High prevalence of autoantibodies among Danish centenarians.

The aim of this study was to investigate the prevalence of organ and nonorgan specific autoantibodies in relation to disability and comorbidity in an unselected population of centenarians. A population-based survey of all persons living in Denmark who celebrated their 100th birthday during the period 1 April 1995 to 31 May 1996, a total of 276 persons, was undertaken. Participants underwent an interview, a physical examination and blood sampling. Organ specific autoantibodies (Tg-ab, TPO-ab, PCA-ab) and nonorgan specific autoantibodies (ANA, IgM RF, IgA RF, MPO-ab, c-ANCA, p-ANCA, oxLDL-ab, IgM ACA, IgG ACA, PR3-ANCA, histone-ab, SSA-ab, SSB-ab, Mit-ab) were measured, and comorbidity and disability (Katz Index of ADL) were registered. In all, 207 (75.0%) of 276 eligible subjects participated, and 148 agreed to blood tests. A large majority (79.3%) had at least one autoantibody detected. Organ specific autoantibodies were present in 32.1% of the centenarians. The high level of autoantibodies did not reflect an equally high level of overt autoimmune disease. While nonorgan specific autoantibodies were equally represented in less-disabled/disabled subjects as well as in subjects with low/high comorbidity, significantly fewer subjects with organ specific autoantibodies were found among less-disabled subjects or subjects with low comorbidity. Autoantibodies (both nonorgan and organ specific) are common in an unselected population of centenarians of today, but do not reflect an equally high level of overt autoimmune disease. Non-organ specific autoantibodies are evenly distributed irrespective of the level of disability or comorbidity, suggesting underlying, undiagnosed pathological processes which may be part of the processes involved in frailty.

Serum thyroglobulin as a marker of thyroid neoplasms after childhood cancer.

AIM: To evaluate serum thyroglobulin (Tg) level as a marker of the development of thyroid disease when following individuals who received neck irradiation therapy in childhood. METHODS: In a non-randomized cross-sectional study Tg was assessed in 172 survivors of childhood cancer 10.8 y (1.9-24) median (range) after diagnosis and 7.9 y (0.9-24.3) median (range) after the end of treatment. The patients were divided into two groups: group 1 included 47 patients who had received irradiation to the neck and group 2 included 125 patients who did not receive irradiation to the neck. RESULTS: Patients who had received irradiation to the neck had significantly higher Tg levels compared with those who did not receive neck irradiation: median 14.0 (1.0-189.0) microg/L vs median 8.8, (0.7-112.2) microg/L (p < 0.001). Six out of seven patients with elevated Tg levels (>70 microg/L) had received neck irradiation. Among these six patients, two patients developed secondary differentiated thyroid cancer and two patients developed benign thyroid neoplasms. None of the patients who had normal levels of Tg developed thyroid cancer. CONCLUSION: A high Tg level should be a cause for further investigation in the follow-up of individuals who have received irradiation therapy in childhood.

A prospective study of thyroid function, morphology and autoimmunity in young patients with type 1 diabetes.

OBJECTIVE: Thyroid autoantibodies (TA) and thyroid ultrasonography are widely used in the diagnosis of autoimmune thyroid disease (AITD). However, we know little of the significance of having ultrasonographic abnormalities (USabn) without having any other signs of AITD. In a previous population-based study of 105 young patients with type 1 diabetes (T1DM) we found a high prevalence (42%) of USabn. In the present study we evaluate the development of both USabn and TA in a 3-Year follow-up of this cohort. DESIGN: Of the 105 previously investigated children and adolescents with T1DM (aged 5-21 Years), 101 were re-examined. Serum concentrations of tri-iodothyronine (T(3)), thyroxine (T(4)), TSH, thyroid peroxidase antibodies (TPOab) and thyroglobulin antibodies (Tgab), as well as thyroid size and morphology were determined in all patients. RESULTS: During the 3 Years follow-up period, the prevalence of thyroid dysfunction increased from 5 to 8%, the prevalence of TPOab was unchanged at 13%, while the prevalence of Tgab decreased from 14 to 7%. The prevalence of USabn increased from 42 to 49%. Most patients presented USabn at both examinations. Patients with USabn had a higher prevalence of TA than those without USabn (P=0.038) and higher serum levels of TSH (P=0.027). All patients with thyroid dysfunction presented with USabn. However, many patients with USabn had no other signs of AITD. CONCLUSIONS: A high prevalence of thyroid dysfunction, TA and thyroid USabn were found in young patients with T1DM. Thyroid USabn was a sensitive but non-specific marker of AITD and is therefore unsuitable for screening purposes. Instead, we recommend regular screening using serum TSH in the follow-up of young diabetic patients.

Rheumatic manifestations in danish women with silicone breast implants.

The aim of this study was to investigate whether women with silicone breast implants (SBI) present with a unique rheumatic symptomatology. We assessed the profile of rheumatic disease in six groups of women identified through Danish hospital and population registers, three groups of women with a prior hospital diagnosis of muscular rheumatism (a non-specific diagnostic code) who had previously undergone SBI surgery (n = 28), breast reduction surgery (n = 29) or no breast surgery (n = 27); and three groups of women without a diagnosis of muscular rheumatism who had undergone SBI surgery (n = 21), breast reduction surgery (n = 27) or no breast sugery (n = 56). All women in the study population (n = 188) underwent a thorough clinical examination, blood tests and a personal interview. In all study groups soft-tissue rheumatism and degenerative diseases were the most frequent diagnoses. Women with a prior diagnosis of muscular rheumatism but no prior breast surgery had a significantly higher prevalence of soft-tissue rheumatism than those with breast implant or reduction surgery. No significant differences in the frequencies of rheumatic diseases were observed among the three groups of women without previous muscular rheumatism. No specific pattern of inflammatory rheumatic disorders or soft-tissue complaints was identified among the women with SBI, and blood tests for autoimmunity revealed no unique pattern. Overall, women with earlier rheumatism had significantly increased frequencies of rheumatic conditions than did those without. We found no evidence of a rheumatic symptomatology unique to women with silicone breast implants. Our study emphasises the need for consideration of prior rheumatic disease when evaluating rheumatic manifestations in women with SBI.

Prevalence and clinical significance of antikeratin antibodies and other serological markers in Lithuanian patients with rheumatoid arthritis.

OBJECTIVES: To assess the clinical value of several serological markers in Lithuanian patients with rheumatoid arthritis (RA) compared with control patients with rheumatic disease and age matched healthy controls. METHODS: Serum samples from 96 patients with RA of approximately 8 years' duration, 90 rheumatic disease controls, and 37 healthy subjects were tested. Antikeratin antibody (AKA), antineutrophil cytoplasmic antibody (ANCA), and antinuclear antibody (ANA) titres were estimated by indirect immunofluorescence (IIF) and serum samples positive for ANA and ANCA were further studied by enzyme linked immunosorbent assay (ELISA). IgA and IgM rheumatoid factors (RF) were measured by ELISA. RESULTS: A positive AKA test was highly specific for RA (diagnostic specificity 97%), being found in 44% of the patients. Although both RF tests had a higher sensitivity, they were less specific for RA. ANCA was detected in 33% of patients with RA but lacked diagnostic specificity. AKA and ANCA were associated with more erosive disease and the presence of extra-articular manifestations. Positivity for AKA, IgA RF, and ANCA was significantly associated with disease activity and worse functional capacity. However, in multiple regression analysis only positivity for AKA was significantly correlated with functional disability (p=0.0001), evaluated by the Steinbrocker functional classification, and no single marker had any relation with radiological damage. CONCLUSION: Although AKA showed the highest disease specificity, all serological markers studied except ANA exhibited interesting associations with important clinical and paraclinical parameters of RA.

High prevalence of coeliac disease in Danish children with type I diabetes mellitus.

UNLABELLED: The purpose of this population-based study was to determine the prevalence of coeliac disease (CD) in 106 Danish children (age 2-18 y) with type I diabetes mellitus compared with 106 age- and sex-matched healthy controls. Serum samples were analysed for immunoglobulin A (IgA) and IgG gliadin antibodies by enzyme-linked immunosorbent assay (ELISA), for IgA endomysium antibodies (EMA) by immunofluorescence and for IgA tissue transglutaminase antibodies (tTGA) by ELISA. None of the controls had EMA or tTGA. Two diabetics previously diagnosed with CD were antibody negative on a gluten-free diet. Ten diabetics had both EMA and tTGA. Intestinal biopsy was performed in nine of them. All biopsies showed a histological picture of partial or total villous atrophy confirming the diagnosis of CD. Diabetics with CD were significantly younger (p = 0.026). had an earlier onset of diabetes (p = 0.005), had a lower height standard deviation score (p = 0.019) and more often had thyroid antibodies (p = 0.040) compared with diabetics without CD. CONCLUSION: A high prevalence of CD of 10.4% (95% confidence interval 4.6-16.2%) was found in young Danish diabetics. Early onset of diabetes may predispose to CD. Routine serological screening for CD may be valuable in patients with type I diabetes mellitus.

Ionic charge, hydrophobicity and tryptophan fluorescence of the folate binding protein isolated from cow's milk.

A high-affinity folate binding protein was isolated and purified from cow's milk by a combination of cation exchange chromatography and methotrexate affinity chromatography. Chromatofocusing studies revealed that the protein possessed isoelectric points in the pH-interval 8-7. Polymers of the protein prevailing at pH values close to the isoelectric points seemed to be more hydrophobic than monomers present at pH 5.0 as evidenced by hydrophobic interaction chromatography and turbidity (absorbance at 340 nm) in aqueous buffer solutions (pH 5-8). Ligand binding seemed to induce a conformation change that decreased the hydrophobicity of the protein. In addition, Ligand binding quenched the tryptophan fluorescence of folate binding protein suggesting that tryptophan is present at the binding site and/or ligand binding induces a conformation change that affects tryptophan environment in the protein. There was a noticeable discordance between the ability of individual folate analogues to compete with folate for binding and the quenching effect.

Prevalence of thyroid peroxidase, thyroglobulin and thyrotropin receptor antibodies in a long-term follow-up of juvenile Graves disease.

OBJECTIVE: To relate the presence of thyroid peroxidase antibodies (TPO ab), thyroglobulin antibodies (Tg ab) and thyrotropin receptor antibodies (TSH-R ab) to the clinical course in a long-term follow-up of patients with juvenile Graves' disease (JGD). DESIGN: Patients with JGD were drawn from a Danish retrospective study and reexamined. RESULTS: A number of 105 patients were reexamined 4-21 years (median 10 years) after diagnosis. Three groups were formed: Gr.1: euthyroid patients with anti-thyroid drug (ATD) cessation more than 12 months before reexamination (n=41). Gr.2: patients still on ATD (n=24). Gr.3: subtotally thyroidectomized patients (n=40). Positive TPO ab titers were found in 75% of the patients. In 13% of the patients the titers were very high: >10,000 U/ml. Positive Tg ab were found in 51%. The prevalence of TPO ab and Tg ab was the lowest in group 3. Stimulating TSH-R ab titers were found in 13%. No patients had blocking TSH-R ab. The prevalence of TSH-R ab was 3% in the euthyroid patients, without surgery performed. 15% in the surgical patients, and 25% in the patients still on ATD. CONCLUSIONS: Many JGD patients were euthyroid at the long-term follow-up in spite of high TPO ab and Tg ab titers. Stimulating TSH-R ab were rare (13%). According to this presence of TPO ab, Tg ab or TSH-R ab does not predict the final outcome of JGD. Further studies are needed.

Ligand binding characteristics of a glycosylphosphatidyl inositol membrane-anchored HeLa cell folate receptor epitope-related to human milk folate binding protein.

The folate receptor (FR) in HeLa cells was characterized as to ligand binding mechanism, antigenic properties and membrane anchor in order to obtain information to be used for the design of biological agents targeting FR in malignant tumors. The receptor displayed the following binding characteristics in equilibrium dialysis experiments (37 degrees C, pH 7.4) with [3H] folate: a high-affinity type of binding that exhibited positive cooperativity with a Hill coefficient > 1.0 and an upward convex Scatchard plot, a slow radioligand dissociation at pH 7.4 becoming rapid at pH 3.5 and inhibition in the presence of other folates. The molecular size of the receptor was 100 kDa on gel filtration with Triton X-100, or similar to that of high molecular weight human milk folate binding protein (FBP). The latter protein represents a 25 kDa molecule which equipped with a hydrophobic glycosylphosphatidyl inositol (GPI) membrane anchor susceptible to cleavage by phosphatidylinositol specific phospholipase C (PI-PLC) forms micelles of 1kDa size with Triton X-100. The HeLa cell FR immunoreacted with antibodies against purified human milk FBP in ELISA, and in a fluorescence activated cell sorting system, where HeLa cells exposed to increasing concentrations of antibody showed a dose-dependent response. Exposure to PI-PLC decreased the fraction of immunolabeled cells indicating a linkage of FR to cell membranes by a GPI anchor. HeLa cells incubated with radiofolate showed a continuous uptake with time, however, with a complete suppression of uptake in the presence of an excess of cold folate. Prewash of cells at acidic pH to remove endogenous folate increased the uptake. Binding and uptake of [3H] folate was increased in cells grown in a folate-deprived medium. The HeLa FR seems to be epitope related to human milk FBP.

Characterization of a folate receptor in parotid gland and a folate binding protein in saliva from humans. Epitope relatedness to human milk folate binding protein.

The present study was performed to establish the antigenic identity and origin of the folate binding protein in human saliva. We identified a folate receptor in human parotid and submandibular gland which immunoreacted with antibodies against human milk folate binding protein, as evidenced by ELISA and immunostaining of ductal epithelium and secretory glandular material. The receptor concentration was 0.4-1.4 nmol 3H-folate bound/g protein. Ligand binding was of a high-affinity (K=10(10) M(-1)) type, exhibited positive cooperativity, a slow radioligand dissociation at pH 7.4, and inhibition by folate analogues. The concentration of immunoreactive folate binding protein in saliva as determined by ELISA with antibodies against human milk folate binding protein was several fold higher than that determined by radioligand binding (nil - 1 nM). This indicates that a major fraction of the immunoreactive material does not bind 3H-folate, and could represent a precursor form of the protein. In conclusion, the folate binding protein in human saliva seems to be a secretory product of the salivary glands. The protein is also epitope-related to folate binding proteins in other human mucosal secretions.

LongoVital in the treatment of Sjögren's syndrome.

OBJECTIVE: Sjögren's syndrome (SS) is a chronic autoimmune disease complex of unknown aetiology. There is no curative treatment for SS, however, in recent years the influence of nutrients on autoimmune processes has attracted increasing attention. LongoVital (LV) (DK. Reg. No. 5178/75) is an herbal-based tablet enriched with the recommended daily doses of vitamins. The purpose of the present study was to investigate whether 4 months' daily intake of LV as compared to placebo would affect clinical and laboratory disease parameters in patients with SS. METHODS: Forty patients with SS participated in a placebo-controlled, double-blind, randomised, clinical, 8 month cross-over study. Group A (n = 22) received LV during the first 4 months and Group B (n = 18) LV during the last 4 months. RESULTS: The unstimulated salivary flow rate increased during the LV period in Group A (p < 0.001). The stimulated salivary flow rate increased in Group B during the LV period (p < 0.05), and in Group A during the subsequent 4 months on placebo (p < 0.05). The rose bengal score decreased in Group B during (p < 0.01) and in Group A after the LV intake (p < 0.05). During the last 4 months of the study both groups showed an increase in serum levels of alpha-amylase (total: Group A, p < 0.01; Group B, p < 0.05; pancreatic fraction: Group A, p < 0.0001; Group B, p < 0.01) and in serum levels of IgM (Group A and B: p < 0.001), while levels of circulating immune complexes decreased (Group A, p < 0.05; Group B, p < 0.001). CONCLUSION: It is concluded that LV has a beneficial and prolonged effect on some of the clinical and immunoinflammatory disease markers in SS.

Thyroid function, morphology and prevalence of thyroid disease in a population-based study of Danish centenarians.

OBJECTIVES: To investigate thyroid function, morphology, and autoimmunity in relation to physical function in an unselected population of centenarians. DESIGN: A population-based survey. SETTING: Denmark. PARTICIPANTS: All persons living in Denmark who celebrated their 100th anniversary during the period April 1, 1995 to May 31, 1996, a total of 276 persons. MAIN OUTCOME MEASUREMENTS: Thyroid hormones (TSH, T4, FT4I, T3, FT3I, and T3RU), thyroid autoantibodies (TPOab and Tgab), thyroid volume, activities of daily living according to the Katz Index of ADL. RESULTS: In all, 207 (75%) of the 276 eligible subjects participated, and 148 agreed to blood tests. Among the participants, 2.9% had previously known hyperthyroidism, and the same proportion had previously known hypothyroidism. The blood tests did not reveal any undiagnosed cases of overt thyroid dysfunction. However 7.2% had a subnormal serum TSH, and 2.9% had an elevated serum TSH; all had normal serum T3 and serum T4 levels. Thyroid autoantibodies were detected in 26 (17.6%) centenarians (11.5% had Tgab and 9.5% had TPOab). Among relatively independent centenarians, low serum T3 was significantly associated with high comorbidity (P = .029), whereas both low serum T3 and thyroid autoantibodies were significantly associated with ADL-dependency (P < .001 and P = .030, respectively). Ultrasonography (n = 50) revealed a small gland with a median volume of 8.3 mL (range 3.2-27.9) compared with an expected volume of 20 mL (14-26) (P < .001). There was no significant relationship to body weight. When examined by ultrasound, only 26% had significant morphological alterations. CONCLUSIONS: Thyroid dysfunction does not seem to be more prevalent among centenarians than among younger old people. Low serum T3 is related to poor physical function and co-morbidity, whereas thyroid autoimmunity is related only to poor physical functioning. Despite atrophy of the thyroid gland, these findings suggest that thyroid function is well preserved in centenarians.

Multicenter evaluation study on a new HEp2 ANA screening enzyme immune assay.

The COBAS Core HEp2 ANA enzyme immune assay (EIA) was evaluated in a precision and a clinical sample study in comparison to indirect immunofluorescence assay (IFA) on HEp2-cells. In the precision study the COBAS Core EIA yielded intraassay coefficient variations (CVs) mostly below 9%, and interassay CVs between 4.7% and 10.4%. When comparing the COBAS Core EIA to IFA, the results corresponded well in healthy subjects, systemic lupus erythematosus, mixed connective tissue disease and rheumatoid arthritis. In the case of Sjögren's syndrome and scleroderma patients the COBAS Core EIA yielded a lower rate of positive results compared to IFA. This discrepancy may be explained by the lack of detection of autoantibodies to nuclear antigens that can be identified only by IFA due to their compartmentalization and higher localized antigen density in HEp2 cells. The discrepancies in the group of dermato/polymyositis patients are due to the fact that the EIA contains mainly nuclear antigens and was able to detect only antibodies against the cytoplasmic Jo1 antigen that was added to the HEp2 nuclear extract. Routine sera were also evaluated; good agreement was found in sera from patients attending tertiary reference centres for autoimmune diseases but a higher number of discrepancies was reported in sera from unselected populations.

Thyroid function, morphology and autoimmunity in young patients with insulin-dependent diabetes mellitus.

OBJECTIVE: An association between insulin-dependent diabetes mellitus (IDDM) and autoimmune thyroid disease is well recognized. We have studied the prevalence of thyroid dysfunction, autoimmunity and morphological abnormalities by ultrasonography in young diabetics. SUBJECTS AND METHODS: Among young IDDM patients less than 18 years old and living in the county of Funen, Denmark, 105 of 116 eligible patients participated. They were compared with 105 healthy children matched for sex and age. Routine thyroid function parameters (thyroxine (T4), tri-iodothyronine (T3), T3 resin uptake and TSH) and thyroid autoantibodies (anti-thyroid peroxidase, TPOab, and thyroglobulin antibodies, Tgab) were measured. Thyroid size and morphology were determined by ultrasonography. RESULTS: Two of the diabetics had previously diagnosed hypothyroidism and three new cases of subclinical hypothyroidism were found. There were no significant differences in thyroid function variables or thyroid volume between diabetics and controls. Thyroid volume correlated significantly with age and weight in both groups. Among diabetics, 17 had thyroid autoantibodies (13 with TPOab, 14 with Tgab and 10 with both) compared with 2 children in the control group (P<0.001). Forty-four with IDDM as opposed to 11 of the controls (P<0.001) had morphological abnormalities at ultrasonography. Most of them had various degrees of hypoechogenicity thought to be a marker of thyroid autoimmunity. Among the 17 diabetics with autoantibodies, 10 had morphological abnormalities at ultrasonography. CONCLUSIONS: A high proportion of young IDDM patients without any clinical signs of thyroid disease have markers of thyroid autoimmunity. Many have thyroid autoantibodies, but even more have abnormalities by thyroid ultrasonography.

High-affinity folate receptor in human ovary, serous ovarian adenocarcinoma, and ascites: radioligand binding mechanism, molecular size, ionic properties, hydrophobic domain, and immunoreactivity.

High-affinity folate receptors are expressed in normal ovaries and ovarian carcinomas. Binding of [3H]folate in human ovary, serous ovarian carcinoma tissue, and ascites is a complex process that has not been well characterized. This study shows changes in binding affinity and mechanism of binding with decreasing receptor concentration, inhibition by folate derivatives, and a slow radioligand dissociation at pH 7.4 becoming rapid and complete at pH 3.5. The receptor seems to be positively charged since it elutes in the front effluent of a DEAE-Sepharose CL-6B ion-exchange column at pH 6.3. The gel filtration profile of Triton X-100-solubilized tissue and ascites contained two peaks of radioligand-bound receptor (25 and 100 kDa). Exposure of ascites to cleavage by phosphatidylinositol-specific phospholipase C resulted in a partial conversion of the 100-kDa peak to a 25-kDa peak. This suggests that the receptor may be anchored to the membrane by a glycosylphosphatidyl residue that inserts into Triton X-100 micelles, resulting in a large molecular size on gel filtration. The receptor in ovarian carcinoma tissue immunoreacts with antibodies against purified human milk folate receptor protein as shown by enzyme-linked immunosorbent assay, immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting (a single band of 45 kDa), and immunohistochemistry. In only three of seven ovarian carcinomas did expression of radioligand-bound receptors exceed levels found in five normal ovaries. However, only receptors in ovarian carcinoma specimens showed a high degree of immunoreactivity. Hence, even without elevations of the total receptor level, a folate receptor isoform homologous to human milk folate receptor protein seemed to prevail in serous ovarian carcinomas.

Characterization of a high-affinity folate receptor in normal and malignant human testicular tissue.

We have characterized the folate receptor in normal and malignant tissue from male gonads. Radioligand binding displayed characteristics typical of other folate receptors. Those included a high-affinity type of binding (K = 10(10M-1)), apparent positive cooperativity changing into non-cooperativity at low receptor concentrations, a tendency to increased binding affinity with decreasing receptor concentrations, a slow dissociation at pH 7.4 becoming rapid at pH 3.5 and inhibition by folates, in particular oxidized forms. The gel filtration profile of Triton X-100 solubilized tissue contained a 25 and 100 kDa peak of radioligand-receptor. The latter peak could represent receptor equipped with a hydrophobic membrane anchor that inserts into Triton X-100 micelles. The concentration of radiolabelled receptor ranged from 0.41 nmol/g protein to 1.68 nmol/g protein in specimens of normal testicular tissue from patients with prostatic carcinomas and from 1.54 nmol/g protein to 3.82 nmol/g protein in testicular tissue from young individuals. Compared to normal testicular tissue the concentration of receptor in seminoma tissue was low (0.38-1.27 nmol/g protein) but showed a higher degree of immunoreactivity in the presence of antibodies against human milk folate binding protein as evidenced by ELISA and immunohistochemistry data. Hence a folate receptor isoform homologous to human milk folate binding protein is apparently expressed in seminomas where the total expression of receptor, however, seems to be lower than in normal testicles.

A folate binding protein in ascitic fluid, serum and ovarian tissue of patients with ovarian adenocarcinoma immunoreacts with antibodies against human milk folate binding protein.

The presence of a folate binding protein which immunoreacts with antibodies against human milk folate binding protein was demonstrated in ascitic fluids from seven patients with ovarian adenocarcinoma. Ascitic fluids collected from two patients with other malignancies contained non-immunoreactive FBP. Tumor tissue specimens from five patients with ovarian carcinoma contained immunoreactive FBP. By contrast to normal ovaries ovarian carcinoma tissue showed positive immunostaining on immunohistochemistry. Ascitic fluids from two patients with ovarian carcinoma exhibited single distinct bands on SDS-PAGE immunoblotting. The gel filtration profile of ovarian carcinoma tissue homogenate from two patients contained 25 and 1OOkDa peaks of radioligand-bound and immunoreactive folate binding protein, while ascitic fluid from one of the patients exhibited a large 100 kDa immunoreactive peak with no radioligand binding activity. The immunoreactive non-functional 100 kDa FBP could represent unprocessed precursor FBP. Future studies are necessary to evaluate whether determination of immunoreactive FBP in ovarian adenocarcinomatosis is of any diagnostic value.

Persistent high prevalence of thyroid antibodies after immunosuppressive therapy in subjects with glomerulonephritis. A prospective three-year follow-up study.

The prevalence of thyroid antibodies, indicating an autoimmune thyroiditis, has been shown to be significantly increased in patients with autoimmune diseases. A 3-year prospective follow-up study of 42 patients with biopsy-confirmed glomerulonephritis is presented. Although the majority of patients had been treated with immunosuppressants, the prevalence of thyroid peroxidase antibodies was unchanged in both females and males, 47 and 15% respectively, at follow-up. Likewise, the prevalence of thyroglobulin antibodies was unaffected as was that of antinuclear antibodies (ANA) when analysing males and females together. However, for males there was a trend to higher prevalence for ANA at follow-up. On the other hand, the prevalence of antineutrophil cytoplasmic antibodies declined. Furthermore, thyroid antibodies were not restricted to membranous nephropathy, and notably found in 4 out of the 8 patients with vasculitis.

Clinical features and serum antinuclear antibodies in 230 Danish patients with systemic sclerosis.

The objective was to investigate the relationship between the presence of different types of antinuclear antibodies (ANA) in patients with systemic sclerosis (SSc) and the presence of clinical features. Sera from 230 patients with SSc were tested for the presence of ANA, including anticentromere antibodies (ab), antitopoisomerase I ab, anti-U1 RNP ab and antinucleolar ab, including anti-Th RNP, anti-U3 RNP and anti-U17 RNP. Clinical features were registered prospectively in a clinical database. Eighty-two per cent of the patients were women. The median age was 58 yr (45-67, quartiles) and median age at disease onset was 44 (30-55) yr. ANA were found in 86% of the patients (anticentromere: 34%; antitopoisomerase I: 14%; anti-U1 RNP: 6.5%; antinucleolar total: 16%; anti-Th RNP: 2.2%; anti-U3 RNP: 3.5%; anti-U17 RNP: 0%). Anticentromere ab were found to be related to a high prevalence of calcinosis, telangiectasia, digital ulcers, acrosclerosis, primary biliary cirrhosis, isolated reduction of pulmonary diffusing capacity, and a low prevalence of radiological evidence of pulmonary fibrosis. Antitopoisomerase I ab were associated with a high prevalence of digital joint deformity, distal osteolysis, radiological signs of pulmonary fibrosis, a low prevalence of calcinosis and late onset of disease. Anti-U1 RNP ab were related to a high prevalence of arthritis and myositis, a low prevalence of calcinosis, and early disease onset. The presence of antinucleolar ab, including anti-U3 RNP and anti-Th RNP, was not significantly related to any particular clinical features in this study; possibly due to the small number of patients with these ab. The presence of anticentromere, antitopoisomerase I and anti-U1 RNP ab in the serum was also found to have previously described clinical correlations in a group of Danish SSc patients.

A high-affinity folate binding protein in fluid of benign cysts of human liver and mammary gland.

The presence of a folate binding protein in fluid of benign cysts of human liver and mammary gland was demonstrated. Radioligand binding was of a high-affinity type (K approximately 10(10) M -1). The gel filtration profile of cystic fluid contained two peaks of radiolabelled folate, a large one of 25 kDa and a small one of 100 kDa. The concentration of radioligand bound protein in samples of cystic fluid ranged from nil to 6 nM. In most cases the protein immunoreacted with antibodies against human milk folate binding protein. The data suggest that fluid of human liver and mammary gland cysts contains a folate binding protein which appears to be homologous to human milk folate binding protein.