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Biomedical subjects

S Koskimies

Publications and source records attributed to S Koskimies.

At least 37 records · Page 2Linked to original sources

Unique HLA antigen frequencies in the Finnish population.

The Finnish Bone Marrow Donor Registry was established 1992 to serve Finnish patients in urgent need of bone marrow transplantation. This study details the HLA antigen frequencies, including those of the A 19 subtypes, in the Finnish population. Large regional variations were found in antigen frequencies between the different geographical areas of Finland. In particular, antigens A9, B12, B35, Cw4 and DR3 display regional frequency deviations, but B7, B8 and B15 also exhibit regional variations. The present population is the largest (n = 10,000) ever HLA-typed in Finland. 97% of the donors were HLA-A-B-DR typed. Confirmation of the serological HLA type was performed by DNA typing on 3% of the donors in the registry. A potential donor was found for 52% of Finnish patients in need of a matched unrelated donor for a bone marrow transplantation. Due to the ethnic origin of the Finns, it is not easy to find suitable bone marrow donors for Finnish patients in worldwide registries. It is thus important to maintain a national bone marrow donor registry which recruits donors from all over the country.

Finland↗

Transfusion-related acute lung injury (TRALI) after fresh frozen plasma in a patient with coagulopathy.

BACKGROUND: Transfusion-related acute long injury (TRALI) is due to specific antigen-antibody reaction involving the donor's leucocyte or granulocyte antibodies towards the recipient's antigens. Aggregation in small pulmonary vessels occurs, leading to derangement of permeability. CASE HISTORY: TRALI after transfusion of four units of fresh frozen plasma (FFP) for factor V deficiency prior to elective cholecystectomy is presented. Within a few minutes after the third unit of FFP a florid pulmonary oedema developed. Hypotension and hypoxia with SpO2 83-87% at FiO2 1.0 followed. Prompt monitoring of central haemodynamics revealed a normal cardiac index without pulmonary hypertension. The operation was then conducted as planned. The bilateral pulmonary oedema resolved after 72 hours with ventilatory support. The patient recovered without complications. When tested postoperatively, the second unit of FFP contained granulocyte antibodies and the third unit contained HLA antibodies. The crossmatch of the patient's granulocytes and lymphocytes towards the two donors of the two units of FFP was positive. CONCLUSION: When TRALI is suspected the donor blood has to be tested against the recipient. Ventilatory support of the patient is continued until adequate oxygenation is reached.

Acute Disease↗

HLA DQ and DP in Finnish families with celiac disease.

We studied DQA1, DQB1, and DPB1 alleles in 31 Finnish families with celiac disease (CD). All healthy first-degree relatives underwent clinical investigation, including in most cases biopsy, to establish whether clinically silent CD was present. Our results indicate that all patients, having either full clinical CD or its silent form, had the susceptibility alleles DQA1*0501 and DQB1*0201. The different clinical outcomes of CD were therefore not directly determined by the DQ alleles. The frequency of DPB1*0101 was also higher in CD patients, but the association appeared secondary to those of DQA1*0501 and DQB1*0201 (DQ2). The primary association of CD with the DQA1*0501 and DQB1*0201 alleles, rather than with HLA haplotypes, was confirmed in multiplex families.

Adolescent↗

TAP1 and TAP2 polymorphism in HLA-B27-positive subpopulations: no allelic differences in ankylosing spondylitis and reactive arthritis.

The polymorphic TAP1 and TAP2 genes encode subunits of the transporter that delivers peptides to the HLA class I molecules. Because the polymorphism of the TAP genes has been shown to affect peptide transport, it has been suggested that TAP genes are potential regulators of the immune response. We studied TAP1 and TAP2 polymorphism in two multifactorial HLA-B27-associated diseases, ankylosing spondylitis (N = 30) and reactive arthritis (N = 30), in order to establish whether TAP genes are involved in the different pathogenesis of these diseases. Healthy HLA-B27-positive individuals (N = 55) were chosen as the primary controls and 93 individuals represented the random Finnish population as secondary controls. We found differences between the random and HLA-B27-positive populations, thus suggesting that certain TAP alleles are prevalent in HLA-B27 haplotypes. No differences were found between the AS and ReA groups nor between either of them and the healthy HLA-B27-positive controls. Thus it seems unlikely that TAP polymorphism, ar the level studied, has a dominant role in the pathogenesis of these diseases. However, a family study is needed in order to determine whether the same TAP complexes are carried by the same haplotypes in these diseases.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Maternal HLA antigens and antibodies to SS-A/Ro and SS-B/La. Comparison with systemic lupus erythematosus and primary Sjögren's syndrome.

To study the maternal immunogenetics in congenital heart block (CHB), 31 mothers of affected children were HLA typed for class I and II antigens, and the results were compared with the corresponding HLA types in 900 healthy controls, in 45 mothers with systemic lupus erythematosus (SLE) and in 21 mothers with primary SS who had healthy children. An enzyme-linked immunosorbent assay was used to study the autoantibody responses to the recombinant 52 and 60 kDa SS-A/Ro, and 48 kDa SS-B/La proteins, and to the affinity-purified SS-A/Ro and SS-B/La antigens. Mothers of children with CHB had HLA B8 and DR3 significantly more often than healthy controls [71 vs 10%; relative risk (RR) 9.8, P < 0.00001 and 74 vs 23%; RR9.8, P < 0.001, respectively]. HLA B35 was protective (RR 0.1, P = 0.0029). Compared to controls with SLE, mothers of children with CHB were more often HLA DR3 and DQ2 positive (RR 4.1, P = 0.0057 and RR 3.1, P = 0.031, respectively), and compared to controls with primary SS less often HLA B15 positive (RR 0.1, P = 0.010). In general, the HLA antigen profile in mothers of children with CHB was more closely related to primary SS than to SLE. Levels of antibodies to all three SS-A/Ro antigens were significantly higher in mothers of children with CHB than in controls with SLE and primary SS (P = 0.0001-0.0014). With regard to SS-B/La, the autoantibody responses were similar (P = 0.32-0.66).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Immunohistochemical findings in jejunal specimens from patients with IgA deficiency.

Jejunal biopsy specimens from 25 patients with IgA deficiency (IgAd) were studied immunohistochemically to find markers of inflammation. Five of the 25 patients had coeliac disease (CD): they were on a gluten free diet and had normal jejunal morphology. Only two of 15 specimens from control subjects had CD25+ cells in the surface epithelium, while this was seen in 19 out of 20 specimens from IgAd patients (p < 0.0001). A significant increase of CD25+ cells was also noted in the lamina propria of IgAd patients. The median percentage of crypt cells in mitosis (Ki67+ cells) was higher in the specimens from IgAd patients (26%) than in those from controls (13%, p < 0.001). The densities of gamma delta T cell receptor positive cells in the surface epithelium and lamina propria did not differ in the specimens from IgAd patients and those of controls nor was the expression of HLA class II antigens augmented in the surface epithelium. These findings were similar for the IgAd patients whether or not the patient had DQB 0201 allele, a genetic marker which is strongly associated with CD. The inadequacy of the local immunoglobulins in patients with IgAd may lead to increased T cell activation, which is accompanied by the appearance of intraepithelial CD25+ cells and with an increase in the mitotic rate in the crypts.

Biomarkers↗

Production of TNF by monocytes of patients with early rheumatoid arthritis is increased.

We studied the production of tumour necrosis factor alpha (TNF) by monocytes of patients with early rheumatoid arthritis (RA) before starting disease modifying anti-rheumatic drug treatment and a median 6 months (range 5-11 months) later, and correlated the pre-treatment results with 3-year prognosis. Monocytes of patients (n = 14) and controls (n = 14), isolated by the density gradient centrifugations, were cultured for 24 h with Escherichia coli lipopolysaccharide (LPS) 0-10 micrograms/ml. Before treatment, levels of TNF were higher in LPS-stimulated RA monocyte cultures than in the control cultures; differences were statistically significant in LPS 10 and 0.01 micrograms/ml. At 6 months, respective differences were not significant. Levels of TNF before treatment did not correlate to clinical or laboratory parameters of inflammation, or development of erosions. The results indicate that monocytes of patients with early RA are primed, and that the state of priming decreases during treatment.

Adult↗

Rheumatoid factor and HLA antigens in wrist tenosynovitis and humeral epicondylitis.

A matched case-referent study was undertaken to assess whether rheumatoid factor (RF) is associated with repeating tenosynovitis or peritendinitis and whether HLA-B27 predisposes to epicondylitis. The study subjects consisted of 25 workers in manually strenuous jobs with a history of at least two episodes of tenosynovitis or peritendinitis in the wrist or forearm, or humeral epicondylitis, and their matched referents. The latex agglutination test was positive in seven of the 23 cases with tenosynovitis and in one of the referents (p = 0.03). The corresponding figures for IgM-RF by enzyme immunoassay were ten and two, respectively (p = 0.008). HLA-B27 antigen was found in five of the 13 workers with epicondylitis and in one worker with no such history (p = 0.13). It is possible that RF-positive repeating tenosynovitis represents an incomplete form of rheumatoid disease.

Case-Control Studies↗

The prevalence of narcolepsy: an epidemiological study of the Finnish Twin Cohort.

We investigated the prevalence of narcolepsy using a well-defined white population previously used for epidemiological investigations: the Finnish Twin Cohort. The Cohort consists of 13,888 monozygotic and dizygotic twin pairs born before 1958. There were 16,179 individuals who participated in the study, with a 77.3% response rate. The study methodology included a questionnaire covering sleep and alertness, the Ullanlinna Narcolepsy Scale (UNS), a scale specifically developed and tested for the study, telephone interviews, and finally, clinical evaluation, polygraphic recording, and HLA blood typing. Seventy-five subjects were selected for telephone interviews and laboratory evaluations based on data from both questionnaires. Five of them were strongly suspected of narcolepsy, but laboratory data identified only 3. All were dizygotic (fraternal) twins discordant for the disease with a negative family history and presence of DR2 DQw1 (i.e., DRw15 DQw6, new World Health Organization classification). The prevalence of narcolepsy in the Finnish population is 0.026% (95% confidence interval, 0.0-0.06). This prevalence is lower than that reported in studies performed without polygraphic recording and is close to that reported in 1945 in the black U.S. population. The tools developed to perform this study, the largest population study of its kind yet performed, can now be used for other population investigations.

Adult↗

Reactive arthritis following an outbreak of Salmonella infection in Finland.

The incidence and clinical features of reactive arthritis (ReA) following an outbreak of enteritis caused by Salmonella enterica ssp. enterica serovar 4,5,12:b:-were studied in the autumn of 1992. The outbreak occurred in several municipalities and originated from sprouted mung beans. A questionnaire on extra-enteric manifestations such as joint and eye symptoms was mailed 2 to 5 months after the outbreak to all bacteriologically proven cases. Two hundred and forty-six of the 272 (90%) subjects responded to the questionnaire; 224 (91%) reported having had enterocolitis, 22 (9%) were asymptomatic. Sixteen subjects fulfilled the criteria for ReA, and one had irities only. Thus, the incidence of ReA/iritis after S. enterica was 6.9%. Only four of the 155 (3%) subjects aged less than 16 yr developed ReA, as compared with 12 of the 91 (13%) older patients (P < 0.001). The only patient with iritis was also more than 16 yr old. The joint symptoms were oligoarticular in 10 (63%), monoarticular in five (31%) and polyarticular in one (6%). The most frequently affected joints were the wrists, knees and ankles. Joints of upper extremities only were affected in three (19%), of the lower extremities only in six (37%) and of both in seven (44%) subjects. In the majority of the patients ReA was mild. The joint symptoms persisted for less than 1 month in six, 2 to 6 months in five and more than 6 months in five. Thirteen subjects with ReA/iritis were tissue-typed for HLA; four (33%) had HLA-B27.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

HLA DQ and DP locus mismatches and their effect on MLC in HLA class I- and DRB1-matched unrelated patient/donor pairs waiting for allogeneic bone-marrow transplantation.

The frequency of HLA DQA1, DQB1, and DPB1 mismatches was evaluated in 110 HLA class I- and DRB1-matched, unrelated pairs who were tested in mixed lymphocyte culture (MLC) in connection with a potential allogeneic bone-marrow transplantation between unrelated persons. After typing of the DQA1, DQB1, and DPB1 genes retrospectively, it was found that only 22% of the pairs were matched for all the loci tested. However, the frequency of this fully matched group was higher (37%) in pairs where both individuals were of Finnish origin as compared to those where the donor originated from a foreign registry. This suggests that the variety of haplotypes may be limited in small populations and justifies local national registries. The overall correlation between class-II match and stimulation in MLC was clear: better matches gave lower responses. However, the correlation was not definitive; for example, no response was observed in some cases with mismatches only in DPB1.

Alleles↗

HSP70-Hom NcoI polymorphism and HLA-associations in the Finnish population and in patients with ankylosing spondylitis or reactive arthritis.

The NcoI polymorphism of the HSP70-Hom gene was investigated in the Finnish population and in two HLA-B27-associated autoimmune diseases. The two HSP70-Hom alleles were shown to be strongly associated to some specific HLA-B/DR haplotypes in random Finnish population and the segregation of the alleles as a part of these haplotypes was confirmed in 18 families. In addition, the HSP70-Hom alleles of 31 patients with ankylosing spondylitis (AS) and 38 with reactive arthritis (ReA) were compared with each other and with 56 unrelated healthy HLA-B27 positive individuals. The results indicated that the HSP70-Hom polymorphic variation is not connected independently to the different pathogenesis of AS and ReA, as no statistically significant differences between the patient groups and/or controls could be found. The HSP70-Hom status was investigated also in 28 homozygous HLA typing cells and when compared with previously published results of HSP70-l and HSP70-2 polymorphisms, it appeared that these three MHC Class-III linked HSP70 genes segregated in fixed allelic combinations.

Arthritis, Reactive↗

Immunohistochemical changes in the jejunum in first degree relatives of patients with coeliac disease and the coeliac disease marker DQ genes. HLA class II antigen expression, interleukin-2 receptor positive cells and dividing crypt cells.

The staining of HLA class II antigens, the presence of cells positive for interleukin-2 receptors, the proportion of crypt cells in mitosis in the jejunal biopsy specimens, and the dose of coeliac disease marker HLA-DQ genes were studied in 75 healthy family members of coeliac disease patients. Eleven had silent coeliac disease; in the rest the morphology of the jejunum was normal. In the specimens from family members, staining of epithelial cells with HLA-DP and -DR antibodies was more widely distributed and stronger than in those from 19 controls. Interleukin-2 receptor+ cells were seen in the epithelium of all eight specimens from subjects with silent coeliac disease, and also in 24 morphologically normal specimens from family members, but not in the 19 control specimens. The proportion of crypt cells in mitosis was increased only in the specimens from the subjects with silent coeliac disease. The staining intensity of the epithelial cells with HLA-DP and -DR antibodies, the presence of interleukin-2 receptor+ cells and the percentage of crypt cells in mitosis were significantly associated with the number of coeliac disease marker DQB genes. Many family members of patients with coeliac disease have signs of inflammation even in morphologically normal jejunum; these inflammatory changes together with coeliac disease marker DQ genes may point to latent disease in these subjects.

Adult↗

Polymorphism of the tumor necrosis factor genes in patients with dermatitis herpetiformis.

In 18 patients with dermatitis herpetiformis (DH) of whom 16 were HLA-DR3 positive and 14 had the HLA-B8, -DR3 haplotype, the frequencies of known mutations of the tumor necrosis factor alpha (TNF-alpha) and TNF-beta genes were investigated using restriction fragment length polymorphism analysis and the single-strand conformational polymorphism technique. In DH, the phenotype frequency (28%) and allele frequency (0.58) of the rare TNF-beta allele TNFB*1 were significantly increased (normal control 12.4% and 0.37). For the TNF-alpha promoter/enhancer polymorphism, the rare allele TNF2 was more frequent in DH patients (11%, 0.47) compared to controls (2%, 0.16). Since functional studies have associated the rare TNFB*1 and TNF2 alleles with a higher secretion of TNF upon activation in vitro, the predominance of these two 'high-response' TNF alleles in DH patients may represent a genetic basis for the chronic inflammatory response in the skin and mucosal tissues of patients with DH.

Alleles↗

Thirty years of renal transplantation in Helsinki.

During triple-drug immunosuppression, consisting of azathioprine, steroids, and cyclosporine, the number of acute rejections was low. Close monitoring of the patient and the graft during the early posttransplant weeks with regular cytological and histological analyses was the cornerstone of early diagnosis and a favorable outcome of acute rejection. Genetic homogeneity of our patient population, third-party transfusion program, and use of well HLA-matched kidney grafts may have been additional factors behind the low rate of acute rejection. Acute rejection within the first three postoperative months did not predispose the renal graft to chronic rejection in the long term. The histologically determined allograft damage index was a reliable predictor of future graft survival. Recipients with systemic diseases such as diabetes and amyloidosis, as well as elderly patients, could be transplanted safely with results only slightly inferior to those achieved with primary kidney disease. Results in diabetic recipients have steadily improved, encouraging the continuation of critical evaluation of the patients' pretransplant status and the preference for cadaveric transplants. Renal transplantation in small children yielded superior patient and graft survival rates. We consider the use of living donors justifiable in these cases. The five million population of Finland offers an ideal size for a transplant center. Continuous education of medical personnel and the general public is crucial for the cadaver transplant program.

Adolescent↗

Paternity after bone marrow transplantation following conditioning with total body irradiation.

A 28-year-old man with chronic myeloid leukaemia received an allogeneic bone marrow transplant after conditioning with daunorubicin, cyclophosphamide and fractionated total body irradiation (TBI). Four years later his wife gave birth to a healthy child. Although the patient was azospermic serologic HLA testing suggested that the patient was the father of the child. DNA fingerprinting as well as analysis of three variable number of tandem repeats (VNTR) loci D1S80 (MCT118), D17S30 (YNZ22) and the apolipoprotein B hypervariable region (apo B 3') gave unequivocal results showing that the patient was the father. Fathering a child after TBI-containing regimen has been very rare and this is the first case where the paternity has been proven with DNA methodology.

Adult↗