Concentrations Of Circulating Immune Complexes Research Articles

Features of immunological reactivity in Sami women

BACKGROUND: The Sami are a small group of indigenous people of the Russian Federation. The Sami have one of the lowest birth rates among all the peoples of the North of Russia. They often have more health problems than residents of other nationalities in the Murmansk region, due to a high incidence of acute respiratory infections. Extreme climatic and geographical conditions of the Arctic have a negative impact on immunological reactivity.
 AIM: To identify the features of immunological reactivity in Sami women.
 MATERIALS AND METHODS: Forty-nine practically healthy Sami women aged from 21 to 44 years living in the Lovozero Village in the Murmansk region were examined. A control group consisting of 50 practically healthy Russian women of the Arkhangelsk region of the same age range was used. The hemogram, phagocytic activity of neutrophils of peripheral venous blood, and the content of lymphocytes with CD3, CD4, CD8, and CD10 phenotypes were studied by indirect immunoperoxidase reaction (Sorbent, Moscow) and flow cytometry (Beckman Coulter Immunotech, France). Additionally, concentrations of IgM, IgG, IgA, sCD54, and sCD62L (Bender MedSystems, Austria) were determined by enzyme immunoassay, circulating immune complexes (CIC) were determined by the precipitation method. The total amount of microflora, cytogram, phagocytic activity of neutrophils, the sorption capacity of epithelial cells, the content of sIgA and CIC IgG were studied in the separated mucous membranes of the pharynx, intestines, and urine. For comparison between groups, the independent samples t-test or the nonparametric MannWhitney U-test was used depending on the distribution.
 RESULTS: In Sami women, the frequency of deficiency of phagocytic activity of blood neutrophils and mucosal secretions was higher than in the control group. Increased reactions of cell-mediated and antibody-dependent cytotoxicity of lymphocytes were recorded. The frequency of elevated concentrations of CIC was higher in the Sami women than in the control group. A remarkable feature of the Sami immune reactivity was high concentrations of IgA and IgM against a background of low IgG content.
 CONCLUSION: In Sami women, the percentage of actively phagocytic neutrophil granulocytes of peripheral venous blood and mucous membranes was lower than in the control. A distinctive feature of the immunoglobulin profile of the blood serum of Sami women was the low IgG content against the background of increased concentrations of CIC, including immunoglobulins of this class. Sami women had higher levels of leukocyte migration into mucosa-associated mucosal tissue, which was correlated with a decrease in the sorption capacity of epitheliocytes, phagocytic activity of neutrophils, and concentrations of secretory immunoglobulins.

СОСТОЯНИЕ ИММУННОЙ СИСТЕМЫ У ЖЕНЩИН ВО ВТОРОМ ТРИМЕСТРЕ БЕРЕМЕННОСТИ ПРИ ОБОСТРЕНИИ ХРОНИЧЕСКОГО ПРОСТОГО БРОНХИТА, ОБУСЛОВЛЕННОМ ГРИППОМ А(Н3N2)

The contents of anti-influenza antibodies, secretory immunoglobulin A (sIgA) and circulating immune complexes (CIC) were studied in 145 women in the second trimester of pregnancy. All women were divided into 5 groups. The first group included 30 women with the physiologic course of pregnancy. The second one consisted of 30 patients with chronic simple bronchitis (CB) in remission. The third group had 30 patients with the exacerbation of CB caused by influenza A(H3N2) (antibody titers were 1:16-1:64); the fourth group included 30 patients with CB, whose exacerbation was caused by influenza (antibody titers were 1:32-1:128). It was found out that in the second group there were higher concentrations of sIgA (7.34±0.37 mg/L) and CIC (0.191±0.006 units of optical density), than in the first group (5.86±0.43 mg/L, p<0.05 and 0.095±0.003 units of optical density, respectively, p<0.001). It can probably be explained by the stimulating influence of persistent virus infection on the local immunity and its important role in the development of autoimmune responses in pregnant women. In the fifth group unlike the third group there were registered minimal contents of sIgA: 3.86±0.25 mg/L (p<0.001) and maximal level of CIC: 0.232±0.006 units of optical density (p<0.001). The revealed changes suggested the decrease of local immune protection of airways and autoimmune alteration of a woman’s body caused by high intensity of humoral immunity to influenza virus A(H3N2) under exacerbation of chronic simple bronchitis in patients in the second trimester of gestation.

СОСТОЯНИЕ ИММУННОЙ СИСТЕМЫ У ЖЕНЩИН ВО ВТОРОМ ТРИМЕСТРЕ БЕРЕМЕННОСТИ ПРИ ОБОСТРЕНИИ ХРОНИЧЕСКОГО ПРОСТОГО БРОНХИТА, ОБУСЛОВЛЕННОМ ГРИППОМ А(Н3N2)

The contents of anti-influenza antibodies, secretory immunoglobulin A (sIgA) and circulating immune complexes (CIC) were studied in 145 women in the second trimester of pregnancy. All women were divided into 5 groups. The first group included 30 women with the physiologic course of pregnancy. The second one consisted of 30 patients with chronic simple bronchitis (CB) in remission. The third group had 30 patients with the exacerbation of CB caused by influenza A(H3N2) (antibody titers were 1:16-1:64); the fourth group included 30 patients with CB, whose exacerbation was caused by influenza (antibody titers were 1:32-1:128). It was found out that in the second group there were higher concentrations of sIgA (7.34±0.37 mg/L) and CIC (0.191±0.006 units of optical density), than in the first group (5.86±0.43 mg/L, p<0.05 and 0.095±0.003 units of optical density, respectively, p<0.001). It can probably be explained by the stimulating influence of persistent virus infection on the local immunity and its important role in the development of autoimmune responses in pregnant women. In the fifth group unlike the third group there were registered minimal contents of sIgA: 3.86±0.25 mg/L (p<0.001) and maximal level of CIC: 0.232±0.006 units of optical density (p<0.001). The revealed changes suggested the decrease of local immune protection of airways and autoimmune alteration of a woman’s body caused by high intensity of humoral immunity to influenza virus A(H3N2) under exacerbation of chronic simple bronchitis in patients in the second trimester of gestation.

Immune Complexes and Complement in Serum and Synovial Fluid of Rheumatoid Arthritis Patients

Immune Complexes and Complement in Serum and Synovial Fluid of Rheumatoid Arthritis PatientsRheumatoid arthritis (RA) is predominantly an intraarticular inflammatory and autoimmune disease that involves different autoantibodies and effector mechanisms. The aim of the study was to determine the utility of Circulating Immune Complexes (CIC) and complement components (C3c, C4) as possible markers for the disease activity in laboratory diagnostics. In a cross-section study 59 patients, according to the clinical criteria, were categorized into two groups: group with moderate (MA, n=24), and group with severe activity (SA, n=35) of RA. The concentration of CIC, C3c and C4 in sera (S) and synovial fluids (SF) was examined by an immunonephelometric method in both groups and compared with values in the control group (n=15) of patients with lesions of the menisci. Obtained results showed that there was no statistical significance in the values of C3c and C4, in both biological fluids, among all tested groups. Significant differences were found in the levels of CIC in both fluids, while testing the parameters (× ± SD, IU/mL) in the sera of groups with SA and MA of RA: 7.43 ± 13.40; 3.01 ± 2.92 (p<0.05) and SF: 13.47 ± 21.1, 5.33 ± 7.53 (p<0.001), respectively. These differences were higher between the group with SA and CG. Results for the concentrations of CIC were significantly higher in SF compared to sera: in the RA group with SA by 77% and group with MA by about 82%. These data could provide a confirmation of the hypothesis about local, intraarticular autoantibodies and subsequent CIC production. It can be concluded that the examination of CIC concentration in serum, and where it is possible in SF, is a useful marker of disease activity in RA patients, in contrast to the tested components of the complement. This statement does not exclude their consumption within immune effector mechanisms, but elicits the possibility that lower molecular fragments (C3d, C4d), as well as the novel activation products, could be better disease activity markers in RA patients.

Circulating immune complexes, immunoglobulin G, salivary proteins and salivary immunoglobulin A in patients with Sjögren's syndrome

Sjögren's syndrome (SS) is a chronic autoimmune disorder, with its major clinical manifestations resulting from changes in exocrine glands. The aim of this study was to evaluate serum concentrations of circulating immune complexes (CIC) and immunoglobulin G (IgG), and salivary proteins (SP) and salivary immunoglobulin A (slgA) in 40 patients with SS, and to correlate these values among themselves, as well as with the unstimulated salivary flow rate (USFR) and the duration of disease. The total of 40 patients were included in this research. CIC was determined using the solution of polyethylene glycol and IgG with the standard procedure of radial immunodiffusion. SP was investigated by the method of Lowry and slgA was separated from the whole saliva using the method of immune chromatography. The values of most of the studied parameters exceeded the normal range in a high degree: CIC 72.5%, IgG 70%, SP 80%. The concentrations of CIC were significantly higher in the patients with the duration of disease less than 10 years. With the decrease of USFR, the concentration of slgA and IgG were increased with statistical significance. The increased prevalence of abnormal values of CIC, IgG and SP indicate that the patients with SS have developed a higher level of immune reactivity. These results could be useful in diagnosis and disease activity monitoring.

Gliadin IgG antibodies and circulating immune complexes

Objective. Circulating immune complexes (CICs) in blood are associated with autoimmune-diseases such as systemic lupus erythematosus, immune complex glomerulonephritis, rheumatoid arthritis and vasculitis. However, slightly increased serum concentrations of such CICs are sometimes also found in healthy individuals. The objective of the current study was to assess whether food antigens could play a role in the formation of CICs. Material and methods. A total of 352 (265 F, 87 M), so far, healthy individuals were tested for CICs containing C1q and immunoglobulin G (IgG) as well as for gliadin IgG antibodies using the ELISA technique. Additionally, fructose and lactose malabsorption was assessed using hydrogen breath tests. Results. In our study, 15.3% (54/352) of the patients presented with elevated CIC concentrations (above 50 µg/ml) and 6.5% (23/352) of the study population were positive for gliadin IgG antibodies (above 20 U/ml). CIC concentration levels were significantly higher in the group with elevated gliadin IgG antibodies (CIC median: 49.0 µg/ml) compared with the group with normal levels of gliadin IgG antibodies (CIC median: 30.0 µg/ml; Mann-Whitney U-test, U=1992; p <0.001). As expected, there was no difference in CIC concentrations (Mann-Whitney U-test, U=6106; p=0.783) and gliadin IgG (Mann-Whitney U-test, U=3761; p=0.411) between patients in the fructose or lactose malabsorber groups and the subjects without malabsorption. Conclusions. The results of this study indicate that certain food antigens (e.g. gluten) could play a role in the formation of CICs. An association between CICs and fructose or lactose malabsorption seems to be improbable.

Circulating immune complexes induced by food proteins implicated in precocious myocardial infarction

BACKGROUND. Circulating immune complexes (CIC) are frequently found in postinfarction patients. The constituents of these CIC are mostly unknown.AIM. The objective of the current study was to assess whether CIC containing alimentary proteins and antibodies against these proteins are implicated in precocious myocardial infarction (MI).METHODS. Seventy-six survivors (67 men and 9 women, mean age 39 years) of a first MI before the age of 45 years were enrolled in this study. Two control groups were included. One group consisted of age-matched, randomly selected, population-based healthy individuals, 79 men and 11 women, without features of coronary heart disease. An additional control group was used only for the determination of serum antibodies against some of the alimentary proteins and consisted of 139 healthy blood donors, 95 men and 44 women, with a mean age of 42 years. Sucrose density gradient centrifugation, gel filtration and precipitation by polyethylene glycol were used for the isolation of CIC, and enzyme-linked immunosorbent assay (ELISA) was used to measure the immunoglobulin levels and specific antibodies against alimentary proteins in both sera and isolated CIC. Sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis and Western blotting were used to determine alimentary proteins in the CIC.RESULTS. Alimentary antigens/antibodies were present in immune complex form in seven out of 14 (50%) postinfarction patients who had persistent high concentrations of CIC, the latter constituting 18% of the entire group. Antibodies of the IgG isotype predominated. A rise in CIC, signs of activation of the classical complement pathway, and a rise in plasma concentrations of von Willebrand factor antigen (vWFAg) were evident within 1 week in four patients subjected to a 2-week elimination diet followed by a single challenge with cow's milk.CONCLUSION. This study suggests that dietary proteins occasionally give rise to persistent CIC, which may predispose to MI at a young age.

Complement haemolytic activity, circulating immune complexes and the morbidity of sickle cell anaemia.

The aim of this study was to find out if the number of crises and complications of sickle cell anaemia (SCA) relate to complement function, or the levels of circulating immune complexes (CIC), complement factor B (Bf), C3 and C4. In 73 steady-state HbSS patients and 50 HbAA control subjects, we determined the haemolytic activity of the alternative pathway of complement (AP50), of the classical pathway (CH50); and the serum concentrations of Bf, C3, C4 and CIC. By clinical examination of each patient and review of the medical records, we determined the number of complications of SCA which had occurred and the mean number of crises per year over a minimum period of 3 years. The mean+/-SD AP50 for the patients (14+/-2 U/ml) was significantly lower than the control value of 16+/-3 U/ml (p<0.001). AP50 had a significant inverse correlation with the number of crises (r=-0.30, p<0.02). Mean+/-SD CIC in patients (0.45+/-0.38 g/l) was significantly higher than in controls: 0.24+/-0.15 g/l (p<0.002). CIC showed a significant direct correlation with the number of complications of SCA (r=+/-0.28, p<0.02). Mean+/-SD Bf in SCA patients (0.19+/-0.09) was higher than in controls (0.17+/-0.05). The difference reached marginal statistical significance (p=0.049). SCA patients and controls had no significant differences in CH50, C3 and C4. These parameters and Bf did not correlate with either the number of crises or complications. The mechanisms underlying the correlations observed in this study are yet to be fully elucidated.

Circulating immune complexes and renal function in canine leishmaniasis.

A third component of complement (C3) capture enzyme-linked immunosorbent assay was used to determine the concentration of IgG circulating immune complexes (CIC) in 91 dogs with naturally acquired leishmania infection and in a control group of 24 healthy dogs. Results were expressed as a percentage of a reference standard. Mean concentrations of CIC were significantly (P < 0.001) higher in leishmania-infected dogs (228.725 +/- 14.283%) than in controls (74.542 +/- 12.614%). An increase in CIC concentration was found in 57.1% of the leishmania-infected dogs. No significant differences could be recorded in CIC levels between males and females in either group. Infected dogs showing hypercreatininemia rendered a statistically significant (P < 0.030) higher serum CIC concentration than sick dogs with normal creatininemia. When hypercreatininemia (> or = 1.30 mg/dl) was used as an indicator for CIC increase, the positive predictive value obtained was 0.9 indicating that renal function impairment was associated with high serum CIC concentration in 90% of the infected dogs.

Immunological variables and acute-phase reactants in patients with ankylosing spondylitis (Bechterew's syndrome) and their relatives.

Serum and EDTA blood from 120 patients with ankylosing spondylitis (Bechterew's syndrome) and serum from 138 first-degree relatives of patients and from 42 adult blood donors were investigated. Increased serum concentrations of IgA and IgG and complement factors C3 and C4 were found in total groups of HLA B27-positive male or female patients compared with controls or relatives. The men had higher serum concentration of IgA and complement factors than the women, whereas IgM concentration was higher in the women. These patterns were found in controls, in relatives and in patients. Increased concentrations of IgA and of C4 were characteristic of all patients whereas IgG and IgM and C3 concentrations were likewise elevated in patients with peripheral joint arthritis/arthropathy. Increased levels of circulating immune complexes (CIC) were associated with peripheral joint arthritis and were strongly correlated with IgG or CRP concentrations in serum. Total haemolytic complement activity in serum was negatively correlated with concentrations of CIC or CRP indicating complement activation in patients with such complexes. No differences in serum concentrations of Ig or complement factor concentrations were seen between HLA B27-positive and negative relatives with normal sacro-iliac joints or between relatives and controls. Strong mutual correlations were seen among IgG, IgM, complement factors, CRP, SAA, sedimentation rate and alpha 2-macroglobulin. When the present findings were combined with our previous results it turned out that AS, and psoriasis with or without arthropathy, and acute anterior uveitis (AAU) in combination with sacro-iliitis, may be described as IgA-related conditions and that increased serum C4 was related to sacro-iliitis in all these disorders.

Circulating immune complexes and their possible relevance to other immunological parameters in Guatemalan onchocerciasis.

Circulating immune complexes (CIC) were demonstrated in sera of Guatemalan patients with onchocerciasis by Raji cell radioimmunoassay. 44% of patients but none of controls had abnormally high concentrations of CIC in their sera. The increased concentrations of CIC were found more frequently in patients with lower density of microfilariae in their skin biopsies. Patients with higher concentrations of CIC appeared to have increased titers of serum antibodies to Onchocerca volvulus. A depression of both humoral immune response to tetanus toxoid and delayed hypersensitivity reaction to PPD were found in patients with onchocerciasis. CIC may be involved in modulation of the immune response in onchocerciasis.

Characterization of Immune Complexes in Serum by Adsorption on Staphylococcal Protein A: Model Studies and Application to Sera of Rats Bearing a Gross Virus-Induced Lymphoma

Abstract A procedure to isolate soluble IgG-containing immune complexes from serum was developed, which combined Sephadex G-150 filtration with affinity chromatography on Staphylococcal protein A-Sepharose. The effectiveness of the method was shown by isolating model immune complexes of 125I bovine plasma albumin (BPA) and antibody to BPA from serum. Functionally intact antibody and antigen were recovered from these complexes by chromatography on Sephadex G-150 at low pH and the degree of purification was demonstrated by NaDod.SO4 polyacrylamide slab gel electrophoresis (PAGE) and autoradiography of the immune complexes and their components. Application of these methods to a Gross virus-induced rat lymphoma model tested their potential for characterizing naturally occurring circulating immune complexes (CIC). Sera from these animals were shown by Raji cell immunofluorescence to contain high concentrations of CIC 15 to 21 days after tumor inoculation. CIC could be isolated from these sera by the procedures developed for model complexes. Analysis by PAGE indicated that they contained primarily a protein of apparent m.w. 79,000 complexed with IgG. This putative antigen component of CIC (79,000 daltons) reacted with a rabbit antiserum directed against the murine leukemia virus (MuLV) envelope glycoprotein, gp70. Techniques using protein A affinity chromatography may also be applicable to characterization of both antigen and antibody components of CIC in human diseases including cancer.