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Biomedical subjects

K Aho

Publications and source records attributed to K Aho.

At least 91 records · Page 5Linked to original sources

Crossreaction between antibodies to oxidised low-density lipoprotein and to cardiolipin in systemic lupus erythematosus.

Serum lipoproteins contain phospholipids and modified low-density lipoprotein (LDL) may thus act as a target for antiphospholipid antibodies. Raised concentrations of IgG antibodies against oxidised LDL were found in 47 of 61 (80%) patients with systemic lupus erythematosus (SLE). 46% of patients also had raised concentrations of IgG anticardiolipin antibodies. Binding of anticardiolipin antibodies to solid-phase cardiolipin was inhibited by oxidised LDL but not by native LDL in 16 of 21 sera from SLE patients. These observations suggest crossreactivity between antiphospholipid antibodies, which are closely associated with thrombosis in SLE, and antibodies to oxidised LDL, thus providing a possible link between thrombotic and atherosclerotic complications in SLE.

Adult↗

Early-onset osteoarthritis linked to the type II procollagen gene. Detailed clinical phenotype and further analyses of the gene.

OBJECTIVE: To specify in detail the clinical phenotype in 2 Finnish families demonstrating linkage between the type II procollagen gene (COL2A1) and osteoarthritis (OA). We also reevaluated the linkage and screened the exon sequences of the COL2A1 gene for mutations. METHODS: We used single-stranded conformation polymorphism and denaturing gradient-gel electrophoresis techniques for the analyses. RESULTS: The patients' phenotype represented typical, but early-onset, OA. There was no clinical or radiographic evidence of chondrodysplasia. No mutation in the protein-coding regions of the COL2A1 gene could be identified. However, the linkage analysis with a new multiallelic marker resulted in a statistically more significant logarithm of odds (LOD) score than has been reported. CONCLUSION: Familial OA with classic clinical and radiographic findings is tightly linked to the COL2A1 gene. Systematic screening of the 54 exons did not, however, reveal any mutations; this suggests that the mutation may lie in the promoter region or within the introns of this 35-kb gene.

Adolescent↗

Multiallelic polymorphism of the cartilage collagen gene: no association with osteoarthrosis.

OBJECTIVES: To determine whether any of the type II collagen alleles are associated with generalised osteoarthrosis or osteoarthrosis of the finger joints in the genetically isolated Finnish population. METHODS: Two patient cohorts with evidence for only primary osteoarthrosis and a cohort of healthy control subjects were selected from the Helsinki University Central Hospital and the Rheumatism Foundation Hospital in Finland. Forty one patients with primary generalised osteoarthrosis, 49 patients with osteoarthrosis of the finger joints, and 48 control subjects were included. Two markers of the type II collagen gene, a PvuII polymorphism and a VNTR polymorphism, were analysed from each subject. RESULTS: Four different alleles of the VNTR marker were observed and the relative risks associated with the different VNTR alleles varied between 0.39 and 1.24 among the patients with generalised osteoarthrosis and between 0.67 and 2.33 among the patients with osteoarthrosis of the finger joints. The PvuII polymorphism detected two different alleles and the associated relative risks were 0.82 and 1.82 for the patients with generalised osteoarthrosis, and 1.04 and 0.96 for the patients with osteoarthrosis of the finger joints. CONCLUSIONS: A major predisposing allele of the type II collagen gene as the causative factor for osteoarthrosis could be excluded in this population. A spectrum of mutations associated with different alleles of this gene could not be excluded, however. Further, these two forms of cartilage disease can be caused by gene defects with reduced penetrance and the effect of such an allele is easily masked under the high frequency of normal alleles.

Alleles↗

Improved immunoturbidimetric method for rheumatoid factor testing.

The performance of two immunoturbidimetric modifications for rheumatoid factor (RF) testing, which differ with respect to the means of complement inactivation (heat treatment and inactivation with polyvinyl sulphonate), were compared in serum samples from 87 patients with rheumatoid arthritis (RA) and from 403 healthy subjects. IgM-rheumatoid factor titres were also measured with an enzyme linked immunosorbent assay (ELISA). Both immunoturbidimetric tests gave positive reactions (rheumatoid factor > or = 20 IU/ml) in 74 out of the 87 (85%) RA sera. In cases with high RF concentrations the results after chemical inactivation tended to be slightly higher compared with heat inactivation. In healthy subjects rheumatoid factor was detected in 19/403 (4.7%) sera using heat inactivation and in 22/403 (5.5%) sera with chemical inactivation of complement. Interrun coefficient of variation in the chemical inactivation assay was 4.4%; with the heat inactivation method it was 8.1%. In the ELISA, a marginally better correlation was noted in the results obtained using chemical inactivation. Inactivation of complement by means of polyvinyl sulphonate offers the advantage of easier test performance and better reproducibility, and the results may reflect more accurately true rheumatoid factor concentrations.

Adult↗

Prospect for an additional laboratory criterion for rheumatoid arthritis.

The aim of the study was to establish the benefit of an additional hypothetical laboratory criterion for rheumatoid arthritis (RA), comprising positivity for antikeratin antibody (AKA) and/or antiperinuclear factor (APF). The tests were applied to a series of 308 hospital patients with various recent-onset inflammatory joint diseases who were followed for 3 years. The performance of APF and AKA was compared with rheumatoid factor (RF). The most sensitive (.72) but the least specific (.86) test for RA was the latex test. The most specific (.96) but the least sensitive (.33) test was AKA. Waaler-Rose and APF were intermediate. AKA and/or APF positive patients had significantly more erosions than patients negative for these autoantibodies. Despite the impressive performance characteristics of APF and AKA, the actual classification impact achieved, as compared to using RF as the sole laboratory criterion, turned out to be moderate. This is because the criteria proved to be interrelated. Unlike RF, AKA and APF are not suited to the general laboratory, at least not in their present form. Moreover they so far lack the broad data base of RF.

Antibodies↗

Antikeratin antibody and antiperinuclear factor as markers for subclinical rheumatoid disease process.

OBJECTIVE: Antikeratin antibody (AKA) and antiperinuclear factor (APF) are antibodies characteristic for rheumatoid arthritis (RA). Our purpose was to obtain information on the occurrence of APF before the onset of clinical disease and on the occurrence of AKA and APF in cases with false-positive rheumatoid factor (RF) reactions. METHODS: AKA and APF were measured with indirect immunofluorescence technique using rat esophagus and buccal mucosa cells, respectively, as antigen source. RESULTS: Five of 30 preillness specimens from subjects who later developed seropositive RA were positive for AKA and APF, 3 sera were positive for only AKA and 3 for only APF. All the eleven sera positive for AKA or APF were RF positive. Both AKA and APF were detected in 6 of 70 sera from RF positive subjects who did not develop RA within a 10-year followup, 3 sera were positive for only AKA and 3 for only APF. CONCLUSION: AKA and APF appear to be linked markers of an immunological process which, in RF positive subjects, predicts the development of clinical arthritis. However, disease manifestations develop in only a proportion of cases.

Adult↗

Smoking and risk of rheumatoid arthritis.

OBJECTIVE: To investigate smoking for its association with the incidence of seropositive and seronegative rheumatoid arthritis (RA). METHODS: A cohort of adult Finns was examined by the Social Insurance Institution's Mobile Clinic in 1966-72. The 24,445 women and 28,364 men who had neither arthritis nor a history of it at the start of the study were followed until the end of 1989 using record linkage with the Institution's population register to identify patients entitled to free antirheumatic medication. Sufficient information was obtained on 512 incident cases of RA, of whom 119 men and 229 women were seropositive and 42 men and 122 women seronegative. RESULTS: There was a close association between smoking and the incidence of seropositive RA in men. It was not due to confounding by age, geographical location of residence, marital status, social class, self-perceived general health, or body mass index, although these factors correlated with smoking history. As adjusted for these factors, the relative risk of seropositive RA was 2.6 (95% confidence interval, 1.3-5.3) in male ex-smokers and 3.8 (95% confidence interval, 2.0-6.9) in current smokers, in comparison with the men who had never smoked. The association persisted throughout the entire followup period, but it was most distinct after the first 14 years of followup. Smoking did not predict seropositive RA in women, nor was it predictive of seronegative RA in men or women. CONCLUSION: Exposure to tobacco smoke, or some factor or cluster of factors associated with smoking, may trigger the production of rheumatoid factors and, in interaction with the male sex, subsequently contribute to the development of clinically manifest RA.

Adolescent↗

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↗

Systemic lupus erythematosus and related systemic diseases in a nationwide twin cohort: an increased prevalence of disease in MZ twins and concordance of disease features.

Concordance rates for systemic rheumatic diseases among monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs ascertained from the older (twins born before 1958) and younger (twins born during the period 1958-1986) parts of the Finnish Twin Cohort were studied. Nine MZ pairs and 10 DZ pairs with at least one member affected by systemic lupus erythematosus (SLE) were identified. Only one MZ pair was concordant for definite SLE by American Rheumatism Association (ARA) criteria. In addition, two more MZ pairs that fulfilled three ARA criteria may have been concordant. None of the DZ pairs were concordant for SLE. MZ twins also had a higher concordance rate for tests of autoantibodies, but the numbers were small. Other systemic rheumatic diseases were infrequent. The cumulative incidence of systemic rheumatic diseases among MZ twin individuals (1.7/1000) was significantly higher than that among DZ twin individuals (0.7/1000).

Adult↗

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↗

Risk factors for subarachnoid hemorrhage in a longitudinal population study.

The known risk factors of atherosclerotic diseases may be involved in the development of a subarachnoid hemorrhage. We studied the morbidity and mortality due to subarachnoid hemorrhage among 42,862 men and women aged 20-69 years who had participated in a large health survey in Finland. During a mean follow-up of 12 years, 102 non-fatal and 85 fatal cases of subarachnoid hemorrhage were observed. The total incidence was 37 per 100,000 person-years. Smoking and hypertension were positively associated and body mass index was inversely associated with the risk of subarachnoid hemorrhage. These associations were not confounded by age or each other. No statistically significant association with risk was detected for serum cholesterol level, hematocrit content, known heart disease, or diabetes. The risk was especially elevated among lean hypertensive subjects and lean smoking subjects. The age-adjusted relative risks of subarachnoid hemorrhage for lean, hypertensive smokers were 18.3 (95% confidence interval (CI), 7.8-42.7) among women and 6.7 (95% CI, 2.3-19.7) among men as compared to the risk among subjects without these risk factors. We conclude that modifiable risk factors are predictive of subarachnoid hemorrhage, for which reason subarachnoid hemorrhage may in part be preventable. Leanness combined with arterial hypertension and/or smoking, in particular, poses a substantially elevated risk.

Adult↗

Rheumatoid arthritis in identical twins: a clinical and immunogenetic study of eight concordant pairs derived from a nationwide twin panel.

The nationwide Finnish Twin Cohort was linked with the national Sickness Insurance Register. Eight identical twin pairs concordant for rheumatoid arthritis (RA) fulfilling the American Rheumatism Association criteria were identified. All 16 cases were known to be seropositive. Four pairs had at least one additional first-degree relative with RA, and the prevalence of RA among all the first-class relatives was 9%. HLA-typing was performed for 15 patients representing the eight pairs; six pairs carried the DR4 allele, and three of these pairs were putative homozygotes. Nodules and Sjögren syndrome occurred fairly frequently (in 7 of 16 and 6 of 13 cases examined, respectively), but concordance within pairs was no higher than that expected by chance. The course of the disease was fulminant in one patient and in several others the disease had led to marked joint destructions. The findings pointed out to some intrapair similarity in the progression of the joint damage and in the type of complications caused by gold.

Adult↗