (88%) ITP patients with a TPO level <99 pg/mL met our definition for a clinical response to treatment with a TPO agonist, only 1 out of 6 patients (17%) with a TPO level >99 pg/mL responded (P <0.005 for the difference in clinical response to TPO agents.) CONCLUSIONS: TPO levels may have diagnostic utility in discriminating between patients with hypoproliferative and consumptive thrombocytopenia. High TPO levels among patients with ITP may predict a poor clinical response to treatment with TPO agonists. Further studies are required to confirm these data. Disclosures: Zhukov: Quest Diagnostics: Employment. Sahud:Quest Diagnostics: Employment. Kuter:Quest Diagnostics: Consultancy, Research Funding.


1980 ◽  
Vol 26 (3) ◽  
pp. 396-402
Author(s):  
R H Kelly ◽  
M A Scholl ◽  
V S Harvey ◽  
A G Devenyi

Abstract On binding of antibody to antigen an immune complex is formed that has a net surface charge different from that of either of the two components. This, together with clonal restriction of the antibody response, gives rise to distinctive patterns that are readily apparent in stained agarose gels after routine zone electrophoresis. Most circulating immune complexes appear as a rectangular pattern, with well-defined edges, located in the gamma-region. The identity of the material responsible for these patterns has been established by three different experimental approaches: analysis of tetanus/anti-tetanus complexes formed in vitro, analysis of sera from rabbits with experimental immune complex disease, and analysis of human type II and type III cryoglobulins. Studies of reproducibility, interfering substances, and correlation with other assays for detecting immune complexes indicate that zone electrophoresis in agarose gel is a sensitive, highly specific technique for immune complex detection, of potential value as a screening tool.


1996 ◽  
Vol 76 (02) ◽  
pp. 156-160 ◽  
Author(s):  
Naoaki Ichikawa ◽  
Fumihiro Ishida ◽  
Shigetaka Shimodaira ◽  
Tomoyuki Tahara ◽  
Takashi Kato ◽  
...  

SummaryTo clarify the regulatory mechanism of thrombopoietin (TPO, c-Mpl ligand) in chronic thrombocytopenic conditions, we determined TPO levels in the sera of patients with aplastic anaemia (AA; n = 26) and idiopathic thrombocytopenic purpura (ITP; n = 32) by an enzyme-linked immunosorbent assay. Despite a similarity in platelet counts, serum TPO levels in the AA group were markedly higher than those in the ITP group: 20.41 ± 9.71 f mol/ml (mean ± SD) and 1.66 ± 0.55 f mol/ml, respectively, both of which were significantly elevated compared to normal subjects (n = 41; 1.22 ± 0.37). In both groups, serum TPO level showed an inverse correlation with the platelet count. We determined the megakaryocyte volume using bone marrow clot section and found that it was markedly small in the AA group; while in the ITP group it was augmented with a correlation to serum TPO level. Our findings suggest that TPO levels may be regulated not only by platelets but also megakaryocytes in AA and ITP.


1993 ◽  
Vol 11 (12) ◽  
pp. 2427-2433 ◽  
Author(s):  
D R Vlock ◽  
S P Schantz ◽  
S G Fisher ◽  
H E Savage ◽  
T E Carey ◽  
...  

PURPOSE To evaluate the correlation between the presence and titer of host-derived antibody reactivity, circulating immune complexes, and clinical course and prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS Serum samples, obtained from untreated patients with squamous cell carcinoma of the larynx entered onto a multiinstitutional trial, were evaluated for the presence of elevated circulating immune complexes (221 patients) and host-derived antibody directed against two SCCHN cell lines (107 patients). RESULTS Patients had significantly elevated levels of circulating immune complexes as measured by C1q binding compared with normal controls. Patients with higher levels of circulating immune complexes were less likely to respond to chemotherapy. No correlations were noted between immune complex levels and stage of disease, nodal status, site of disease, recurrence, or survival. Evaluation of native antibody titers for their relationship to clinical correlates showed no statistically significant associations. In sera subjected to immune complex dissociation, patients with moderately or poorly differentiated tumors had significantly higher antibody titers when compared with patients with well-differentiated tumors. Because marked variation in the increase of antibody titers following immune complex dissociation was noted, the ratio of immune complex-dissociated to native antibody titer was examined. Patients with a high ratio had a lower proportion of complete and partial responses to chemotherapy. CONCLUSION Our results support the conclusion that the formation of tumor-associated immune complexes in patients with SCCHN is associated with a decreased response to chemotherapy.


1980 ◽  
Vol 3 (1) ◽  
pp. 42-49
Author(s):  
A.M. Pitt ◽  
D.S. Terman ◽  
C.K. Colton ◽  
B.A. Solomon

The binding of immune complexes to immobilized bovine conglutinin (K) was studied in order to develop an ex vivo immunoadsorbent system for the removal of circulating immune complexes. K was immobilized to the surface of solid, polymeric beads of two different sizes (1–3 um and 38–63 um diameter) which were activated with N-hydroxysuccinimide ester groups. The binding of both a model immune complex, aggregated human globulin (AHG) and an actual immune complex, bovine serum albumin (BSA): anti-BSA, to the immobilized K were determined utilizing both batch and flow conditions. The binding of AHG occurred rapidly (within 15 min.) at 37°C and additional binding was attained by using a subsequent low temperature incubation (37°C, 30 min., followed by 4°C, 18 hrs.). Uptake of AHG from solution was 2.6 g/g immobilized K. The binding of the 125I-AHG to immobilized K was found to be linear with concentration over the range of 20-2,000 ug AHG/ml tested. Similarly, the binding of BSA:anti-BSA complexes in solution to immobilized K was 0.16 ug 125I-BSA:anti-BSA/ug immobilized K. Significant amounts of the bound AHG were found to be released nonspecifically in the presence of buffered protein solutions, including human serum albumin (HSA) and BSA, while bound BSA:anti-BSA complexes were not released by similar treatments. Effluents of solution perfused over immobilized K showed no toxicity upon intravenous infusion into mice. These studies suggest that K may be immobilized on a biocompatible solid support and in this state retains functional capacity to extract immune complexes from solution. Hence, this may represent a promising system for use as an extracorporeal immunoadsorbent to remove circulating immune complexes in vivo.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4655-4655
Author(s):  
Hemasri Takala ◽  
John A. Davis ◽  
Kenneth A. Schwartz

Abstract Introduction:Confirmatory laboratory assays for heparin induced thrombocytopenia (HIT) can broadly be classified as functional which have high specificity and rely on activation of platelets by the platelet factor 4 (PF4)-heparin-IgG immune complex or as immune based assays that are relatively more sensitive. At the time when the clinician is evaluating heparin as a cause of thrombocytopenia the 4 "T" criteria are helpful. However, an increase in the patient's platelet count after the heparin has been stopped is critical for confirmation of the diagnosis. Methods: We developed a variation of a previously described technique (Newman Thromb Haemost 1998;80:292) and used clinical criteria as the standard for comparison to evaluate the assay. Radiolabeled 125-I-PF4 is incorporated into the immune complex of PF-4-heparin-immunoglobulin and the amount of radiolabeled immune complex is measured after binding to staphylococcal A protein sepharose (Staph-A). The hospitalized subjects medical record was reviewed to: measure a 4 "T" score, to determine if the patient's platelet count increased after heparin was stopped and to exclude other plausible causes of thrombocytopenia. Aim: The assay relies on the binding of the heparin immune complexes to Staph A. Staph A preferentially binds to larger as compared to smaller immune complexes and the larger complexes produce a greater degree of F(c) mediated platelet activation when compared with the smaller complexes. This suggests the hypothesis that a Staph A based assay will have have better specificity and sensitivity than the currently used methodologies. Results: 28 patient samples were evaluated. True positives were observed in 4 hospital patients and 4 known positives. 19 were true negatives and included 7 from hospital patients and 12 from thrombocytopenic patients who were not treated with heparin. 1 sample was negative in our assay, and was judged as false negative. Concordance between the radiolabeled PF-4 assay and the commercial PF-4 assay was observed in all the 28 patients. Conclusions: To date when judged using clinical criteria, the radiolabeled PF-4 assay correctly distinguished true positives and true negatives in 27 of the 28 samples. Disclosures No relevant conflicts of interest to declare.


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