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Biomedical subjects

A Tiilikainen

Publications and source records attributed to A Tiilikainen.

At least 19 recordsLinked to original sources

Immunogenetic profile of psoriasis vulgaris: association with haplotypes A2,B13,Cw6,DR7,DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201.

Psoriasis vulgaris is a skin disease with an immunological and genetic background present in 1-3% of the population. We studied the genetic susceptibility to psoriasis vulgaris in Finns with serological HLA typing and genomic HLA class II typing of the DQ and DP loci to evaluate the risk of developing psoriasis. The haplotypes most frequently distinguishing between psoriatics and controls were those that carried Cw6 (P < 10(-8)), DQA1*0201 (P = 9.3 x 10(-6)) and DR7 (P = 3.9 x 10(-5)). The two most frequent marker haplotypes were A2,B13,Cw6,DR7, DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201, which were not found among the control subjects. A deficit of haplotype B8,DR3,DQ2 (2 out of 124 in the patients versus 15 out of 106 in the controls, P = 1.5 x 10(-4)) was found, and this was in accordance with a slightly decreased frequency of DQA1*0501 (P = 3.1 x 10(-2)), which was usually linked with this haplotype. These results stimulate the research for a genetic resistance factor in psoriasis. Thus, this report sheds further light on the immunogenetic background of psoriasis in Finland. We conclude that the inheritance of psoriasis has a polygenic mode, in which the Cw6,DR7,DQA1*0201 combination seems to be important (P = 7.5 x 10(-7), relative risk 24.4, aetiological factor 0.29).

Adult

HLA risk haplotype Cw6,DR7,DQA1*0201 and HLA-Cw6 with reference to the clinical picture of psoriasis vulgaris.

Psoriasis vulgaris has HLA associations. We have previously defined HLA-Cw6,DR7,DQA1*0201 as the central element of the risk haplotypes for psoriasis. On the other hand, Cw6 as a single gene has the strongest association with psoriasis. The aim of this study was to determine whether the risk haplotype and Cw6 correlate with the clinical parameters of the disease. The series consisted of 64 patients and the clinical parameters were age at onset, family history of psoriasis, arthritis and the frequency of inpatient treatment. The HLA risk haplotype Cw6,DR7,DQA1*0201 had previously been found in 30% and Cw6 alone in 54% of the patients. The presence of Cw6 correlated with early age at onset (Pc = 0.01). The presence of the risk haplotype correlated with a positive family history of psoriasis among the first-degree relatives (Pc = 0.02) and an overall positive family history (Pc = 0.04), but Cw6 had a stronger correlation with an overall positive family history (Pc = 0.01). There were no positive correlations with arthritis or the number of inpatient treatment periods. Only type I psoriasis was associated with Cw6 (Pc = 0.0006). In conclusion, Cw6 and the haplotype Cw6,DR7,DQA1*0201 are important in the heredity of psoriasis vulgaris, but the presence of Cw6 alone is sufficient to indicate a clinically significant risk for psoriasis.

Adult

HLA five-locus haplotypes in Finns.

The extreme polymorphism of HLA genes makes them a powerful tool for distinguishing between different genetic populations. Five-locus HLA haplotypes of Finns (from Oulu, Northern Finland) are described here in order to characterize further the migration pathways of the population to Finland after the Ice Age. From random families, 364 haplotypes were obtained. The most frequent Finnish haplotype A3,Cw4,B35,DR1,DQ1 (7.7%) is a Caucasoid ancestral haplotype and is shared with Italians of Celtic and non-Celtic origin. The haplotype A1,Cw7,B8,DR3,DQ2, which occurs in 4.7% of Finns, is the most frequent haplotype in Caucasoids. The haplotypes A3,Cw7,B7,DR2,DQ1 (3.6%) and A2,Cw7,B7,DR2,DQ1 (2.5%) are shared with several Caucasoid populations and the latter also with Jamaican blacks. A2,Cw5,B44,DR5,DQ3 (0.8%) is shared with Italians of Celtic and non-Celtic origin, A2,Cw6,B13,DR7,DQ2 (1.1%) with Caucasoids in the USA and A9,Cw4,B35,DR1,DQ1 (0.8%) with Mongoloids. The haplotypes A2,CW3,B62,DR4,DQ3 (3.0%), A2,Cw2,B27,DR8,DQ4 (1.7%), A2,Cw3,B62,DR6,DQ1 (1.4%) and A2,Cw1,B27,DR4,DQ3 (1.4%) were also found to be among the most frequent in the Finnish population. The most frequent HLA haplotypes are consistent with the postulated ancient migration of populations from southern Scandinavia and Germany to Finland, the most frequent haplotype suggesting a common Celtic origin and one less frequent haplotype suggesting an influence from the east.

ATP Binding Cassette Transporter, Subfamily B, Mem

Chronic sclerosing osteomyelitis of the mandible in monozygotic twins.

Identical female twins with chronic sclerosing osteomyelitis of the mandible are presented. The diagnoses of both at the age of 12 years were based on typical history, and on clinical, radiographic, and histologic findings. High concentrations of IgA and IgG were detected in the serum of both patients, but deviations were not observed in other immunologic variables. The normally commensal organism, Propionibacterium acnes grew from a bone biopsy specimen from the mandible of one twin. No oral focus of the disease was confirmed in either case. We suggest that hereditary factors must have played a role in the pathogenesis of these cases of chronic osteomyelitis.

Child

HLA-DQA1 and DQB1 loci in nickel allergy patients.

Since an association has been reported between nickel allergy and HLA-DQA TaqI restriction fragment length polymorphism, we typed the DQA1 locus by a more precise method to confirm the association and characterize it better. Typing was extended to the DQB1 locus. The loci were typed using polymerase chain reaction and sequence-specific oligonucleotides. The DQA1 allele 0601 was slightly overrepresented among the patients, but the p value was not significant. The frequencies of DQB1 locus alleles did not differ from those of the controls. Thus we were unable to confirm any association between HLA and nickel allergy.

Adult

Normal C3b receptor (CR1) genomic polymorphism in patients with insulin-dependent diabetes mellitus (IDDM): is the low erythrocyte CR1 expression an acquired phenomenon?

Expression of the erythrocyte complement receptor (C3bR = CR1 = CD35) and its genomic polymorphism (HindIII RFLP) was studied in a group of 80 patients with IDDM, 31 healthy siblings and 101 healthy blood donors. Defective CR1 expression was found in 26% of the patients with IDDM compared with 9% of the controls (P less than 0.05) and 0% of the siblings. The CR1 gene polymorphism of the IDDM patients did not significantly differ from that of the controls. The presence of a 6.9 kb (L) CR1 gene fragment was associated with a low CR1 expression in the patients (P less than 0.05) and especially in the controls (P less than 0.001). No significant association was found between the presence or absence of the HLA risk antigens for IDDM and CR1 expression. The results confirm that erythrocyte CR1 expression is genetically determined, but the CR1 deficiency associated with IDDM seems to be an acquired rather than a genetic phenomenon.

Adolescent

Differences in HLA antigens between patients with mixed connective tissue disease and systemic lupus erythematosus.

Patients with mixed connective tissue disease (MCTD, n = 32) or systemic lupus erythematosus (SLE, n = 60) were typed for HLA-A, B, C, Dw, and DR antigens. All patients with SLE fulfilled at least four criteria of SLE and the patients with MCTD met the criteria proposed by Alarcon-Segovia (1989). The presence of antibodies to Sm was not considered as an exclusion for MCTD. In the patients with SLE, Dw3, DR3, and the associated B8 and A1 antigens were increased, whereas in the patients with MCTD an increased frequency of Dw4 was found (45 v 18% in controls v 14% in SLE). Of the subtypes of DR4, Dw4 was present in all but one of the DR4 positive patients. The frequency of DR4 in patients with MCTD (52%) differed significantly from that of controls (28%). The strong association of MCTD to one DR4 subtype was further seen in the significantly increased frequency of the B15, DR4 combination. Thus the genetic background seems to be different in patients with MCTD from that in patients with SLE. This could partly explain the clinical differences between these diseases.

Female

B27-bearing HLA haplotypes in rheumatoid arthritis: characterization in Finnish patients.

The frequency of human leukocyte antigen (HLA)-B27 has been found to be increased in rheumatoid arthritis (RA) in Finland and marginally also in some other populations. In the present study HLA-B27-bearing haplotypes in RA patients were found to carry DR1 and DR4 genes more often than do B27 haplotypes in control population. B27;DR4,DW14;DQw7 was a typical B27-DR4 haplotype whereas DR4 in the majority of other haplotypes occurs with Dw4 and DQw8 genes. The result indicates that the B27 association with RA is not independent of DR1 and DR4, but whether the B27;DR4;DQw7 haplotype subjects a person to a higher disease risk than do other DR4 haplotypes, or is associated with a more severe course of the disease, remains to be investigated.

Arthritis, Rheumatoid

Maturation of immunoglobulin G avidity after rubella vaccination studied by an enzyme linked immunosorbent assay (avidity-ELISA) and by haemolysis typing.

Two tests were introduced recently for assessment of the avidity of rubella immunoglobulin antibodies. In the quantitative test--avidity-enzyme linked immunosorbent assay (ELISA)--IgG antibodies obtained from individuals shortly after primary infection with rubella virus are distinguished from those with past immunity by their antigen-elution characteristics. This method uses agents that disrupt hydrophobic bonds in proteins [Kamoun PP (1988): Denaturation of globular proteins by urea: Breakdown of hydrophobic bonds? Trends in Biological Sciences 13:424-425.]. In the semiquantitative, presumptive test--haemolysis typing--the low-avidity rubella-IgG antibodies are distinguished from the high-avidity antibodies by the quality of their haemolytic zones in a radial haemolysis test. In the present study, both tests were applied to sera taken before and after vaccination with two different strains (Cendehill or RA 27/3) of live attenuated rubella virus. It was found that after vaccination of previously nonimmune subjects, IgG synthesized during the first 2 months had a very low avidity; IgG avidity increased dramatically during the subsequent 4 months and less markedly between 6 and 12 months after vaccination. On the contrary, the initially high IgG avidity of previous immune vaccinees remained at an elevated level postvaccination. These results provide a basis for identification of recent primary rubella virus infections, or vaccination reactions, by the avidity of specific IgG and also for their separation from rubella reinfections.

Adult

The expression of autoimmune polyglandular disease type I appears associated with several HLA-A antigens but not with HLA-DR.

We studied HLA-A, -B, -C, and -DR antigens in 45 patients (from among 34 families), aged 10.2-60 yr, with polyglandular autoimmune disease type I (APG I) and in other family members. HLA-A28 was more frequent in the patients (25%) than in unaffected siblings (16%; P less than 0.05) or in normal Finnish subjects (8.8%; P less than 0.005, corrected P less than 0.2). Compared with the normal subjects, HLA-A28 was more frequent in the patients with hypoparathyroidism (31%; P less than 0.001, corrected P less than 0.04), adrenocortical failure (27%; P less than 0.01), insulin-dependent diabetes mellitus (IDDM; 66%; P less than 0.01), keratopathy (53%; P less than 0.001, corrected P less than 0.04), and alopecia (40%; P less than 0.001, corrected P less than 0.04), but not in the patients with ovarian failure (9%; P = NS). HLA-A28 was more frequent in the patients with hypoparathyroidism (31%) than in APG I patients without it (13%; P less than 0.005, corrected P less than 0.2). It was also more frequent in the patients with IDDM (66%) than in those without it (21%; P less than 0.05). HLA-A3 was more frequent in the patients with ovarian failure (82%) than in APG I patients with normal ovarian function (22%; P less than 0.025) and in normal subjects (45.5%; P less than 0.05). HLA-A9 was less frequent in the patients with ovarian failure (0%) than in those with normal ovarian function (55%; P less than 0.005, corrected P less than 0.2), and it was less frequent (P less than 0.025) in the patients with adrenocortical failure than in those with normal adrenal function. No association was found with any single DR antigen, but of 4 DR-typed IDDM patients, 3 were DR3 or DR4 positive (P = NS). The occurrence of adrenocortical failure, but not hypoparathyroidism, was familial and associated with HLA haploidentity among sets of affected siblings.

Autoimmune Diseases

Isoprinosine enhances PHA responses and has potential effect on natural killer cell (NK) activity of uremic patients in vitro.

We studied the effect of an immuno-stimulating agent, isoprinosine, which is being marketed as an antiviral drug, on some immune functions in vitro in 14 uremic patients treated by hemodialysis and in 10 healthy controls. PHA and PPD induced stimulations of DNA synthesis and interleukin-2 (Il-2) production and NK cell activity were measured from peripheral blood mononuclear cells cultured with and without isoprinosine. PHA responses were enhanced by isoprinosine (100 micrograms/ml) both in the patient group (p less than 0.001) and in the control group (p less than 0.05) but PPD responses in neither. The enhancement of PHA responses was not due to an increased production of Il-2(T-cell growth factor). Isoprinosine augmented NK activity in those patients whose NK activity was initially low. No enhancement could be seen in the controls or in those patients whose NK activity was comparable to that of the controls. Our results motivate a clinical study with isoprinosine in uremic patients at the risk of virus infection.

Adjuvants, Immunologic

Nocardia water soluble mitogen (NWSM), a human B-lymphocyte mitogen.

Nocardia water soluble mitogen (NWSM), which is a peptidoglycan, was prepared from Nocardia opaca. Its effect on human B-lymphocyte proliferation, the number of immunoglobulin secreting B-cells, and bone marrow stem cell growth was studied in vitro. NWSM stimulated the proliferation of B-lymphocytes of all ten healthy subjects studied very effectively (P less than 0.0005). No T-cell activation occurred. NWSM did not increase the amount of antibody producing cells. The growth of bone marrow stem cells was enhanced only in one patient out of the eight studied. Thus NWSM is a B-lymphocyte mitogen with a potential effect on hematopoietic stem cells. However, production of NWSM was faced with difficulties because not all lots prepared had B-cell stimulating activity.

Antibody-Producing Cells

Association of different HLA antigens with various toxic effects of gold salts in rheumatoid arthritis.

An association of gold induced proteinuria with HLA-D(R)3 has been reported. To investigate other possible relationships between gold toxicity and HLA antigens we studied 85 patients with rheumatoid arthritis (RA) divided into four subgroups: patients with gold induced interstitial pneumonitis, mucocutaneous lesions, proteinuria, and patients without gold toxicity. The HLA frequencies in patient groups and 283 healthy controls were compared in different pairwise combinations. Gold induced pneumonitis was associated with HLA-B40 and Dw1. An association between gold induced proteinuria and HLA-Dw3 was also seen. The increased prevalence of Dw4 in RA was observed only in the control patient group without gold induced side effects. The frequencies of HLA-B7 and Dw2 were decreased in all patient groups compared with the control population. These results further support the view of the heterogeneity of RA as manifested by the unique HLA associations with resistance and susceptibility to gold induced side effects characterising different subgroups.

Adult