Circulating immune complexes in ulcerative colitis. I. Correlation to disease activity

Twenty-two patients with ulcerative colitis were studied for occurrence of circulating immune complexes (IC) by three independent methods, a complement consumption assay, a Clq-binding assay and a RF-binding assay. All patients had the disease in an active stage when the study was initiated. Positiveness in two or more test systems was considered to indicate the presence of IC in the serum sample examined. By this criterion, circulating complement-fixing IC were detected in eight out of the twenty-two patients (36%; 95% confidence limits: 17–60%). IC were detected most frequently in patients with long-standing disease.

A correlation between the occurrence of circulating IC and disease activity, in terms of visible blood in faeces and number of bowel movements per day, was demonstrated. Cytological examination of the rectal mucus indicated moderate to severe inflammation in all IC-positive patients. Six out of the eight IC-positive patients were subjected to short-term glucocorticosteroid treatment; only one of these patients exhibited circulating IC and high disease activity after treatment —this patient was colectomized. Salazosulphapyridine treatment showed no relation to IC occurrence. Four out of the twenty-two patients (18%; 95% confidence limits 5–40%) were positive for organ non-specific antinuclear factor (ANF), but the presence of ANF did not correlate with circulating IC. Neither was any significant correlation between antibody titres to E. coli O119:B14 antigen and IC occurrence demonstrable.

     

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 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 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, complement and complement component levels in childhood Hodgkin's disease.

Serum levels of circulating immune complexes (CIC) assayed by the Raji cell radioimmunoassay, total haemolytic complement (TCH50), Clq and C3 were correlated with clinical stage, histological type, age, sex and treatment of eighty-six children with Hodgkin's disease over a period of 4 years. Most significant findings were the changes of levels of CIC, TCH50, Clq and C3 during disease activity and following treatment. Significant perturbations were also seen in association with relapse. Levels of C and CIC were significantly elevated (P less than 0.001) at the time of diagnosis prior to splenectomy and/or any treatment. In the group before treatment, 81 percent of CIC levels were above 16 micrograms/ml with a maximum value of 1120 micrograms/ml. During treatment 33 percent were still above normal with a maximum of 320 micrograms/ml. Within 1 year after cessation of treatment, 37 percent also remained above normal levels with a maximum of 240 micrograms/ml. At relapse prior to treatment, 63 percent were again elevated with a maximum of 1280 micrograms/ml. The most significant difference on TCH50 levels relates to treatment periods. Sera of patients with active disease who are previously untreated show elevation of TCH50 levels (P less than 0.001) (average 127 CH50 mu/ml. During and after treatment eht TCH50 levels drop to 96 and 102 CH50 mu/ml, as compared to normal control of 100 CH50 mu/ml. In sera of patients at the first, second or third relapse, the combined TCH50 levels are significantly different from controls and across treatment periods (P less than 0.005).     

Humoral immune system and ulcerative colitis activity. III. Immune complexes

Serum immune complexes (IMC) were examined by means of 4.166% polyethylene glycol precipitation. IMC were found in 33.3% of all examined patients (12.8% of inactive and 51.1% of active colitis). Polyethylene glycol serum precipitation was correlated with the activity of the disease, and was found to be increased in patients with extensive morbid process and with duration of the disease. In the patients with extraintestinal manifestations IMC increased particularly in those with skin lesions. Our study confirmed suggestion of other authors on the possible role of the pathogenesis of UC and in extraintestinal complications. Their secondary role however, cannot be excluded.     

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 serum from patients with dengue haemorrhagic fever.

Circulating immune complexes were detectable in 80% of serum from patients with dengue haemorrhagic fever. The immune complexes were detected for the first time on day two after the onset of the fever. The amount of complexes reached the maximum value on day 4 or 5 after onset, or when the patients developed shock or subsidence of fever, after which the complexes decreased in number. The number of complexes also correlated well with the clinical grading (severity) of the disease, i.e. the maximum amount was shown in grade III. These complexes may play a part in the pathogenesis of this disease.     

Circulating antibodies to heat-shock protein 60 in Crohn''s disease and ulcerative colitis.

Heat-shock proteins (HSPs) are highly conserved immunogenic intracellular molecules that are induced by inflammatory mediators and may induce autoimmune phenomena in vivo. We have recently demonstrated the increased expression of HSP-60 in the colonocytes of patients with ulcerative colitis. To study further the role of HSP-60 in inflammatory bowel disease, we have now measured antibodies to recombinant mycobacterial HSP-65 (a member of the HSP-60 family) in patients with Crohn's disease, ulcerative colitis, healthy volunteers and, as disease controls, patients with confirmed bacterial diarrhoea. In comparison with healthy controls (n = 20; median level of 89 ELISA units; range 24-292), serum IgA HSP-60 antibodies were elevated in Crohn's disease (n = 21; 157; 57-364; P < 0.05) and active ulcerative colitis (n = 16; 188; 58-373; P < 0.01) but not bacterial diarrhoea (n = 10; 106; 51-285). Increased IgA HSP-60 antibody levels in patients with inflammatory bowel disease may occur as the result of HSP release from injured gut epithelium; alternatively, increased intestinal permeability could facilitate mucosal access of luminal antigens and the generation of cross-reactive anti-bacterial HSP antibodies.     

基质Gla蛋白MGP甲基化水平与溃疡性结肠炎患者免疫功能的相关性研究

目的 研究基质Gla蛋白(MGP)在溃疡性结肠炎(ulcerative colitis,UC)中的表达和启动子区甲基化状态,探讨MGP对UC免疫平衡的影响.方法 纳入UC患者105例,并收集健康者外周血为对照组,2组均被用于观察MGP的表达和甲基化变化.使用DSS构建小鼠UC模型,荧光定量PCR检测MGP的mRNA表达...     

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.     

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.     

Immune complexes in ulcerative colitis and Crohn's disease.

Sera from 156 patients with ulcerative colitis and Crohn's disease were tested for the presence of immune complexes, by the detection of anti-complementary activity and 125I-labelled Clq precipitation. Using aggregated IgG, a comparison between the two tests indicated that the anti-complementary test was most sensitive to aggregates of 11S in size, while the 125I-labelled Clq test detected aggregates over 20S in size. Excess anti-complementary activity was common in patients with active bowel disease, and in those with extra-intestinal manifestations, particularly acute arthritis, ankylosing spondylitis and liver disease. Large complexes were only common in patients with liver disease. Immune complexes in the gut mucosa may play a role in the pathogenesis of these diseases, and the deposition of circulatory immune complexes may explain at least some of the extra-intestinal manifestations.     

Circulating immune complexes in six patients with trichinosis.

The sera of six patients infected with Trichinella spiralis were studied for the presence of circulating immune complexes (CIC). CIC were present in all six patients studied 1 month after infection. In two patients in whom serial serum samples were available, as clinical improvement occurred there was a decrease in the level of CIC and an increase in the fluorescent antibody titres.     

Circulating immune complexes in patients with diabetes mellitus.

Circulating immune complexes (CIC) were detected by the solid phase C1q binding assay in 16% of 103 diabetic patients and by the fluid phase C1q binding assay in 31% of patients as compared to 5% of 58 control subjects for each assay. Plasma glucose determinations revealed that most patients were moderately hyperglycaemic (mean glucose = 264 mg/dl), and thus were not selected for tight metabolic control. All but six patients had elevated levels of plasma insulin, including both the insulin treated and diet treated subgroups. There was no correlation between the presence of CIC detected by either assay and plasma glucose, insulin, or the presence of microangiopathy. Multiple factors must contribute to the increase in CIC in both insulin deficient and insulin resistant diabetics. The role of these various factors remains to be defined.     

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 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.