The complement system and circulating immune complexes in burn patients

The results of the study of humoral immunity in 80 burn patients are presented. A typical feature of all burn patients was a decrease in the total activity of the alternative path of the activation of complement and its factors B and D, beginning from the first day after the trauma. The character of changes in the functional activity of components C1-C5 of the classical path depended on the area of damages with their activation if burn area was less than 20% of the skin surface and deactivation if the burn area exceeded 20%.     

High levels of circulating interleukin-10 in diabetic nephropathy patients

AIMS: The aim of our study was to analyse the level of circulating interleukin-10 (IL-10) and relate it to the grade of albuminuria in patients with diabetic nephropathy (DN) due to type 1 diabetes mellitus (DM). Since IL-10 has met the criteria for an anti-inflammatory and an immunosuppressive cytokine, its activity may be important for clinical outcome of DN. METHODS: The IL-10 level was measured by ELISA in serum samples from thirty patients with DN due to type 1 DM, and compared with thirty patients with type 1 DM without DN and a control group of thirty, healthy, age- and sex-matched people. RESULTS: We observed a greatly elevated concentration of circulating IL-10 in 30/30 DM patients with DN (mean 140 pg/mL +/- 102), compared to DM patients without DN in whom IL-10 was detectable in only 11/30 patients (0.79 pg/mL +/- 1.24), and the group of healthy people in whom IL-10 was detectable in only 3/30 donors (0.92 pg/mL +/- 0.17). IL-10 appeared to be the strongest independent predictor of albuminuria, followed by HbA1c, diastolic blood pressure and DN duration. There was a positive correlation between the values of IL-10 and albuminuria in DM patients with DN. The patients in the fourth quartile of albuminuria had a distinctly higher concentration of IL-10 than those in the lower quartiles. CONCLUSIONS: The increased concentration of IL-10 in the serum samples from DM patients with DN seems to depend on the severity of the nephropathy. The excessive IL-10 production may indirectly contribute towards DN progression. On the other hand, it may explain the relatively long course of diabetic nephropathy.     

Evaluation of circulating immune complexes in lymphomas and leukemias using two different assays

Summary Circulating immune complexes (CICs) have been detected in the sera of patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease, chronic myeloid leukemia, and acute lymphoblastic leukemia by using C1q-binding and L1210-binding assays. Both assays gave broadly similar patterns of reactivity in terms of frequency and magnitude, though there are some differences. Significantly elevated CIC levels were observed in all pathologic groups. However, sera from NHL patients with an unfavorable prognosis consistently exhibited the highest frequency of positive values and mean CIC levels in both these assays.The two tests showed concordance in 66.6% of the NHL patients' sera and were significantly correlated. Of the sera from NHL patients 12.7% were positive in the C1q-binding assay only and 15.9% in the L1210-binding assay only. Both the assays gave positive results in some patients, and a degree of overlap indicates the presence of different types of CIC in cancer patients' sera. The combined use of two methods for detecting CICs may be useful for evaluation of the activity, the extent, and the prognosis of the malignant disease.     

Characterization of circulating and cutaneous IgA immune complexes in patients with dermatitis herpetiformis

Dermatitis herpetiformis (DH) is a chronic, blistering skin disease characterized in part by deposits of IgA at the dermal-epidermal junction. Eighty-five percent of DH patients have granular IgA deposits and have an associated gluten-sensitive enteropathy (GSE). In contrast, 15% of DH patients have a linear pattern of IgA deposits and no associated intestinal abnormality. Although circulating IgA antibodies against skin are not present in these patients, 40% of DH patients do have IgA-containing circulating immune complexes (IgA-CIC). The role and origin of the cutaneous IgA and the IgA-CIC in patients with DH are unknown; however, the association of GSE with the granular IgA deposits suggests that a mucosal immune response may be important in the pathogenesis of DH. We have characterized the IgA subclass composition of the cutaneous IgA deposits in patients with DH, and have isolated and characterized the IgA-CIC from these patients. Twenty-nine of 29 patients with DH and granular IgA deposits were found to have only IgA1 deposits. Ten of 11 patients with linear IgA deposits also had only IgA1 deposits; one of 11 had IgA2 deposits. Isolated IgA-CIC from the sera of eight patients with DH and granular IgA deposits were found to contain both IgA1 (58% +/- 5, mean percent of total IgA +/- SEM) and IgA2 (42% +/- 5), as were IgA-CIC from two patients with ordinary GSE without cutaneous IgA deposits. The IgA subclass composition of the isolated immune complexes was significantly different from the serum IgA1 and IgA2 composition (serum IgA1 = 76% +/- 6; IgA2 = 24% +/- 5, p less than 0.025, Student's t-test), and suggests that the IgA-CIC may arise from gut-associated lymphoid tissue (GALT). Sequential anti-IgA1 absorption of serum which contained IgA-CIC did not remove all the IgA-CIC, suggesting that the complexes circulate as separate IgA1 and IgA2 complexes. The finding of IgA1 alone in the skin of patients with DH suggests that the cutaneous IgA may not arise from GALT, or that IgA1, possibly arising in GALT, is preferentially bound to DH skin. Because IgA-containing CIC which contain both IgA1 and IgA2 were found in the serum of patients with DH and with ordinary GSE, it seems unlikely that IgA-containing CIC are responsible for the cutaneous IgA deposits seen in DH.     

Treponemicidal activity of anti-treponemal lymphotoxins and their relation to circulating immune complexes and autolymphocytotoxins

Abstract It was previously reported that spleen cells of rabbits infected with Treponema pallidum produced anti-treponemal lymphotoxins (ATL). This ability was distinctly disturbed when circulating immune complexes (CIC) and autolymphocytotoxins (AL) were present in the sera of cell donors. ATL liberated from cells of donors without CIC and AL displayed a marked ability to immobilize treponemes. The percentage of immobilized treponemes varied according to the type of cells used for ATL liberation and their density. The most active was ATL from T cells (density 4 × 10⁸ ml⁻¹) and the weakest was the one from B lymphocytes. In the presence of CIC in sera of cell donors the weakest ATL was from macrophages and in the presence of AL from T lymphocytes. When both factors (CIC and AL) were present ATL from T lymphocytes did not immobilize treponemes. This seems to suggest that the impairment of the cells' ability to produce ATL may facilitate the survival of treponemes in the host despite the presence of immunologically competent cells.     

Stage-associated incidence of serum circulating immune complexes in patients with untreated bronchogenic carcinoma

Summary Serum circulating immune complexes were quantitated by means of a C1q-binding enzyme-linked immunosorbent assay in the serum from 46 untreated bronchogenic carcinoma patients, and the results compared with those obtained in 48 patients with nonmalignant thoracic diseases and 75 normal healthy donors. The incidence and levels of serum immune complexes in the bronchogenic carcinoma patients were found to be akin to those previously observed, and no modifications of their levels were found to result from surgery. We also found a high degree of association between the presence of immune complexes and the lung cancer stage as defined by the tumor (T), node (N), metastasis (M) system. However, our data indicate that their occurrence has neither a prognostic value, as determined after analyzing the late outcome of the patients, nor a diagnostic one, since the incidence of immune complexes in patients with nonmalignant thoracic diseases was found to be similar to that in the bronchogenic carcinoma patients.     

Evaluation of neutrophil acetyltransferase activity in patients with inflammatory disorders

The acetyltransferase activity of neutrophils from patients with inflammatory disorders was assayed using the homogenate preparation of neutrophils. The enzyme activity was evaluated on both non-stimulated and stimulated neutrophils. The enzyme activity of neutrophils from 21 patients with rheumatoid arthritis and 10 patients with Behcet's disease was not significantly different from that of the control group. In contrast, it was significantly elevated in patients with bacterial infection, especially that of non-stimulated cells. The increase in the enzyme activity best correlated with the degree of fever. The elevated enzyme activity tended to normalize during convalescence.     

Free and bound Brucella antigen and the level of circulating immune complexes in brucellosis patients

The aggregate hemagglutination test has been shown to be a highly sensitive and specific method for the detection of infectious antigenemia in different forms of brucellosis, permitting the determination of free Brucella antigen in 34% of patients with the acute form of the disease and in 53% of patients with the chronic course of brucellosis. The results of the determination of the quantitative level of circulating immune complexes (CIC) indicate that in the acute form of the disease their level exceeds the CIC level observed in the chronic course of brucellosis. The preliminary dissociation of CIC in the patients' blood sera has been found to increase the overall release of Brucella antigen to 80%.     

Specific circulating immune complexes and antibody titers in candidiasis]

Titers of antibodies to Candida albicans and specific circulating immune complexes have been studied in patients with chronic candidiasis of the genitals, skin and mucous membranes. In most patients with candidiasis of the skin and mucous membranes specific immune complexes have been detected in the blood serum; their determination increases the diagnostic value of serological tests in this disease.     

Blood levels of immunoglobulins G,A,M, circulating immune complexes, complement and proteins in patients on intermittent peritoneal dialysis

The study involved 17 patients on IPD. Blood serum levels of IgG, IgA, IgM, circulating immune complexes, complement and proteins were determinated at the beginning of therapy, after 3, 6, 12 months on IPD and after 1 year on hemodialysis. The frequency of peritonitis was noted during this time. Peritonitis was the most frequent during first 3 months on IPD. No differences in blood serum levels of IgG, IgA, IgM, in the specific periods of IPD were noted. A significant increase in blood serum circulating immune complexes in patients on IPD and hemodialysis compared to the control group was found. A significant decrease in blood serum of C3 complement in patients on IPD and hemodialysis in comparison with the controls were found. A significant decrease in blood serum proteins at the beginning of IPD and after 3 months IPD in comparison with proteins concentration in patients on hemodialysis was observed.     

Ultrastructural study of circulating immune complexes in three hemopathic diseases

Summary Polyethylene glycol precipitation (PEG) is a technique commonly used for the dosage of circulating immune complexes (CIC). Ultrastructural analysis of these precipitates shows vesicles, lamellar fragments with cell membrane structure and lipid-like inclusions on a proteinaceous background. These morphologically characterized elements are noticed both in normal individuals and in hemopathic patients (acute lymphoid or myeloid leukemia, hematosarcoma). Their number is higher in the patients, however, and the cholesterol/protein ratio is significantly elevated in pathological precipitates. In the present state of our observations it is premature to tell whether they are precipitated with CIC or represent the real antigens.     

Recovery of a cell surface fetal antigen from circulating immune complexes of melanoma patients

Summary A well-characterized 69.5×10³ dalton glycoprotein fetal antigen (FA), isolated from the spent culture medium of a melanoma cell line, UCLA-SO-14 (M14), was utilized to characterize the antigen component of circulating immune complexes (CIC) from melanoma patients. Ten serum samples from five patients with stage II melanoma at 1 and 4 months prior to the clinical detection of recurrent disease were selected for study. The CIC were dissociated with low pH and ultrafiltered through a 100¢10³ dalton exclusion limit membrane. The low pH treatment resulted in an increase in antibody titer in eight of ten serum samples. The antibody activity in membrane immunofluorescence was quantitatively inhibited by the filtered antigen fraction and purified FA, suggesting the presence of anti-FA antibodies in the treated serum, which possibly were complexed with FA in the untreated sample. As determined by competitive inhibition in an enzyme-linked immunosorbent assay, the filtrate (antigen fraction) contained an antigen that was immunologically similar to FA. These results clearly demonstrate that FA, expressed on the cell surface of melanoma cells, is present in CIC of selected melanoma patients.Supported in part by NIH grants CA 30019, CA 12582, CA 09010, CA 29605 awarded by DHSS     

Serial tests of the change in concentration of circulating immune complexes in healthy subjects and in tumor patients

Authors performed by using various tests serial examinations of the circulating immune complex (IC) concentration in healthy persons, untreated rats, as well as in patients with multiple myeloma or leukemia, and in immunocytoma bearing rats. A characteristic fluctuation of the IC values has been observed in the untreated rats and the healthy persons. The discrepant IC values obtained in the identical sample with the different tests suggest the heterogeneity of IC components. As compared to healthy individuals a significantly higher fluctuation of IC values has been found characteristic in immunocytoma. Authors analyzed the composition of IC and discussed the possible importance of the tumor specific antigens and the natural antibodies reacting with them.     

A method for determining specific circulating immune complexes in patients with acute Sonne dysentery]

The antigen-specific method for the determination of specific immune complexes in the blood serum of patients with acute Sonne dysentery has been developed on the basis of the enzyme-linked immunosorbent assay with the use of reagents manufactured in the USSR. The possibility of the early prognostication of prolonged carrier state by using the proposed method for the determination of the level of specific circulating immune complexes has been shown.     

Comparative study of assays detecting circulating immune complexes and specific antibodies in patients infected with Toxocara canis

A sandwich ELISA method using previously described E/S antigen-specific monoclonal antibodies has been developed to detect circulating immune complexes in patients infected with Toxocara canis. This technique could be used for the study of the dynamics of the parasite-host relationship, as we believe the detection of immune complexes and/or soluble antigen to be an improvement over detection of antibodies only. In this parasitosis, antibodies may be present in residual levels for prolonged periods after active infection.