Circulating immune complexes and complement in bancroftian filariasis.

Sixty filarial cases, 30 endemic normal individuals and 10 non endemic subjects were investigated for the presence of Circulating Immune Complexes (CICs) and Complement Component C3. Using Polyethylene Glycol precipitation and Polyethylene Glycol precipitation-Complement Consumption methods, it was observed that CICs were raised significantly in chronic lymphatic filariasis and Tropical Pulmonary Eosinophilia (TPE) groups. The results observed by both the techniques for detection of CICs were comparable. Low levels of C3 were detected in chronic lymphatic filariasis cases by single radial immunodiffusion method, suggesting the utilization of complement by immune complexes.     

Circulating immune complexes and complement concentrations in patients with alcoholic liver disease.

A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence of CIC in these patients may be due to a depressing effect of ethanol on clearance of CIC or to increased immunological reactivity, or to both.     

Circulating immune complexes and complement in rheumatoid arthritis

Rheumatoid arthritis is characterized immunologically by the detection of rheumatoid factor (RF) and circulating immune complexes (CIC). The pathogenesis role played by these CIC has been discussed a long time. A part of this theoretical question, it could be of interest to know if these technics could help the clinician in the diagnosis or in the follow up of the patients with RA.     

Circulating immune complexes in advanced Hodgkin's disease: qualitative analysis and prognostic significance

The level of circulating immune complexes (CIC) may be a reflection of the underlying malignancy and appears to be related to the stage of disease, tumor burden and prognosis. Prognostic factors at diagnosis, clinical response, survival and CIC were analyzed in 89 patients with Hodgkin's disease. All patients were newly diagnosed, in advanced stage and treated with MOPP regimen. The median follow-up was 41 months. CIC were estimated by the polyethylene glycol precipitation test. The median age was 40 years and 52% were under the age of 45. Nodular sclerosis and mixed cellularity were the most common histologies, 36 and 35% respectively. "B" symptoms were present in 65%, bulky disease in 29% and bone marrow involvement in 4% of the total. The erythrocyte sedimentation rate (ESR) was over 30 in 72% of patients and 27% had one or two extranodal localizations. Complete remission (CR) was obtained in 69 patients (77%). The only factor influencing the CR rate was the number of extranodal localizations (p<0.05). The ten-year relapse-free survival (RFS) and overall survival (OS) were 63 and 83%, respectively. RFS was adversely influenced by lymphocyte depletion histology (p=0.009) and by performance status over 1 (p=0.003). Elevated CIC levels were detected in 58% of the total. Patients with ESR over 30 had significantly higher values of CIC (p<0.05). Qualitative analysis of the CIC showed high levels of positivity to immunoglobulin G and M. C-reactive protein (CRP) was identified in 42% of all samples. CRP is an acute phase protein which shows conformational similarity to the immunoglobulin molecule. There were no significant correlations between levels of CIC and the other prognostic factors. Survival was not influenced by the CIC level.     

Circulating immune complexes and complement activation in primary biliary cirrhosis

We evaluated 20 patients with primary biliary cirrhosis and seven controls with extrahepatic biliary obstruction for presence of circulating immune complexes, having found serologic evidence of alternate complement-pathway activation in eight of the 20. Immune complexes were isolated by cryoprecipitation from serum and measured directly by the sensitive Raji-cell radioimmunoassay. Cryoproteins, found in high concentrations in 90 per cent of the patients with cirrhosis but undetectable in the controls, were composed of IgM (60 per cent), IgG-IgM (25 per cent) and IgA-IgM (5 per cent) and were capable of activating the complement system in vitro. Immune complexes detected by the Raji assay were found in 95 per cent of the patients with cirrhosis and circulated in exceedingly high concentrations (474 microgram per milliliter; range, 16.2 to 2192) but were absent in the controls. Furthermore, the alternate complement pathway was activated in eight cirrhotic patients. These complement-fixing immune complexes differ from immune complexes isolated from other types of liver diseases and may be important in the pathogenesis of primary biliary cirrhosis.     

Circulating immune complexes in dermatologic disease

Summary Assays for circulating immune complexes have proven to be useful tools in investigating the pathophysiology of a number of diseases. Soluble immune complex-like material has been detected in the sera of patients with connective tissue, infectious, neoplastic, and renal diseases, as well as many others. In some instances good correlations exist between the presence and levels of immune complexes and clinical disease activity, while in others the association is less striking or non-existent. The importance of these findings is undergoing constant re-evaluation as more and more studies are performed.In this chapter we have attempted to briefly outline some of the more widely used immune complex assays and to review the data on immune complexes in some dermatologic diseases. The work in almost all diseases must be viewed in light of the fact that none of the assays utilized are antigen specific, and that false positive results can occur in all systems. Additionally, the demonstration of immune complex-like material, even in a high percentage of patients with a given disease, does not necessarily mean that immune complexes play a primary role in the pathophysiology of that disease. Immune complexes may in some instances be formed secondary to tissue damage caused by other mechanisms.In dermatologic diseases or diseases with a significant dermatologic component, good evidence exists that circulating immune complexes are at least partially responsible for the tissue damage seen in systemic lupus erythematosus and necrotizing vasculitis. In most other dermatologic diseases, the evidence is much weaker. Further in-depth studies of dermatologic diseases using sequential observations with several different sensitive assays and physicochemical characterization of the complexes are necessary to elucidate the importance of soluble antigen-antibody complexes in these entities.     

Circulating immune complexes in inflammatory bowel disease

Evidence for circulating immune complexes in sera of patients with ulcerative colitis or Crohn's disease is described. Such sera produced significantly greater inhibition of antibody-induced cytotoxicity mediated by lymphocytes than did sera from normal control subjects. Inhibitory activity of patients' sera showed a positive correlation with severity of disease, the height of the ESR and, in the case of ulcerative colitis, with the severity of inflammation as seen at sigmoidoscopy. Using gel filtration on Sepharose 6B, inhibitory activity was found in fractions of higher molecular weight than monomeric IgG but of lower molecular weight than IgM. These fractions were shown to contain IgG measured by immunodiffusion. Evidence that inhibition is not due to aggregated IgG molecules is provided by the fact that no correlation was found between inhibitory activity and total IgG concentration. A possible role of immune complexes in the pathogenesis of ulcerative colitis and Crohn's disease is proposed.     

DNA levels in circulating immune complexes decrease at severe SLE flares-correlation with complement component C1q.

The objective of this study was to investigate the relationship of DNA content in circulating immune complexes with disease course and activity in SLE. The DNA content in circulating immune complexes containing anti-DNA antibodies of IgG class was determined in serial samples from 28 patients with SLE by a quantitative immunochemical assay. The patients presented various active disease manifestations over 5-55 months. Disease activity (SLEDAI-score), drug treatment and ACR-criteria were recorded. Levels of anti-dsDNA, CRP, leukocytes, complement components C3, C4 and C1q were measured. Patients with severe flares and high SLEDAI scores had low Clq levels at onset of active disease manifestations. The patients with low C1q serum levels during flare (n=13) had significantly lower amounts of DNA in immune complexes than patients with normal Clq (P=0.001). Levels of DNA in immune complexes correlated with Clq at flares (r=0.62, P<0.0001) and correlated inversely with SLEDAI scores (r=-0.47, P=0.012). In conclusion, the low levels of DNA in circulating immune complexes found in severely ill SLE patients with concomitantly low serum concentrations of Clq prior to flares might be related to tissue deposition of immune complexes.     

Circulating immune complexes and complement levels in relation to the clinical presentation of Nigerian children with acute poststreptococcal glomerulonephritis.

Circulating immune complexes have been detected in the sera of 24 Nigerian children with acute poststreptococcal glomerulonephritis using two methods. There was a significant correlation between levels of soluble complexes, detected in samples taken from patients in the oliguric phase of acute nephritis, and severity of disease, as judged by blood urea levels. Serial estimation of immune complexes was more useful than serial C3 estimation in predicting the onset of anuria in two patients admitted with mild disease who subsequently deteriorated. With one exception, C4 values were normal. Factor B levels were low in 90% of cases, in keeping with activation of the alternate complement pathway.     

Serum immunoglobulins, complement component levels and autoantibodies in liver disease

Serum immunoglobulins, complement component levels and autoantibodies were measured in patients presenting with acute and chronic liver disease. One-hundred and seventeen patients were studied and the results of the immunological estimations were found to be of value in the differential diagnosis of liver disease when considered in conjunction with clinical and other laboratory findings. The results of the study are of interest in discussing the possible pathogenesis of liver disease.     

Circulating immune complexes in schistosomiasis.

Circulating immune complexes (CIC) were investigated by the [125I]Clq binding test, the complement fixation test (CFT) and optical density measurement after redissolving 3% polyethylene glycol precipitates of serum from patients infected by Schistosoma mansoni. A highly significant correlation was obtained among these three techniques. More than 60% of the patients demonstrated significantly higher values than control individuals. The level of CIC was found to be higher in the mild than in the hepatosplenic form of the disease. Parasite antigen, IgG, IgM and IgE were characterized in these CIC. In experimental schistosomiasis in mice, maximum levels of CIC, evaluated by the CFT, were observed between the 40th and the 70th day of infection.     

Circulating immune complexes in onchocerciasis.

Circulating immune complexes were detected in sera of patients with both localized and generalized onchocerciasis by a 125I-Clq binding assay but not by the IgG latex agglutination inhibition method. Gel filtration of sera demonstrated high molecular weight Clq-reactive material(greater than 2 x 10(6) Daltons) which contained IgM but no IgG. Antibody titres to Onchocerca volvulus antigen were higher in patients with generalized disease than in those with the localized form. The lack of correlation between antibody titres and levels of immune complexes suggests that these immune complexes contain antigens other than those derived exclusively from the parasite. Although few of the symptoms of this disease are likely to be due to deposition of circulating immune complexes, the depression of delayed hypersensitivity reactions to the parasite found in patients with generalized onchocerciasis may be due to IgM immune complexes exerting an immuno-regulatory role on T cell function.     

Inhibition of the interaction between the complement component Clq and immune complexes.

Several groups of compounds were examined for their ability to inhibit in vitro the binding of Clq to insoluble immune complexes. As expected from previous studies, polyinosinic acid, liquoid, sodium pentosan polysulfate, aliphatic diamines and heparin are good inhibitors. This study shows that compounds with much lower toxicity, such as certain amino acids and substances with vitamin B6 activity (pyridoxal-5-phosphate:P5P) were also capable of decreasing the binding of Clq. Using methods of equilibrium dialysis and difference spectra, it was shown that this compound binds to both, Clq und IgG antibody by forming Schiff bases. Clq binds approximately 10 times more P5P when compared to IgG. Immune complexes prepared with IgG antibody modified by P5P and stabilized with sodium borohydride had the same complement-fixing and Clq-binding capacity as normal immune complexes. This suggests that the inhibition of Clq-binding to immune complexes by P5P is due to a modification of lysyl resides in Clq. Collagen and IgG fragments derived from Fc were also found to inhibit Clq binding to immune complexes, but at higher concentrations than the above small-molecular compounds and with a different mode of action.     

Circulating and deposited immune complexes in renal disease and their clinical correlation.

In 48 patients undergoing renal biopsy there was a strong correlation (chi 2 11.45 (P less than 0.01)) between the demonstration of circulating and deposited immune complexes. Serial studies of circulating immune complex levels have shown fluctuations which only sometimes appear to coincide with clinical changes in individual patients.     

Circulating immune complexes in acute schistosomiasis.

The sera of patients with acute and chronic schistosomasis were tested for the presence of circulating immune complexes with the 125I-Clq binding assay. Fourteen out of fifteen (93%) patients with acute schistosomiasis had elevated 125I-Clq binding activity, while only two out of eleven (18%) patients with chronic disease had C1q binding complexes. This difference was significant (P less than 0.001) and paralleled the degree of clinical didsease activity between the two groups of patients. IgG and IgM were readily detected in all of these circulating complexes but the specific parasite antigens initiating their formation could not be defined. The level of circulating immune complexes was inversely correlated with the absolute eosinophil counts for individuals in the acutely infected group, an observation compatible wiht the hypothesis that a functional role for the eosinophil is the destruction and elimination of immune complexes.     

Circulating immune complexes in experimental filariasis.

Circulating immune complexes have been investigated in jirds (Meriones unguiculatus) infected with the filarial nematode Brugia pahangi. Two-month-old male jirds were inoculated with seventy-five B. pahangi infective larvae into the left groin. At 8 months post-infection, sera of individual animals from a group of seventeen infecteds and seventeen age-matched controls were analysed for immune complexes by (1) a solid-phase C1q binding assay (Clq-SP) and (2) precipitation with 3.5% polyethylene glycol followed by binding of 125I-labelled rabbit anti-jird Ig antiserum (PEG). A significant increase in the level of circulating immune complexes was shown in the infected group as compared with the controls for both assays, with a P value = 0.005 for PEG and P = 0.001 for Clq-SP. Using the mean of the control group +/- 2 s.d. as the upper limit of the normal range, 24% of the infected group had elevated immune complex levels by the PEG assay, and 41% were elevated in the C1q-SP assay. A high degree of variability was noted in the levels of immune complexes among individual animals in the infected group by each test. No correlation between immune complex levels and numbers of circulating microfilariae was found in either assay.     

Circulating immune complexes during immunotherapy.

Chronic immunization may lead to the production of circulating immune complexes (CICs). This study was undertaken to determine the presence of circulating IgG immune complexes in 95 subjects with allergic rhinitis/asthma receiving immunotherapy, 46 individuals with similar diagnosis but not on immunotherapy, and 64 healthy controls. Modified Raji cell and murine leukemia cell (L-1210) assays, selected for a high density of Fc receptors and devoid of Epstein-Barr virus membrane antigen, were used. Other immunological parameters such as immunologlobulins G, A, M, E, and rheumatoid factor activity were also studied. The CIC concentrations in the treated group did not differ significantly from the untreated group, although both groups did have a significantly higher concentration than the healthy controls. The presence of CICs has no relationship with age or sex of patients, dosage of allergen administered, number and nature of allergens received, period between the time of last injection and the blood sampling, and the duration of immunotherapy. Serum IgG, IgA, IgM, and rheumatoid factor activity did not differ between the treated and untreated groups. IgE was significantly higher in the treated group when compared with the untreated, and IgE levels in treated patients with elevated CICs were significantly increased compared with CIC-negative treated patients. These data suggest that CICs are present in serum of atopic diseases such as allergic rhinitis/asthma. Significantly, an association of elevation of CICs with immunotherapy could not be demonstrated.     

Circulating immune complexes in retinal vasculitis.

The second case of C3b inhibitor deficiency is described in an 11-year-old girl who presented with recurrent attacks of meningitis, in between which she was well. Her serum showed all of the complement component changes noted in the first described case, although showing only a relatively slight defect in its ability to opsonize bacteria for phagocytosis and killing by polymorphonuclear leucocytes. This correlated with the patient's freedom from other infections.     

Circulating immune complexes after splenectomy.

Circulating immune complexes were evaluated in 25 patients (age range 10 to 46 years) who had undergone splenectomy for non-malignant conditions by studying a polyethylene glycol insoluble serum fraction. Although the extent of binding to Clq was within normal limits, these patients had increased concentrations of factor B in the immune complex serum fraction. These findings indicate that an unusual type of circulating immune complex may be detected after splenectomy, suggesting a possible role for the spleen in the removal of circulating immune complexes.