Circulating Immune Complexes Research Articles

Analysis of circulating immune complexes containing pain-associated molecules in patients with knee osteoarthritis: from the laboratory to the clinic

Purpose: Today's leading laboratory researchers, pharmacy and biotech decision-makers, technology companies and clinicians are focusing on the uses of biomarkers in the field of osteoarthritis research. Osteoarthritis of the knee (kOA) has in the past been considered a predominately degenerative joint disease, affecting more people than any other arthritis. In kOA disease, pathogenic pain-associated molecules are used for development of diagnostic criteria, monitoring of disease activity, and prognosis. As such, the body has many pain messengers, receptors and neural pathways to sense that information. Analysis of circulating immune complexes (CICs) produced during an immune response may be useful in elucidating some aspects of kOA process. To investigate the presence of immune complexes containing pain-associated molecules such as interleukin 6 (IL-6), interleukin 18 (IL-18), angiotensin-converting enzyme (ACE), prostaglandin E2 (PGE2) in the peripheral blood sera of kOA patients and to evaluate their potential as markers of kOA pathogenesis. This knowledge increases he quality of medicine and surgery. Methods: Circulating biomarker-Ig immune complexes were measured in serum samples from 54 patients with kOA and from 54 healthy controls using a novel ELISA (INR, Mexico). kOA severity as defined by increasing Kellgren & Lawrence (KL) grade. Pain was measured using a visual analogue scale (VAS, 0-100 mm). kOA biopsies were obtained at arthroscopy. Apoptosis was assessed using Caspase-Glo 3/7 assay. Results: We applied our strategy to the analysis of CICs in kOA patients and healthy controls. Our technique for CICs analysis uses routine clinical samples, simple protocols, and widely available equipment. CICs containing PGE2 and IL-18 were found in the serum of 81% and 65% of kOA patients. Serum PGE2-IgG and IL-18-IgG are significantly higher in the kOA group than those in the control group (P<0.01). A significant positive correlation was noted between their expressions (r=0.863, P<0.01). No correlation between the serum PGE2-IgG and IL-6-IgG was found. Deficiency in the sera ACE-IgM predisposes the expression of high affinity PGE2-IgG in kOA patients. There was a negative correlation between serum PGE2-IgG and ACE-IgM in kOA patients (r=-0.58, P<0.05). No statistically significant differences were found between serum levels of biomarker-IgM and biomarker-IgA for kOA patients. Conclusions: Blood still represents an ideal clinical source of markers because of its known role in reflecting systemic changes associated with disease. Improved analytical methods are required to accommodate the analysis of large numbers of samples for biological and epidemiological monitoring. Our method may be generally applicable to the study of the relationship between CICs and kOA diseases. The ICs in the serum of a majority of the OA patients contained PGE2 or ACE, and these ICs may have potential as alternative biomarkers. The role of ACE-IgM and PGE2-IgG in the modulation of the immune response, pain and inflammation has been regarded as important. The biomarkers in combination (ACE-IgM and PGE2-IgG) work better.

264 Basophil-Mediated Anaphylaxis Triggered by Drug-Activated Complement Alternative Pathway Without Mastocyteʼs nor Immunoglobulins Involvement

BackgroundIt's well known that drugs may induce complement alternative pathway's activation. On the other hand there is evidence that anaphylaxis may occur in absence of IgE and IgG antibodies (so-called non-immune anaphylaxis). We determined the tryptase, complement and circulating immune complexes (CIC) levels to understand the nature of anaphylaxis occurred in a woman during high rate infusion of high concentrated iron.MethodsA 46 years-old woman was admitted to our department because of mixed anemia, iron and cobalamin deficiency-related, started after a surgical intervention (bilio-pancreatic derivation) for heavy obesity occurred 7 years ago (starting Hgb = 7g/dl). Ev. hydroxicobalamin and iron infusions were planned, but during high rate (100 gtt/m’) infusion of high concentrated (0,5 mg/mL) iron, the patient suffered from discomfort, sweat and drop in blood pressure (BP 60/30). Blood samples were taken to evaluate tryptase, complement and CIC levels; standard treatment of anaphylaxis was started (im. epinephrine, inhaled O2 with steroids and beta-agonists, ev. electrolyte solution and vital parameters continuous evaluation). The shock resolution was gained in 3 hours.ResultsThe level of tryptase was normal (4 mcg/mL; N.R.-Normal Range-= 1–20), while C3 and C4 were impaired (C3 = 65 mg/dl; N.R. = 75–165; C4 = 12 mg/dl; N.R. = 20–55). The search for CIC IgG, IgA, IgM was negative. Six months later the low rate (30 gtt/m’) low concentration (0,25 mg/mL) iron infusion was well tolerated by the patient, so excluding any IgE sensitization.ConclusionsWe describe here for the first time a case of human anaphylaxis without mastocyte nor IgE involvement. The high infusion rate and hyperosmolality of hyperconcentrated drug caused complement alternative pathway's activation. The only cell type able to release anaphylaxis mediators other than mastocytes are the basophils, having anaphylotoxins receptors. So, we conclude that drug-induced complement alternative pathway's activation with consequent basophil's involvement was responsible for the patient's “non-immune” anaphylaxis.

Expression and significance of leukocyte membrane cofactor protein transcript in systemic lupus erythematosus

Membrane cofactor protein (MCP) is a complement regulatory protein ubiquitously expressed on most nucleated cells. Since MCP protects autologous cells from complement-mediated injury, it is suggested to have a protective role against the self-tissue damage in inflammatory conditions such as systemic lupus erythematosus (SLE). However, the relevance of MCP in human SLE is not well explored. To assess the significance of MCP in SLE, we studied expression of leukocyte MCP transcript in 60 healthy individuals (controls) and 60 patients with SLE and correlated that with the levels of circulating immune complex (CIC), C3, C3d and SLEDAI scores. The levels of leukocyte MCP transcript were significantly higher (p < 0.001) in patients with SLE than the controls. Furthermore, MCP transcript levels exhibited significant positive correlations with SLEDAI scores and CIC level and a negative correlation with C3d level in patients. Twelve patients were followed-up until remission. The levels of MCP transcripts decreased significantly during remission as compared with the state of active disease. These findings suggest that in SLE, the expression of leukocyte MCP at the mRNA level is closely related to disease activity. A protective role of MCP in response to increased disease burden may be speculated. The follow-up study suggested MCP as a potential disease marker.

Serum circulating immune complexes as prognostic indicators in premalignant and malignant lesions of oral cavity during and following radiotherapy

The aim of the study has been to quantitatively estimate and compare the circulating immune complexes (CIC) in pre-malignant and malignant lesions of oral cavity and to serially monitor the CIC levels in oral squamous cell carcinoma (SCC) during / following radiotherapy as to assess the status of the disease and to understand the prognostic significance. The present study was carried out on 90 individuals divided into three groups and CIC was estimated by spectrophotometric method using polyethylene glycol (PEG) precipitation method. The mean CIC level was determined in each group and was correlated with the degree of differentiation and degree of dysplasia in malignant and pre-malignant group respectively. The effect of radiotherapy on the level of CIC was studied after 2400 rad and after one week of 4500 - 5000 rad. It was observed that the mean CIC level in the control group was significantly lower (59.56 ± 8.11) when compared with the pre-malignant group (75.93 ± 12.89) and malignant group (92.66 ± 13.96). Among the pre-malignant group, leukoplakia had the highest mean CIC level followed by lichen planus and oral submucous fibrosis (OSMF), suggesting its greater malignant potential. No correlation could be established between degree of differentiation and degree of dysplasia with the CIC levels in malignant and premalignant groups respectively. There was a definite decrease in the mean CIC levels in patients undergoing radiotherapy. The pretreatment value of CIC can be used as a prognostic indicator. A high CIC level would probably indicate a poor prognosis.

Circulating Immune Complex Levels are Associated with Disease Severity and Seasonality in Children with Malaria from Mali

Complement receptor one (CR1) is essential for removing circulating immune complexes (CIC), with malaria infection contributing to the formation of large amounts of CIC. We investigated CIC levels in children with malaria, of varying severity and seasonality. Two hundred age and sex-matched severe and mild malaria cases were studied during and after active disease. Pediatric controls had increased CIC levels (mean = 32 μg mEq/mL) compared to adult controls (mean = 26.9 μg mEq/mL). The highest levels of CIC were reported in severe malaria (mean = 39 μg mEq/mL). Higher levels of CIC were recorded in younger children and those with low E-CR1 copy numbers. Our data suggest that low levels of E-CR1 copy numbers, found in children with severe malaria, may adversely affect the ability to remove IC. Furthermore, the high background for circulating immune complex imply that Malian children are under constant assault by other pathogens that evoke a strong immune response.

Progressive increase of serum circulating immune complexes and its significance in patients during the progression from chronic hepatitis B to hepatocellular carcinoma

To investigate the significance of increasing circulating immune complex (CIC) in patients during the progression from chronic hepatitis B to hepatocellular carcinoma (HCC). Serum levels of CIC from 20 hospitalized patients diagnosed by pathology with primary HCC, and 13 with hepatic hemangioma, and from 45 subjects with chronic HBV infection who finally developed into HCC (45 cases), and age- and gender-matched 45 subjects who kept the chronic HBV infection after consecutively followed up for 10 - 13 years by June of 2009 were quantified by ELISA. The serum levels of anti liver-kidney microsomal (anti LKM-1) antibodies were also measured by ELISA, and that of HBV-DNA were quantified by Taqman probe-based real time PCR in the followed up chronic HBV infection subjects. In the 45 chronic HBV subjects who finally developed into HCC and the 45 controls, serum samples were collected and determined at 3 time points: the baseline when the subjects were recruited, the middle point during the follow-up, and the end of follow-up. The serum level of CIC was significantly higher in the 20 HCC patients than that in the 13 hemangioma cases (P < 0.001). When HCC was diagnosed, the CIC concentration was significantly higher than that in the baselines (P < 0.001) in the 45 chronic HBV subjects who finally developed into HCC after the consecutively follow-up for 5 - 13 years. Of them, 36 patients (80.0%) showed progressively increased CIC during the follow-up (P < 0.001). In the controls, the CIC levels were kept relatively stable during the follow-up. Among them, 17 patients (37.8%) showed CIC slightly increased (P = 0.046). Kaplan-Meier survival analysis indicated that elevated serum CIC during the follow-up increased cumulative HCC incidence (HR = 2.77, 95%CI 1.47 - 5.22). In addition, the serum levels of anti-LKM-1 and HBV-DNA were also significantly higher in the patients who finally progressed into HCC than that in the controls and maintained at a high level during the follow-up tested at all the 3 time points. Further analysis indicated that the serum level of CIC was correlated with that of serum HBV-DNA only when HCC was diagnosed (r = 0.344, P = 0.026). Progressive increase of serum CIC level may be one of risk factors reflecting HCC development from chronic HBV infection.

Detection of Circulating ADAMTS13 Immune Complexes by Antibody Class-Specific ELISA

Abstract 4361A severe functional deficiency of the von Willebrand factor (VWF) cleaving protease ADAMTS13 results in the accumulation of uncleaved, highly adhesive VWF multimers in plasma leading to increased platelet aggregation and thrombus formation in the microcirculation. Anti-ADAMTS13 autoantibodies that either neutralize ADAMT13's activity or enhance protein clearance are the major cause of severe ADAMTS13 deficiency in acquired thrombotic thrombocytopenic purpura (TTP). Circulating anti-ADAMTS13 immune complexes that may play a role in disease pathogenesis have been described in plasma of TTP patients. We have developed a new ELISA assay to specifically determine the levels of ADAMTS13-specific circulating immune complexes (CIC) in which the antigen portion is immobilized by a polyclonal anti-ADAMTS13 IgG and the immunoglobulin component detected by a class-specific antibody. An inverse correlation between levels of circulating anti-ADAMTS13 autoantibodies and ADAMTS13-specific CIC has been observed in plasma of acquired TTP patients. The correlation between free anti-ADAMTS13 titer and the level of CIC and insight into the immunoglobulin (sub) classes involved may provide valuable prognostic information about disease severity and progression, and aid patient treatment monitoring. Disclosures:Plaimauer:Baxter Innovations GmbH: Employment. Ferrari:Baxter Innovations GmbH: Employment. Gruber:Baxter Innovations GmbH: Employment. Rottensteiner:Baxter Innovations GmbH: Employment. Turecek:Baxter Innovations GmbH: Employment. Ehrlich:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter Innovations GmbH: Employment.

Circulating immune complexes correlate with collagen carboxypropeptide in patients with essential hypertension

Recent evidence indicates that skewed immune responses occur in patients with essential hypertension (EH), which may be involved in the development of EH. This study aimed to evaluate the plasma levels of immune complexes (IC), procollagen type I collagen carboxypropeptide (TICP), and von Willebrand factor (vWF) in EH patients. A total of 121 patients with EH were enrolled in this study (EH group). Thirty healthy volunteers were recruited to serve as the control group. The plasma levels of circulating IC (CIC), vWF and procollagen TICP were measured. Multiple linear regression assays were performed with the data to determine the correlation between EH and these parameters. The results showed that compared with the healthy control group, the plasma levels of CIC, vWF and TICP in the EH group were significantly higher than that in healthy control group, which was positively correlated with EH. The levels of CIC were also positively correlated with vWF and TICP in plasma. The results suggest that skewed immune responses exist in patients with EH.

Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia.

BackgroundWhereas the complement system alterations contribute to schizophrenia, complement receptors and regulators are little studied. We investigated complement receptor type 1 (CR1) expression on blood cells, the levels of circulating immune complexes (CIC) containing ligands of CR1, C1q complement protein and fragments of C3 complement protein (C1q-CIC, C3d-CIC), and CR1 C5507G functional polymorphism in schizophrenia patients and controls.ResultsWe found an increased C1q-CIC level and CR1 expression on blood cells, elevated number of CR1 positive erythrocytes and reduced number of CR1 positive lymphocytes and monocytes in patients compared to controls. No difference in the levels of C3d-CIC between groups was observed. Higher CR1 expression on erythrocytes in CC genotype versus CG+GG for both groups was detected, whereas no difference was observed for other cell populations. Our results indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level.ConclusionsOur study for the first time indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Further studies in other ethnic groups are needed to replicate these findings.

IgA1 immune complexes from pediatric patients with IgA nephropathy activate cultured human mesangial cells

Circulating immune complexes (CIC) containing galactose (Gal)-deficient IgA1 from adults with IgA nephropathy (IgAN) induce proliferation of cultured mesangial cells, but activities of CIC from pediatric patients with the disease have not been studied. CIC of different sizes were isolated from sera of pediatric and adult IgAN patients and their effects on cultured human mesangial cells (MC) were assessed by measuring cellular proliferation, expression of IL-6 and IL-8 and laminin and phosphotyrosine signaling. Large CIC from pediatric IgAN patients (>800 kDa) containing Gal-deficient IgA1 stimulated cellular proliferation, whereas in some patients, smaller CIC were inhibitory. Addition of stimulatory and inhibitory CIC to MC differentially altered phosphorylation patterns of three major tyrosine-phosphorylated proteins of molecular mass 37, 60 and 115 kDa. The stimulatory CIC transiently increased tyrosine-phosphorylation of the 37-kDa protein and decreased phosphorylation of the other two proteins, whereas the inhibitory CIC increased phosphorylation of all three proteins. Furthermore, we investigated the influence of IgA1-containing CIC from sera of children with IgAN with clinically active disease (i.e., abnormal urinalysis and/or serum creatinine concentration) or inactive disease (i.e., normal urinalysis and serum creatinine concentration) on the expression of IL-6 and IL-8 genes by mesangial cells. Real-time reverse transcription-polymerase chain reaction results showed that the CIC from a patient with active disease stimulated MC to express the two cytokine genes at higher levels than did the CIC from a patient with inactive disease. Moreover, stimulatory CIC increased production of the extracellular matrix protein laminin. These data indicate that sera of pediatric IgAN patients contain biologically active CIC with Gal-deficient IgA1.

Heightened Measures of Immune Complex and Complement Function and Immune Complex–Mediated Granulocyte Activation in Human Lymphatic Filariasis

The presence of circulating immune complexes (CICs) is a characteristic feature of human lymphatic filariasis. However, the role of CICs in modulating granulocyte function and complement functional activity in filarial infection is unknown. The levels of CICs in association with complement activation in clinically asymptomatic, filarial-infected patients (INF); filarial-infected patients with overt lymphatic pathologic changes (CPDT); and uninfected controls (EN) were examined. Significantly increased levels of CICs and enhanced functional efficiency of the classical and mannose-binding lectin pathways of the complement system was observed in INF compared with CPDT and EN. Polyethylene glycol-precipitated CICs from INF and CPDT induced significantly increased granulocyte activation compared with those from EN, determined by the increased production of neutrophil granular proteins and a variety of pro-inflammatory cytokines. Thus, CIC-mediated enhanced granulocyte activation and modulation of complement function are important features of filarial infection and disease.

Immune Complexome Analysis of Serum and Its Application in Screening for Immune Complex Antigens in Rheumatoid Arthritis

Analysis of circulating immune complexes (CICs) produced during an immune response may be useful in elucidating some aspects of this process. Identification of antigens incorporated into CICs provides information that may be helpful in developing diagnostic and treatment strategies for autoimmune diseases, infection, cancer, and transplantation therapy, and such information might be more relevant than information on free antigens. Because CICs may contain many antigens, comprehensive identification and profiling of such antigens is more effective than immunoblotting detection. We developed a novel proteomic strategy (immune complexome analysis) in which immune complexes (ICs) are separated from serum, digested directly with trypsin, and then subjected to nano-liquid chromatography-tandem mass spectrometry for identifying and profiling antigens in CICs. We applied this strategy to the analysis of CICs in 21 rheumatoid arthritis (RA) patients. Serum samples from 13 healthy donors and 8 osteoarthritis patients were used as controls. CICs containing thrombospondin-1 (TSP-1) and platelet factor 4 (PF4) were found in the serum of 81% and 52% of RA patients, respectively, and in none of the controls. The ICs in the serum of a majority of the RA patients contained TSP-1 or PF4, and these ICs may have potential as alternative biomarkers. Our technique for immune complexome analysis uses routine clinical samples, simple protocols, and widely available equipment. This method may be generally applicable to the study of the relationship between CICs and certain diseases associated with the immune response in animals and humans.

Autoantibodies associated with RNA are more enriched than anti-dsDNA antibodies in circulating immune complexes in SLE

Background and objectiveWe have earlier shown that polyethylene glycol (PEG)-precipitated circulating immune complexes (CIC) from systemic lupus erythematosus (SLE) patients induce cytokines in vitro, and that levels of both CIC...

Polymorphisms of CD16A and CD32 Fcγ receptors and circulating immune complexes in Ménière's disease: a case-control study

BackgroundAutoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease. The Fcγ receptors bind IgG subtypes modulating the clearance of circulating immune complexes (CIC). The inner ear damage in Ménière's disease (MD) could be mediated by an immune response driven by CIC. We examined single-nucleotide polymorphism (SNPs) in the CD16A and CD32 genes in patients with MD which may determine a Fcγ receptor with lower binding to CIC.MethodsThe functional CD16A (FcγRIIIa*559A > C, rs396991) and CD32A (FcγRIIa*519A > G, rs1801274) SNPs were analyzed using PCR-based TaqMan Genotyping Assay in two cohorts of 156 mediterranean and 112 Galicia patients in a case-control study. Data were analyzed by χ2 with Fisher's exact test and Cochran-Armitage trend test (CATT). CIC were measured by ELISA for C1q-binding CIC.ResultsElevated CIC were found in 7% of patients with MD during the intercrisis period. No differences were found in the allelic frequency for rs396991 or rs1801274 in controls subjects when they were compared with patients with MD from the same geographic area. However, the frequency of AA and AC genotypes of CD16A (rs396991) differed among mediterranean and Galicia controls (Fisher's test, corrected p = 6.9 × 10-4 for AA; corrected p = 0.02 for AC). Although genotype AC of the CD16A receptor was significantly more frequent in mediterranean controls than in patients, [Fisher's test corrected p = 0.02; OR = 0.63 (0.44-0.91)], a genetic additive effect for the allele C was not observed (CATT, p = 0.23). Moreover, no differences were found in genotype frequencies for rs396991 between patients with MD and controls from Galicia (CATT, p = 0.14). The allelic frequency of CD32 (rs1801274) was not different between patients and controls either in mediterranean (p = 0.51) or Galicia population (p = 0.11).ConclusionsElevated CIC are not found in most of patients with MD. Functional polymorphisms of CD16A and CD32 genes are not associated with onset of MD.

Systemic adverse events following rituximab therapy in patients with Graves’ disease

Rituximab (RTX) therapy has shown promising results in Graves' disease (GD), with or without ophthalmopathy. We examined the occurrence of adverse events in GD patients treated with RTX. Ten patients received RTX and methimazole, while 10 patients received methimazole only. Adverse events were recorded, and the presence of circulating immune complexes (CIC) was measured as IgG, IgM and complement component 3 (C3) depositing on normal monocytes following incubation with patient plasma. Five patients had benign infusion-related adverse events at first infusion. Two patients developed a serum sickness-like reaction 11 days after the first RTX-infusion. One of these patients developed diarrhea, raised orosomucoid levels, lowgrade inflammation in colonoscopic biopsies, and iridocyclitis 1 yr later. At day 14, the most pronounced immunoglobulin/ C3-adherent to the test monocytes, indicative of CIC, was observed in the presence of plasma from these 2 patients (p=0.003 to p=0.01 vs asymptomatic patients). A 3rd patient had recurrent fever and symmetric polyarthritis from day 38, and colonoscopy-verified ulcerative colitis at day 68. This patient had the 3rd highest increase in Ig deposition on monocytes by day 14. The arthralgias persisted in 2 of the patients, despite glucocorticoid rescue therapy. We report articular adverse events in 3 and gastrointestinal symptoms in 2 out of 10 GD patients who received RTX without concurrent immunosupression. The joint symptoms were related to CIC formation.

Clinical presentation and some parameters of nonspecific resistance in Q-fever

The paper presents the results of a clinical observation and complex examination of 48 patients with Q-fever, the blood samples from 20 of them were tested for lysozyme, complement, and circulating immune complexes (CIC). The swing of the disease was characterized by the maximum clinical manifestations of the disease. Early reconvalescence was marked by a decrement in the clinical symptoms of the disease and a gradual recovery of the body's impaired functions. The study indicated a relationship between the level of nonspecific resistance factors and the stage of the pathologic process. The swing of the disease showed an increase in the amount of CIC with lower complement activity and normal lysozyme levels. In early reconvalescence, there was an increase in the levels of CIC and a decrease in total complementary activity as compared with those in the previous period. At the same time blood lysozyme activity substantially increased and exceeded the control values.

CA125 Immune Complexes in Ovarian Cancer Patients with Low CA125 Concentrations

About 20% of women with ovarian cancer have low concentrations of serum cancer antigen 125 (CA125), and this important tumor marker cannot be used to monitor their disease. The measured concentration for mucin 1 (MUC1), or CA15-3, another tumor marker, can be lowered in breast and ovarian cancer patients when circulating immune complexes (CICs) containing antibodies bound to the free antigen are present. Because CA125 and MUC1 are related members of the mucin family, we sought to determine whether CICs might also exist for CA125 and interfere with its clinical assay. We developed an antigen capture-based assay to determine the presence of CICs for CA125. We spotted mouse antibodies to CA125 onto nanoparticle slides, incubated them with patient serum, and added Cy5-tagged goat antihuman IgG antibodies. Fluorescence intensities were read and normalized to the intensities for glutathione S-transferase A1 as a control. Assay results for 23 ovarian cancer cases with high CA125 concentrations, 43 cases with low CA125 concentrations, and 19 controls (mean CA125 concentrations, 2706, 23, and 11 kilounits/L, respectively) revealed mean fluorescence intensities for CA125 CIC of 2.30, 2.72, and 1.99 intensity units (iu), respectively. A generalized linear model adjusted for batch and age showed higher CA125 CIC fluorescence intensities in low-CA125 cases than in high-CA125 cases (P = 0.03) and controls (P = 0.0005). Four ovarian cancer patients who had recurrent disease and always had low CA125 values had a mean CA125 CIC value of 3.06 iu (95% CI, 2.34-4.01 iu). These preliminary results suggest the existence of CICs involving CA125, which may help explain some ovarian cancer cases with low CA125 concentrations.

Deficiency of Activating Fcγ-Receptors Reduces Hepatic Clearance and Deposition of IC and Increases CIC Levels in Mercury-Induced Autoimmunity

BackgroundInorganic mercury (Hg) induces a T-cell dependent, systemic autoimmune condition (HgIA) where activating Fcγ-receptors (FcγRs) are important for the induction. In this study we examined the influence of activating FcγRs on circulating levels and organ localization of immune complexes (IC) in HgIA.Methods and Principal FindingsMercury treated BALB/c wt mice showed a significant but modest increase of circulating IC (CIC) from day 12 until day 18 and day 35 for IgG2a- and IgG1- CIC, respectively. Mercury-treated mice lacking the trans-membrane γ-chain of activating FcγRs (FcRγ−/−) had significantly higher CIC levels of both IgG1-CIC and IgG2a-CIC than wt mice during the treatment course. The hepatic uptake of preformed CIC was significantly more efficient in wt mice compared to FcγR−/− mice, but also development of extrahepatic tissue IC deposits was delayed in FcRγ−/− mice. After 35 days of Hg treatment the proportion of immune deposits, as well as the amounts was significantly reduced in vessel FcRγ−/− mice compared to wt mice.ConclusionsWe conclude that mice lacking functional activating FcγRs respond to Hg with increased levels and altered quality of CIC compared with wt mice. Lack of functional activating FcγRs delayed the elimination of CIC, but also significantly reduced extrahepatic tissue localization of CIC.

Elimination of hepatitis B virus surface antigen and appearance of neutralizing antibodies in chronically infected patients without viral clearance

Seroconversion from hepatitis B surface antigen (HBsAg) to antibodies against HBsAg (anti-HBs) usually indicates resolution of hepatitis B virus (HBV) infection. Here, two HBV-infected patients with seroconversion to anti-HBs were found to be persistently positive for HBeAg and HBV DNA. Immunohistology of liver biopsies confirmed the expression of HBV proteins in the liver of one patient. The neutralizing ability of anti-HBs in patient sera was demonstrated by blocking HBV infection of primary tupaia hepatocytes. Analysis of the HBsAg-encoding region of HBV isolates from patients indicated the coexistence of heterogeneous HBV genomes in patients. The majority of recombinant variant HBsAg was reactive in HBsAg assays and was able to bind to anti-HBs. Circulating immune complexes (CIC) of HBsAg in patient sera could be detected by polyethylene glycol precipitation and trypsin digestion. Thus, neutralizing anti-HBs may appear in chronic HBV carriers for long periods but does not necessarily lead to complete viral clearance.

Low internal radiation alters innate immune status in children with clinical symptom of irritable bowel syndrome

Adverse health effect of low radiation is clear. The aim of this study was to determine effect of internal low radiation on innate immune status in Ukrainian children with spastic colitis as a result of Chernobyl disaster. The test population consisted of 95 participants: 75 rural participants with clinical symptom of irritable bowel syndrome, aged 4 to 18, who lived in a contaminated area exposed to radio nucleotide due to the disaster in reactor in Chernobyl nuclear power plant (categorized in three groups) and 20 healthy urban participants from Kiev, aged 5 to 15, as the control group. Internal radiation activity has been measured by gamma-ray spectrometry. Peripheral blood leukocytes were analyzed for CD16(+) subset, serum concentration of circulation immune complex was measured by the polyethylene glycol method. Phagocytic activity function was assessed by using latex article and phagocytic index were calculated. p < 0.05 was considered significant. Percent of CD16(+) cell in groups II and III increased significantly in comparison to control group (p < 0.05). Concentration of circulating immune complexes increased significantly in all study groups compared to control group (p < 0.001). Phagocytes activity and phagocyte index decreased significantly in all study groups in comparison to control group (p < 0.001). The innate immune status of study groups has changed. Our data have demonstrated that this change may be related to radioactivity from technogenic pollution due to the disaster in reactor in Chernobyl nuclear power plant.