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H Engler

Publications and source records attributed to H Engler.

At least 37 records · Page 2Linked to original sources

p53 gene therapy in a rat model of hepatocellular carcinoma: intra-arterial delivery of a recombinant adenovirus.

p53 tumor suppressor gene therapy has been proposed for cancers characterized by inactivation of p53 function, and successful therapy will require efficient strategies for gene delivery. To maximize transgene expression in tumors, a clinical strategy has been proposed to treat neoplasms in the liver via hepatic artery administration of a recombinant adenovirus encoding wild-type p53 (rAd-p53). We have developed a syngeneic rat model using a p53mut hepatocellular carcinoma cell line (McA-RH7777) that results in multifocal liver tumor nodules to provide experimental support for this strategy. Treatment of McA-RH7777 cells with rAd-p53 in vitro resulted in efficient transgene expression, growth suppression, and apoptosis. Intrahepatic artery dosing with rAd-p53 or an adenovirus encoding beta-galactosidase (rAd-betagal) increased transgene expression in tumor tissue and decreased systemic exposure when compared with i.v. dosing. Daily hepatic artery dosing of rAd-p53 suppressed tumor growth when compared with untreated rats or animals treated with rAd-betagal. These data demonstrate the potential for arterial gene delivery to tumors using recombinant adenoviruses, and support continued investigation of rAd-p53 gene therapy for liver malignancies.

Adenoviridae↗

Early reactivation of cytomegalovirus and high risk of interstitial pneumonitis following T-depleted BMT for adults with hematological malignancies.

Reactivation of cytomegalovirus (CMV) is a major cause of morbidity and mortality following allogeneic bone marrow transplantation (BMT) and early reactivation with increased risk of interstitial pneumonia (IP) has been reported in T cell-depleted BMT. In 21 patients at risk for CMV reactivation following T cell-depleted BMT for hematological malignancies, CMV reactivation was the main cause of transplant-related mortality: 19 (90.5%) reactivated CMV and five (26% actuarial) developed fatal IP. Median reactivation time post-BMT was 22 days for IP and 39.5 days for non-IP patients (P = 0.04). Patients developing IP showed no increase in lymphocyte count following CMV reactivation. There was a trend for higher pp65 antigen load at reactivation in patients who relapsed with CMV or progressed to IP. Donor lymphocyte transfusions (DLT) were given to pre-empt leukemic relapse and viral infection (15 patients) or to treat IP in two. Nine of 19 patients reactivated CMV before receiving DLT on day 30 post-BMT and DLT were ineffective in established IP. However DLT from seropositive donors did not cause IP. These results confirm the relationship of donor T cell function with CMV reactivation following BMT. They suggest that patients receiving T cell-depleted BMT should be protected from CMV disease with prophylactic rather than pre-emptive treatments.

Adolescent↗

[CYFRA 21-1: initial experiences in bronchus carcinoma and other tumors].

CYFRA 21-1 (CYFRA) is a new tumor-associated marker which appears to be useful in monitoring non-small cell bronchial carcinoma. We examined 193 sera from tumor patients (92 of whom had bronchial carcinoma), and 62 patients with benign lung disease. Sensitivity and specificity of CYFRA was compared with that of CEA, TPA, TPS and SCC in squamous cell bronchial carcinoma and with that of NSE in small cell bronchial carcinoma. The sensitivity of CYFRA in other tumor localizations was also assessed. In squamous cell bronchial carcinoma CYFRA proved to be the best marker with respect to sensitivity (58%) and specificity (98%). In gastrointestinal tumors CYFRA had a similar sensitivity to CEA. Since the two markers do not correlate their sensitivity is additive. In conclusion, CYFRA is confirmed as marker of first choice in squamous cell bronchial carcinoma. In other tumors CYFRA displayed a similar sensitivity to CEA.

Adult↗

Anti-thyroid peroxidase (anti-TPO) antibodies in thyroid diseases, non-thyroidal illness and controls. Clinical validity of a new commercial method for detection of anti-TPO (thyroid microsomal) autoantibodies.

The identification of the thyroid peroxidase (TPO) as the main antigen of the thyroid microsomal fraction has enabled the development of a sensitive and specific assay for detection of the corresponding autoantibodies. We evaluated the diagnostic validity of the anti-TPO assay in 303 patients with different types of thyroid disease and in controls. Clearly elevated anti-TPO values (anti-TPO > 500 units/ml) were found in 59% of patients with thyroiditis but in none of the controls or the patients with non-thyroidal illness. The mean anti-TPO levels in these two control groups were 26 +/- 31 units/ml (mean +/- S.D.) and 39 +/- 34 units/ml, respectively. The highest frequency of positive results (88%) was obtained in patients with auto-immune hypothyroidism (clinical diagnosis: Hashimoto's thyroiditis) followed by patients with Graves' disease (53%). With a cut-off point of 200 units/ml, a sensitivity of 96% was obtained for Hashimoto's thyroiditis and of 59% for Graves' disease with a specificity of 100% (50 cases). The new method (anti-TPO, Dynotest) was compared with three conventional methods (35 samples). The results for all measurements were in general agreement. In two cases the results were clearly discordant: one sample contained high anti-thyroglobulin antibody concentrations, the other was obtained from a patient with non-thyroidal illness. In both instances the 'classical' assays yielded false-positive results. Treatment of autoimmune hyperthyroidism resulted in a median decrease in anti-TPO levels of over 50% after reaching the euthyroid state (P < 0.05), whereas in persistent hyperthyroidism no consistent changes were observed. In autoimmune hypothyroidism a marked variability in anti-TPO levels was noted. Some patients showed a clear decrease in anti-TPO levels during T4 substitution whereas in others no consistent changes were observed.

Autoantibodies↗

Effect of thyroid function on concentrations of lipoprotein(a)

The effect of thyroid hormones on concentrations of lipoprotein(a) [Lp(a)] was analyzed in 60 patients with active thyroid dysfunction (hyperthyroidism 30 cases, hypothyroidism 32 cases, and 2 cases with opposite changes) and after normalization of the thyroid state. Treatment of hyperthyroidism increased the mean Lp(a) concentrations by 60% (from 73 to 102 mg/L, P < 0.002); at the same time, low-density lipoprotein cholesterol (LDL-C) increased by 53% (from 2.6 to 3.7 mmol/L, P < 0.0001) and apolipoprotein B (apo B) by 35% (from 0.91 to 1.17 g/L, P < 0.0005). In hypothyroidism, the opposite changes were observed: mean Lp(a) decreased from 136 to 114 mg/L (10%, P < 0.02), LDL-C from 4.6 to 3.9 mmol/L (13%, P < 0.01), and apo B from 1.51 to 1.20 g/L (14%, P < 0.01). Although the changes in Lp(a) concentrations did correlate with changes of LDL-C during treatment of hyperthyroidism (r = 0.43, P < 0.05), and with changes in apo B during thyroxine-substitution therapy for hypothyroidism (r = 0.46, P < 0.05), we observed no associations between Lp(a) and LDL-C or apo B in the euthyroid state. These data cannot rule out the possibility that the thyroid hormone-induced increase in LDL-C receptor activity was responsible for the decreased concentrations of Lp(a) in hyperthyroidism. Given that LDL-C is approximately 30% of the Lp(a) molecule but the changes in Lp(a) concentrations are comparable with those in LDL-C (60% vs 53%), and given that Lp(a) is metabolized by an LDL-C-receptor-independent pathway, the present data suggest a direct effect of thyroid hormones on Lp(a) synthesis.

Adult↗

[Diagnostic value of autoantibodies against microsomal thyroid peroxidase (anti-TPO)].

With the identification of thyroid peroxidase (TPO) as the main antigen of the thyroid microsomal fraction, the development of a sensitive and specific assay for detection of these antibodies became possible. The diagnostic value of the anti-TPO assay was evaluated in patients with different types of thyroid disease and in controls. 65% of patients with thyroiditis had elevated anti-TPO values. The frequency of elevated anti-TPO levels in patients with active autoimmune thyroiditis was 90% (clinical diagnosis Hashimoto thyroiditis) compared to 64% in patients with overt hyperthyroidism (clinical diagnosis Graves' disease). None of the controls or the patient with non-thyroidal illness showed elevated anti-TPO levels.

Autoantibodies↗

[Evaluation of a strip test (Micral test) for the semi-quantitative assessment of microalbuminuria in clinical practice].

Microalbuminuria (AER 20-200 micrograms/min) is the earliest clinical sign of incipient diabetic nephropathy. Current methods for measuring urinary albumin are not suitable for use in an office setting. A test strip (Micral-Test, Boehringer Mannheim [D]) based on immunochemical principles has recently been developed which allows semiquantitative detection of urinary albumin concentrations. In this study Micral-Test results were compared with conventional immunoturbidimetric laboratory measurement. 65 single-void urine samples of diabetic patients were analyzed (38 type 1, 27 type 2). Urinary albumin values as obtained from Micral-Test and laboratory measurement showed a significant correlation (r = 0.85, p less than 0.001). An interclass correlation was performed for normal urinary albumin values (less than 20 micrograms/ml) and for microalbuminuric values (20-200 micrograms/ml) and resulted in correlation coefficients of 0.56 and 0.81 respectively. Interindividual variation was checked by three observers reading the same 13 urine samples. The values obtained from the three observers correlated significantly (r greater than 0.95, p less than 0.001). The test strip must be evaluated after precisely 5 minutes in order to avoid false pathological results. In conclusion, the Micral-Test is a good screening method for easy and quick detection of microalbuminuria in an office setting.

Adult↗

[Does isolated TSH elevation need treatment? Study of risk factors for the development of manifest hypothyroidism].

Isolated elevations of basal TSH levels are frequently observed in the general population. In a prospective study we analyzed the spontaneous evolution of thyroid function over time in such patients. The mean observation period was 5.4 (0.5-12) years. During the follow-up period 20% of these patients developed overt hypothyroidism. The risk of developing hypothyroidism was determined primarily by the initial TSH value and an additive effect was found for the thyroid antibodies and the thyroidal reserve (delta-T3) after TRH stimulation (Cox proportional hazard model). The cumulative risk for overt hypothyroidism after 10 years was only 22% for a mean TSH level of 12 mU/l for patients with negative thyroid antibodies and a good thyroidal reserve (low-risk), but increased to 63% for patients with positive antibodies and impaired T3 reserve (high-risk). Therefore, patients with isolated elevation of TSH can be divided into two subgroups according to the results of TSH, antibody status and T3 reserve: (1) In the "low-risk group" with good prognostic factors the patients should be followed up by periodic laboratory testing only (TSH, FT4, every 2-3 years). (2) In the "high-risk group" with clearly abnormal parameters, however, frequent controls are mandatory (every 6-12 months) or treatment with thyroxine may be indicated.

Adult↗

Spectrum of subclinical and overt hypothyroidism: effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues.

PURPOSE: Subclinical hypothyroidism is found in about 7.5% of females and in about 3% of males. It appears to be a risk factor for atherosclerosis and for coronary heart disease and can affect various other target organs. The morbidity and clinical significance of subclinical hypothyroidism are controversial. Therefore, we evaluated the metabolic impact of progressive thyroid failure in patients with various degrees of hypothyroidism compared with control subjects. PATIENTS AND METHODS: We investigated 86 female patients with the whole spectrum of subclinical hypothyroidism (n = 69) and of overt hypothyroidism (n = 17) and 52 euthyroid women as controls. All subjects underwent full medical and endocrine evaluations (including measurements of thyrotropin [TSH], TSH beta- and alpha-subunits, and prolactin before and after oral administration of thyrotropin-releasing hormone [TRH]) as well as lipid profiles and different tests of peripheral thyroid hormone action. All hypothyroid patients were divided into five categories according to disease severity: grades I to III (subclinical hypothyroidism, with normal thyroxine [T4] levels) and grades IV and V (overt hypothyroidism, with diminished T4). RESULTS: In grade I subclinical hypothyroidism (basal TSH below 6 mU/L), we found significant changes in the clinical index (p less than 0.05), apoprotein A-I level (p less than 0.05), and stimulated prolactin level after oral TRH (p less than 0.001). The findings were similar in grade II (TSH 6 to 12 mU/L). Further changes could be demonstrated in grade III (TSH above 12 mU/L) with a definite elevation of ankle reflex time (p less than 0.001), serum myoglobin level (p less than 0.01), and, to a lesser extent, creatine kinase (p greater than 0.1). The mean low-density lipoprotein cholesterol (LDL-C) level showed an increase of 18%, which was not significant because of marked individual variations (p = 0.15). The frequency of elevated LDL-C levels was definitely higher in patients with grade III disease compared with the controls (42.9% versus 11.4%, p less than 0.05) and with patients with grades I and II disease. Total cholesterol, triglycerides, apoprotein B, and the systolic time intervals (pre-ejection period, corrected for heart rate [PEPc]) were clearly elevated only in overt hypothyroidism (grades IV and V) (p less than 0.01). CONCLUSION: Subclinical hypothyroidism has significant effects on some peripheral target organs at an early stage (grades I and II), but affects LDL-C, skeletal muscle, and myocardial contractility only at a later stage (grades III, IV, and V). Our data of elevated LDL-C in grade III subclinical hypothyroidism provide a likely pathophysiologic explanation for the reported association of coronary heart disease with this syndrome. The impact of increased prolactin secretion, observed in subclinical hypothyroidism, on gonadal function and infertility has yet to be clarified. Therapy with thyroxine should be recommended in at least some patients with subclinical hypothyroidism. Patients with high TSH levels (above 12 mU/L) will require treatment because of the metabolic effects on several target organs. Before treatment is advocated in all patients with subclinical hypothyroidism, the benefits and long-term side effects of thyroid hormone therapy should be clarified by prospective studies in larger groups of patients.

Administration, Oral↗

Clinical application of two computerized diabetes management systems: comparison with the log-book method.

In two consecutive studies the clinical application and suitability of two computer-assisted data management systems (Camit and Cadmo) were evaluated in a prospective manner. In each study nineteen long-standing, stable insulin-dependent patients were randomly assigned to one of two groups. In study I assessment of metabolic control and insulin dose adjustments were based either on the Camit S1 data analysis or on the conventional log-book method, whereas in study II the Camit S2 and the Cadmo simulation programs were evaluated. HbA1c values decreased significantly in both studies (p < 0.05). A clear decline in hypoglycemic events as well as a significant reduction of the percentage of glucose values below 4.0 mmol/l (p < 0.005) and a marked increase (p < 0.05) in the percentage of glucose levels in the target range (4.0-10.0 mmol/l) were observed. We found both computerized assessment systems to be reliable and suitable for the assessment of blood glucose control and for insulin dose finding. The graphical and statistical presentation of the numerous glucose and insulin data allowed a better summary of blood glucose control and metabolic trends. More time could be spent for problem solving, which proved to be much less exhausting with the computer for the attending physician. Further studies should address the educational potential of computerized systems for the patient as well as for the physician.

Adult↗

[The practical assessment of micro-albuminuria as a marker for beginning diabetic nephropathy in: which urine sampling method?].

Microalbuminuria, i.e. elevated urinary albumin excretion rate between 20 and 200 micrograms/min, is a strong predictor of subsequent overt diabetic nephropathy. Screening for microalbuminuria is essential, since it has been shown that development of overt nephropathy can be delayed or even prevented by therapeutic measures such as strict metabolic control, early aggressive antihypertensive treatment, or restriction of protein intake. Several urine collection methods for the measurement of microalbuminuria have been proposed. In a prospective study with 40 diabetic outpatients we have compared albumin excretion in urine collected over 24 h, during a timed overnight period, and in a spot urine sample collected at random while the patient attended the outpatient clinic. In addition, the reproducibility of the three urine collection methods was assessed. For this purpose, each patient underwent 3 consecutive collections at an interval of at least 4 weeks. Our data indicate that calculation of an albumin/creatinine quotient in a spot urine probe is a reliable screening test for microalbuminuria. If this quotient is increased (greater than 2), timed overnight collection should be performed.

Adolescent↗

Pharmacokinetics of ibuprofen enantiomers in dogs.

Inversion of inactive (R)-ibuprofen to active (S)-ibuprofen has been suggested to occur presystemically only. In order to investigate the site of inversion in dogs we administered both enantiomers either intravenously or intraduodenally (10 mg/kg) to adult, male beagle dogs (n = 3) in a crossover design. Plasma, urine, and bile were collected for up to 6 h and analyzed stereospecifically by HPLC, according to a previously published method. Pharmacokinetic parameters were calculated using a linear computer program. Absorption after intraduodenal administration occurred rapidly, resulting in maximum plasma concentrations 0.2 h after giving the enantiomer. Approximately 70% of the (R)-enantiomer (according to AUC) was inverted to the S-enantiomer independent of route of administration. No R-ibuprofen could be detected in plasma after (S)-ibuprofen administration. Mean residence time was found to be 2 to 3 times longer for (S)- than for (R)-ibuprofen. Total systemic clearance from plasma was twice as high for (R)- than for (S)-ibuprofen. There were no differences between plasma clearances after intravenous and intraduodenal administration. Between 8 and 17% of dose was recovered in bile [especially as free and conjugated (S)-ibuprofen] and 3-12% in urine [as (S)-ibuprofen, hydroxy- and carboxyibuprofen, free and conjugated forms]. Small amounts of (R)-ibuprofen were detected in bile after intraduodenal administration of (R)-ibuprofen only (1.8% of dose). In short, the unidirectional inversion of R-ibuprofen appears to occur systemically rather than presystemically in dogs.

Animals↗

Primary antiphospholipid syndrome (PAPS). Two case reports and therapeutic implications.

Antiphospholipid antibodies (aPL) interfere with the coagulation system and can cause thrombosis and other clotting disorders. The combination of recurrent venous thrombosis, arterial embolism and recurrent fetal loss is nowadays considered to be primary antiphospholipid syndrome (PAPS), provided an underlying systemic lupus erythematosus (SLE) has been excluded and aPL have been detected. We report on two patients with PAPs, and show the course of their IgG- and IgM-anticardiolipin antibody (aCL) titers during immunosuppressive therapy with prednisone and azathioprine or cyclophosphamide. Over a period of 18 months this therapy was effective in preventing relapses of thrombo-embolism and other complications. Therapy with cyclophosphamide resulted in normalization of the aCL titers in one of the two reported cases. Azathioprine treatment reduced the aCL titer in the other patient, without fully normalizing it. Based on our observation, we propose to treat PAPS-associated severe and recurrent thrombo-embolic complications by aggressive immunosuppression, including azathioprine and cyclophosphamide.

Adolescent↗

A new approach to adoptive immunotherapy of cancer using tumorcytotoxic macrophages grown from peripheral blood monocytes.

Clinical trials to evaluate the potential of adoptive immunotherapy in cancer patients have been restricted to the use of lymphoid effector cells. Of the other probably even more important host defense system against tumor growth, the mono-nuclear phagocyte system, only monocytes (mo) have been reinfused which, however, represent immature precursor cells and acquire full functional competence only upon further maturation. This is a report on 7 patients who received autologous macrophages (MO) grown in vitro from blood mo and activated by interferon-gamma (IFN gamma). Mononuclear cells were isolated from whole blood by cytapheresis and cultured for 7 days with 2% autologous serum on hydrophobic Teflon foils. Eighteen house before cell harvest, recombinant human IFN gamma was added at 200 IU/ml. Mo-derived MO were purified by counter-current elutriation. Starting with 10(8) MO cells, therapy was escalated up to the maximal number of MO obtainable from one single preparation cycle. Currently, 26 therapies have been performed with the maximal dose being 1.7 x 10(9) MO per infusion. Except for low grade fever (less than 38 degrees C), MO autografts were well tolerated, with no side effects observed. Biological response was followed by analyzing the serum levels of beta 2-microglobulin, neopterin, interleukin-6, tumor necrosis factor, and lysozyme. While in 3 out of 7 patients serum neopterin increased in response to MO therapy, other biological response parameters remained at pretreatment levels. Radiolabeled MO were shown to first accumulate in the lungs, then to pool into liver and spleen.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopterins↗

Adoptive transfer of tumor cytotoxic macrophages generated in vitro from circulating blood monocytes: a new approach to cancer immunotherapy.

Cells of the macrophage lineage are considered to be of special importance in the defense of the host against tumor development and spread. Immunotherapeutic strategies to stimulate macrophage (MAC) tumor cytotoxicity make use of activating compounds such as gamma-interferon which are given systemically. However, there are several lines of evidence that in malignant disease the generation of cytotoxic effector MACs is impaired. Both defective cell maturation and loss of responsiveness to activation are described. Here, a first clinical phase I trial of adoptive immunotherapy in cancer patients using autologous MACs generated in vitro from blood monocytes (MOs) is reported. Mononuclear cells were isolated by cytapheresis and density centrifugation and cultured in hydrophobic Teflon bags for 7 days with 2% autologous serum and recombinant human gamma-interferon being present for the last 18 h. Cytotoxic MO-derived MACs were then purified by countercurrent elutriation and reinfused into the patient. A total of 72 therapies have been performed with patients being treated i.v. (n = 8) and i.p. (n = 7). In vitro generated MACs proved to be mature as judged by the expression of maturation-associated surface molecules (MAX antigens, CD16, CD51, CD71), were cytotoxic to U937 tumor cells, and were efficient secretory cells. Cell dose escalation was performed in the first patients beginning with 10(8) MACs to finally infuse the total number of cells recovered from one single cycle of isolation and culture. MAC yield varied from 1 to 17 x 10(8) representing 13-79% of MOs initially seeded. Adoptive MAc transfer was well tolerated. Side effects observed were low-grade fever (less than 38.5 degrees C), induction of the coagulation cascade, and abdominal discomfort after i.p. application. The procoagulant activity of MAC autografts was cell dose dependent and demonstrated by detection of circulating fibrin monomers and thrombin-antithrombin complexes. Biological responses observed included elevated serum neopterin levels and the appearance of interleukin-6 in sera and ascitic fluids. Indication of a possible therapeutic effect was only observed in i.p.-treated patients and consisted of disappearance of malignant ascites in 2 of 7 patients.

Adult↗

Coronary reperfusion studies with pro-urokinase in acute myocardial infarction: evidence for synergism of low dose urokinase.

Pro-urokinase is a single chain precursor of two chain urokinase, which has been shown to induce fibrin-selective plasminogen activation. In the present study, thrombolytic efficacy of 9 million U of glycosylated pro-urokinase administered intravenously was compared with that of a combined regimen utilizing 4.5 million U of pro-urokinase and 0.2 million U of urokinase. Seventy-five patients with a first myocardial infarction were randomized to receive high dose pro-urokinase (n = 40, group A) or the combination therapy (n = 35, group B). Reperfusion of the infarct-related artery was assessed by repeat coronary angiography. Thrombolysis in Myocardial Infarction trial (TIMI) grade II or III reperfusion was achieved in 73% of group A patients compared with 66% of group B patients (p = NS). A trend toward faster reopening of the infarct-related artery was observed in patients in group B. Coronary artery reocclusion occurred in 5 (10%) of 49 patients in whom angiography was repeated within 36 h after the start of therapy. Clot-selective thrombolysis was indicated by a minimal fibrinogen decline (15% and 13%, respectively, in groups A and B). Alpha 2-antiplasmin levels, however, decreased more rapidly in patients in group B (p less than 0.05). This finding and the equivalent reperfusion rate in the combined treatment group strongly suggest synergistic interaction between these two thrombolytic agents. In summary, the high incidence of reperfusion, the low rate of early reocclusion and the paucity of side effects, particularly with regard to bleeding complications, indicate that pro-urokinase possesses the characteristics of an ideal thrombolytic agent.

Drug Synergism↗

[Carbimazole therapy in Basedow's disease: therapy results in individual dosage adjustment].

We analyzed the results of 85 treatments with carbimazol in 71 patients with Graves' disease. The initial dose ranged from 45 to 60 mg/day, which was gradually reduced to the lowest possible maintenance dose; the mean treatment period was 17 months. All patients achieved euthyroid function after 12 weeks at the latest. Normalization of the pituitary TSH-reserve occurred late (after 6-12 months in most cases). 60% of the patients treated for the first time (n = 58) and 59% of the whole group remained in remission. The maintenance dose of carbimazol had no effect on the rate of remission. It is interesting to note that in 66% of the patients a very low dose (less than or equal to 5 mg/day) was fully effective and resulted in a remission rate of 54%. Therefore, the dose should always be reduced individually. Relapses occurred within the first year after the end of treatment in 77% of the cases, but were also observed after 2-3 years. Hence follow-up should be continued after cessation of therapy.

Adult↗

Assessment of antithyroglobulin and antimicrosomal autoantibodies in patients with autoimmune thyroid disease: comparison of haemagglutination assay, enzyme-linked immunoassay and radioligand assay.

Four different assay systems for detection of antithyroglobulin (T-Ab) and thyroid antimicrosomal autoantibodies (M-Ab) were evaluated: two passive haemagglutination assays (PHA), an enzyme-linked immunoassay (ELISA) and a radioligand assay (RLA). Antibody levels measured with these methods correlated well (T-Ab: r = 0.72 to 0.88; M-Ab: r = 0.63 to 0.84; p less than 0.0001). However, when the results of the measured samples were classified as normal, slightly elevated and pathological, only 40-50% of the samples showed congruous results in all tests; 60-70% agreed in PHA and ELISA, whereas 80 to 90% corresponded in the two PHAs. RLA and ELISA gave more frequently positive results for T-Ab and negative results for M-Ab than the PHAs. Despite the lower sensitivity of the quantitative methods for M-Ab detection, they depicted more readily small changes after thyroxine treatment than the PHAs. We suggest that differences in autoantibody levels found with different methods may be due to autoantibody heterogeneity.

Autoantibodies↗