Detection of drug specific circulating immune complexes from in vivo cynomolgus monkey serum samples

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.

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Detection of Circulating Immune Complexes in the Sera of Rabbits with Experimental Syphilis: Possible Role in Immunoregulation

Infection and Immunity ◽

10.1128/iai.29.2.575-582.1980 ◽

1980 ◽

Vol 29 (2) ◽

pp. 575-582

Author(s):

Robert E. Baughn ◽

Kenneth S. K. Tung ◽

Daniel M. Musher

Keyword(s):

Immune Complexes ◽

Proteolytic Enzymes ◽

Suppressor Cell ◽

Suppressive Effect ◽

Circulating Immune Complexes ◽

Time Period ◽

Infected Cells ◽

Disseminated Disease

The in vivo and in vitro immunoglobulin G plaque-forming cell responses to sheep erythrocytes (SRBC) are nearly obliterated during disseminated syphilitic infection (3 to 8 weeks post-intravenous injection) in rabbits. Splenic and lymph node cells obtained from infected rabbits during this time period were capable of suppressing the normal in vitro responses of uninfected, SRBC-primed cells. Cell-free washings of cells from infected animals were also suppressive. This finding coupled with the fact that treatment of infected cells with proteolytic enzymes abrogated the suppressive effect constitute arguments against involvement of a specific suppressor cell population. The incidence of elevated levels of circulating immune complexes in the sera of rabbits with disseminated disease was also significantly different from that of uninfected controls or infected rabbits before the onset or after the regression of lesions. When added to cultures of lymphocytes from uninfected, SRBC-sensitized rabbits, sera containing complexes caused dose-related suppression of the in vitro immunoglobulin responses. Unlike immune complexes, no correlation was found between the presence of mucopolysaccharide materials and the stage of infection or the ability of serum to suppress the immunoglobulin responses to SRBC.

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The in vivo effect of thymic factor (thymostimulin) administration on circulating immune complexes and serum lysozyme levels in untreated Hodgkin's disease patients.

Journal of Clinical Oncology ◽

10.1200/jco.1983.1.2.117 ◽

1983 ◽

Vol 1 (2) ◽

pp. 117-125 ◽

Cited By ~ 4

Author(s):

A Velardi ◽

F Spinozzi ◽

P Rambotti ◽

A Tabilio ◽

A Losito ◽

...

Keyword(s):

Immune Complexes ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Serum Levels ◽

Mean Value ◽

Circulating Immune Complexes ◽

Calf Thymus ◽

Serum Lysozyme ◽

Thymic Factor

The in vivo effect of a calf thymus extract, thymostimulin, on the levels of circulating immune complexes (CIC) and serum lysozyme was evaluated in 32 patients with untreated Hodgkin's disease. Using the platelet aggregation test for detecting CICs, 12 patients (37%) had positive titers before thymostimulin treatment; 3 patients (10%) remained positive following therapy. Serum levels of Clq-binding immune complexes were evaluated (greater than 24.5 micrograms/ml) in 8 patients prior to thymostimulin therapy (mean value: 42.3 micrograms/ml); 3 patients continued to have elevated levels after treatment. Serum lysozyme levels for Hodgkin's patients was similar to control values (10.6 vs. 8.3 micrograms/ml); however, the Hodgkin's patients with initially elevated CICs had a lower serum lysozyme level than patients with initially normal CICs (12.9 vs. 7.3, p less than 0.02). Thymostimulin increased serum lysozyme levels in the Hodgkin's patients in whom the CICs were initially elevated (7.3 vs. 10.4 micrograms/ml, p less than 0.05). These data suggest that thymostimulin exerts an effect on the nonspecific immune system of Hodgkin's disease patients.

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Atherogenesis in human - clinical aspects of circulating immune complexes

Clinical Medicine (Russian Journal) ◽

10.18821/0023-2149-2016-94-5-325-332 ◽

2016 ◽

Vol 94 (5) ◽

pp. 325-332

Author(s):

Yanina D. Babintseva ◽

A. M. Sergeeva ◽

V. P. Karagodin ◽

A. N. Orekhov

Keyword(s):

Immune Complexes ◽

Neutral Lipids ◽

Diagnostic Yield ◽

Circulating Immune Complexes ◽

Clinical Aspects ◽

Healthy Human ◽

Coronary Artery Atherosclerosis ◽

Atherosclerotic Process ◽

Aortic Intima

It has been suggested that circulating immune complexes containing low density lipoproteins (LDL-CIC) play a role in atherogenesis and are involved in the formation of early atherosclerotic lesions. The complexes, as well as anti-LDL antibody were found in the blood of patients with atherosclerotic process in various cardiovascular diseases, well as in the blood of animals with experimentally modulated atherosclerosis. One can assume that the presence anti-LDL antibodies in blood is a result of an immune response that is induced by modification of lipoproteins. LDL-CIC differ from native LDL in many aspects. They have much lower levels of sialic acid, a smaller diameter and a higher density electronegativity than native LDL. The fraction of the LDL-CIC in serum is an important manifestation of the atherosclerotic process. LDL-CIC, unlike the native LDL is able to induce intracellular accumulation of neutral lipids, especially esterified cholesterol in cell cultures obtained from healthy human aortic intima and macrophages in culture. After removal of the LDL-CIC, the serum of CHD-patients loses its atherogenic properties. The titer of the LDL-CIC in the blood serum significantly correlate with the progression of atherosclerosis and in vivo has the highest diagnostic yield of measured among other lipid parameters. Increasing CIC- cholesterol could also increase the risk of coronary artery atherosclerosis.

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In Vivo Interactions of Autoantibodies to Factor VIII with the Factor VIII Complex

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657243 ◽

1982 ◽

Vol 48 (02) ◽

pp. 142-145 ◽

Cited By ~ 2

Author(s):

J P Allain ◽

M P Croissant ◽

D Lerolle ◽

L Houbouyan ◽

M Zuzel ◽

...

Keyword(s):

Elderly Patients ◽

Factor Viii ◽

Immunosuppressive Therapy ◽

Immune Complexes ◽

Circulating Immune Complexes ◽

Factor Viii Related Antigen ◽

Coagulant Activity ◽

Ristocetin Cofactor ◽

Sequential Measurements

SummaryTwo non-haemophilic elderly patients who had developed autoantibodies to factor VIII were studied over a period of 9 months to 5 years. Sequential measurements of antibody to factor VIII (anti-VIII: C), factor VIII coagulant activity (VIII: C), factor VIII coagulant antigen (VIII: CAg), factor VIII-related antigen (VIIIR: Ag), and factor VIII ristocetin cofactor (VIII: WF) were performed. Before treatment, low VIII: C, norlnal or increased VIII: CAg and high VIIIR: Ag levels were found and were indicative of the presence of circulating immune complexes. Immunosuppressive therapy induced progressive correction of VIII: C and VIIIR: Ag values. High levels of VIII: CAg subsided in the patient who relapsed. It is suggested that antibodies to factor VIII bind and remove VIII: C from the circulation thereby inducing an increased synthesis of VIII: CAg which may be associated with an augmented release or production of VIIIR: Ag.

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Circulating Immune Complexes in Human Malignant Melanoma

Tumori Journal ◽

10.1177/030089168206800603 ◽

1982 ◽

Vol 68 (6) ◽

pp. 469-472 ◽

Cited By ~ 1

Author(s):

Raffaele D'Amelio ◽

Brian Cooke ◽

John R. Hobbs

Keyword(s):

Malignant Melanoma ◽

Immune Complexes ◽

Solid Phase ◽

Serum Antibody ◽

Specific Protein ◽

Circulating Immune Complexes ◽

Serum Samples ◽

Human Malignant Melanoma ◽

Third Stage ◽

Solid Phase Assay

The sera from 34 patients with malignant melanoma at various clinical stages of the disease were examined for the presence of circulating immune complexes (CIC) by the C1q solid-phase assay. Their urine and serum samples had been previously examined for the presence of an urinary melanoma-specific protein (MSP) and the corresponding serum antibody. Low levels of CIC (only in the third stage of the disease) and no positive correlation with the presence of MSP were found. The discordance between our and other author's data stresses again the fact that the different laboratory methods for CIC evaluation reveal in a different way the various CIC populations occurring in several diseases.

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Low Density Lipoprotein-Containing Circulating Immune Complexes: Role in Atherosclerosis and Diagnostic Value

BioMed Research International ◽

10.1155/2014/205697 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 16

Author(s):

Igor A. Sobenin ◽

Jukka T. Salonen ◽

Andrey V. Zhelankin ◽

Alexandra A. Melnichenko ◽

Jari Kaikkonen ◽

...

Keyword(s):

Immune Complexes ◽

Neutral Lipids ◽

Low Density Lipoprotein ◽

Atherosclerotic Lesion ◽

Density Lipoprotein ◽

Diagnostic Value ◽

Circulating Immune Complexes ◽

Low Density ◽

Sialic Acid Content

It has been suggested that low density lipoprotein-containing circulating immune complexes (LDL-CIC) play a role in atherogenesis and are involved in the formation of early atherosclerotic lesion. These complexes, as well as anti-LDL autoantibodies, have been found in the blood and in the atherosclerotic lesions of patients with different cardiovascular diseases, as well as in the blood of animals with experimental atherosclerosis. It can be suggested that the presence of anti-LDL antibodies in the blood is a result of immune response induced by lipoprotein modification. LDL-CIC differs from native LDL in many aspects. It has much lower sialic acid content, smaller diameter, and higher density and is more electronegative than native LDL. Fraction of LDL-CICs is fundamental to the serum atherogenicity manifested at the cellular level. LDL-CIC, unlike native LDL, is able to induce intracellular accumulation of neutral lipids, especially esterified cholesterol, in cells cultured from uninvolved human aortic intima and in macrophage cultures. After removal of LDL-CIC, the CHD patient’s sera lose their atherogenic properties. Titer of LDL-CIC in blood serum significantly correlates with progression of atherosclerosis in humanin vivoand has the highest diagnostic value among other measured serum lipid parameters. Elevated CIC-cholesterol might well be a possible risk factor of coronary atherosclerosis.

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Extracorporeal removal of immune complexes: Preparation and characterization of immobilized bovine conglutinin

The International Journal of Artificial Organs ◽

10.1177/039139888000300111 ◽

1980 ◽

Vol 3 (1) ◽

pp. 42-49

Author(s):

A.M. Pitt ◽

D.S. Terman ◽

C.K. Colton ◽

B.A. Solomon

Keyword(s):

Serum Albumin ◽

Immune Complex ◽

Immune Complexes ◽

Ex Vivo ◽

Circulating Immune Complexes ◽

Protein Solutions ◽

Polymeric Beads ◽

C 30

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.

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The characteristics of serum circulating immune complexes of patients with atopic asthma with different severity degree

Kazan medical journal ◽

10.17816/kmj1934 ◽

2013 ◽

Vol 94 (5) ◽

pp. 744-748 ◽

Cited By ~ 1

Author(s):

Y V Skibo ◽

N S Kurmaeva ◽

V N Tsibulkina ◽

I G Mustafin ◽

Z I Abramova

Keyword(s):

Severe Asthma ◽

Bronchial Asthma ◽

Immune Complexes ◽

Wave Length ◽

Molecular Complexes ◽

Electrophoretic Analysis ◽

Circulating Immune Complexes ◽

Atopic Asthma ◽

Control Group ◽

Serum Samples

Aim. To evaluate the serum level of pathogenic circulating immune complexes in patients with mild and severe atopic bronchial asthma. Methods. Serum samples of patients with atopic asthma of mild persistent (30 patients) and severe persistent (20 patients) forms were analyzed. The control group consisted of 15 healthy volunteers. To detect the giant, large, medium and small-sized serum immune complexes, 3, 3.5, 4 and 7% polyethyleneglycol-6000 solutions were used. For quantitative evaluation of the immune complexes we measured the ultraviolet optical density at 280 nm wave length. To separate the immune complexes from immunoglobulin, Protein-G-Sepharose was used. Determination of the protein composition of circulating immune complexes was performed by electrophoresis in 8% polyacrylamide gel. Results. The concentration of immune complexes was increased in patients with bronchial asthma compared to healthy donors. Small and medium-sized immune complexes were prevailing, their concentrations correlated with the severity of asthma. Large, medium and small-sized immune complexes participated in immunopathological reactions in patients with both mild and severe asthma, with immune complexes pathogenicity coefficient significantly increased depending on the severity of the disease. Electrophoretic analysis of circulating immune complexes has shown the presence of proteins with molecular weight of 60 kDa in the complexes of all sizes. In the severe asthma group, an antigen fraction with a molecular mass of 36 kDa within the small-sized molecular complexes was revealed. Conclusion. The observed increase of small and medium-sized circulating immune complexes serum levels in patients with bronchial asthma may be an indicator of of these patients predisposal to autoimmune reactions development.

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Homosexual men with thrombocytopenia have impaired reticuloendothelial system Fc receptor-specific clearance

Blood ◽

10.1182/blood.v70.2.392.bloodjournal702392 ◽

1987 ◽

Vol 70 (2) ◽

pp. 392-395 ◽

Cited By ~ 1

Author(s):

BS Bender ◽

TC Quinn ◽

JL Spivak

Keyword(s):

Immune Complexes ◽

Fc Receptor ◽

Red Cells ◽

Circulating Immune Complexes ◽

Homosexual Men ◽

Severe Thrombocytopenia ◽

Half Time ◽

Igg Antibody ◽

Platelet Counts

Classic immune thrombocytopenia purpura (ITP) occurs predominantly in women and is associated with either normal or impaired Fc receptor- mediated clearance of antibody-coated cells. Recently, an increasing incidence of thrombocytopenia has been observed in homosexual men, but whether Fc receptor-mediated clearance of antibody-coated cells is normal or impaired in these men is unknown. To study this question, we measured the in vivo clearance of anti-Rho(D) IgG antibody-sensitized 51Cr-labeled autologous red cells in five homosexual men with thrombocytopenia without an evident cause. All five had antibodies to human immunodeficiency virus, and four had circulating immune complexes as determined by a Clq-binding assay. Two of the men tested also had an increase in platelet-associated IgG. In the four homosexual men with platelet counts of 20,000/microL or less, the clearance half-time of IgG-sensitized red cells was prolonged (mean, 106 minutes; range, 72 to 140 minutes) as compared with the clearance of such cells in five hematologically normal men (mean, 39 minutes; range 30 to 50 minutes; P less than .005). One homosexual man with a platelet count of 81,000/microL had a normal clearance half-time (30 minutes). Three patients whose platelet counts increased after corticosteroid therapy were restudied. In all three, the clearance of antibody-coated cells was shortened and returned to normal in the one patient who had achieved a complete remission. No correlation was observed between the presence of platelet-associated IgG or circulating immune complexes and the clearance half-time. These data indicate that severe thrombocytopenia occurring in homosexual men as in some patients with classic ITP is associated with defective in vivo Fc receptor-mediated clearance of antibody-coated cells.

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