Circulating immune complex levels measured by new ELISA kits utilizing monoclonal anti-C1q and anti-C3d antibodies correlate with clinical activities of SLE but not with those of RA

The authors studied sera from both patients with SLE and from those with RA to evaluate clinical usefulness and significance of circulating immune complexes (CIC) detected with new ELISA kits utilizing monoclonal anti-C1q and anti-C3d antibodies. CIC values of patients with SLE significantly correlated to severity of disease activities evaluated by clinical symptoms and laboratory tests, especially for serum complement levels. Since substances detected with the ELISA kits were closely related to serum complement components, it was determined that a direct relationship exists between clinical activities and CIC values appearing in SLE patients with hypocomplementemia. In RA patients, CIC values did not correlate to clinical activities evaluated by Lansbury's index, anatomical bone damage with X-ray or functional assessment of activities of daily living, but did significantly correlate to levels of IgM-RF, serum IgG concentrations and some markers of systemic inflammation. Detection of IC after fractionation of RA sera revealed a broad range of molecular sizes detectable with the ELISA kits, which indicated that CIC in vivo were heterogenic and complicated in formation, degradation and interaction with serum complements.     

Detection of circulating immune complexes in patients with squamous cell carcinoma of the oral cavity

Circulating immune complexes (CICs) have been quantitated from the sera of untreated oral cancer patients and those treated with radiation or surgery using C1q binding assay in terms of percent binding activity (C1q BA) and microgram/ml equivalent of aggregated human gamma globulin (AHG). Sera from a total of 108 oral cancer patients and 47 normal healthy donors were evaluated for CICs. Out of these, 48 patients were tested before treatment and 60 were tested 6 months to 1 yr after treatment. Levels of CICs were elevated in 70.8% patients before treatment (mean % C1q BA 29.6 +/- 2.2) when compared to healthy controls (4.2% positive, mean % C1q BA 9.0 +/- 0.8). Treated patients showing no evidence of the disease had reduced CIC levels, only 11.7% patients showing C1q BA at the level of 13.2 +/- 1.4. On the other hand, treated patients showing recurrence of the disease had much higher CIC levels (mean % C1q BA 42.8 +/- 3.5, 92.3% positive) even higher than the untreated patients. Status of CIC levels as well as recurrence rate in patients treated with either radiation or surgery were comparable. One out of 4 individuals with premalignant changes such as oral leukoplakia showed elevated levels of CICs.     

Circulating immune complexes in sarcoidosis

Circulating immune complexes (CIC) were detected in 100 out of 112 sera from 33 sarcoidosis patients. Five tests were used representing three different basic principles. All patients had detectable CIC at some stage of their disease. The three platelet tests detecting IgG complexes exhibited the highest positive titres in the acute cases. The ClqB-ELISA test, which detects complement fixing IgG complexes, was the test most frequently positive in the chronic cases. The presence of extra-pulmonary lesions or corticosteroid therapy did not influence the appearance or disappearance of CIC. No positive correlation was found between CIC and elevated levels of serum angiotensin-converting enzyme (ACE) and/or serum lysozyme (LZM). The evaluation of CIC in sarcoidosis requires a battery of different tests carried out at regular intervals during the follow up.     

Serial circulating immune complexes and mononuclear phagocyte system function in infective endocarditis

Twenty patients with infective endocarditis were followed prospectively and all had elevated levels of circulating immune complexes (CICs) detected by staphylococcal binding assay. Mean CIC levels declined for the group as a whole (193 micrograms/ml +/- 24 to 100 +/- 17, p less than 0.05) and became undetectable in eight patients (47%) who were cured. Patients who died or had complicated courses had higher mean CIC levels at the start and finish (254 micrograms/ml +/- 24 and 145 +/- 37) of antibiotic therapy than patients with uncomplicated courses (178 micrograms/ml +/- 19 and 38 +/- 24), p less than 0.05. CIC levels did not decline significantly in patients with glomerulonephritis or arthritis, in contrast to patients without these features. Despite elevated CIC levels, 10 patients had enhanced mononuclear phagocyte system (MPS) function as assessed by Fc-dependent IgG-coated red blood cell clearance. These data suggest that CICs probably are pathogenic in endocarditis and may contribute to the development of arthritis and glomerulonephritis. Elevated CICs in infective endocarditis do not appear to be directly related to defective MPS function.     

Circulating immune complexes in pulmonary tuberculosis

The presence of circulating Immune complexes (CIC) in sera from patients with pulmonary tuberculosis was demonstrated by 3 techniques (a) latex agglutination (b) 3.5% PEG precipitation and determination of optical density (O.D.) at 280 nm and (c) radioimmunoassay (RIA) of CIC using bovine spermatozoa. 40 normal control sera and 100 T.B. patients sera were included in the study. 12% cases were positive for CIC by all the 3 methods mentioned above, 13% were negative by all the 3 methods and the remaining patients were positive by one or more methods of detection. To correlate the levels of CIC as detected by different techniques with the activity of the disease, patients were broadly grouped as (a) sputum positive and (b) sputum negative. Higher levels of CIC were obtained in sputum positive cases than sputum negative by all the 3 methods studied. While IgG, IgA and IgM were elevated in the CIC of T.B. patients, and IgG and IgA were also present in controls, IgM immunoglobulins were detected only in patients and not in controls. The effect of antitubercular treatment on the levels of CIC was also evaluated and it was found that the levels of CIC remained unchanged even after prolonged chemotherapy.     

猪血补体成分在人循环免疫复合物测定中的应用

为更好测定人血清循环免疫复合物（ＣＩＣ），从新鲜猪血中据取高纯度的猪血补体成分Ｃ１ｑ，采用酶联免疫吸附技术建立了猪血Ｃ１ｑ测定ＣＩＣ的方法。人血清ＣＩＣ测定结果用热凝集免疫球蛋白（ＡＨＧ）表示，正常人群血清ＣＩＣ＜３３ｍｇ／ＬＡＨＧ。测定３７例急性肾小球肾炎和１４例川崎病患者，其血清ＣＩＣ浓度在发病急性期普遍升高，经过治疗缓解或病愈后，ＣＩＣ浓度逐步降为正常水平。该法所用的猪血来源丰富，可避免乙型肝炎、艾滋病源的污染，降低了实验背景的测定值，使结果更接近于真实水平，有助于临床对免疫复合物性疾病的诊断及疗效判断。     

Serum neopterin in hepatitis B]

Activation of the immunity system commonly followed the development of viral diseases. Neopterin is evidently a marker of the activation. Elevation of neopterin levels in AIDS and tumor patients correlates with the severity of the disease. Radioimmunoassay of neopterin content was performed in the sera of 11 patients with virus B hepatitis (6 patients with its acute pattern, 3 with its acute pattern concurrent with delta-infection and 2 subjects with chronic active virus B hepatitis). Mean neopterin content in the sera of virus B hepatitis patients was 19.9 +/- 5.7 nM/l being significantly higher than that in donors (5.0 +/- 0.8 nM/l) (p less than 0.001). In this line neopterin levels higher than 9 nM/l (the upper normal limits) were identified in 63% of the patients. Mean content of beta-2-microglobulin in hepatitis patients was 3.3 +/- 0.53 mg/l being significantly different from that in donors (1.8 +/- 0.3 mg/l) (p less than 0.05). Association between higher neopterin levels and the severity of the disease was fully proved clinically, with the exception of the two expired persons whose neopterin levels were within normal limits. The data obtained evidenced an increase in neopterin levels associated with virus B hepatitis. It widened the understanding of the disease pathogenesis and permitted the determination of neopterin levels be used in correlation with clinical data as a prognostic value for the course of the disease.     

HBsAg as the antigen component of circulating immune complexes in HIV-infected patients.

Seeing the same transmission pattern of HIV and HBV coinfection by these two agents is not an uncommon feature. Immunity impairment due to HIV infection can be the cause of a higher rate of HBV replication with less intensive liver damage and less effective immune response to HBV, while the pathological course in both infections involves elevated levels of circulating immune complexes (CIC). These were the reasons for us to examine the frequency of HBsAg involvement as the antigen component of circulating immune complexes formed in sera of HIV-infected patients in different stages of HIV disease. We tested 67 sera of HIV-positive patients in different stages of HIV disease for the presence of HBsAg and HIV antigen p24 (with and without acid dissociation of immune complexes), for the presence of anti-Hbc antibodies and circulating immune complexes. HBsAg was positive in 13.8% sera prior to and 33.8% after acid pretreatment. Anti-HBc antibodies were present in 76.9% serum samples tested. Fifty percent of sera were positive for both HBsAg and p24 antigen after dissociation of immune complexes. The level of CIC was elevated in 65.9% of sera. Our results suggest that HBsAg is commonly associated in immune complexes formed in the sera of HIV-infected patients and that they may simultaneously contain HIV and HBsAg in patients coinfected with both agents. This may contribute to their mutual interaction and influence the diagnosis and follow-up of patients.     

Antigen/antibody content of circulating immune complexes in HIV-infected patients

Dual infection with HIV and hepatitis B virus (HBV) is not an uncommon feature. Immunity impairment due to HIV infection can be the cause of a higher rate of HBV replication with less intensive liver damage and less effective immune response to HBV. Many HIV-infected patients have an elevated level of circulating immune complexes (CIC) in serum, throughout all stages of illness evolution. The aim of our study was to estimate p24 and HBsAg content of CIC in dually infected patients, and the prevalence of major classes of complexed antibodies (IgM and IgG). We examined 146 samples of sera from 105 HIV positive patients of the Institute for Infectious and Tropical Diseases during 1992 and 1993. On those sera we performed p24Ag and HbsAg detection, with and without prior dissociation of CIC, we determined serum level of CIC and immunoglobulin classes IgM and IgG level in sera and in polyethilenglycol (PEG) precipitates of sera. Acid dissociation of immune complexes revealed a high proportion of HIV antigen positive sera in all stages of HIV disease progression. HbsAg in serum of HIV positive patients was also found coupled in immune complexes much more frequently than in the HIV negative control group. In many instances both antigens were simultaneously found coupled in CIC. Immune complexes detected have been shown to contain both IgM and IgG immunoglobulins, while IgM antibodies were associated to immune complexes in higher proportion than IgG, compared to total serum immunoglobulins.     

Antibody response of patients with poliomyelitis to virus recovered from their own alimentary tract

Of 20 strains of virus recovered from 40 patients with poliomyelitis only 9 possessed a titer of 10(-3) or more, permitting significant quantitative neutralization tests in monkeys. Seven of the 9 high titer strains were derived from patients whose illness was ultimately paralytic, and tests with their undiluted sera indicated that the acute phase as well as the 3 month convalescent specimens neutralized maximum amounts of the patient's own virus. However when varying dilutions of the sera were tested against a single dose of virus, it was found that the antibody was present in lowest concentration early after onset and progressively increased in titer over a period of weeks during convalescence. The 2 remaining high titer strains were recovered from patients with a non-paralytic illness, and in both of these the acute phase sera were without significant amounts of antibody for their own virus. Antibody was demonstrable at 14, 28, and 92 days after onset in one of these patients, while the other had none at 1 month and only a minimal amount at 3 and 8 months. Tests with the Lansing virus on the same sera, clearly established the specificity of the antibody response to the strain of virus recovered from each patient under investigation. Five of the 9 patients, whose sera were studied with both viruses, had no antibody for the Lansing virus during the acute phase and none 3 months later. Two had antibody during the acute phase but serum dilution tests showed no increase in titer in the 3 month convalescent specimen. In 2 others, who were without antibody for the Lansing virus during the acute phase but had it at 3 months after onset, it was possible to show that this antibody appeared later than 1 month after the illness and that the virus recovered from these patients during their illness was not antigenically of the Lansing type.     

Immunoglobulins from the sera of immunologically activated persons with pairs of electrophoretic restricted bands show a greater tendency to aggregate than normal

From in vitro data, it has been speculated that pairs of endogenous restricted bands migrating in close proximity in the gamma region upon high resolution serum electrophoresis (HRE) represent circulating immune complexes (CIC). Using a polyethylene glycol (PEG) method to separate CIC, we found a very high correlation between the presence of such band pairs and elevated levels of CIC (CHI2 = 25.7, p less than 0.001) in 51 sera. HRE appears to be a good screening technique to identify, with a high degree of certainty, samples with elevated levels of CIC for delineation by more specific methods. Yet, examination by gel-filtration chromatography and precipitation with PEG indicated that the molecules comprising the band patterns were not CIC, but polyclonal 7S IgG. These bands are usually found in patients with chronic activation of the immune system. Fractionation of the sera from 5 such patients with various cuts of PEG indicated that the average IgG concentration in the 2.5-5%, and 5-7.5% cuts from patients was 3.99 g/l and 2.2 g/l, while from healthy subjects the concentrations were 0.68 g/l and 2.88 g/l. This reversed precipitation pattern was seen both for absolute levels of IgG and for percent of total IgG. On the average the amount of precipitation of IgG in the 2.5-5% fraction of patients was about 5-fold above that seen in the healthy subjects. The endogenous bands were not associated with any specific cut of PEG, but appeared to be proportionally distributed in accord with the levels of IgG. The data is consistent with the idea that immunologically activated patients exhibit a greater tendency for immunoglobulins to associate than normal. This propensity to aggregate may cause CIC to form in situ in local compartments even though CIC do not appear to be present upon analysis by biochemical techniques.     

Effect of the method of extracorporeal heparin precipitation of plasma proteins (selective plasmapheresis) on the level of immune complexes in the blood

A study was made of the effect of selective plasmapheresis (SPP) on the concentration of circulating immune complexes (CIC). The method is based on precipitation at 4 degrees C of plasma fibronectin and associated macromolecular complexes by means of heparin. Sterile plasma of the patient is separated from the precipitate, frozen and kept at -20 degrees C till the next plasmapheresis during which it is returned to the patient instead of the donor's one. All 15 patients examined were exposed to 6 SPP with an interval made every 2 to 5 days. Six patients were diagnosed to have rheumatoid arthritis, 2 systemic lupus erythematosus, 3 hemorrhagic microthrombovasculitis, and 4 multiple sclerosis. The concentration of CIC was measured by precipitation with 3.5% polyethylene glycol before and after SPP, in some cases between sessions. All the patients with rheumatoid arthritis and systemic lupus erythematosus and 2 out of the 3 patients with hemorrhagic vasculitis showed an elevated content of CIC (greater than 0.150 Units OD). The CIC content appeared normal in all the patients with multiple sclerosis. After SPP 4 patients manifested a reduction in the CIC concentration, whereas in 6 it returned to normal. Such a time course correlated with the improvement of other clinical and laboratory findings. It was established that after the first session of SPP the CIC content sharply declined followed by a gradual increment and exceeded the initial values toward the beginning of the second session. After the second SPP the patients manifested the same tendencies. The CIC content reached a maximum by the third SPP and then fell from session to session.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of human ventricular myosin light chain-1 by monoclonal solid-phase enzyme immunoassay in patients with acute myocardial infarction

A monoclonal solid-phase enzyme immunoassay has been developed for the detection of human serum ventricular myosin light chain-1. Cross-reactivity of this with human skeletal muscle myosin was observed, but the enzyme immunoassay with the sera of patients with acute myocardial infarction gave similar results with radioimmunoassay. The human ventricular myosin light chain-1 levels in the healthy subjects were 0.2-6.6 ng/ml in males and 0.2-4.1 ng/ml in females. Within-run and between-run precision (CVs) of the assays was on the order of 2.3-4.7% and 4.3-8.7, respectively. Sensitivity of the assay was 1.0 ng/ml, and working range was 5-100 ng/ml. In all patients with define acute myocardial infarction, serum ventricular myosin light chain-1 levels increased three- to ten-fold the upper reference range within 6 hr after the onset of chest pains. Two types of subtrend were discovered: its levels remain elevated for 3-4 days and its levels increased and then decreased 1-2 days after the initial rise but became elevated again for the next 4-7 days after the onset of chest pain, which is in contrast to the case with all conventionally used biochemical cardiac markers.     

Binding of complement component C5 to model immune complexes and the use of anti-C5 antibodies for determination of C5-containing circulating immune complexes

When normal human or mouse serum is added to micro ELISA plates coated with monomeric or aggregated IgG, complement component C5 binds to IgG. C5 binding was demonstrated with a specific chicken anti-C5 antibody. Hydrazine treatment of the serum or addition of EDTA to the serum abolished the binding of C5. C5-deficient mouse serum was negative for C5 binding, whereas the same serum supplemented with human C5 restored the binding of C5. Chicken anti-C5-coated plates were used for determination of C5-containing circulating immune complexes (CIC). Increased concentrations of CIC were found in sera from patients with rheumatoid arthritis and Bell's palsy.     

Thymus-dependent and -independent regulation of Ia antigen expression in situ by cells in the synovium of rats with streptococcal cell wall-induced arthritis. Differences in site and intensity of expression in euthymic, athymic, and cyclosporin A-treated LEW and F344 rats.

Euthymic LEW rats, when injected with streptococcal cell walls, exhibited rapid onset development of acute exudative arthritis coincident with enhanced synovial expression of Ia antigen. By 21 d after injection, the expression of Ia was markedly increased compared with basal conditions and paralleled the severity of the later developing proliferative and erosive disease. Immunodeficient athymic and cyclosporin A-treated LEW rats developed only the early phase arthritis, which was again paralleled by synovial Ia expression. Chronic expression of high levels of Ia antigen was not observed. Histocompatible F344 rats, both athymic and euthymic, developed minimal, if any, clinically significant arthritis and did not exhibit the enhanced Ia expression demonstrated in the LEW rats. Our results indicate that enhanced synovial Ia expression parallels clinical disease severity and varies by rat strain, and that the rapid onset enhanced synovial Ia expression is thymus independent, whereas the markedly enhanced chronic phase Ia expression is thymus dependent.     

Immunological characteristics of patients with acute coronary syndrome (unstable angina and myocardial infarction)]

Admission and discharge values of rosette formation, adhesive and phagocytic ability of neutrophils, exercise tests with calculation of the tension index (TI), serum concentrations of IgG, IgA and IgM, circulating immune complexes (CIC) and cardiolipin antibodies (CAB) were studied in 48 males with unstable angina pectoris and acute myocardial infarction. Acute coronary syndrome is shown to be associated with marked immune alterations, primarily, with elevated levels of CIC and CAB, reduced TI. These alterations persisted for 3-5 weeks of the hospital stay and provoked the risk of repeated infarctions and thrombotic complications after relief of clinical symptoms of acute coronary failure.     

Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-gamma in sera of children with dengue.

It has been reported that the severe complication of dengue virus infection, dengue hemorrhagic fever (DHF) is much more commonly observed during secondary dengue virus infections than primary infections. In order to elucidate the role of T lymphocytes in the pathogenesis of DHF, we attempted to determine whether T lymphocytes are activated in vivo during dengue virus infections, by examining the levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8), interleukin-2 (IL-2) and interferon-gamma (IFN gamma) in the sera of 59 patients with DHF and 41 patients with dengue fever (DF). The levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma were significantly higher in the acute sera of patients with DHF than in the sera of healthy children (P less than 0.001 for all markers). The acute sera of patients with DF contained higher levels of sIL-2R, sCD4, IL-2, and IFN gamma than the sera of healthy children (P less than 0.001 for sIL-2R, IL-2, and IFN gamma; P less than 0.05 for sCD4), but did not have elevated levels of sCD8. The levels of sIL-2R (P less than 0.05), sCD4 (P less than 0.001), and sCD8 (P less than 0.001) were higher in DHF than in DF on days 3-4 after the onset of fever. The levels of IL-2 and IFN gamma in patients with DHF were highest 1 d before defervescence. There were no significant differences in the levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma among grades 1, 2, and 3 of DHF. These results indicate (a) T lymphocytes are activated and produce IL-2 and IFN gamma in vivo during DHF and DF, (b) CD4+ T lymphocytes are activated in DHF and DF, and the level of activation is higher in DHF than in DF, and (c) activation of CD8+ T lymphocytes is evident in DHF, but not in DF.     

Elevated Levels of Antibodies to Epstein-Barr Virus Antigens in Sera and Synovial Fluids of Patients with Rheumatoid Arthritis

The frequencies and levels of antibodies to Epstein-Barr virus (EBV)-specific antigens were determined in paired sera and synovial fluids from patients with rheumatoid arthritis (RA) and in sera from patients with other connective tissue diseases; i.e., systemic lupus erythematosus, progressive systemic sclerosis, and osteoarthritis (OA). The specimens were also tested for the presence of antibodies to RA-associated nuclear antigen. Compared to healthy controls, the patients' sera showed increased frequencies of elevated antibody titers (≥320) to Epstein-Barr viral capsid antigen, a correspondingly enhanced (twofold to threefold) geometric mean titer, and an increased frequency of antibodies at elevated titers (≥10), usually to the restricted component and rarely the diffuse component of the early antigen complex. Levels of antibody to the EBV-associated nuclear antigen were within the normal range. Enhancement of antibody titers was more pronounced in seropositive RA patients (i.e., positive for rheumatoid factor) than in those who were not. Enhancement was also found in systemic lupus erythematosus and progressive systemic sclerosis. Antibody to RA-associated nuclear antigen was detected at an increased frequency only in the group of seropositive RA patients (90%), as compared to 8-15% in the other connective tissue diseases and 6-8% in healthy controls. The antibody titers in the synovial fluids equaled or were at most twofold higher or lower than those in the sera. In addition, levels of EBV-specific antibodies were studied serially over a period of 6-10 mo in patients with RA and OA. Parameters of disease activity were determined and compared to antibody levels. EBV-specific antibodies in sera of OA patients remained constant and within normal limits throughout the study. Although EBV-specific antibodies were often elevated in RA patients, they also remained constant, with the exception of three patients, who showed gradual increases in one of the four antibodies, which did not correlate with disease activity.     

Immune complexes in myocardial infarct

604 patients were investigated with C1q solid phase RIA in regard to circulating immune complexes (CIC) shortly after myocardial infarction. 118 (19.6%) of these 604 patients had CIC, which disappeared in 99 patients (83.7%) or decreased significantly in 9 cases (7.6%) after 2-4 weeks. Only 10 patients (8.3%) showed persisting CIC. 12 parameters assessing clinical features and laboratory data were compared with the results of CIC investigation in altogether 251 patients, of whom 54 (21.5%) were CIC-positive. No differences between CIC-positive and CIC-negative patients were observed with regard to generally accepted factors predisposing to infarction. However, CIC-positive patients differed significantly from CIC-negative cases in the higher incidence of a history of respiratory tract infection before infarction (p less than 0.001) and the more frequent absence of a family history of cardiac and circulatory disease (p less than 0.0005). Interpretation of these results indicates a transient appearance of CIC after liberation of heart - tissue antigens during infarction, but does not exclude the possible existence of a group of patients manifesting CIC already before the onset of infarction, whereby the CIC may have contributed towards triggering off the infarction. In this case persistence of CIC after infarction may be regarded as an unfavourable sign.     

Circulating and intra-articular immune complexes in patients with rheumatoid arthritis. Correlation of 125I-Clq binding activity with clinical and biological features of the disease.

The correlation between the incidence and level of immune complexes in serum and synovial fluid and the various clinical and biological manifestations of rheumatoid arthritis has been studied. Immune complexes were quantitated using a sensitive radioimmunoassay, the 125I-Clq binding test, in unheated native sera and synovial fluids from 50 patients with seropositive (RA +) and 45 with seronegative (RA -) rheumatoid arthritis, 17 with other inflammatory arthritis, and 37 with degenerative and post-traumatic joint disease. The following observations were made: (a) when compared to the results from patients with degenerative and post-traumatic joint diseases, the 125I-Clq binding activity (Clq-BA) in synovial fluid was found to be increased (by more than 2 SD) in most of the patients with RA + (80%) and RA - (71%) and in 29% of patients with other inflammatory arthritis; the serum Clq-BA was also frequently increased in both RA + (76%) and RA - (49%) patients, but only exceptionally in patients with other inflammatory arthritis (6%); (b) a significant negative correlation existed between the Clq-BA and the immunochemical C4 level in synovial fluids from patients with RA + and RA -; (c) neither the serum nor the synovial fluid Clq-BA in rheumatoid arthritis significantly correlated with the erythrocyte sedimentation rate, the clinical stage of the disease, or the IgM rheumatoid factor titer; and (d) the serum Clq-BA in patients with rheumatoid arthritis and extra-articular disease manifestations (40 +/- 34% in those with RA +,32 +/- 29% in those with RA -) was significantly increased as compared to the serum Clq-BA in patients with joint disease alone (24 +/- 30% in those with RA +, 10 +/- 13% in those with RA -). Experimental studies were carried out in order to characterize the Clq binding material in rheumatoid arthritis. This material had properties similar to immune complexes: it sedimented in a high molecular weight range on sucrose density gradients (10-30S) and lost the ability to bind Clq after reduction and alkylation, or after acid dissociation at pH 3.8, or after passage through an anti-IgG immunoabsorbant. DNase did not affect the Clq BA. These results support the hypothesis that circulating as well as intra-articular immune complexes may play an important role in some pathogenetic aspects of rheumatoid arthritis. The 125I-Clq binding test may also be of some practical clinical value in detecting patients who have a higher risk of developing vasculitis.