Evidence of streptococcal origin of acute non-necrotising cellulitis: a serological study.

Bacteriological diagnosis is rarely achieved in acute cellulitis. Beta-haemolytic streptococci and Staphylococcus aureus are considered the main pathogens. The role of the latter is, however, unclear in cases of non-suppurative cellulitis. We conducted a serological study to investigate the bacterial aetiology of acute non-necrotising cellulitis. Anti-streptolysin O (ASO), anti-deoxyribonuclease B (ADN) and anti-staphylolysin (ASTA) titres were measured from acute and convalescent phase sera of 77 patients hospitalised because of acute bacterial non-necrotising cellulitis and from the serum samples of 89 control subjects matched for age and sex. Antibiotic treatment decisions were also reviewed. Streptococcal serology was positive in 53 (69%) of the 77 cases. Furthermore, ten cases without serological evidence of streptococcal infection were successfully treated with penicillin. Positive ASO and ADN titres were detected in ten (11%) and three (3%) of the 89 controls, respectively, and ASTA was elevated in three patients and 11 controls. Our findings suggest that acute non-necrotising cellulitis without pus formation is mostly of streptococcal origin and that penicillin can be used as the first-line therapy for most patients.

Enterovirus infections in early childhood and the risk of atopic disease--a nested case-control study.

BACKGROUND: Enterovirus infections in childhood have been associated with a reduced risk of atopy in cross-sectional studies. OBJECTIVE: To study the relation between enterovirus infections in the first 2 years of life and atopic disease with IgE sensitization in a prospective study setting. METHODS: This was a nested case-control study among children who had been followed from birth. Neutralizing antibodies against 12 enterovirus serotypes were analysed at the age of 2 years from 71 atopic children and 142 non-atopic control children. Atopy was defined as having an atopic disease and IgE antibodies against at least one aeroallergen by the age of 5 years. RESULTS: Cumulative exposure to different enterovirus serotypes was inversely associated with atopy [odds ratio (OR) 0.73; 95% confidence interval (CI): 0.56-0.96]. The most pronounced protection was seen when echoviruses were analysed as a separate group (OR 0.63; 95%CI: 0.46-0.88). CONCLUSIONS AND CLINICAL RELEVANCE: We propose that exposure to several different enteroviruses in early childhood is inversely associated with atopic diseases. Our results support the hypothesis that repeated microbial infections in early life may protect from atopic sensitization and atopic diseases.

Introduction of complementary foods in infancy and atopic sensitization at the age of 5 years: timing and food diversity in a Finnish birth cohort.

OBJECTIVE: To study the associations between timing and diversity of introduction of complementary foods during infancy and atopic sensitization in 5-year-old children. METHODS: In the Finnish DIPP (type 1 diabetes prediction and prevention) birth cohort (n = 3781), data on the timing of infant feeding were collected up to the age of 2 years and serum IgE antibodies toward four food and four inhalant allergens measured at the age of 5 years. Logistic regression was used for the analyses. RESULTS: Median duration of exclusive and total breastfeeding was 1.4 (interquartile range: 0.2-3.5) and 7.0 (4.0-11.0) months, respectively. When all the foods were studied together and adjusted for confounders, short duration of breastfeeding decreased the risk of sensitization to birch allergen; introduction of oats <5.1 months and barley <5.5 months decreased the risk of sensitization to wheat and egg allergens, and oats additionally associated with milk, timothy grass, and birch allergens. Introduction of rye <7.0 months decreased the risk of sensitization to birch allergen. Introduction of fish <6 months and egg ≤11 months decreased the risk of sensitization to all the specific allergens studied. The introduction of <3 food items at 3 months was associated with sensitization to wheat, timothy grass, and birch allergens; the introduction of 1-2 food items at 4 months and ≤4 food items at 6 months was associated with all endpoints, but house dust mite. These results were particularly evident among high-risk children when the results were stratified by atopic history, indicating the potential for reverse causality. CONCLUSIONS: The introduction of complementary foods was consecutively done, and with respect to the timing of each food, early introduction of complementary foods may protect against atopic sensitization in childhood, particularly among high-risk children. Less food diversity as already at 3 months of age may increase the risk of atopic sensitization.

Reactive arthritis in a population exposed to an extensive waterborne gastroenteritis outbreak after sewage contamination in Pirkanmaa, Finland.

OBJECTIVES: To assess the occurrence, clinical picture, and triggering infections of reactive arthritis (ReA) associated with a large waterborne gastroenteritis outbreak. METHODS: After an extensive sewage contamination of the water supply system, an estimated 8453 of the 30 016 inhabitants of the town of Nokia fell ill. General practitioners and occupational physicians were advised to refer any patients with suspicion of new ReA to rheumatological examination including faecal culture, human leucocyte antigen (HLA)-B27 and antibody tests for Campylobacter, Salmonella, and Yersinia. RESULTS: Forty-five patients (33 females, 12 males) aged 16-77 years (median 53) were referred. ReA was diagnosed in 21, postinfectious arthralgia in 13, and other musculoskeletal conditions in 11 patients. HLA-B27 was positive in five out of 44 patients (11%). Of the 21 patients with ReA, possible triggering infections were observed in seven (33%), Campylobacter in four, Yersinia in three, and Salmonella in one, who also had Campylobacter infection. ReA was mild in all but one patient who presented with persistent Salmonella enterica serotype enteritidis infection. CONCLUSIONS: Taking into account the large population contaminated with potentially arthritogenic agents, the occurrence of ReA was rare and mild in character.

Anti-citrullinated peptide antibodies and the progression of radiographic joint erosions in patients with early rheumatoid arthritis treated with FIN-RACo combination and single disease-modifying antirheumatic drug strategies.

OBJECTIVES: To evaluate the impact of antibodies to cyclic citrullinated peptide (ACPAs) on radiographic progression in patients with early rheumatoid arthritis (RA) initially treated either with a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or with a single DMARD. METHODS: This study included 129 patients with early active RA initially randomised to treatment either with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone (FIN-RACo) (n=69) or with a single DMARD (initially sulfalasalazine) with or without prednisolone (SINGLE) (n=60). After 2 years, the use of DMARDs and prednisolone became unrestricted. Radiographic progression in hands and feet was assessed at baseline and at 1, 2, 3, 4 and 5 years. ACPAs at baseline were determined with enzyme immunoassay. RESULTS: ACPAs were positive in 92 (71%) patients. ACPA-positive vs. negative patients were more frequently rheumatoid factor (RF) positive (83% vs. 22%, p<0.001) and had an erosive disease (54% vs. 22%, p<0.001) at baseline. The presence of ACPA was associated with radiographic progression in FIN-RACo group even when the impact of RF was controlled; the radiographic progression was remarkably slower in ACPA-negative than in ACPA-positive cases (RF adjusted change over time between groups p=0.034). In the SINGLE group, the radiographic changes progressed parallel in ACPA-negative and positive patients. CONCLUSIONS: Most ACPA-positive RA patients have joint erosions already at diagnosis. ACPA positivity in early RA was related to radiographic progression even in patients treated initially with the FIN-RACo regimen. The initial FIN-RACo therapy seems to slow down the progression of joint damage in ACPA-negative patients.

Cardiolipin and ß2-Glycoprotein I antibodies associate with cognitive impairment and seizure frequency in developmental disorders.

Cardiolipin (CL) and ß(2)-Glycoprotein I (ß(2)-GpI) antibodies have been shown to associate with various neurological symptoms including seizures and cognitive dysfunction. Here we studied the prevalence of CL, ß(2)-GpI and antinuclear (ANA) antibodies in 74 patients with various developmental disorders with epilepsy and 70 healthy controls. Developmental disorders were classified into genetic syndromes and diseases, genetic and/or acquired conditions, cortical dysgenesias and acquired encephalopathias. IgM-CL and ß(2)-GpI antibodies were significantly more common in patients (46% vs. 20%, p<0.001 and 10% vs. 0%, p<0.05). Patients with most frequent seizures were more likely to have IgM-CL antibodies. The risk for positive IgM-CL, IgG-CL and ß(2)-GpI antibodies increased concomitantly with increasing intellectual disability. Present data demonstrates that epilepsy with frequently recurring seizures may be associated with secondary immune system activation.

Hippocampal sclerosis in refractory temporal lobe epilepsy is associated with gluten sensitivity.

BACKGROUND: Previous studies have associated coeliac disease (CD) and gluten sensitivity (defined as the presence of anti-gliadin antibodies and positive immunogenetics) with cerebellar degeneration and epilepsy with occipital calcifications. Hippocampal sclerosis (HS) in temporal lobe epilepsy (TLE) is a potentially progressive disorder with unknown aetiology; however, autoimmunity has been implicated as one of the possible mechanisms leading to HS. The purpose of this study is to analyze CD-associated antibodies and gluten sensitivity in a well-characterised group of patients with refractory focal epilepsy. METHODS: We measured anti-gliadin, anti-tissue-transglutaminase and anti-endomysium antibodies, and coeliac-type human leukocyte antigen (DQ2 and DQ8), in 48 consecutive patients with therapy-resistant, localisation-related epilepsy. The patients were categorised into the following three groups on the basis of ictal electro-clinical characteristics and the findings of high resolution MRI: TLE with HS (n = 16), TLE without HS (n = 16) and extratemporal epilepsy (n = 16). Patients with suspected CD or gluten sensitivity underwent duodenal biopsies. RESULTS: Seven patients in total were gluten sensitive; all of these patients fell in the TLE with HS group. On the other hand, none of the TLE without HS patients or those with extratemporal epilepsy were gluten sensitive (p<0.0002). The results of duodenal biopsies showed that three of the seven gluten-sensitive patients had histological evidence of CD and four had inflammatory changes consistent with early CD without villous atrophy. Four of the patients with gluten sensitivity had evidence of dual pathology (HS+another brain lesion), whereas none of the remaining patients did (p<0.0002). CONCLUSIONS: The present study demonstrates a previously unrecognised link between gluten sensitivity and TLE with HS. This association was very robust in this well-characterised group of patients; thus gluten sensitivity should be added to the list of potential mechanisms leading to intractable epilepsy and HS.

The high prevalence of antiphospholipid antibodies in refractory focal epilepsy is related to recurrent seizures.

BACKGROUND: Previous studies have shown the association between antiphospholipid antibodies with epilepsy but there are no studies addressing the effect of seizure frequency, duration of epilepsy, epilepsy type and aetiology on the prevalence of these antibodies in well-evaluated refractory epilepsy. METHODS: Anticardiolipin, anti-beta2-glycoprotein I and antinuclear antibody levels were measured in 105 well-evaluated patients with refractory focal epilepsy. Clinical determinants included the patient history, electroclinical classification and high resolution brain magnetic resonance imaging. RESULTS: Patients with seizures during the month prior to sampling (recent seizures) had increased prevalence of immunoglobulin (Ig) G class anticardiolipin antibodies (29%) compared with healthy controls [13%; age-adjusted odds ratio (OR): 3.09, 95% confidence interval (CI): 1.30-7.34] and patients with no recent seizures (11%; age-adjusted OR: 4.00, CI: 0.84-19.02). The patients with recent seizures had increased prevalence of moderate positive IgG class anticardiolipin antibodies (12%) compared with the controls (4%) and the patients with no recent seizures (0%; age-adjusted OR: 4.45, CI: 1.14-17.36). The prevalence of IgG class anticardiolipin antibodies was not associated with epilepsy type, duration or aetiology. CONCLUSION: The presence of antiphospholipid antibodies is associated with recurrent seizures in patients with refractory focal epilepsy. The measurement of these antibodies may be useful in evaluating the outcome of epilepsy.

Allergic sensitization and microbial load--a comparison between Finland and Russian Karelia.

Epidemiological data have indicated that some infections are associated with a low risk of allergic diseases, thus supporting the idea (hygiene hypothesis) that the microbial load is an important environmental factor conferring protection against the development of allergies. We set out to test the hygiene hypothesis in a unique epidemiological setting in two socio-economically and culturally markedly different, although genetically related, populations living in geographically adjacent areas. The study cohorts included 266 schoolchildren from the Karelian Republic in Russia and 266 schoolchildren from Finland. The levels of total IgE and allergen-specific IgE for birch, cat and egg albumen were measured. Microbial antibodies were analysed against enteroviruses (coxsackievirus B4), hepatitis A virus, Helicobacter pylori and Toxoplasma gondii. Although total IgE level was higher in Russian Karelian children compared to their Finnish peers, the prevalence of allergen-specific IgE was lower among Russian Karelian children. The prevalence of microbial antibodies was, in turn, significantly more frequent in the Karelian children, reflecting the conspicuous difference in socio-economic background factors. Microbial infections were associated with lower risk of allergic sensitization in Russian Karelian children, enterovirus showing the strongest protective effect in a multivariate model. The present findings support the idea that exposure to certain infections, particularly in childhood, may protect from the development of atopy. Enterovirus infections represent a new candidate to the list of markers of such a protective environment. However, possible causal relationship needs to be confirmed in further studies.

Anticardiolipin and antinuclear antibodies in epilepsy--a population-based cross-sectional study.

Increased prevalence of autoantibodies has been suggested in patients with epilepsy. This study determined the presence of autoantibodies in a representative cohort of 960 patients with epilepsy. The frequency of antinuclear antibodies (ANA), immunoglobulin G class anticardiolipin antibodies (aCL) and anti-B2-glycoprotein I antibodies were studied in 960 consenting adult patients with epilepsy and in 580 population-based reference subjects identified from the Finnish Population Registry. Overall the frequencies of the autoantibodies studied did not differ between patients with epilepsy and reference subjects. aCL were present in 4.5% of the patients and in 5.0% of the reference subjects and 17% of both the patients and the reference subjects had antinuclear antibodies. However, patients with partial epilepsy for > or =30 years were three times more likely to have aCL than patients with partial epilepsy for <10 years. Patients with partial epilepsy and > or=1 seizure per month were 2.2 times more likely to have aCL than patients with partial epilepsy with <1 seizure per month. Moreover, ANA tended to be more frequent among patients with > or =1 seizure per month. No association was found between the major antiepileptic drugs and autoantibodies. Overall the frequencies of the autoantobodies studied were similar in the large epilepsy cohort and in matched reference subjects from the general population. However, a long duration of epilepsy and poor seizure control were associated with an increased presence of aCL in patients with partial epilepsy.

Alpha/beta intraepithelial lymphocytes, serum gliadin antibodies and allergy test positivity in children.

AIM: To determine whether the amount of alphabeta-positive intraepithelial lymphocytes (IELs) is connected to allergy test positivity in children with gastrointestinal symptoms and whether elevated serum gliadin antibodies have any role in the diagnosis. METHODS: Twenty-seven children suffering from gastrointestinal-symptoms in whom intestinal biopsies had previously been obtained via endoscopy or with capsule biopsy to exclude coeliac disease were included into the study. The other inclusion criteria were increased amounts of CD3 and alphabeta-positive IELs with normal amounts of gammadelta-positive IELs in duodenal or jejunal biopsy specimens. At the control visit, the children underwent a physical examination and parents filled in a questionnaire concerning gastrointestinal- and atopic symptoms. Skin prick- and patch tests were done and serum gliadin, endomysium, transglutaminase antibodies and specific IgEs were measured. RESULTS: Only nine children (33%) had at least one positive result in the allergy tests, the rest remaining test negative. In children with digestive symptoms, IgG-class gliadin antibody titres were higher than those of the non-symptomatic children. A significant correlation was found between IgG-class gliadin antibodies and total amount of alphabeta-positive IELs (p = 0.017). CONCLUSION: No positive skin test or specific IgE positivity for cereals in children with high intestinal T-cell densities was observed. The correlation between IgG-class gliadin antibodies and the total amount of alphabeta-TCR positive-cells is likely to be a reflection of local immune response of the gut.

Humoral beta-cell autoimmunity is rare in patients with the congenital rubella syndrome.

The congenital rubella syndrome (CRS) is associated with increased risk for diabetes and thyroid disease. However, the mechanisms by which the rubella virus may cause these diseases are poorly characterized. Previous studies were carried out before modern immunological methods were available. The present study aimed at evaluating whether autoimmune mechanisms are involved in the pathogenesis by analysing antibodies to biochemically characterized autoantigens. The incidence of clinical diabetes, thyroid disease, coeliac disease and related antibodies (islet cell antibodies, ICA; insulin autoantibodies, IAA; antibodies to the tyrosine phosphatase related IA-2 molecule, IA-2 A and glutamic acid decarboxylase, GADA; thyroid peroxidase, TPO; tissue transglutaminase, TTGA; and gliadin, AGA) and HLA risk genotypes were analysed in 37 subjects affected by or exposed to rubella during fetal life (mean age 22.5 years). One patient had diabetes and four patients had clinical hypothyroidism at the time of the examination. ICA, IAA, GADA or IA-2 A were not detected in any of the patients, while five patients tested positive for TPO antibodies. Coeliac disease or TTGA were not observed. Eight patients carried the HLA-DR3-associated HLA-DQB1*02-DQA1*05 haplotype. These results provide no evidence of an increased frequency of markers for humoral beta-cell autoimmunity in patients with CRS suggesting that diabetes in CRS may be caused by other than autoimmune mechanisms.

Immunoglobulin G antibodies against indoor dampness-related microbes and adult-onset asthma: a population-based incident case-control study.

Immunoglobulin G (IgG) antibodies against microbes related to indoor dampness problems have been used as potential biomarkers of fungal exposure in clinical investigations. There is limited information on their relation to asthma. We conducted a population-based incident case-control study to assess the risk of asthma in relation to specific IgG antibodies to eight dampness-related microbes: Aspergillus fumigatus, A. versicolor, Cladosporium cladosporioides, Fusarium oxysporum, Sporobolomyces salmonicolor, Stachybotrys chartarum, Streptomyces albus and Trichoderma citrinoviride. We recruited systematically all new cases of asthma during a 2.5-year study period and randomly selected controls from a source population of adults 21-63 years of age living in the Pirkanmaa Hospital District, South Finland. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and the control series of 932 controls selected randomly from the source population. IgG antibodies were analysed with ELISA. An increased risk of developing asthma in adulthood was significantly related to IgG antibodies to T. citrinoviride, but not to the other moulds. There was no evidence of a dose-response relation between the IgG antibody level and the risk of asthma. T. citrinoviride may play a role in the aetiology of adult-onset asthma or serve as an indicator of other causal factors.

Indicators of inflammation after recent tonic-clonic epileptic seizures correlate with plasma interleukin-6 levels.

Cerebrospinal fluid (CSF) and peripheral blood pleocytosis have been observed after epileptic seizures without any evidence of infections, but no systematic studies on the acute phase reaction in such patients have been performed. We have previously reported increased levels of interleukin-6 (IL-6) in patients with recent tonic--clonic seizures. Because IL-6 is a major inducer of the systemic acute phase reaction, we decided to study various indicators of inflammation in the blood as well as their correlation with plasma and CSF IL-6 levels. CSF and blood samples were studied from 37 patients with previously undiagnosed and untreated tonic-clonic seizures without any clinical evidence of systemic or central nervous system infections as well as from 40 controls. The mean peripheral blood and CSF-leukocyte counts were significantly higher in patients compared with controls ( 7.9 x 10(9)vs. 6.1 x 10(9), P= 0.002 and 1.9 x 10(6)vs. 1.1 x 10(6), P= 0.032, respectively). There was some indication of increased concentration of C-reactive protein (CRP) and no difference in haptoglobin levels. There was a significant correlation between plasma but not CSF IL-6 concentration and those of both B-leukocyte count ( r= 0.051, P= 0.009) and CRP ( r= 0.42, P= 0.009). Epileptic seizures provoke a production of cytokines such as IL-6 that may in turn cause an activation of the acute phase reaction. Thus, CSF pleocytosis and increase in some indicators of inflammation should not automatically be attributed to systemic or CNS infections in patients with acute seizures.

Allele 2 of interleukin-1 receptor antagonist gene increases the risk of thyroid peroxidase antibodies in subacute thyroiditis.

Subacute granulomatous thyroiditis (SAT) is a self-limiting systemic inflammatory disorder with possible transient expression of thyroid antibodies. Persistent hypothyroidism is uncommon. The interleukin-1 receptor antagonist IL-1ra is an inhibitor of IL-1 activity and allele 2 of the IL-1ra gene is associated with inflammatory diseases and IL-1ra production. Forty-eight subjects with SAT were investigated. Polymorphisms of IL-1ra, IL-1beta-511 and TNFalpha genes were studied with respect to thyroid peroxidase antibodies (TPOab), thyroglobulin antibodies, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Serum IL-1ra levels were measured. An increased allelic frequency (43% vs 22%, p=0.039) and carriage rate (79% vs 41%, p=0.018) for IL-1ra allele 2 were observed with expression of TPOab in 14 (29.2%) subjects compared with those with negative findings. The carriage rate for both IL-1ra allele 2 and IL-1beta-511 allele 2 was also increased with TPOab expression (71% vs 27%, p=0.004, respectively). No difference in allele frequency or carriage rate was found compared with healthy controls. Serum IL-1ra levels correlated with S-CRP (r=0.41, p=0.004) and ESR (r=0.34, p=0.016), but the association with genes or thyroid antibodies was statistically insignificant. S-CRP levels and ESR were lower and negatively correlated with expression of TPOab (r=-0.27, p=0.046 and r=-0.32, p=0.017). This study describes the multiplicity of the mechanisms responsible for the severity of the acute-phase response during the course of SAT. IL-1ra may have a significant anti-inflammatory role in SAT. Presence of IL-1ra allele 2 increases the risk of developing TPOab.

High prevalence of antiphospholipid antibodies in children with epilepsy: a controlled study of 50 cases.

Evidence of immune system aberrations in patients with epilepsy includes antiphospholipid antibody positivity in adult patients with epilepsy with a prevalence of 19-26% and in 13% of children with partial epilepsy. Also immunoglobulin A deficiency has been reported to exist in up to 25% of epilepsy patients. The possible role of immune mechanisms in the pathogenesis of childhood epilepsy is clinically supported by the effectiveness of immunomodulatory treatments in cases with catastrophic childhood epilepsies. We analyzed a set of various autoantibodies in 50 consecutive children with epilepsy and in 20 healthy control subjects. None of the children had any clinical signs of immune system disorders. The main result was a significantly (P=0.011) higher prevalence of antiphospholipid antibodies in the study group (44%) compared with controls (10%). These antibodies were unexpectedly common (71-80%) in children with multiple seizure types associated often with symptomatic etiology, early onset and high frequency of seizures. There was no evidence of the antiphospholipid positivity being induced by certain AEDs (e.g. phenytoin or carbamazepine). Even though the significance of these autoantibodies remains unknown, their increased prevalence indicates that immune system mediated mechanisms may have a role in the manifestation of epilepsy in some children.

Antibody reactivity against thyroid peroxidase and myeloperoxidase in autoimmune thyroiditis and systemic vasculitis.

Potential cross-reactivity between thyroid peroxidase (TPO) and myeloperoxidase (MPO) molecules was evaluated by analysing the binding of 199 TPO antibody- and MPO antibody-positive sera to TPO and MPO molecules. Sera from six patients with autoimmune thyroiditis (AITD) and four patients with systemic vasculitis (SV) with different TPO-MPO antibody findings were then chosen for further analyses. All six patients with AITD had TPO antibodies in enzyme immunoassay (EIA) and four of them had simultaneously MPO antibodies in EIA. In AITD patients antibody binding to TPO could not be inhibited by adding native MPO to the serum diluent, suggesting that the possible cross-reactive epitopes were exposed in the denaturated MPO molecule. Similarly, the MPO ab reactivity of patients with systemic vasculitis could not be inhibited by native TPO. To study whether TPO and MPO antibodies recognize linear epitopes, the binding of antibodies to synthetic TPO and MPO peptides was analysed. Several TPO and MPO peptides were reactive, including peptides reacting with both TPO and MPO antibody-positive sera. One of the most cross-reactive peptides contained AA 586-601 in TPO, showing also particularly high AA homology (88%) with MPO (AA 594-609). The results suggest that TPO and MPO molecules contain cross-reactive epitopes that are exposed in denaturated molecules and may thus cause false positive antibody findings in solid phase EIA assays.

Thyroid antibodies in association with thyroid malignancy II: Qualitative properties of thyroglobulin antibodies.

Qualitative properties of thyroglobulin (Tg) antibodies, in association with thyroid malignancy, suspected malignancy or other thyroid diseases, were studied in 177 patients. Retrospective clinical analysis revealed 137 patients to have thyroid carcinoma and 40 to have other thyroid diseases. Serum Tg was assayed by an immunoradiometric method. Thyroid microsomal (AMC) and Tg antibodies were measured by the particle agglutination method and the avidity of Tg antibodies by enzyme immunoassay (EIA). Assessment of the qualitative properties of Tg antibodies revealed that the high-avidity antibodies especially seem to bind circulating Tg. Thus any Tg value from a sample with detectable Tg antibodies is unreliable and should be interpreted with caution.

Circulating myeloperoxidase may cause false negative findings in the analysis of myeloperoxidase antibodies in systemic vasculitis.

In systemic vasculitis reliable detection of myeloperoxidase antibodies (MPO-Abs) is of great clinical importance in the diagnosis and follow-up of patients. We have studied whether circulating myeloperoxidase (MPO) could have an effect on MPO-Ab findings. Serum MPO and MPO-Abs were measured in 50 healthy individuals, 35 patients and in the follow-up samples from two patients with Wegener's granulomatosis. Heating the sera at 56 degrees C for 30 min reduced the concentration of immunoreactive MPO both in control and patient sera. In 71% of the patient sera heating made initially negative MPO-Abs detectable. In a few cases with severe vasculitis the antibody findings remained totally negative. These results, together with the data from the follow-up samples from two patients with Wegener's granulomatosis, revealed that the serological diagnosis of vasculitis may be considerably delayed if only native samples are analysed for MPO-Abs. These findings are of considerable clinical significance for the interpretation of MPO-Ab results. Circulating myeloperoxidase affects MPO-Ab measurements, causing false negative findings in MPO-Ab assays. Therefore, it is recommended to denaturate circulating MPO by heating the sera before the analysis of MPO-Abs and to re-evaluate the cut off-values.

Thyroid antibodies in association with thyroid malignancy. I. Simultaneous occurrence of thyroiditis and thyroid malignancy.

Occurrence of thyroid antibodies and thyroiditis in association with thyroid malignancy, suspected malignancy or other thyroid diseases was studied in 177 patients. Retrospective clinical analysis revealed that 137 patients had thyroid carcinoma (108 papillary carcinomas, 10 occult papillary carcinomas, 14 follicular carcinomas, and 5 other carcinomas) and 40 had other thyroid diseases. Thyroid microsomal (AMC) and thyroglobulin antibodies (ATG) were measured by the particle agglutination method. Clinically significant thyroid antibody titers and histological or clinical features of thyroiditis were seen in nine patients with thyroid carcinoma, being equally prevalent in follicular and papillary carcinomas. Taking into account the prevalence of positive AMC antibodies and thyroid carcinoma in Finland, the highest predicted prevalence of simultaneously occurring thyroid carcinoma and thyroiditis in the under 40 age group should be 0.002% and in the over 40 age group 0.006%. In the present material the observed occurrences in corresponding age groups were unexpectedly high (4.7% and 5.2%). The results may partly be due to patient selection, but they also suggest that there might be a link between thyroiditis and thyroid carcinoma.