Circulating immune complexes during immunotherapy in allergy to dog.

Circulating immune complexes (CIC) were determined from dog-allergic asthmatic children (n = 35) receiving immunotherapy with dog dander and hair extract. The results from CIC are expressed in SDU (standard deviation units) and presented as follows: pretreatment results (n = 20), rush results (n = 11), mid-schedule results (n = 20), maintenance results (n = 15) and the results of the placebo-treated group (n = 12). The results of the placebo-treated group (n = 12) and those of the untreated atopic (n = 12) and non-atopic (n = 14) were controls. CIC levels were analysed by means of KgB-ELISA (conglutinin binding enzyme linked immunosorbent assay), C1qB-ELISA (C1q-binding enzyme linked immunososrbent assay), RFb-ELISA (rheumatoid factor binding enzyme linked immunosorbent assay) and by PIPA (platelet 125J-labelled staphylococcal protein-A test). The CIC level determined by KgB-ELISA in dog-allergic asthmatic children was higher than that of the atopic controls (P less than 0.05) already before the onset of the hyposensitization. During conventional hyposensitization with dog dander and hair the CIC level remained the same as before treatment. On day 5 of rush hyposensitization the mean level of CIC showed no increase when compared with the pretreatment values. A statistically significant correlation (P less than 0.01) was observed between the dog dander and hair-specific IgG antibodies and the CIC level measured by KgB-ELISA during the maintenance period of conventional immunotherapy. The samples of sera to measure this correlation were collected before the injection of allergen and after 2 weeks of injection during maintenance treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Malignant neuroleptic syndrome. Literature review and case report]. / Malignes neuroleptisches Syndrom. Literaturüberblick und Kasuistik.

The neuroleptic malignant syndrome, first described by Delay and Deniker in 1968, is a rare but severe complication of neuroleptic treatment. According to the literature the syndrome particularly affects young men undergoing rapidly intensified neuroleptic treatment ("rapid neuroleptization"). The diagnosis is based on the triad of hyperthermia, extrapyramidal signs, and autonomic dysfunction, once infectious disease has been ruled out. The clinical features, course and therapy of the syndrome are described on the basis of a case report.

Serum immune complexes and rheumatoid factors in superficial bladder tumours.

Serum immune complex (IC) and rheumatoid factor (RF) levels of 39 patients with a transitional cell tumour of the bladder were analyzed using 4 different IC and 2 RF assays. Elevated serum immune complex and rheumatoid factor levels were observed in the majority of the patients (95%). Conglutinin-binding (KgB), C1q-binding (C1qB), platelet iodinated protein A test (PIPA) and RF-enzyme immunoassay (RF-EIA) gave positive results in 31%, 62%, 23% and 31% of the cases, respectively and separated cancer sera from normal blood donors (p less than 0.001). Elevated titers were also observed with platelet aggregation test (PAT) and latex agglutination for RF in 23% and 67% of the cases, respectively. A negative correlation (p less than 0.01) was observed with the stage of the disease and RF-values. Other IC tests did not correlate significantly with stage, histological grade or progression of the disease. The best prognostic marker was the histological grade of the tumour. Males had more undifferentiated tumours than females. Multivariate analysis was carried out to correlate several laboratory parameters simultaneously with clinical variables and it revealed that elevated IC tests values (KgB, C1qB and PIPA) and low RF-values correlated to stage (p = 0.009) but not to histological grade or progressive course of the disease.

Elevated serum immune complex levels in Pogosta disease, an acute alphavirus infection with rash and arthritis.

Circulating immune complexes (CIC) were studied in Pogosta disease, an acute alphavirus infection with fever, rash and arthritis. The disease is caused by a virus antigenically closely related to Sindbis virus. 75 serum specimens from 25 patients with serologically verified infection were obtained from 1-87 days after the onset. Six different CIC detection methods were used and CICs were observed in all patients at least with one test. Tests based on CIC binding onto human platelets followed the natural course of the disease and maximal values were observed between 10-15 days after onset. Slightly elevated levels were observed 2-3 months after onset. The mean conglutinin binding test values were slightly elevated during the whole follow-up period. The severity of arthritis did not directly correlate to CIC levels. C3c and C1q-binding test were positive only in a few cases. Latex and enzyme immunoassay tests for rheumatoid factors gave low positive values in some of the sera. Agarose gel electrophoresis of serum proteins revealed non-specific changes in alpha 1-alpha 2 interzone characteristic of an acute infectious disease. The presence of CIC in the sera of patients with Pogosta disease may indicate body's natural clearange mechanisms of viral antigens. CIC may have a pathogenic role in the prolonged arthritis, even though no direct correlation with CIC levels and severity of arthritis was observed.

Natural course of juvenile autoimmune thyroiditis.

Forty-six patients with juvenile autoimmune thyroiditis were followed for an average of 6.5 years. The diagnosis was based on a firm goiter and on cytologic findings of lymphocytic thyroiditis. The thyroid function and the size of the thyroid gland were regularly evaluated, and thyroid cytologic findings reevaluated once about 4.5 years after the diagnosis was made. Initially, 24 patients were euthyroid, 16 subclinically hypothyroid, and six hypothyroid. At the end of follow-up, 29 patients were euthyroid, six subclinically hypothyroid, and 11 hypothyroid, but there had been an extensive exchange of individual patients among these three groups. At cytologic reevaluation, the changes were virtually unaltered. Thyroid antibodies and circulating immune complexes were repeatedly tested: on one or more occasions, 85% of the patients had positive test results for thyroid antibodies, and about 50% for circulating immune complexes. Hypothyroidism at the end of follow-up correlated with the initial hypothyroid state and with thyroglobulin antibodies of IgG class detected by enzyme immunoassay. The best predictors of the final hypothyroid state were female sex, initial hypothyroidism, IgG thyroglobulin antibodies by EIA, and IgG circulating immune complexes assayed by conglutinin-binding test-EIA.

Circulating immune complexes in hypertensive disorders of pregnancy.

Circulating immune complexes (CICs) were measured in sera of pregnant women with pre-eclampsia and other hypertensive disorders of pregnancy and pregnant women with renal disease, using four different CIC assays: platelet 125I-labelled staphylococcal protein A test ( PIPA ), conglutinin-binding ELISA, C1q-binding ELISA and rheumatoid factor binding inhibition ELISA. CICs were shown to be present in the sera of 47% of women with severe pre-eclampsia, in 20% with mild pre-eclampsia and in 18% of women with normal pregnancy using the PIPA test. The PIPA test was capable of discriminating between patients with renal disease, which were all positive, and women with uncomplicated hypertension, which were all negative. All patients positive in the PIPA test, and most patients with a positive RFbI -ELISA test, had various amounts of proteinuria. Although half of the women with severe pre-eclampsia showed the presence of CICs in the PIPA test, the amount of these complexes was low and not constant in serial samples from the same patient.

Clinical correlates of circulating immune complexes in patients with recent yersiniosis.

Circulating immune complexes (CICs) and rheumatoid factor were studied in 31 patients with serologically confirmed yersiniosis (12 in a pilot series and 19 in a prospective series). Yersiniosis is an intestinal infection complicated occasionally by extraintestinal symptoms such as aseptic arthritis. Four tests representing three main principles (affinity of human platelets and of C1q for complexed IgG and of conglutinin for C3) were used for the detection of CICs, which were found in all patients. Fifty-five of 62 specimens of serum from the prospective series of 19 patients reacted positively in at least one test. The conglutinin-binding assay and the platelet-125I-labeled staphylococcal protein A test gave positive results most frequently (74% and 84% of the time). Mean levels of CICs were significantly higher in patients with prolonged gastroenteritis than in those with histocompatibility leukocyte antigen B27-positive arthritis. During follow-up, the mean level of CICs (as measured by the platelet-protein A test) decreased significantly in patients with arthritis, while CICs and rheumatoid factor persisted in patients with prolonged gastroenteritis.

Circulating immune complexes and rheumatoid factors in patients with farmer's lung.

Circulating IgG immune complexes (CICs), IgM rheumatoid factors (RFs), complement level (C3 and C4), and IgG antibodies to Aspergillus fumigatus, Aspergillus umbrosus, Thermoactinomyces vulgaris, and Micropolyspora faeni were analysed in the sera of 14 patients with farmer's lung (FL), 10 in the acute and four in the subacute phase of the disease. Ten spouses of FL patients served as exposed healthy controls. C3 and C4 were measured fluoronephelometrically. C3 levels were above the normal range and C4 levels near the upper limit of the normal range in both patients and controls; no statistically significant difference between patients and controls were observed. CICs were determined by enzyme immunoassays (EIA) of conglutinin-binding (KgB) and Clq-binding (ClqB). CIC levels above the normal range were detected in 12 (KgB-EIA) and nine (ClqB-EIA) of the patients and three (KgB-EIA) and six (ClqB-EIA) of the controls. No statistically significant differences were found in the mean levels between patients and controls. In contrast, RF levels in the acute phase of FL were significantly higher in the patients (P less than 0.01) than in the controls. CICs correlated positively with most microbial IgG antibodies, but negatively with RFs. RFs also correlated negatively with microbial IgG antibodies, as well as with both C3 and C4. In FL, the increased RF level may, in the absence of increased CIC and decreased complement levels, represent an immune response (IgM anti-IgG autoantibodies) induced by local mechanisms of IgG immune complexes in the lungs.

Immune complexes in serum and cerebrospinal fluid of multiple sclerosis patients and patients with other neurological diseases.

Paired serum and cerebrospinal fluid (CSF) specimens from 30 multiple sclerosis (MS) patients and 30 patients with other neurological diseases (ONDs) were analyzed for the presence of immune complexes (ICs). With each of the 4 tests used, ICs were found more frequently in sera from both MS and OND patients than in sera from healthy blood donors. IC-positivity for MS and OND patient CSF varied from 10-33% and from 10-17% in different tests. The number of IC-positive sera or CSF in MS patients did not differ significantly from those in OND patients. For both MS and OND patients, the positivity pattern for serum and CSF specimens in each IC test was essentially unique. Furthermore, because several CSF IC-positive and serum IC-negative paired specimens were found, intrathecal IC formation may be independent of IC formation in peripheral blood. The presence of ICs in serum or CSF did not correlate with the clinical status of or laboratory data on the MS patients, nor was a correlation found with the diagnosis of the OND patients. In total, these results suggest that the presence or absence of ICs in MS or OND patients may simply reflect changes in the immunological regulation of individual patients.

Interference by rheumatoid factor and C1q in the detection of IgG complexes: studies of model systems by ELISA.

Interference by purified IgM rheumatoid factors (RFs) and C1q in the detection of model complexes was studied by enzyme-linked immunosorbent assay (ELISA). Soluble monoclonal and polyclonal cryoglobulin IgM RFs and human or porcine C1q inhibited dose-dependently the binding of human IgG complexes to solid-phase IgM RF, C1q, and bovine conglutinin (Kg). The inhibition patterns of the Kg binding were dependent on the order of confrontation between the reactants. To achieve inhibition, C1q or RF had to be offered to the complexes before treatment with fresh normal human serum (NHS); complexes pretreated with fresh NHS (alexinated complexes) were resistant to inhibition. Heating at 56 degrees C or 63 degrees C, which destroyed the alexinating capacity of NHS, did not affect the Kg binding of alexinated complexes. On the basis of present and previous findings it is concluded that intrinsic C1q and RFs are likely to interfere with detection of circulating immune complexes (CICs) in C1q- or RF-binding assays; they are less likely to interfere with detection of CICs in Kg-binding assays. The problems associated with selective removal of intrinsic C1q and RFs are discussed.

Evaluation of six tests for circulating IgG complexes with special reference to IgM rheumatoid factors: analysis of systemic lupus erythematosus and rheumatoid arthritis series.

Six tests for circulating immune complexes (CIC) developed in four laboratories and representing four main principles [affinity of human platelets, Clq, of RF for aggregated IgG, and of conglutinin (Kg) for complex-bound C3] were evaluated on series of SLE and definite RA. All tests detected human model complexes in the presence of NHS and discriminated the patient series from the blood donor series, most powerful being the PIPA (platelet test). The high correlation between the RF-binding inhibition tests (RFbI) and the RF-latex test suggested interference due to intrinsic RFs. This received further support from experimental analyses in which RA sera mixed with varying doses of heat-aggregated IgG were assayed by the pRFbI test.

Significance of monospecific antisera in the diagnosis and prognosis of autoimmune haemolytic anaemias.

The significance of the monospecific antiglobulin test in the diagnosis and prognosis of autoimmune haemolytic anaemia (AIHA) was tested in 74 patients with AIHA and 59 patients with secondary AIHA. There were 48 female and 26 male patients. Idiopathic AIHA patients more often had two or more positive monospecific reactions in the direct antiglobulin test than secondary AIHA patients. Increased serum lactate dehydrogenase levels, indicating increased intravascular haemolysis, were found more frequently in patients with two or more positive monospecific antiglobulin tests. The number of thromboembolic complications and deaths correlated positively with the number of positive monospecific reactions in antiglobulin test. In particular, positive direct antiglobulin test with monospecific anti-IgA was often combined with severe AIHA.

Circulating immune complexes, immunoconglutinins, and rheumatoid factors in nephropathia epidemica.

Circulating immune complexes (CICs), immunoconglutinins, and antiglobulins were studied in nephropathia epidemica, an acute infectious hemorrhagic fever occurring in Finland and Scandinavia. Sixty-one serum specimens from 18 serologically confirmed patients were collected between day -5 and day 230 from the onset of fever. Five CIC tests, three immunoconglutinin tests, and various other tests were used to characterize the disease immunologically. CICs were found in all patients. The percentage detection of positive cases varied in the tests from 100% to 22%. A marked stimulation of levels of the IgM class of immunoglobulins were observed. Antiglobulin tests were positive for all of the patients. No correlation between the test results and the clinical severity of the disease could be found. Of special interest was the delay in the rise of CIC levels compared with the chromologic pattern of the clinical course. In some patients a prolonged appearance of CICs for eight months was observed.