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K Aho

Publications and source records attributed to K Aho.

At least 19 recordsLinked to original sources
PubMed2005

Finnish case-control and family studies support PTPN22 R620W polymorphism as a risk factor in rheumatoid arthritis, but suggest only minimal or no effect in juvenile idiopathic arthritis.

Several studies have identified the PTPN22 allelic variant 1858 C/T that encodes the R620W amino-acid change as a putative susceptibility factor in autoimmune diseases. The current study was undertaken to examine a large cohort of Finnish rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) subjects using both population control and, importantly, family-based association methods. The latter is particularly important when, as is the case for the 1858 C/T polymorphism, the frequency of the variant allele (T) differs in both major ancestral populations and in subpopulations. The analysis of rheumatoid factor-positive 1030 RA probands from Finland provides strong support for association of this variant in both population studies (allele specific odds ratio (OR)=1.47, 95% confidence interval (CI)=1.27-1.70, P=3 x 10(-7)) and in family studies (P<10(-6)). In contrast, no allelic association was seen with JIA (230 probands) and only weak evidence for a genotypic effect of 1858T homozygotes was observed in this population.

Alleles↗
PubMed2004

Smoking history and serum cotinine and thiocyanate concentrations as determinants of rheumatoid factor in non-rheumatoid subjects.

OBJECTIVES: Smoking is associated with false-positive rheumatoid factor (RF). We explored the dose-response relationship of this association, using smoking history and serum cotinine and thiocyanate concentrations as measures of tobacco exposure. METHODS: A total of 6947 men and women aged 30 yr or over and free of clinical arthritis were included in the Mini-Finland Health Survey carried out between 1978 and 1980. Detailed histories of smoking and RF (sensitized sheep cell agglutination test) were obtained in the basic examination. In 2000, serum cotinine and thiocyanate were determined from serum samples collected at baseline and stored at -20 degrees C. A cut-off point of 100 microg/l was used for serum cotinine and 10 micromol/l for thiocyanate to indicate active smoking. RESULTS: There was a close association between smoking and strongly positive RF. After adjustment for age, sex, coffee consumption and region, the odds ratios (95% confidence intervals in brackets) in current smokers and in those who had quit smoking were 3.94 (2.04-7.61) and 2.71 (1.33-5.53), respectively, compared with those who had never smoked. Among current smokers, the intensity, duration or tertiles of pack-years of smoking were not related to RF. No relationship between serum cotinine or thiocyanate and RF positivity was observed within the subgroups of current smokers and those who had quit. Among those who reported that they had never smoked but who nevertheless had serum cotinine levels at least 100 microg/l, the adjusted odds ratio of strongly positive RF was 4.48 (1.48-13.50) compared with people who had never smoked and whose serum cotinine levels were less than 100 microg/l. CONCLUSIONS: The results are not in line with the hypothesis of a dose-response relationship between smoking exposure and RF positivity.

Adult↗
PubMed2004

HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: more complexity within the MHC.

This study further defines genetic susceptibility to JIA in the region centromeric to HLA-DRB1. DNA from 234 Finnish JIA nuclear families and 639 elderly Finnish control individuals was genotyped for five functional SNPs within the TAP2 and TAP1 loci ( approximately 200 kb centromeric of HLA-DRB1). Subsets of the controls (186) and patients (145) that had been previously typed for HLA-DRB1 were also genotyped by sequence for the HLA-DPB1 locus. Case/control and transmission disequilibrium test (TDT) methods revealed an association with the DPB1(*)030101 allele for JIA (OR 2.3, 95% CI 1.5-3.5). Notably, a detailed haplotypic analysis of the TAP2/TAP1 loci and their interaction with the HLA-DPB1(*)030101 and DRB1(*)08 and (*)11 alleles showed a variety of over-represented and under-represented TAP2/TAP1 haplotypes not evident in the single marker analysis. The strongest effect was observed in the polyarticular RF negative JIA subgroup for the 2-2-1-2-1 TAP2/TAP1 haplotype (TAP2B and TAP1A alleles) which showed an independent effect from both DRB1(*)08 and (*)11 (P<0.000003) and DPB1(*)030101 (P=0.02). We have provided evidence that the extended haplotypes (including HLA-DRB1, TAP2/TAP1, and HLA-DPB1) of pauciarticular and polyarticular RF negative disease are distinct. This observation may have implications for functional etiological differences between the pauciarticular and polyarticular JIA patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Joint symptoms and diseases associated with moisture damage in a health center.

Rheumatic diseases do not usually cluster in time and space. It has been proposed that environmental exposures may initiate autoimmune responses. We describe a cluster of rheumatic diseases among a group of health center employees who began to complain of symptoms typically related to moldy houses, including mucocutaneous symptoms, nausea and fatigue, within a year of moving into a new building. Dampness was found in the insulation space of the concrete floor below ground level. Microbes indicating mold damage and actinobacteria were found in the flooring material and in the outer wall insulation. The case histories of the personnel involved were examined. All 34 subjects working at the health center had at least some rheumatic complaints. Two fell ill with a typical rheumatoid factor (RF)-positive rheumatoid arthritis (RA), and 10 had arthritis that did not conform to any definite arthritic syndrome (three met the classification criteria for RA). Prior to moving into the problem building one subject had suffered reactive arthritis, which had then recurred. Another employee had undiagnosed ankylosing spondylitis and later developed psoriatic arthritis, and another developed undifferentiated vasculitis. A total of 16 subjects developed joint pains, 11 of these after beginning work at the health center. Three subjects developed Raynaud's symptom. Fourteen cases had elevated levels of circulating immune complexes in 1998, 17 in 1999, but there were only three cases in 2001, when the health center had been closed for 18 months. The high incidence of joint problems among these employees suggests a common triggering factor for most of the cases. As some of the symptoms had tended to subside while the health center was closed, the underlying causes are probably related to the building itself and possibly to the abnormal microbial growth in its structures.

Adult↗
PubMed2003

Analysis of MHC region genetics in Finnish patients with juvenile idiopathic arthritis: evidence for different locus-specific effects in polyarticular vs pauciarticular subsets and a shared DRB1 epitope.

This study used Finnish juvenile idiopathic arthritis (JIA) probands with pauciarticular and rheumatoid factor (RF) negative polyarticular subtypes of JIA to further define the genetic susceptibility to JIA. We examined 16 markers spanning an 18 cM region of chromosome 6 encompassing the MHC and surrounding genomic region in a set of 235 Finnish JIA nuclear families and 639 Finnish control individuals. Analysis by case/control association and transmission disequilibrium test (TDT) methods each demonstrated strong evidence for a susceptibility locus near the D6S2447 microsatellite (P<10(-6) for both methods) that is flanked by DQB1 and DRB1. Analysis of the DRB1 locus suggested that DRB1*0801 and DRB1*1101 rather than DQA1 or other HLA alleles may be responsible for conferring susceptibility to disease. These findings are consistent with the most compelling results of previous reports on HLA associations and suggest a JIA DRB1 shared epitope encompassing critical amino-acid residues in the third hypervariable region of this molecule. Most importantly, in pauciarticular patients, the strong association does not extend to proximal markers as it does in polyarticular patients (P<0.00001). Analysis strongly suggests that the difference is because of additional JIA susceptibility loci within the MHC being present in polyarticular RF negative patients.

Age of Onset↗
PubMed2003

Filaggrin related antibodies among the aged.

BACKGROUND: The mean age at onset of new cases of rheumatoid arthritis (RA) has increased markedly. Because the prevalence of false positive rheumatoid factor reactions increases with advancing age, the diagnostic value of this test has limitations among the aged. OBJECTIVE: To study the occurrence of two filaggrin related antibodies in an aged population. METHODS: The study covered 300 subjects aged 78-88 years, one of whom had RA. The sera were tested with enzyme linked immunosorbent assays (ELISAs), using filaggrin purified from human skin and citrullinated cyclic peptide (CCP) as antigens. RESULTS: One patient with RA was positive for both antibodies. When the cut off level for positive reactions was set at the 98th centile of healthy blood donors, 24 (8%) of the other subjects were positive for antibodies against filaggrin, but only one against CCP. CONCLUSION: The test for anti-CCP antibody has better specificity than the test for antibodies against filaggrin among the aged.

Aged↗
PubMed2003

Regional differences in Finland in the prevalence of rheumatoid factor in the presence and absence of arthritis.

OBJECTIVES: To look for possible regional differences in the prevalence of rheumatoid factor (RF) in the presence and absence of arthritis. METHODS: The study covered a representative sample of the Finnish population aged 30 years or over, primarily comprising 8000 people, of whom 7217 participated in the field survey carried out in 1978-80. RF from serum samples from 7116 subjects was determined by the Waaler-Rose (sensitised sheep cell agglutination) test. Titres >or=32 were regarded as positive and titres >or=128 as strongly positive. Arthritis was diagnosed by a thorough clinical examination. RESULTS: In the absence of arthritis the prevalence of positive and strongly positive RF reactions was 2.1% and 1.0%, respectively. The lowest prevalence of strongly "false positive" RF occurred in south western Finland. After adjustment for age, sex, smoking, and coffee consumption the odds ratio of having a strongly "false positive" RF reaction in eastern Finland was 3.16 (95% confidence interval 1.29 to 7.72) and in northern Finland 2.94 (1.13 to 7.64) compared with south western Finland. The corresponding odds ratio of strongly RF positive arthritis in eastern Finland was 5.08 (1.41 to 18.27). CONCLUSION: Regional differences are found in the prevalence of a strongly positive RF reaction in the Finnish population. The findings are in accordance with recent results from another study concerning regional differences in the incidence of rheumatoid arthritis in Finland.

Adult↗
PubMed2001

Occurrence of uveitis in recently diagnosed juvenile chronic arthritis: a prospective study.

OBJECTIVE: To examine the occurrence and characteristics of uveitis in patients with recently diagnosed juvenile chronic arthritis (JCA). DESIGN: A prospective observational case series. PARTICIPANTS/METHODS: The study covered the new cases detected with JCA (426 children), all of whom were referred to an ophthalmologic consultation during 1989 to 1996 at the Pediatric Department of the Rheumatism Foundation Hospital, Heinola, Finland. MAIN OUTCOME MEASURES: The children with JCA were followed by ophthalmologic and pediatric examinations two to four times a year. The type and course of arthritis and presentation and characteristics of uveitis were examined prospectively. RESULTS: Uveitis was detected in 104 of 426 children (24%). Two thirds of all patients and the same proportion of those with uveitis were girls. Proportionally, uveitis was found to be as common among children with oligoarthritis (27%) as among those with seronegative polyarthritis (25%). Antinuclear antibodies (ANA) were detected significantly more frequently in patients with uveitis (66%) than among those without uveitis (37%) (P < 0.001). The uveitis was asymptomatic in 99 cases; only 5 children had episodes of acute anterior symptomatic uveitis. Uveitis was found before or within 3 months from the onset of recent arthritis in 51 of 104 children (49%) and later on in 53 of 104 children (51%). The mean age at diagnosis of uveitis was 5.9 years (range, 1.1-17.7; median, 4.9 years). The mean period from the diagnosis of JCA to the diagnosis of uveitis was 1.1 years (range, -2.4-6.5; median, 0.3 years). The mean age at diagnosis of JCA was 4.8 years (range, 0.6-15; median, 3.2 years) among those with uveitis and 7.3 years (range, 0.9-16; median, 6.7 years) among those who did not have it (P < 0.001). Uveitis was ongoing in 63 children at the end of the follow-up period. The mean follow-up time was 4.5 years (range, 0-9.7) for all children and 5.6 years (range, 1.3-9.6) for those with uveitis. In most instances, the visual prognosis was good. In 25 of 104 patients (24%) one or more complications of uveitis were found, but in only three children did the visual acuity decrease to 20/60 or less, and none became blind. All the other patients had visual acuity > or = 20/40. CONCLUSIONS: In this patient group, uveitis in JCA frequently appeared very early after the onset of arthritis. The uveitis was significantly more common in patients with an early onset of arthritis combined with ANA positivity. The proportion of children with uveitis was as large in those with polyarthritis as in those with oligoarthritis, with no predilection to girls.

Administration, Topical↗
PubMed2001

Uveitis in sibling pairs with juvenile idiopathic arthritis.

OBJECTIVE: To ascertain the occurrence and characteristics of uveitis in sibling pairs affected with juvenile idiopathic arthritis (JIA). METHODS: The sibling series comprised 80 JIA patients from 37 families with two or three JIA children, seen at the paediatric department of the Rheumatism Foundation Hospital in Heinola, Finland. An ophthalmologist examined the children for uveitis two to four times a year and the course of the condition was recorded during the follow-up. RESULTS: Uveitis was diagnosed in 21 of the 80 patients (26%). Three pairs (3.4 pairs expected) were concordant for the presence of asymptomatic uveitis. Two patients with enthesitis-related arthritis had acute unilateral uveitis. Among the remaining cases, uveitis was chronic and continuously active at the end of follow-up in 13 instances, but in spite of this only one patient had impaired vision. HLA allele B27 occurred more frequently in patients with uveitis than in those without uveitis (52 vs 30%, P=0.073) and all six subjects in the pairs concordant for chronic uveitis carried this allele. CONCLUSIONS: The observed concordance rate for uveitis did not differ from that expected. Although the uveitis was chronic in most instances, its course was usually mild.

Adolescent↗
PubMed2001

Association of autoantibodies to filaggrin with an active disease in early rheumatoid arthritis.

OBJECTIVE: To evaluate the clinical significance of antifilaggrin antibodies (AFA) measured by an enzyme linked immunosorbent assay (ELISA) in serial specimens from patients with recent onset rheumatoid arthritis (RA). METHODS: Filaggrin was purified from human skin and used as an antigen in ELISA. The AFA test was applied to five serial specimens from 78 patients with recent onset RA followed up for three years. Rheumatoid factor (RF) had been measured earlier from the same samples by quantitative immunoturbidimetry. RESULTS: The mean AFA level was highest at entry (54% positive), followed by a statistically significant decline at six months and a slight increase at three years. AFA were persistently positive in 23 patients and persistently negative in 28 patients. Eleven of the latter patients were persistently negative for RF. At study entry AFA levels correlated to some degree with RF levels. In general, raised AFA levels at entry were associated with an active and treatment resistant disease, but they did not predict radiological progression. CONCLUSIONS: The test for AFA has potential for an additional immunological test for RA.

Adult↗
PubMed2001

Regional differences in the incidence of rheumatoid arthritis in Finland in 1995.

OBJECTIVE: To investigate regional differences in the incidence of rheumatoid arthritis (RA). METHODS: Those subjects entitled to receive drug reimbursement for chronic inflammatory joint diseases in 11/21 central hospital districts (population base about 1.8 million adults) in Finland during 1995 were studied. The incidence rates from these central hospital districts were compared. RESULTS: A total of 1213 subjects were entitled to drug reimbursement for chronic inflammatory joint disease which had started at the age of 16 or over. Of these, 598 subjects satisfied the American Rheumatism Association 1987 criteria for RA. The age adjusted incidence of RA was 31.7/100 000 (95% CI 29.2 to 34.4) and varied significantly (p<0.001) among the central hospital districts, ranging from 16.3 to 44.8/100 000. CONCLUSION: There are regional differences in the incidence of RA. The reasons for these are probably environmental rather than genetic.

Adolescent↗
PubMed2001

Type I collagen degradation does not diminish with RA disease duration.

OBJECTIVE: To assess the relation between type I collagen degradation and the duration of rheumatoid arthritis (RA). METHODS: The serum concentrations of cross linked carboxyterminal telopeptide of type I collagen (ICTP) measured earlier in a community based series (90 patients) and a hospital based series (59 patients) were re-evaluated with reference to the duration of RA. RESULTS: The serum ICTP showed a positive correlation with the duration of the disease in the hospital based series (r(s)=0.40, p<0.01) but not in the community based one (r(s)=0.18, p=0.10). CONCLUSIONS: Type I collagen degradation predominantly reflecting pathological bone destruction does not seem to diminish in longlasting RA.

Arthritis, Rheumatoid↗
PubMed2001

Uveitis as a cause of visual loss in arthritides and comparable conditions.

OBJECTIVE: To examine the role of inflammatory rheumatic diseases and comparable conditions in the etiology of severe uveitis leading to visual impairment and blindness. METHODS: A retrospective study based on the Finnish Register of Visual Impairment. At the end of 1996, the Finnish Register of Visual Impairment included 296 uveitis patients in whom uveitis was the main cause of visual impairment. The patient records were examined retrospectively to investigate the etiology of severe uveitis. Due to the incompleteness of data obtained of the patients blinded a long time ago, we included only 174 uveitis patients whose visual handicap (best corrected visual acuity in the better eye < 20/60 or severe visual field loss) was stated during 1980-1996. RESULTS: A total of 174 uveitis patients were found, 72 male and 102 female. A diagnosed or presumed inflammatory rheumatic disease or comparable condition was found in 38/174 (22%) patients: juvenile rheumatoid arthritis in 14 (8%), spondyloarthropathy (ankylosing spondylitis or reactive arthritis) in 10 (6%), sarcoidosis in 5 (3%), seronegative rheumatoid arthritis in 4 (2%); Behçet's disease was diagnosed in 2 (1%), 1 patient had polymyositis, 1 polyarteritis nodosa, and 1 juvenile systemic lupus erythematosus. In addition to the above, 10 (6%) patients had chronic back pain and 5 (3%) patients various noninflammatory joint problems. Diverse other ophthalmologic or systemic disease was detected in 38 (22%) cases. Trauma or surgery caused uveitis in 9 (5%) patients. For 74/174 (43%) uveitis patients no specific associating condition could be shown. Legal blindness was documented in 65/174 (37%) patients, including 8 totally blind persons. CONCLUSION: This study provides first data on the relative importance of inflammatory rheumatic diseases and comparable conditions in the etiology of severe uveitis leading to visual handicap and blindness.

Adolescent↗
PubMed2000

Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins.

OBJECTIVE: Twin concordance data for rheumatoid arthritis (RA) on their own provide only limited insight into the relative genetic and environmental contribution to the disease. We applied quantitative genetic methods to assess the heritability of RA and to examine for evidence of differences in the genetic contribution according to sex, age, and clinical disease characteristics. METHODS: Data were analyzed from 2 previously published nationwide studies of twins with RA conducted in Finland and the United Kingdom. Heritability was assessed by variance components analysis. Differences in the genetic contribution by sex, age, age at disease onset, and clinical characteristics were examined by stratification. The power of the twin study design to detect these differences was examined through simulation. RESULTS: The heritability of RA was 65% (95% confidence interval [95% CI] 50-77) in the Finnish data and 53% (95% CI 40-65) in the UK data. There was no significant difference in the strength of the genetic contribution according to sex, age, age at onset, or disease severity subgroup. Both study designs had power to detect a contribution of at least 40% from the common family environment, and a difference in the genetic contribution of at least 50% between subgroups. CONCLUSION: Genetic factors have a substantial contribution to RA in the population, accounting for approximately 60% of the variation in liability to disease. Although tempered by power considerations, there is no evidence in these twin data that the overall genetic contribution to RA differs by sex, age, age at disease onset, and disease severity.

Adult↗
PubMed2000

Serum selenium, serum alpha-tocopherol, and the risk of rheumatoid arthritis.

Antioxidant micronutrients have been hypothesized to provide protection against rheumatoid arthritis. We investigated serum selenium and serum alpha-tocopherol for their prediction of subsequent development of rheumatoid arthritis in a case-control study nested within a Finnish cohort of 18,709 adult men and women who had neither arthritis nor a history of it at the baseline examination in 1973-1978; by late 1989, 122 had developed rheumatoid arthritis. Of the incident cases, 34 were rheumatoid factor-negative. Three controls per each incident case were individually matched for sex, age, and municipality. Serum selenium and alpha-tocopherol concentrations were measured from stored serum samples collected at baseline. Serum selenium was inversely related to subsequent occurrence of rheumatoid factor-negative but not rheumatoid factor-positive rheumatoid arthritis. The relative risks, adjusted for smoking and serum total cholesterol, for the highest relative to the lowest tertile of serum selenium, were 0.16 [95% confidence interval (CI) = 0.04-0.69] for rheumatoid factor-negative and 0.96 (CI = 0.49-1.90) for rheumatoid factor-positive rheumatoid arthritis. During the first 10 years of follow-up, the relative risk for rheumatoid arthritis for the highest compared with the lowest tertile of serum alpha-tocopherol was 0.44 (CI = 0.19-0.99). No association was found for longer follow-up periods. Low selenium status may be a risk factor for rheumatoid factor-negative rheumatoid arthritis, and low alpha-tocopherol status may be a risk factor for rheumatoid arthritis independently of rheumatoid factor status.

Adult↗
PubMed2000

Reduced incidence of alcohol related deaths in subjects with rheumatoid arthritis.

OBJECTIVES: It has previously been shown that people with ankylosing spondylitis have an increased incidence of alcohol related deaths from accidents and violence. This study investigated alcohol related deaths in subjects with rheumatoid arthritis (RA). METHODS: The study covered the subjects, 1666 in number, who had died in 1989 and had been entitled under the nationwide sickness insurance scheme to receive specially reimbursed medication for RA. RESULTS: There were eight alcohol related deaths among the 480 men and three deaths among the 1186 women with RA. The standardised mortality ratios and their 95% confidence intervals (CI) were 0.40 (95% CI 0.20, 0.80) and 0.40 (95% CI 0.13, 1.26), respectively. CONCLUSION: Alcohol either protects from RA or, subjects with RA curtail their drinking after the manifestation of RA.

Adolescent↗