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Biomedical subjects

T Palosuo

Publications and source records attributed to T Palosuo.

At least 19 recordsLinked to original sources

Immunopathology of rheumatoid arthritis. Antikeratin antibodies precede the clinical disease.

OBJECTIVE: We sought to determine whether circulating antikeratin antibodies (AKA) precede the onset of rheumatoid arthritis (RA). METHODS: By matching the registers of 2 previous population studies with the registry of patients receiving antirheumatic drugs several years later, pre-illness serum specimens could be obtained from 39 individuals who subsequently developed RA. AKA were assayed with the standard indirect immunofluorescence technique. RESULTS: Ten of 39 serum specimens from individuals who subsequently developed seropositive RA, and 1 of 15 sera from individuals who developed seronegative RA, were positive for IgG-class AKA by immunofluorescence assay. The AKA-positive sera were also positive for rheumatoid factors. CONCLUSION: The findings focus attention on the role of pre-illness immunologic events in the pathogenesis of RA.

Antibodies

Characterization of latex antigens and allergens in surgical gloves and natural rubber by immunoelectrophoretic methods.

Allergy to natural rubber (latex) products is increasingly frequent among both medical personnel and lay subjects. Although individual antigens and allergens in latex products have not been fully characterized, they are believed to derive from the sap of the rubber tree. Rabbit IgG and human IgE antibodies against rubber proteins were used to characterize antigens and allergens in surgical latex gloves and natural rubber by crossed immunoelectrophoresis and its modifications. The results from crossed-line immunoelectrophoresis demonstrated that the surgical latex gloves had at least 10 antigens in common with natural rubber sap and ammoniated latex. In crossed radioimmunoelectrophoresis, at least six of the 10 protein antigens in the surgical glove extract and natural rubber were allergens since they bound IgE antibodies from the latex-allergic patients' sera. The surgical glove extract also demonstrated one allergen not found in natural rubber, suggesting that rubber proteins may be altered during glove manufacture.

Animals

A sensitive enzyme-linked immunosorbent assay for determination of bovine beta-lactoglobulin in infant feeding formulas and in human milk.

We developed a sensitive sandwich-type ELISA for measuring low levels of cow's milk (CM) beta-lactoglobulin. Purified anti-beta-lactoglobulin was used as coating antibody and also as second antibody conjugated with alkaline phosphatase. Polyethylene glycol 6000 was added to the incubation buffers to improve sensitivity. The detection limit of the assay was 0.002 microgram/l, which is much better than sensitivities reported for other beta-lactoglobulin assays. The sensitivity was not impaired by the presence of other CM proteins. The recovery from breast milk was 93% and from the diluting buffer 127%. The coefficient of variation within day was 5-15% and between days 10%. One hour after oral intake of milk, beta-lactoglobulin could be detected in the breast milk of three mothers at concentrations of about 1-2 micrograms/l. Widely different concentrations of beta-lactoglobulin were measured in two protein hydrolysates based on CM whey and casein proteins; the observed concentrations were 200 and 0.0056 micrograms beta-lactoglobulin/g dry weight, respectively.

Animals

Antiphospholipid antibodies and thrombosis in systemic lupus erythematosus: comparison of three lupus anticoagulant assays and anticardiolipin ELISA in 188 patients.

The presence of antiphospholipid antibodies (aPL) in 188 unselected patients with systemic lupus erythematosus was studied using the recalcification time, kaolin clotting time (KCT), dilute Russell's viper venom time (dRVVT) and anticardiolipin ELISA (aCL) to identify patients with a high or low risk of thrombosis among patients with aPL. aPL were detected by at least one method in 104 (55%) of the patients. Despite heterogeneity, lupus anticoagulant (LA) methods correlated reasonably well with each other (r = 0.736-0.968), but poorly with aCL (r = 0.241-0.549). Positivity in LA assays and immunoglobulin G (IgG)-aCL were associated with patients who experienced thrombosis (P less than 0.001 for all assays). Patients with both LA and aCL had experienced thrombosis more often than those having only one (odds = 6.3, P less than 0.001). When patients with aPL were ranked by relative strength of the finding and divided into tertiles, a history of thrombosis was associated with membership in the strongest tertile of at least one assay (odds = 4.2, P = 0.002). LA and aCL had similar sensitivities for thrombosis (61% and 63%, respectively), but LA was more specific than aCL (79% vs 53%). The best combination of two assays was KCT with dRVVT (61% sensitivity, 87% specificity). Maximal sensitivity (71%) for thrombosis could be achieved by adding IgG-aCL to these two assays, but specificity was lower (73%). In conclusion, a high thrombotic risk among patients with aPL was indicated by the simultaneous presence of both LA and aCL, strongly positive aPL, and, among aCL, IgG-class antibodies.

Adolescent

Antinuclear antibodies heralding the onset of systemic lupus erythematosus.

On the basis of record linkage with the Social Security Institution's population register, 16 specimens from healthy subjects who subsequently developed systemic lupus erythematosus or mixed connective tissue disease could be traced from stored sera collected in connection with nationwide maternity welfare program in Finland. The sera were tested for antinuclear antibodies (ANA) using an immunofluorescence technique. Ten of the 16 specimens were positive. Eight of 11 cases were positive when the interval from taking the blood specimen to the onset of the first symptoms of disease was 2 years or less and 2 of 5 cases were positive when the interval was over 3 years. Eighteen of 21 sera with established disease and 5 of 85 control sera from the same serum collection were positive. Thus, ANA as detected by a sensitive technique frequently precede the onset of disease indicating that they are not a secondary manifestation of inflammation or tissue destruction.

Adult

Cutaneous reactivity to mosquito bites: effect of cetirizine and development of anti-mosquito antibodies.

Cutaneous reactivity to mosquito bites was examined in 27 adult volunteers exposed to Aedes communis mosquitoes. Twenty-three subjects showed a combination of immediate wealing and delayed bite-papules, two subjects each experienced only immediate or delayed cutaneous reactions and two were non-responsive to the bites. The mean size of wealing and the mean score of pruritus was similar in 19 non-atopic and in eight atopic volunteers. These results confirm that normal subjects exhibit different stages of sensitization to mosquito bites. At the onset of the mosquito season, immunoblotting showed that four of 21 subjects (19%) had IgG-class antibodies to a recently described 21.5 kD Aedes communis mosquito antigen. After a 10-day exposure to a mean of 47 mosquito bites, these antibodies were found in 10 subjects (48%) who exhibited both strong and weak cutaneous bite-lesions. A placebo-controlled, double-blind study with cetirizine 10 mg was performed to examine the effect of this non-sedating antihistamine on mosquito bites. The bite lesions were measured and pruritus scored at 15 min, 60 min, 12 hr, and 24 hr. Cetirizine decreased significantly immediate wealing and pruritus (P less than 0.01), but had no effect on the delayed symptoms. This result supports the view that immediate mosquito-bite reactions are histamine-mediated.

Adolescent

Surgical latex glove allergy: characterization of rubber protein allergens by immunoblotting.

Immunoblot analysis employing IgE antibodies derived from sera of 3 physicians and 2 nurses allergic to surgical latex gloves, disclosed 10 allergens in natural rubber sap. Nine of the 10 allergens were detected in ammoniated natural rubber latex, but only 4 allergens in a latex glove extract. The allergenic proteins had apparent molecular weights ranging from 14 to 70 kD. Allergens with molecular weights of 14 and 21 kD showed the most intense immunoblot reactions suggesting that these proteins could be the major allergens in the natural rubber. An 11-kD protein and a 26-kD protein were only seen in the glove extract, indicating that they could be modified rubber proteins formed during glove manufacture.

Adult

Lupus anticoagulant and the skin. A longterm follow-up study of SLE patients with special reference to histopathological findings.

Skin manifestations were described in lupus anticoagulant (LA) positive and in LA negative SLE patients. Necrotic ulcers appearing at the beginning of the disease process characterized the 33 LA positive patients. Thirteen patients had a "peripheral vascular syndrome"; small leg ulcers of livedoid vasculitis type following deep venous thromboses, in 3 patients developing into pyoderma gangrenosum like ulcers and in 2 patients into pseudo-sarcoma Kaposi. The lesions were histologically characterized by capillary angiogenesis with extravasated red blood cells, sparse inflammatory cell infiltrates and microthromboses. Three patients had ulcers clinically and histologically resembling those seen in Degos' disease. Five patients had anetoderma showing elastic tissue depletion and microthromboses histologically. A different pattern of skin changes was seen in the LA negative patients. Our findings suggest that antiphospholipid antibodies play a pathogenetic role in the described skin manifestations of LA positive SLE patients.

Adolescent

Rheumatoid factors antedating clinical rheumatoid arthritis.

The relationship between rheumatoid factors (RF) and rheumatoid arthritis (RA) was studied in the Mini-Finland Health Survey. This covered a representative sample of the Finnish population over 30 years of age, initially comprising 8,000 persons, of whom 7,217 participated in the field survey carried out in 1978-80. The participants were followed using record linkage with the Social Insurance Institution's population register to identify patients entitled to free medication. Until the end of 1988, 21 persons had developed new seropositive RA. In 15 cases, preillness specimens contained elevated levels (greater than or equal to 20 IU/ml) of RF. In the remaining 6 cases with RF negative preillness specimens, the interval from taking the blood specimen to the onset of disease was 4 years or more. RF represent a key element in the rheumatoid inflammatory process. Their occurrence in preillness specimens suggests that they may have a primary role in the pathogenesis of the disease.

Adult

Measuring rheumatoid factor in nonrheumatoid subjects: immunoturbidimetric assay, latex slide test, and enzyme-linked immunosorbent assay compared.

Previous studies of patients with rheumatoid arthritis (RA) have shown a good correlation between results from immunoturbidimetric assays of rheumatoid factor (RF) and latex fixation tests. To extend the research to non-RA subjects, we tested sera from 1000 pregnant women, half each in the first and third trimesters. By turbidimetry, 24 non-RA sera were regarded as positive for RF (greater than or equal to 20 int. units/mL) and 18 sera as borderline (15-19 int. units/mL). By the latex fixation test, 28 non-RA sera gave a clear reaction (positive) and 17 sera a weak reaction (borderline). The association between the tests was statistically highly significant (P less than 0.001). All sera with positive and borderline reactions were tested by enzyme-linked immunosorbent assay for RF isotypes, together with a random subsample of about one-sixth of the original serum samples. Positive RF results by immunoturbidimetry were predominantly due to the presence of IgM-RF. In contrast to some earlier findings, we saw no difference in the prevalence of positive RF reactions between sera from the first and third trimesters.

Enzyme-Linked Immunosorbent Assay

Reference intervals for immunoglobulins IgA, IgG and IgM in serum in adults and in children aged 6 months to 14 years.

Reference intervals were estimated for immunoglobulins IgA, IgG and IgM in serum in 313 healthy adults aged 17 to 64 years and in 399 children aged 6 months to 14 years. In adults a nonparametric method was chosen for estimating reference interval limits. In children the limits were estimated age-specifically using regression analysis. Immunoglobulin assays used in this study were standardized with a Finnish secondary standard which was calibrated against the World Health Organisation 67/99 immunoglobulin standard. Later, another international primary standard (US National protein standard preparation) was used, the immunoglobulin levels of which are calibrated against the WHO standard. The nominal immunoglobulin concentrations assigned by the manufacturers of several commercial immunoglobulin standard preparations were found to differ from the concentrations measured with the international calibrator used in this study. In conclusion, the reference intervals estimated in this study should be transferable to any laboratory using immunoglobulin assays calibrated against the WHO standard. The usefulness of commercial immunoglobulin standard preparations not calibrated against these primary standards is limited.

Adolescent

Immunology and treatment of mosquito bites.

Cutaneous reactions to mosquito bites are usually pruritic weals and delayed papules. Arthus-type local and systemic symptoms can also occur but anaphylactic reactions are very rare. Both clinical and experimental evidence suggest that the various bite reactions result from sensitization to the mosquito saliva injected into the skin during feeding. Recent immunoblot studies have shown both IgG- and IgE-class anti-mosquito antibodies, but their species-specificity and clinical importance is at present unknown. In addition to an Arthus-type mechanism, both cutaneous late-phase reactivity and cell-mediated immunity may be involved in the pathophysiology of delayed mosquito-bite lesions. Cutaneous sensitization to mosquito bites can be divided into five different stages ranging from the stages of immediate wealing and delayed bite papules, to the stage of non-reactivity. No desensitization treatment is generally available for mosquito allergy but it has recently been shown that cetirizine, a potent non-sedating antihistamine, is effective against the wealing and pruritus caused by mosquito bites.

Animals

Occurrence of two germline-related rheumatoid factor idiotypes in rheumatoid arthritis and in non-rheumatoid seropositive individuals.

Human rheumatoid factor (RF) paraproteins express two distinct light chain cross-reactive idiotypes defined by the monoclonal antibodies 17.109 and 6B6.6. These germline gene-related cross-reactive idiotypes are both carried on VK3 light chains and are each present on about one-third of IgM RF paraproteins. We assessed the degree to which these idiotypes are represented in polyclonal RFs. We used rheumatoid arthritis (RA) and non-RA RF-positive sera selected from a large cross-sectional population study (the Mini-Finland Health Survey), and sera from a community-based follow-up study of recent-onset RA patients from Heinola, Finland. In the Mini-Finland Health Survey, elevated levels of the 17.109 RF idiotype were seen in sera of 13% of the RA and 19% of the non-RA group; 6B6.6 RF was seen in 26% of the RA and 28% of the non-RA group. In sera of the Heinola follow-up study, 17.109 RF was seen in 12% initially, but in only 3% at 8 years. Similarly, 6B6.6 RF was detected in 25% initially, but in only 7% at 8 years. Ten sera positive for RF prior to the onset of clinical RA were identified from individuals of a second large population study from Finland (North Karelia project); two of these sera exhibited the 6B6.6 idiotype; none exhibited the 17.109 idiotype. The data are consistent with the concept that these germline gene-related cross-reactive RF idiotypes occur frequently in the polyclonal RF of non-RA as well as RA sera, and that in RA the idiotypes may sometimes be reduced or lost as a consequence of somatic diversification of the RF through somatic mutation, usage of new germline genes, or both.

Arthritis, Rheumatoid

Smoking, lung function, and rheumatoid factors.

Positive rheumatoid factor (RF) reactions commonly precede the onset of clinically manifest rheumatoid arthritis (RA). Thus if items associated with RF reactions were traced at the community level this might provide clues to the cause of RA. The relations between smoking and lung functions and the occurrence of RA and RFs in a population sample representative of the adult Finnish population were studied. Rheumatoid factor testing was performed for 7124 subjects (89% of the sample) by the sensitised sheep cell agglutination test. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured with spirometry. 'False positive' RF reactions occurred twice as often in current smokers and ex-smokers than in those who had never smoked. The prevalence of high titres was fourfold greater among current smokers than among those who had never smoked. These associations were statistically significant and independent of age, FVC, and FEV1 in both sexes. The women with airflow limitation (FEV1/FVC less than 70%) had a significantly increased occurrence of RFs which was independent of their smoking history, but no such relationship was found in men. The results suggest an impact of smoking on RF production; a follow up study may show whether the raised RF titers in smokers will be reflected as an increased incidence of RA.

Adult

Immunization of rabbits with mosquito bites: immunoblot analysis of IgG antimosquito antibodies in rabbit and man.

Rabbits immunized with 50-60 Aedes communis mosquito bites developed IgG antibodies recognizing a 21.5-kD mosquito antigen detected by the immunoblot technique. This protein seems to be a major immunogen in the saliva of A. communis mosquitoes. Studies on 60 human sera revealed that IgG antibodies recognizing the 21.5-kD antigen occurred in about 50% of young children and adults but were not found in the sera of 20 unexposed infants. The present immunoblot method allows further characterization of antigens and antibodies specific to mosquito saliva and contributes to understanding their role in mosquito bite reactions.

Aedes

Antibodies to synthetic peptides from Epstein-Barr nuclear antigen-1 in sera of patients with early rheumatoid arthritis and in preillness sera.

We studied IgG antibody levels to synthetic peptides (p62, E11 and E3) from Epstein-Barr nuclear antigen-1 (EBNA-1) protein sequence in sera of patients with rheumatoid arthritis (RA), in pre-RA and in rheumatoid factor (RF) positive non-RA sera from Finland. Anti-E11 and anti-E3 antibody levels were significantly elevated in RA sera, compared with both RF negative and RF positive nonrheumatoid controls. The concentrations of anti-E11 and anti-E3 antibodies in the preillness sera were lower than those in RA sera. Eight-year followup samples of patients with RA had slightly decreased levels of anti-E3 and anti-E11 antibodies compared with samples taken within 6 months of the disease onset. Anti-p62 antibody levels did not differ significantly between any of the groups studied. Thus, elevated levels of antibodies to 2 of the glycine containing EBNA-1 peptides were associated with clinical RA.

Adult