Circulating Immune Complexes Levels Research Articles

Prevalence of circulating immune complexes in anti-HCV reactive chronic renal failure patients

Chronic hepatitis C has been shown to be associated with a series of autoimmune diseases. HCV-anti HCV circulating immune complexes (CIC) may be involved in tissue damage. To assess the role of HCV-anti HCV immune complexes mediated renal immunopathogenesis, frequency of raised CIC-C1q was studied in anti-HCV reactive chronic renal failure (CRF) patients. The study group was comprised of 103 patients, of which 70 patients were CRF and for the comparison CIC levels in 33 viral hepatitis patients without renal problems were also checked. Among them, 43 CRF patients and 18 viral hepatitis patients were found to be anti-HCV antibody reactive. Elevated CIC-C1q levels (>50 μg eq ml −1) were seen in 68% of anti-HCV reactive CRF patients in comparison with 19% of the anti-HCV non-reactive CRF patients. While 22% of the anti-HCV reactive and 20% of the anti-HCV non-reactive viral hepatitis patients had CIC-C1q levels >50 μg eq ml −1. The elevated levels of CIC in anti-HCV reactive CRF patients suggests the possible role of immune complex mediated immunopathogenesis.

The Presence and Clearance of Immune Complexes in the Untreated Generalised Psoriasis

Psoriasis is a hyperproliferative inflammatory disease and 70% of patients develop a chronic plaque form of the disease. The pathogenesis of psoriasis is not known but evidence exists that changes in micro vascular occur. There are micro vascular abnormalities in the capillaries which display a multilayer basement membrane with fenestration. Study of involved synovium in psoriatic arthritis reveals endothelial cell swelling, thickening of the vessel walls and inflammatory cell infiltration. Investigation on expression of CD35 molecules that clear the immune complexes were carried out in this study. CD35 is single chain glycoprotein (MW160–240 kD) and is located on the long arm of the chromosome 1. FACScan was used as laser flow cytometer. Initially 40 blood samples from normal individuals, 35 untreated Lupus Erythematosus Systemic and 35 Rheumatoid arthritis patients were studied as controls for reference values of CD35, Circulating immune Complexes (CIC), Complement C3 & C4. Next 34 patients suffering from psoriasis were studied for, Circulating immune Complexes (CIC), Complement C3 & C4. Comparison of these results with those of reference values normal ranges showed significant increase of CIC (P<0.05) and decrease of CD35 (P<0.001). Where as, the complement component levels C3 (P>0.05) and C4(P>0.05) indicates werenot significantly altered. This study shows that the decrease in expression of CD35 on Red blood cells in psoriasis patients is more crucial than C3 and C4 levels. Thus decrease of CD35 molecule in psoriasis may cause increased levels of CIC in patients' sera and promotion of inflammatory responses.

Effects of Cascade Apheresis in Patients with Psoriasis and Psoriatic Arthropathy

Eight patients with psoriasis, all with skin scales and 7 with disabling psoriatic arthritis, were subjected to cascade apheresis starting with three treatments per week for 2 weeks, followed by one treatment a week, comprising ten treatments in all. Six out of 7 patients (86%) with arthropathy and 3 out of 8 patients (38%) with scales experienced a beneficial effect. There was a large drop in the levels of circulating immune complexes (CIC) due to the treatment, and the removal of CIC was followed by reduced inflammatory activity in skin lesions and joints as evaluated by pain, morning stiffness, grip strength, plaque score, and PASI index. However, there was no correlation between the level of CIC, disease activity, or treatment response. From the present results it is concluded that CIC may play a more significant role regarding psoriatic arthropathy than in skin manifestations, and apheresis may be beneficial in patients not responding to conventional therapy.

Immunoglobulins and circulating immune complexes in nephrotic syndrome.

Serum immunoglobulin (IgG, IgA and IgM) levels were measured in 40 children with idiopathic nephrotic syndrome and 20 healthy controls. Significantly decreased IgG (P < 0.001), normal IgA and increased IgM (P < 0.05), averaging 92 per cent, 99 per cent and 104 per cent of normal mean, respectively, were observed in active nephrotic syndrome (ANS). The mean immunoglobulin levels did not differ significantly among different subgroups of ANS cases. In remission, a significant increase in IgG (P < 0.01), a decrease in IgA (P < 0.05) and in IgM (P < 0.01) levels were found in comparison to their corresponding ANS values. Their concentrations were significantly abnormal also when compared with controls. The circulating immune complexes (CIC), detected by polyethylene glycol (PEG) per cent index, demonstrated that overall mean serum level was significantly higher (P < 0.01, 168 per cent of normal) in ANS patients. Among different subgroups, the mean level was significantly elevated (P < 0.001, 205 per cent of normal) only in relapsing nephrotic syndrome cases. Thus, the abnormal levels of immunoglobulins were found both in active as well as in remission stage of the disease, while elevated levels of CIC were seen only in patients with relapse.

Immune Complex Mediated Vasculitis in Hepatitis B and C Infections and the Effect of Antiviral Therapy

Case reports of seven patients with vasculitis and past or present viral hepatitis infection are presented, including studies on circulating immune complexes (CICs) and cryoglobulins by sucrose density gradient centrifugation or gel filtration, before and after antiviral therapy. Three patients had unusual vasculitic manifestations: coronary, large vessel, and muscle vasculitis, respectively. All the patients had high levels of CICs by the above methods, but only two had CICs by the C1q binding and conglutinin methods. The CICs/cryoglobulins contained HBV and/or HCV antibodies, antigens, and genome. The concentration of hepatitis antibodies in immune complex form was severalfold higher than in the free form in serum. In one patient, the HBs antigen was present only in the CICs and in another, only hepatitis antibodies (no antigen/genome) were present in the serum or the cryoglobulins. With antiviral therapy, six patients went into longlasting remissions. There was a temporal relationship between the regression of the vasculitic lesions and the decline in the levels of CICs/cryoglobulins.

Serum Concentration of Circulating Immune Complexes in Cats Infected with Feline Immunodeficiency Virus Detected by Immune Adherence Hemagglutination Method.

Circulating immune complexes (CIC) in the sera from 45 clinically healthy cats and 23 feline immunodeficiency virus (FIV) infected cats were measured by an immune adherence hemagglutination (IAHA) method. The level of CIC in the sera from FIV sera-negative healthy cats was 47.2 +/- 47.3 micrograms/ml when expressed as heat aggregated feline IgG equivalent value in IAHA reactivity. On the other hand, the level of CIC in the sera from FIV infected cats was 757.4 +/- 910.5 micrograms/ml, which was significantly higher than that of healthy ones. CIC levels of 11 symptomatic cats and 12 asymptomatic ones were 837.8 +/- 1138.2 micrograms/ml and 683.0 +/- 684.2 micrograms/ml, respectively. These results showed that IAHA method was reliable to detect CIC levels of cat sera and that CIC levels in the sera of cats infected with FIV were higher than those of healthy ones.

Fibronectin and circulating immune complexes in Behçet's disease

Being a high-molecular-weight adhesive glycoprotein, fibronectin (Fn) is suggested to be a component of immune complexes and may participate in the clearance of immune complexes. In Behçet's disease (BD), a multisystem disorder of unknown etiology, immune complexes have been shown to be deposited in affected tissue during disease activity, suggesting an immune mechanism. This study investigates the relationship between Fn and circulating immune complexes (CIC) and evaluates the changes in the levels of Fn and CIC along with disease activity. In 63 patients (31 active, 32 inactive) with BD, plasma Fn and serum CIC, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and the third and fourth components of the complement system (C3, C4) were studied. The mean ESR, CRP, C3 and C4 levels of active BD patients were found to be significantly higher than those of the inactive BD patient group. Although the mean Fn and CIC levels of BD patients were not significantly different from those of the healthy control group, Fn and CIC values of active BD patients were significantly lower than in the inactive group. Moreover, no significant correlation was observed among Fn levels and ESR, CRP, C3, C4 and CIC levels in BD patients. The result of this study suggest that the variation in Fn concentration is independent of the acute-phase response. The lack of relationship between the CIC and Fn concentrations indicates that IC deposition in the vessel wall is independent of the CIC levels. In order to determine the exact roles of Fn and IC, further studies in tissue specimens are required.

Increased IgM Class Circulating Immune Complexes in Acute Hepatitis A Virus Infection

For assessing the role of circulating immune complexes (CIC) in acute hepatitis A, IgM- and IgG-specific CIC were determined, by C1q and conglutinin (K) assays, in 205 patients with acute hepatitis A and 60 healthy controls. The concentration of each type of CIC in patients was higher than healthy controls (P= 0.0001). CIC was a common feature of acute hepatitis A with 95.6% of cases having at least one abnormal test result. The prevalence of abnormal IgM class CIC was significantly higher than IgG class CIC. There were significantly inverse correlations between levels of IgM class CIC and interval between onset of symptoms and patient presentation. The prevalence of abnormal IgM CIC was higher in patients with higher alanine aminotransferase (P= 0.001) and patients with jaundice (P= 0.0002). In conclusion, IgM class CIC is the predominant CIC in acute hepatitis A and correlated with disease activity. CIC may play a role in the pathogenesis of acute hepatitis A.

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.

Detection of circulating immune complexes in dog sera by immune adherence hemagglutination method.

Circulating immune complexes (CIC) in the sera from 102 clinically healthy dogs and from 16 Dirofilaria immitis (D. immitis) infected dogs were measured by the immune adherence hemagglutination (IAHA) method. The level of CIC in the sera from healthy dogs was 28.2 +/- 29.1 micrograms/ml. There was no significant difference in the levels of CIC regarding sexes or ages. On the other hand, the level of CIC in the sera from D. immitis infected dogs was 230.3 +/- 117.1 micrograms/ml, which was significantly (p < 0.01) higher than that of healthy dogs. The results of this study confirm that IAHA method is one of the reliable means of detecting and/or diagnosing immune complex mediated diseases in dogs.

Antigen/antibody content of circulating immune complexes in HIV-infected patients

Dual infection with HIV and hepatitis B virus (HBV) is not an uncommon feature. Immunity impairment due to HIV infection can be the cause of a higher rate of HBV replication with less intensive liver damage and less effective immune response to HBV. Many HIV-infected patients have an elevated level of circulating immune complexes (CIC) in serum, throughout all stages of illness evolution. The aim of our study was to estimate p24 and HBsAg content of CIC in dually infected patients, and the prevalence of major classes of complexed antibodies (IgM and IgG). We examined 146 samples of sera from 105 HIV positive patients of the Institute for Infectious and Tropical Diseases during 1992 and 1993. On those sera we performed p24Ag and HbsAg detection, with and without prior dissociation of CIC, we determined serum level of CIC and immunoglobulin classes IgM and IgG level in sera and in polyethilenglycol (PEG) precipitates of sera. Acid dissociation of immune complexes revealed a high proportion of HIV antigen positive sera in all stages of HIV disease progression. HbsAg in serum of HIV positive patients was also found coupled in immune complexes much more frequently than in the HIV negative control group. In many instances both antigens were simultaneously found coupled in CIC. Immune complexes detected have been shown to contain both IgM and IgG immunoglobulins, while IgM antibodies were associated to immune complexes in higher proportion than IgG, compared to total serum immunoglobulins.

Identification of Acute-Phase Proteins (APP) in Circulating Immune Complexes (CIC) in Esophageal Cancer Patients' Sera

The occurrence of increased circulating immune complexes (CIC) in sera of patients with esophageal cancer and their usefulness for diagnosis and prognosis have not been demonstrated. Circulating acute-phase proteins (APP) related to esophageal cancer have been described but without any association with CIC. This is a study to measure CIC, C-reactive protein (CRP), and alpha 1-acidic glycoprotein (AAG) in pretreatment esophageal cancer sera and to analyze the presence of both APP associated with these CIC. Increased CIC levels were found in 57% of sera from esophageal cancer patients; elevated CRP was detected in 87% and AAG in 47%. Western blot analysis showed the presence of CRP and AAG in CIC-derived fractions. We conclude that: (1) CIC, CRP, and AAG are elevated in esophageal cancer sera; (2) they may be considered possible useful clinical parameters in pretreatment esophageal cancer patients; (3) these APPs appear in CIC precipitates and may possibly be involved in their composition.

Circulating immune complexes in various forms of Behçet's disease.

The etiology of Behçet's disease (BD) is uncertain but there is strong evidence that the immune system is implicated in its pathogenesis. We assessed circulating immune complexes (CIC) in peripheral blood of 34 patients with BD, forming eight clinical groups, using a laser nephelometer to obtain more insight in the pathogenesis of different clinical forms of BD. Twenty healthy controls and eight patients with recurrent oral ulcerations were also included in the study. Levels of CIC were significantly higher in patients (1.83 +/- 0.93 microgram/mL) than in controls (0.84 +/- 0.51 microgram/mL; P < 0.001). High titers were found in the groups of patients with erythema nodosum (3.14 +/- 0.44 microgram/mL), neurologic manifestations (2.9 +/- 0.58 microgram/mL), and ocular manifestations (2.34 +/- 0.93 microgram/mL). Compared to patients with recurrent oral ulcerations (1.91 +/- 0.77 microgram/mL), the mean value of CIC in patients with BD did not differ significantly, but the groups of patients having erythema nodosum, positive pathergy, and neurologic manifestations had significantly higher levels (P < 0.05) and the group of patients at the mild end of the spectrum (group 8) had a significantly lower level (1.09 +/- 0.41 microgram/mL) (P < 0.05). Only the groups having erythema nodosum, positive pathergy, and neurologic manifestations had significantly higher levels of CIC when compared to other groups lacking these clinical features, whereas group 8 had a significantly lower level (P < 0.05) when compared to all other groups. Our results show that CIC may be involved in the pathogenesis of BD, especially in those clinical forms of the disease with erythema nodosum, neurologic manifestations, and ocular manifestations. Patients at the mild end of the BD spectrum do not show significant changes in CIC levels compared to healthy control subjects. We can, therefore, suggest that in BD CIC may be implicated more in the pathogenesis of some features than of others.

The role of circulating immune complexes; antinuclear and rheumatoid factor autoantibodies in aging in Nigerians

The concentrations of circulating immune complexes (CICs) have been measured in healthy Nigerians aged 6–95 years by the polyethylene glycol precipitation technique. The prevalence of antinuclear antibodies (ANAs) and rheumatoid factors (RFs) was also studied in these Nigerians. Significant positive correlation between CIC concentrations and age was observed; but no sex-related differences. Weakly reacting ANAs plus age-associated increase in ANA prevalence were noted. Positivity rate for RFs detected by latex agglutination was significantly higher ( χ 2 = 3.948; P < 0.05) in old subjects (> 65 years of age; 9.4%) compared to younger ones (< 65 years of age; 2.7%). Semi-quantitative Rose-Waaler technique gave 22% RF seropositivity rate in subjects with age > 65 years. The age groups 46–65 years, 26–45 years, and 6–25 years had 13.5%, 7.5% and 2.5% positivity rates, respectively. There was significant positive correlation between RF concentrations and CIC levels; and increased prevalence of RF autoantibody in subjects with CIC (10%) compared with those without (4.7%). Four percent of subjects with CICs, and none of those without, were positive for ANAs. Autoantibodies may contribute to increased prevalence of CICs in old individuals.

Correlation of IgG Fc receptors on granulocytes with serum immune complex level in systemic lupus erythematosus.

The expression of Fc gamma RI, Fc gamma RII and Fc gamma RIII on granulocytes in the blood of patients with systemic lupus erythematosus was investigated. The relationship between the receptor expression and serum immune complex (IC) concentration was analysed. The decrease in mean fluorescence intensity of both Fc gamma RII and Fc gamma RIII of patients' granulocytes stained by specific monoclonal antibodies (using MoAb IV.3 and 3G8) was significant. The detected decrease of Fc gamma RII was inversely correlated with the high circulating IC level in patients' sera.

Circulating immune complexes in intracranial neoplasms.

The levels of circulating immune complexes (CIC) were assayed in the sera of 109 patients with intracranial space occupying lesions. The CIC levels were significantly increased in all the brain tumours. After treatment, the CIC levels were still significantly increased when compared to the controls but showed no change when compared to their respective pre-operative values. Further, no change was observed in the CIC levels between the malignant and benign tumour case. Moreover, in brain tumours, 90% of the CIC precipitate consisted of IgG. However, the CIC levels fail to prognosticate the process of the disease in these patients.

Increased IgM-Containing Circulating Immune Complexes in Patients Co-infected with Hepatitis C and Hepatitis B

To assess the role of circulating immune complexes (CIC) in chronic hepatitis C virus (HCV) infection, the relative frequency of CIC was determined in 60 patients with chronic hepatitis C alone, 19 patients co-infected with hepatitis B and C, 15 asymptomatic HCV carriers, and 54 healthy controls. Levels of CIC were determined with immunoglobulin-specific C1q-binding and conglutinin (K)-binding immune complex assays. Although there was no statistical difference in the levels of each type of CIC between asymptomatic HCV carriers and healthy controls, elevated levels of CIC containing IgM and IgG were common in patients with chronic HCV infection. Compared to patients with hepatitis C alone, patients co-infected with hepatitis B and C have a higher frequency of abnormal IgM-containing CIC and significantly higher levels of IgM-containing CIC. CIC levels in patients with chronic active hepatitis were significantly higher than those in patients with chronic lobular hepatitis or chronic persistent hepatitis. In conclusion, although CIC containing IgM and IgG were common in patients with chronic hepatitis C, abnormal IgM-containing CIC are the major types of CIC in patients co-infected with hepatitis B and C. An immune-mediated mechanism may play a role in the pathogenesis of chronic hepatitis C.

Relationship between immune complex and total hemolytic complement in endolymphatic hydrops.

Recently there has been considerable investigation into the relationship of the immune system and immune disorder to Meniere's disease. Immunoglobulin G (IgG) antibody and complement are both present in endolymphatic fluid and it is possible that endolymphatic hydrops is due to immune complex. The authors' results show that patients with endolymphatic hydrops had elevated levels of circulating immune complex (CIC) of IgG (24.80 micrograms/mL). The levels of functional complement activity (CH50) were significantly lower in patients (249.7 HU) than in controls. Circulating levels of CIC and CH50 were positively correlated. Immunoglobulin G, immunoglobulin M (IgM), and subpopulation of B lymphocytes were elevated, but there was no alteration in subpopulations of T-helper, T-suppressor, and natural killer (NK) cells in peripheral blood.

Immunomodulation by levamisole in patients with recurrent aphthous ulcers or oral lichen planus

The purpose of this study was to evaluate the effect of levamisole on the immune system of patients with recurrent aphthous ulcers (RAU) or oral lichen planus (OLP) in an open trial. Lymphocyte subsets, serum immunoglobulins, and circulating immune complexes (CIC) in patients with RAU or OLP and in normal control subjects were determined by an indirect immunofluorescence (IIF) technique with monoclonal anti-lymphocyte antibodies, by single radial immunodiffusion, and by precipitation with 3% polyethylene glycol, respectively. In addition, the anti-nuclear antibodies (ANA) and anti-basal cell antibodies (anti-BCA) in sera were detected by an IIF technique. We found a significant improvement in clinical symptoms and normalization of the decreased CD4/CD8 ratio in RAU patients after levamisole treatment. Moreover, the decreased CD4/CD8 ratio, which persisted until the remission stage in the untreated RAU patients, reverted to normal in the active late stage in the levamisole-treated patients. This reversion of aberrant cellular immunity in an earlier stage of the ulcer cycle may explain why RAU patients experience symptom improvement after levamisole treatment. Although RAU patients treated with levamisole for 1 to 3 or 4 months still had higher than normal levels of CIC and serum immunoglobulins, the levels of their IgA and IgM returned to normal values after 4 months of levamisole treatment. The serum ANA detected in 6 patients with RAU and 3 patients with erosive OLP disappeared after 1-22 months of levamisole treatment. The disappearance of serum anti-BCA was also observed in 50% of the anti-BCA-positive patients with erosive OLP after 3-13 months of levamisole treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlations of C1q- and C3d-bearing circulating immune complexes with immunopathological disease activity in lupus nephritis patients.

The serum levels of circulating immune complexes (CIC) measured by three different types of enzyme immunoassay (EIA) using monoclonal anti-C1q and antibodies and C1q as solid phase reagents were compared with clinical disease activity and immunohistological glomerular lesions in 29 SLE patients. Three types of CIC measured by these assays (anti-C1q CIC, anti-C3d CIC and C1q SP CIC) showed significantly higher levels in patients than in controls and were significantly associated with the clinical and serological disease activities. Anti-C1q CIC showed good correlation not only with mesangial IgG depositions (P < 0.01), but also with that of C1q (P < 0.05). C1q SP CIC also showed a weak correlation with mesangial C1q deposition (P < 0.05). Serum levels of anti-C3d CIC increased with the degree of mesangial IgG and complement depositions. Analysis of the clinical course of a patient with active SLE revealed a more rapid decrease of anti-C1q CIC and anti-C3d CIC along with the improvement of disease activity, including the mesangial lesion, than that of C1q SP CIC. According to these results, the CIC detected with assays using monoclonal antibodies against complement fragments, especially the anti-C1q assay, is likely to provide specific information regarding the clinical, serological and immunohistological disease activity in lupus nephritis.