Circulating Immune Complexes Values Research Articles

Assessing the values of circulating immune complexes in multiple sclerosis patients following immunomodulator or corticosteroid treatment

Multiple sclerosis is defined as an immune-mediated disease that affects the central nervous system, and also is characterized by the presence of immune cells and mediators which contribute to the subsidiary neuroinflammation associated with multiple sclerosis. Throughout the evolution of multiple sclerosis, it has been observed that circulating immune complexes (CICs) have higher values in these patients, especially in the acute phase of the disease. Thus, the aim of the present study was to observe, if in acute attack, relapsing-remitting multiple sclerosis patients still present high values of CICs after treatment with glatiramer and prednisone. We divided 70 patients with multiple sclerosis with high values of CICs into two treatment groups, one treated with glatiramer (Copaxone) (immunomodulatory treatment) and the other with prednisone (corticosteroid treatment). After three months of treatment, we assessed the levels of CICs of the two multiple sclerosis groups and we observed that the patients that followed the immunomodulatory treatment had lower values of CICs than the group that followed the corticosteroid treatment. In addition, another observation established was that the glatiramer treatment group had higher levels of vitamin D in the serum than the prednisone group of multiple sclerosis patients. To conclude, better outcomes, from the point of view of the results obtained from the comparative analysis of the values of CICs and vitamin D, were demonstrated by following immunomodulatory treatment.

Вміст циркулюючих імунних комплексів у хворих на дифузний токсичний зоб, ускладнений автоімунною офтальмопатією

Одним із важливих показників, що характеризує стан гуморальної ланки імунної системи організму, є рівень циркулюючих імунних комплексів (ЦІК). За умов надлишкового утворення, ЦІК зберігаються впродовж тривалого часу і можуть відкладатися в різних органах та судинах, де здатні ініціювати запальні процеси. Автоімунна офтальмопатія (АО) — автоімунне захворювання, яке являє собою комплексне ураження тканин орбіти, супроводжується інфільтрацією, набряком і проліферацією ретробулярної жирової клітковини, м’язів і сполучної тканини. АО може зустрічатися як самостійне захворювання, так і в сполученні з дифузним токсичним зобом (ДТЗ) або автоімунним тиреоїдитом. Припускають, що патогенетичні механізми прогресування АО можуть бути пов’язані з активацією автоімунних процесів в орбітальних тканинах на фоні високого рівня антитіл до рецепторів тиреотропного гормону (рТТГ). Метою роботи було дослідження вмісту ЦІК у хворих на ДТЗ, ускладнений АО. Матеріал і методи. Проведено визначення кількості ЦІК: у 24 хворих (19 жінок та 5 чоловіків) із ДТЗ віком від 22 до 67 років (середнє значення — (47,2±2,8) року), у 29 хворих (19 жінок та 10 чоловіків) на ДТЗ, ускладнений АО, віком від 18 до 71 року (середнє значення — (46,1±2,5) року) і в 16 донорів (контрольна група) відповідного віку та статі. Результати. У хворих на ДТЗ обох груп вміст ЦІК вірогідно вищий за відповідний показник у донорів: відповідно (92,7±6,1) ум. од./мл і (113,5±6,7) ум. од./мл проти (67,7±6,1) ум. од./мл, (р<0,05). У групі хворих на ДТЗ, ускладнений АО, кількість осіб із високими значеннями ЦІК істотно більша, ніж у групі хворих на ДТЗ. Так, високі значення ЦІК (100 ум. од./мл і більше) виявлено в 17 із 29 (58,6%) хворих на ДТЗ, ускладнений АО, тоді як у хворих на ДТЗ їх було 7 із 24 (29,2%). Висновки. Збільшення продукції ЦІК у хворих на ДТЗ, ускладнений АО, імовірно, є результатом активації гуморальної ланки імунної системи та підтвердженням автоімунного ґенезу захворювання. Високий вміст ЦІК може свідчити про розлад імунного гомеостазу, зокрема, про дисфункцію ретикуло-ендотеліальної системи, яка відповідає за їх елімінацію і виведення.

Borna disease virus (BDV) infection in psychiatric patients and healthy controls in Iran.

BackgroundBorna disease virus (BDV) is an evolutionary old RNA virus, which infects brain and blood cells of humans, their primate ancestors, and other mammals. Human infection has been correlated to mood disorders and schizophrenia, but the impact of BDV on mental-health still remains controversial due to poor methodological and cross-national comparability.MethodThis first report from the Middle East aimed to determine BDV infection prevalence in Iranian acute psychiatric disorder patients and healthy controls through circulating immune complexes (CIC), antibodies (Ab) and antigen (pAg) in blood plasma using a standardized triple enzyme immune assay (EIA). Samples of 314 subjects (114 psychiatric cases, 69 blood donors, and 131 healthy controls) were assayed and data analyzed quantitatively and qualitatively.ResultsCICs revealed a BDV prevalence of one third (29.5%) in healthy Iranian controls (27.5% controls; 33.3% blood donors). In psychiatric patients CIC prevalence was higher than in controls (40.4%) and significantly correlating with bipolar patients exhibiting overt clinical symptoms (p = 0.005, OR = 1.65). CIC values were significantly elevated in bipolar (p = 0.001) and major depressive disorder (p = 0.029) patients as compared to controls, and in females compared to males (p = 0.031).ConclusionThis study supports a similarly high prevalence of subclinical human BDV infections in Iran as reported for central Europe, and provides again an indication for the correlation of BDV infection and mood disorders. Further studies should address the morbidity risk for healthy carriers and those with elevated CIC levels, along with gender disparities.

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

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

Non-specific immunological determinations in Meniere’s disease: any role in clinical practice?

Several studies supported the hypothesis that an autoimmune response may be a pathogenetic factor in Meniere's disease occurrence. It has been demonstrated that the endo-lymphatic sac has an important role in the immuno-mediated reaction and it has also become evident that an immunological mechanism may be involved in the development of endo-lymphatic hydrops. The present study was carried out in order to analyse the validity of serological non-specific immune tests in determining the possible role of immune pathology in 200 Meniere's suffering patients. The immune activity was investigated determining the erythrocyte sedimentation rate (ESR), the C-reactive protein levels, the rheumatoid factor, the serum immunoglobulin levels by group, the complement levels, the lymphocyte sub-populations, the cryoglobulines, the circulating immune complexes (CIC), organ and non-organ auto-antibodies. Levels of Ig, ESR, C-reactive protein, rheumatoid factor, complement fractions and cryoglobulines were either negative or non-significant in the considered cohort of Meniere's disease suffering patients. On the other hand, in more than half of the sample group high values of CIC were found. Data concerning T-lymphocyte sub-population indicates a clear increase in T-helper compared to T-cytotoxic cells, with an increase in the CD4/CD8 ratio. The datum of particular interest concerns analysis of T-cells activation complexes. Our present findings show that early activated T-lymphocytes change and in particular changes occur in the expression of the interleukin-2 receptor. Moreover, it seems to be possible to correlate the alteration of the immunological tests and the phase of the disease. Present data showed that the immunological factor should be considered a relevant element in most of the cases of Menière's disease.

Western Blot Immunoassay for HSP-70 Antibodies in Idiopathic Tinnitus: A Preliminary Report

Our preliminary study investigated the role of nonspecific immunologic tests and immunoassay for heat shock protein 70 (HSP-70) in supporting the possibility of an autoimmune inner ear process determining idiopathic tinnitus. Thirty-six consecutive patients with idiopathic tinnitus without other otologic or autoimmune diseases and 20 healthy blood donor subjects underwent determinations of circulating immune complexes (CICs) and other nonspecific immunologic factors and immunoassay for HSP-70. The mean CIC values were 4.2 microg/mL in the tinnitus patients and 0.9 microg/mL in the control group (p = .012). Thirteen of the 36 tinnitus patients and none of the control group were HSP-70-positive. Ten of the 13 HSP-70-positive patients had CIC values higher than normal. In the tinnitus group, the mean CIC values were 6.9 microg/mL and 2.6 microg/mL in the HSP-70-positive and -negative subgroups, respectively (p = .024). It may be hypothesized that in a significant number of cases, idiopathic tinnitus could be induced by immune response to inner ear-specific HSP-70.

Squamous cell carcinoma antigen, circulating immune complexes, and immunoglobulins in monitoring squamous cell carcinoma of head and neck: a study of the hellenic co-operative oncology group (HeCOG).

This study investigates the clinical utility of squamous cell carcinoma antigen (SCC-Ag), circulating immune complexes (CIC), and immunoglobulins (IgA, IgG, IgM) in the diagnosis, monitoring, and prognosis of 117 squamous cell carcinoma of the head and neck (SCC-HN) patients having local and/or systemic treatment. Serum marker levels were measured in a prospective study. SCC-Ag was positive in 28.2% of patients, the CIC in 63.2%, the IgA in 11.1%, the IgG in 15.4%, and the IgM in 9.44%. Statistically significant correlation was found between the initial SCC-Ag levels and tumor localization, whereas the CIC levels were increasing significantly with progressing disease stages. It was also found that the significant decrease of SCC-Ag, IgA, and CIC levels at the end of treatment was correlated with an increased incidence of disease-free status. The initial values of IgG and the disease stage were significantly correlated with a favorable treatment outcome. The pretreatment elevated SCC-Ag and IgM serum values showed a significant trend to predict a disease progression. Using a Cox proportional hazards model the IgG serum values, the primary site, and the disease stage were significant predictors for time to progression. The significant decrease of SCC-Ag, IgA, and CIC values at the completion of treatment was correlated with an increased incidence of disease-free status. This study indicates that only the estimation of SCC-Ag and in some degree the IgM and/or IgG is a potential tool for monitoring the efficacy of treatment or disease recurrence in SCC-HN.

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.

Circulating immune complexes in sera from patients with Alzheimer's disease and subjects with age-associated memory impairment.

Before, we reported a higher frequency of circulating immune complexes (CIC) in the sera from institutionalized Alzheimer's disease (AD), multi-infarct dementia and Down's syndrome patients than from age-matched controls. In this study, we tested the presence of CIC in the sera from an extended series of hospitalized AD patients, AD patients living in the community, from age-associated memory impairment (AAMI) subjects as well as from nursing home and community controls. We used two methods to measure CIC, C1q binding Elisa (C1qB-Elisa) and conglutinin binding (KgB-Elisa). The AD patients showed the highest frequency of positive findings and differed from the controls in KgB (42% vs. 17%) (Chi-square, p = 0.01) and C1qB (30% vs. 11%) (p < 0.05). In severe AD, 14/19 patients were KgB positive and 11/19 were C1qB positive and differed from controls. The frequency of CIC for the patients with moderate or mild dementia, the AAMI subjects and controls was similar. In the multivariate linear regression analysis, high CIC values of the AD patients significantly associated with a long disease duration and a history of recurrent urinary infections but not with age, sex, hospitalization, or the Mini-Mental Status score. We conclude that AD patients with severe dementia frequently show CIC but those with mild or moderate disease do not. The CIC relate to a long disease duration and a history of recurrent urinary infections.

Characteristic of the immune status in persons working with videoterminals

The content of immunoglobulins (IgG, IgA, IgM) as well as circulating immune complexes (CIC) is determined in the blood scrum of 58 programmers working with videodisolay terminals (VDT) and 19 employees not working or seldom using VDT. The higher IgG and IgA levels are revealed, with most of the persons having the exceeding norm of IgA and CIC values in the basic group. The considerable influence of work satisfaction on IgA and IgM levels and expression degree of working and chronic organization stress on CIC levels is revealed: index levels being lower at work satisfaction and at low values of stress scales. The influence of the electromagnetic 9200 kHz range fields on the indices of the immune status is not detected. It is concluded that the immune system is made more active at work with VDT and the psychosocial factors are of great importance in this process.

Circulating immune complexes in sera from patients with Alzheimer's disease, multi-infarct dementia and Down's syndrome

Recent data suggest that immunological mechanisms may be implicated in the pathogenesis of Alzheimer's disease (AD). We tested the presence of circulating immune complexes (CIC) in the sera from dementia and Down's syndrome (DS) patients and age-matched controls using two methods: C1q-binding Elisa (C1qB-Elisa) and conglutinin-binding Elisa (KgB-Elisa). The probable AD and multi-infarct dementia (MID) patients had more frequently CIC in their sera as compared to elderly non-demented subjects (Chi-square; P<0.05). The highest frequency of positive findings was detected for 10 DS patients (8 KgB-Elisa and 7 C1qB-Elisa positive) whereas only 1 of 10 young controls showed C1qB-positivity. In the AD patients the cognitive decline as assessed by the Mini-Mental Status test correlated significantly with CIC values. The study supports the view that systemic autoimmune mechanisms may be involved, at least partly, in dementing processes.

Role of circulating immune-complexes as prognostic indicators of lympho-reticular and mesenchymal malignancies in children.

Circulating immune complexes (CIC) were estimated in 28 cases of Non-Hodgkin's lymphomas, Hodgkin's disease, bone and soft tissue sarcomas in the pediatric age group by polyethylene glycol (PEG) precipitation and latex agglutination inhibition (LAI) techniques. Results were compared with 25 age-matched controls. Highly significant CIC values were obtained by LAI technique (P less than 0.01) as compared to PEG pptn technique (P less than 0.05) in malignancy. However, seropositivity for CIC in lymphomas and Hodgkin's disease was 85.71 per cent by LAI test as compared to 57.14 per cent by PEG pptn test. In sarcoma group, seropositivity for CIC was 57.11 per cent by LAI test and 28.57 per cent by PEG pptn test. Combination of both these tests increases the sensitivity of immune complex detection in serum of cancer patients. CIC begin to rise in serum in early stages of neoplastic transformation, and the level of CIC is directly proportional to proliferating tumour mass in vivo.

The value of tumour markers in lung cancer.

The pre-treatment serum levels of neuron-specific enolase (NSE), phosphohexose isomerase (PHI) and circulating immune complexes (CC) as tumour markers were compared to measurements of standard haematology and biochemical indices in 73 patients with lung cancer, as an aid to differentiation of tumour type, estimating disease extent, predicting response to therapy and prognosis. Elevated NSE greater than or equal to 12.5 ng ml-1, PHI greater than or equal to 55 mgl-1 levels were observed in 55% of cases for NSE, 90% for PHI and 49% for CC. NSE was significantly elevated in 61% (25/41) of patients with SCLC (P less than 0.005) compared to 41% (13/32) with NSCLC. CC levels were significantly raised in 72% (23/32) of patients with NSCLC (P less than 0.05) compared to 32% with SCLC. The levels of NSE and PHI were not related to tumour stage but CC was significantly raised in limited compared to extensive disease in SCLC (P less than 0.05). Serum albumin was significantly lower in NSCLC compared to SCLC, and median values of alkaline phosphatase, gamma-glutamyltranspeptidase and aminoaspartate transferase were significantly higher in patients with extensive disease. The pre-treatment serum values of NSE, PHI, and CC did not predict the response to therapy or prognosis in the 73 patients with lung cancer. The most important prognostic factor was the number of abnormal routine laboratory parameters (greater than 4) in this group of patients.

Evaluation of neutrophil activity and circulating immune complexes levels in diabetic patients.

We have studied chemiluminescence produced by neutrophils stimulated by opsonized zymosan in insulin dependent (IDD) and non insulin dependent (NIDD) diabetic patients. Chemiluminescence was evaluated as the integral and maximum peak, total time and time to maximum peak of the response curve to opsonized zymosan. These values were then compared with circulating immune complexes (CIC) and glucose levels. Both IDD and NIDD patients had significantly higher values of chemiluminescence and CIC than normal controls. We also observed that patients who had the highest values of CIC and chemiluminescence levels were the ones with clinical microvascular complications.

Clinical importance of circulating immune complexes in human acute lymphoblastic leukemia.

A total of 122 sera from acute lymphoblastic leukemia (ALL) patients were analyzed for circulating immune complexes (CIC) by two methods: the 125I-Clq binding assay and the polyethylene glycol precipitation test (PEG). The results were correlated with induction, remission and relapse stages of the disease. Using the first method the levels of CIC in induction were 15.18 +/- 9.15, with 19/29 positive cases (65.50%), P less than 0.001 compared with controls. In the remission phase the levels were 9.02 +/- 5.62, 11/45 (24.49%) nonsignificant P value, and in relapse they were 16.14 +/- 11.17 28/48 (58.33%) P less than 0.001. The PEG precipitation test results were: 0.33 +/- 0.10, 8/22 (36.36%); 0.24 +/- 0.11, 10/48 (20.83%) and 0.28 +/- 0.10, 6/28 (21.42%), respectively. Thus the values of CIC as measured by PEG in the three clinical of phases ALL did not differ significantly from controls. This contrasts with results obtained by the radioiodinated C1q binding assay, where the incidence of positive values was significantly higher in induction and in relapse and lower in the remission phase. These observations were extended in sequential vertical studies performed in a group of patients. These results suggest that raised CIC detected by the 125I-C1q method may reflect a progressive state in ALL and that quantitation of these immune complexes may provide an adequate biochemical marker for prognosis.

Immune complexes in retinitis pigmentosa.

In a group of 46 patients with retinitis pigmentosa (RP) we studied the presence of circulating immune complexes (CIC) and the alterations in the complement system. Our results showed the presence of CIC in 43.5% of the patients studied, reduced levels of the complement components C3 and C4 (p less than 0.001), and of the haemolytic activity CH50 (p less than 0.001) when compared with a control group consisting of a 100 healthy subjects. We found a statistically significant correlation between the values of C3 and CIC (p less than 0.01), C4 and CIC (p less than 0.01), and between CH50 and CIC (p less than 0.001). These findings indicate that the CIC may play a role in the pathogenesis of primary retinitis pigmentosa.

Serum lysozyme and circulating immune complexes in patients with leprosy

Fifty-eight leprosy patients were tested for serum lysozyme and circulating immune complexes (CIC). Serum lysozyme activities were measured by lyso-plate method and CIC were detected by Clq solid-phase radioimmunoassay using 125I labeled protein A.The mean of serum lysozyme activity in lepromatous leprosy patients with ENL was significantly greater than that of healthy controls. The mean values were 30.6±17.0μg/ml for lepromatous patients with ENL, 12.5±5.2μg/ml for lepromatous patients without ENL, and 9.9±3.9μg/ml for tuberculoid patients.There was found that serum lysozyme values were correlated with CIC values in sera of patients with lepromatous leprosy (r=0.63, p<0.01).According to the serial observations of 3 lepromatous cases for about 6 months, it was found the serum lysozyme activities were increased just after the treatment with RFP and decreased by treatment with steroid or thalidomide. And the degrees of increasing or decreasing of serum lysozyme activities associated with drug therapies were larger than that of CIC. These results seemed to support that serum lysozyme may be a more useful parameter clinically than CIC for treatment and control of ENL reaction.

Immune complexes in retinitis pigmentosa.

In a group of 46 patients with retinitis pigmentosa (RP), we studied the levels of IgM, the presence of a rheumatoid factor (RF), the circulating immune complexes (CIC) and the alterations in the complement system. Our results showed increased IgM levels in two patients (226 and 260 mg/dl), the presence of RF in three patients (205, 187 and 80 IU/ml), the existence of CIC in 43.5% of the subjects, reduced levels of the complement components C3 and C4 (p less than 0.001) and of the haemolytic activity CH50 (p less than 0.001) when compared with a control group consisting of 100 healthy subjects. We found a statistically significant correlation between the values of C3 and CIC (p less than 0.01), C4 and CIC (p less than 0.01) and between CH50 and CIC (p less than 0.001).

The platelet factor 3 assay and circulating immune complexes as studied on non-thrombocytopenic patients with systemic lupus erythematosus.

Sera from 21 patients with systemic lupus erythematosus (SLE) were tested with a platelet factor 3 (PF3) assay. A control serum (pooled blood group AB serum) was always run in parallel with the test sera. The test and control sera were run in duplicate and for each patient the mean recalcification time was used for the calculation of the test serum: AB serum ratio. Concomitantly, the patients' serum concentrations of circulating immune complexes (CIC) were measured by using the Raji cell radioimmunoassay. 20 healthy hospital employees served as controls. In the latter subjects the mean test serum: AB serum ratio was 0.99 (range 0.92-1.09), their CIC concentrations being less than or equal to 16 micrograms/ml. 7 of the SLE patients had CIC values less than or equal to 16 micrograms/ml, and their test serum: AB serum ratios ranged 0.95-1.09. All the remaining SLE patients had elevated values for CIC. In the total material of SLE there was a highly significant (r = -0.87; P less than 0.001) negative correlation between the test serum: AB serum ratios and the values for CIC. It is widely held that the so-called PF3 immunoinjury test detects circulating antiplatelet antibodies. The present results, however, strongly suggest that the assay rather or also detects CIC which like antiplatelet antibodies may damage platelets as we and others have shown in prior publications.

Evidence that circulating immune complexes remove transfused platelets from the circulation.

Fifteen recently diagnosed patients with acute leukemias admitted for induction chemotherapy were selected for study. When thrombocytopenic (venous platelet count less than 20 X 10(9)/l) these patients received prophylactic platelet transfusions. A total of 67 platelet transfusion therapies were administered and evaluated. Using the Raji cell radioimmunoassay, the serum concentrations of circulating immune complexes (CIC) were measured immediately before and 10-12 hr after each platelet transfusion. In 36 instances, elevated values of CIC were present in the recipient's pretransfusion samples. The corresponding posttransfusion values being significantly lower (P less than 0.05). Furthermore, in those 36 instances the mean percentage for the posttransfusion platelet increment was significantly lower (P less than 0.001) than in the remaining 31 instances in which normal pretransfusion values of CIC were measured. We conclude that CIC were an important factor in rapidly removing transfused platelets from the circulation, thereby, adversely affecting the benefit of platelet transfusions.