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K Laiho

Publications and source records attributed to K Laiho.

At least 19 recordsLinked to original sources
PubMed2005

Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis.

OBJECTIVE: To determine the influence of HLA-B27 homozygosity and HLA-DRB1 alleles in the susceptibility to, and severity of, ankylosing spondylitis in a Finnish population. METHODS: 673 individuals from 261 families with ankylosing spondylitis were genotyped for HLA-DRB1 alleles and HLA-B27 heterozygosity/homozygosity. The frequencies of HLA-B27 homozygotes in probands from these families were compared with the expected number of HLA-B27 homozygotes in controls under Hardy-Weinberg equilibrium (HWE). The effect of HLA-DRB1 alleles was assessed using a logistic regression procedure conditioned on HLA-B27 and case-control analysis. RESULTS: HLA-B27 was detected in 93% of cases of ankylosing spondylitis. An overrepresentation of HLA-B27 homozygotes was noted in ankylosing spondylitis (11%) compared with the expected number of HLA-B27 homozygotes under HWE (4%) (odds ratio (OR) = 3.3 (95% confidence interval, 1.6 to 6.8), p = 0.002). HLA-B27 homozygosity was marginally associated with reduced BASDAI (HLA-B27 homozygotes, 4.5 (1.6); HLA-B27 heterozygotes, 5.4 (1.8) (mean (SD)), p = 0.05). Acute anterior uveitis (AAU) was present in significantly more HLA-B27 positive cases (50%) than HLA-B27 negative cases (16%) (OR = 5.4 (1.7 to 17), p<0.004). HLA-B27 positive cases had a lower average age of symptom onset (26.7 (8.0) years) compared with HLA-B27 negative cases (35.7 (11.2) years) (p<0.0001). CONCLUSIONS: HLA-B27 homozygosity is associated with a moderately increased risk of ankylosing spondylitis compared with HLA-B27 heterozygosity. HLA-B27 positive cases had an earlier age of onset of ankylosing spondylitis than HLA-B27 negative cases and were more likely to develop AAU. HLA-DRB1 alleles may influence the age of symptom onset of ankylosing spondylitis.

Adult↗
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↗
PubMed2005

Capability for daily activities in old people with rheumatoid arthritis: a population based study.

OBJECTIVE: To describe the functional capacity for daily activities in old people with clinical rheumatoid arthritis (including juvenile rheumatoid arthritis (JRA)) in a population based cohort. METHODS: A cohort of 700 people was randomly collected from the population older than 75 years in a Finnish town. Altogether 601 persons (86%) participated. Data were collected from clinical records and by interview, clinical examination, and questionnaire. Ability to carry out activities of daily living (ADL) was assessed by the Barthel index, and the IADL (instrumental activities of daily living) by the Lawton and Brody questionnaire. RESULTS: 16 people had clinical rheumatoid arthritis (one with JRA). The prevalence was 16/601 (2.7% (95% confidence interval, 1.7% to 4.5%)). Eight patients with rheumatoid arthritis (50%) obtained the best possible ADL figures, while three (19%) had very poor results. Seven (44%) could not dress themselves without help. Three (19%) were unable to walk, and five (31%) could not climb stairs. Sex and age adjusted results showed no statistical difference (ADL and IADL) between patients with clinical rheumatoid arthritis and rest of the cohort. Four patients (25%) had dementia, which was associated with the poor functional capacity. CONCLUSIONS: The prevalence of the disease was unexceptional. The ability of old people with rheumatoid arthritis to carry out activities of daily living did not differ from the general population, but the disease may lead to severe disability on an individual level, especially when associated with dementia. It therefore remains a considerable challenge to the health care and social systems.

Activities of Daily Living↗
PubMed2004

Albumin as a marker of plasma transudation in experimental skin lesions.

Liquid chromatography measurements of albumin levels were obtained for experimental incision wounds, excoriations, and heat and freezing injuries of different ages. Hemoglobin levels in tissue specimens were measured and an equivalent amount of blood-related albumin was subtracted from the analysis results. In specimens taken immediately after death, the mean albumin level as compared to control skin was increased by about 2-fold in freezing injuries aged 60 min. In all other lesions, the same increase was observed even after 30 min. The mean albumin level was about 3-fold as compared with the control skin in excoriations aged 30 min, heat and freezing injuries aged 4 h, and incision wounds aged 12 h. An approximately 5-fold increase was seen in heat and freezing injuries aged 1 and 2 weeks. A marked decrease occurred in mean albumin levels in all lesions aged 4 weeks. An increase in albumin in wounds and excoriations was demonstrable also in specimens taken 3 days postmortem. Postmortem hypostasis resulted in a 1.1 to 1.4-fold increase in mean albumin levels in wounds and excoriations inflicted 1 min postmortem.

Animals↗
PubMed2004

Anaemia of chronic disease in AA amyloidosis is associated with allele 2 of the interleukin-1beta-511 promoter gene and raised levels of interleukin-1beta and interleukin-18.

OBJECTIVE: In amyloid A (AA) amyloidosis the receptor for advanced glycation end products is a target for the circulating amyloid precursor protein (SAA) resulting in upregulation of the proinflammatory cytokine pathway. Besides inducing hepatic SAA synthesis the interleukin-1 cytokine family is involved in the regulation of haematopoiesis. We therefore studied the relationship between the circulating levels of interleukin-1beta (IL-1beta) and interleukin-18 (IL-18), a new member of the IL-1 complex, as well as polymorphisms within the IL-1 cluster with the occurrence of anaemia in patients with AA amyloidosis. DESIGN, SETTING AND SUBJECTS: The study included 54 adult patients with biopsy-proven reactive amyloidosis allocated into three groups on the basis of haemoglobin (Hb) level: group I included all patients with Hb < 110 g L(-1) (n = 16); group II patients (Hb > 110 g L(-1), n = 16) were selected to match group I patients with respect to sex, age, underlying disease (seropositive, erosive rheumatoid arthritis) and renal function; and group III patients (n = 38) represented all patients (unselected) with Hb > or = 110 g L(-1). Gene polymorphisms were studied by polymerase chain reaction restriction length assay and included the base exchange at position-889 of the IL-1alpha gene, the polymorphic region at position-511 and the polymorphic locus at exon 5, position +3954 of the IL-1beta gene, as well as the IL-1 receptor antagonist (IL-1Ra) exon 2 polymorphism caused by the 86-bp tandem repeats. Plasma IL-1beta, IL-1alpha, IL-18, IL-1 Ra, SAA, ferritin, soluble transferrin receptor and erythropoietin levels were studied by enzyme immunoassays. RESULTS: Circulating IL-beta and IL-18 were significantly raised in the anaemic patients with AA amyloidosis when compared with group II patients (matched, Hb > 110 g L(-1)) as well as group III patients (nonmatched, Hb > or = 110 g L(-1)). A significant inverse relationship was found between IL-1beta and haemoglobin levels, as well as between IL-18 and haemoglobin levels. The frequency of allele 2 (T) of the IL-1beta-511 promoter gene was significantly increased and that of allele 1 (C) decreased in anaemic amyloid patients (group I) when compared with group II and III patients. Circulating IL-1beta levels tended to be higher amongst the IL-1beta-511 allele 2 carriers than amongst the noncarriers, as well as amongst the anaemic amyloid patients filling all criteria of anaemia of chronic disease. CONCLUSION: The occurrence of anaemia in patients with AA amyloidosis is associated with allele 2 (T) of the IL-1beta-511 promoter gene and elevated levels of circulating IL-1beta and IL-18. In AA amyloidosis the raised cytokine levels may generate a vicious cycle leading to accelerated amyloidogenesis, suppression of erythropoiesis and aggravation of the underlying inflammatory disorder.

Adult↗
PubMed2004

A novel human leucocyte antigen-DRB1 genotyping method based on multiplex primer extension reactions.

We have developed and validated a semi-automated fluorescent method of genotyping human leucocyte antigen (HLA)-DRB1 alleles, HLA-DRB1*01-16, by multiplex primer extension reactions. This method is based on the extension of a primer that anneals immediately adjacent to the single-nucleotide polymorphism with fluorescent dideoxynucleotide triphosphates (minisequencing), followed by analysis on an ABI Prism 3700 capillary electrophoresis instrument. The validity of the method was confirmed by genotyping 261 individuals using both this method and polymerase chain reaction with sequence-specific primer (PCR-SSP) or sequencing and by demonstrating Mendelian inheritance of HLA-DRB1 alleles in families. Our method provides a rapid means of performing high-throughput HLA-DRB1 genotyping using only two PCR reactions followed by four multiplex primer extension reactions and PCR-SSP for some allele groups. In this article, we describe the method and discuss its advantages and limitations.

Alleles↗
PubMed2003

The effect of transforming growth factor beta1 gene polymorphisms in ankylosing spondylitis.

OBJECTIVES: To determine whether genetic polymorphisms in or near the transforming growth factor beta1 (TGFB1) locus were associated with susceptibility to or severity of ankylosing spondylitis (AS). METHODS: Five intragenic single-nucleotide polymorphisms (SNP) and three microsatellite markers flanking the TGFB1 locus were genotyped. Seven hundred and sixty-two individuals from 184 multiplex families were genotyped for the microsatellite markers and two of the promoter SNPs. One thousand and two individuals from 212 English and 170 Finnish families with AS were genotyped for all five intragenic SNPs. A structured questionnaire was used to assess the age of symptom onset, disease duration and disease severity scores, including the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index). RESULTS: A weak association was noted between the rare TGFB1 +1632 T allele and AS in the Finnish population (P = 0.04) and in the combined data set (P = 0.03). No association was noted between any other SNPs or SNP haplotype and AS, even among those families with positive non-parametric linkage scores. The TGFB1 +1632 polymorphism was also associated with a younger age of symptom onset (English population, allele 2 associated with age of onset greater by 4.2 yr, P = 0.05; combined data set, allele 2 associated with age of onset greater by 3.2 yr, P = 0.02). A haplotype of coding region SNPs (TGFB1 +869/+915+1632 alleles 2/1/2) was associated with age of symptom onset in both the English parent-case trios and the combined data set (English data set, haplotype 2/1/2 associated with age of onset greater by 4.9 yr, P = 0.03; combined data set, haplotype 2/1/2 associated with greater age of onset by 4.2 yr, P = 0.006). Weak linkage with AS susceptibility was noted and the peak LOD score was 1.3 at distance 2 cM centromeric to the TGFB1 gene. No other linkage or association was found between quantitative traits and the markers. CONCLUSION: This study suggests that the polymorphisms within the TGFB1 gene play at most a small role in AS and that other genes encoded on chromosome 19 are involved in susceptibility to the disease.

Adult↗
PubMed2003

Tumor necrosis factor alpha, its soluble receptor I, and -308 gene promoter polymorphism in patients with rheumatoid arthritis with or without amyloidosis: implications for the pathogenesis of nephropathy and anemia of chronic disease in reactive amyloidosis.

OBJECTIVE: To study tumor necrosis factor alpha (TNFalpha) -308 gene promoter polymorphism and circulating levels of TNFalpha and soluble TNF receptor type I (sTNFRI) in rheumatoid arthritis (RA) patients with and without reactive amyloidosis. METHODS: In a retrospective study, we examined 55 RA patients with biopsy-proven reactive amyloidosis and 55 control RA patients without amyloidosis (matched for age, sex, rheumatoid factor titer, and RA duration). Inflammatory activity was assessed by measuring the erythrocyte sedimentation rate and C-reactive protein level. TNFalpha gene promoter polymorphism was studied using polymerase chain reaction-restriction fragment length polymorphism assay. Cytokine and receptor levels were measured by enzyme-linked immunoassays. RESULTS: Patients with RA and amyloidosis had significantly higher TNFalpha and sTNFRI levels than did the control RA patients. The increased circulating levels of TNFalpha correlated with interleukin-18 levels, but not with the serum amyloid A protein levels or with TNFalpha -308 gene promoter polymorphism (reported to be associated with high TNFalpha levels and certain disease susceptibilities). In the patients with RA and amyloidosis, those with anemia had significantly higher TNFalpha and sTNFRI levels than did those without anemia, and circulating TNFalpha and sTNFRI levels correlated negatively with hemoglobin concentrations. In the patients with RA and amyloidosis, those with nephropathy had significantly higher TNFalpha and sTNFRI levels than did those without nephropathy; in patients with isolated proteinuria (but no creatinine elevation) the TNFalpha level was also significantly increased, indicating that the TNFalpha elevation was not merely a consequence of impaired renal function. CONCLUSION: This study shows that circulating levels of TNFalpha and sTNFRI are significantly increased in RA patients with amyloidosis as compared with control RA patients without amyloidosis and that the increased levels may be implicated in the pathogenesis of certain disease manifestations, including anemia of chronic disease and renal pathology in reactive amyloidosis.

Adult↗
PubMed2003

Interleukin 10 polymorphisms in ankylosing spondylitis.

Genetic polymorphisms of the IL10 promoter region have been implicated in many autoimmune diseases, including seronegative spondyloarthropathies. We studied three SNPs (IL10-1087, -824, and -597) and two microsatellites (IL10R and IL10G) lying within the promoter region of IL10 for association with susceptibility to and clinical manifestations of ankylosing spondylitis (AS), a common form of spondyloarthritis. Four hundred and sixty-eight individuals from 182 Finnish families affected with AS were studied. No association between individual IL10 promoter region polymorphisms or marker haplotype was observed with susceptibility to AS, but weak association was noted between the IL10-597 and -824 SNPs and age of disease onset (P=0.01 for each SNP). The IL10.G4 allele was associated with BASFI (corrected for disease duration) (P=0.03). We conclude that IL10 promoter polymorphisms have no significant effect on susceptibility to AS, but may play a minor role in determining age of disease onset and disease severity.

Alleles↗
PubMed2003

Can we rely on magnetic resonance imaging when evaluating unstable atlantoaxial subluxation?

OBJECTIVES: To examine whether functional radiography and functional magnetic resonance imaging (MRI) are equally efficient in detecting the extent of unstable anterior atlantoaxial subluxation (aAAS) in rheumatic patients. METHODS: 23 patients with unstable aAAS (diagnosed by functional radiography) were examined by functional MRI because of a neck symptom. Twenty two patients had rheumatoid arthritis and one had juvenile idiopathic arthritis. aAAS was diagnosed if the anterior atlantoaxial diameter (AAD) was >3 mm and was considered unstable if the AAD differed by >2 mm between flexion and extension radiographs. The AAD was measured from radiographs (flexion and extension) and MRI images (flexion and neutral). RESULTS: The extent of aAAS during flexion measured by radiography was greater than that found by MRI in all 23 patients (mean difference 3 mm (95% confidence interval 2 to 4)). In four (17%) patients flexion MRI could not demonstrate aAAS detected by radiography. The difference between the AAD measurements during flexion by these two methods was substantial (that is, >or=4 mm) in nine (39%) cases. Severe aAAS (>or=9 mm) was seen in 15 (65%) patients by functional radiography and in four (17%) by functional MRI. CONCLUSIONS: The magnitude of aAAS was often substantially smaller when measured by functional MRI rather than by functional radiography. Thus one cannot rely on the result of functional MRI alone; functional radiographs are needed to show the size of unstable aAAS. The maximal extent of the subluxation must be taken into account when the possible compression of neural structures is evaluated by MRI.

Adult↗
PubMed2002

Probiotics: on-going research on atopic individuals.

The challenge for the modern health care system is to fight against the increasing prevalence of atopic disease. The introduction of scientifically composed probiotic functional foods for prophylactic or therapeutic purposes could be one solution. Probiotics are live microbial food supplements or components of bacteria which have beneficial effects on human health. Specific strains have been demonstrated to exert powerful anti-pathogenic, anti-inflammatory and anti-allergic effects. The hygiene hypothesis suggests that atopic disease may arise from a lack of counterbalancing microbial exposure at an early age. The initial compositional development of the gut microflora is considered a key determinant of the development of both the immune responder phenotype and normal gut barrier functions. The regulatory role of probiotics in human allergic disease was first emphasised in the demonstration of a suppressive effect on lymphocyte proliferation and interleukin-4 generation in vitro. Subsequently, a significant improvement in the clinical course of atopic eczema was reported in infants given a probiotic-supplemented diet. The potential of probiotics to reduce the risk of atopic disease has recently been demonstrated in a double-blind, placebo-controlled study: probiotics administered pre- and postnatally for 6 months to at-risk subjects reduced the prevalence of atopic eczema to half of that observed in infants receiving placebo. Ongoing research is directed towards the development of novel techniques to characterise the gut microflora. Future research will clarify the mechanisms to control specific physiological processes in the evolution of atopic disease in at-risk populations or in the management of allergic diseases.

Diet↗
PubMed2002

Carriers of the aspartylglucosaminuria genetic mutation and chronic arthritis.

OBJECTIVE: To ascertain whether being a carrier of an autosomal recessive disease, aspartylglucosaminuria (AGU), predisposes to chronic arthritis, as does AGU disease. METHODS: A group of 173 unrelated patients with rheumatoid arthritis (RA) but with no family members with AGU each gave a blood sample for AGUFin major mutation DNA analysis. A group of 131 AGU carriers who were parents of patients with AGU completed a questionnaire on joint symptoms and gave a blood sample for rheumatoid factor (RF) analysis. Eight RF positive parents with prolonged joint symptoms had a rheumatological evaluation. RESULTS: Six patients (1/28) with RA were carriers of the AGUFin major mutation, whereas the carrier frequency among Finns in general is 1/50 to 1/85. Three AGU carriers had chronic arthritis (2.3%), and 17 (13%) were RF positive; the respective percentages among Finns in general are 1.4% and 5%. CONCLUSION: As for AGU disease, carrier status may also predispose to chronic arthritis.

Adult↗
PubMed2002

The cervical spine in patients with psoriatic arthritis.

OBJECTIVE: To establish the incidence of clinically important inflammatory cervical spine abnormalities in radiographs of patients with psoriatic arthritis (PsA). METHODS: Patients were selected from a rheumatological outpatient clinic and one ward of the Rheumatism Foundation Hospital, Heinola, Finland, by examining 160 consecutive PsA cases. A total of 65 patients (38 women, 27 men) with PsA were identified who had cervical spine radiographs available. These were evaluated for inflammatory changes, and patient records studied for disease characteristics, laboratory and clinical findings. RESULTS: In 12 cases (18%) inflammatory cervical spine changes were seen in the cervical spine radiographs. The most frequently detected was apophysial joint ankylosis, seen in seven patients (11%). Anterior atlantoaxial subluxation (aAAS) was seen in five (8%) and atlantoaxial impaction in three (5%). In 20 of the 40 patients who had the rotational range of neck motion measured the measurement was < or =45 degrees either to the left or the right side. CONCLUSION: Inflammatory cervical spine changes were not commonly seen in radiographs of patients with PsA. Apophysial joint ankylosis and aAAS were detected most often. PsA may decrease the rotational range of neck motion significantly.

Adult↗
PubMed2002

Raised circulating interleukin-18 levels in reactive AA-amyloidosis.

OBJECTIVE: To study the circulating levels of interleukin-18 (IL-18), a proinflammtory cytokine implicated in the T helper I response, in patients with rheumatoid arthrtitis (RA) with or without amyloidosis. METHODS: Plasma IL-18 levels were studied by enzyme-linked immusorbent assay in 55 RA patients with reactive amyloidosis and in 55 RA patients without amyloidosis matched with respect to age, sex, seropositivity, disease duration and inflammatory activity, as well as in 55 healthy control subjects. RESULTS: Plasma IL-18 levels were significantly elevated in RA patients as compared with control subjects. Those RA patients who had amyloid had significantly higher circulating level of IL-18 than those without amyloid (418.1 +/- 32.1 ng/l versus 317.0 +/- 21.3 ng/l, P<0.02). This difference was not due to differences in inflammatory activity, nor was it related to renalfunction. CONCLUSION: RA is associated with increased levels of plasma IL-18, the levels being significantly higher in patients with amyloid than in those without amyloid The increased level in the amyloidosis patients may reflect the interaction ofamyloid with cellular meatbolic pathways or, possibly, suggest a direct role of IL-18 in amyloidogenesis.

Amyloid↗