Interleukin-6-174 G/C promoter polymorphism is associated with persistence of Chlamydia pneumoniae antibodies in young men.

A promoter polymorphism -174 G/C in the inflammatory cytokine interleukin-6 (IL-6) gene has been associated with differences in serum IL-6 levels and a risk for inflammatory conditions, such as cardiovascular diseases. We investigated whether this polymorphism is associated with Chlamydia pneumoniae, a common causative agent of respiratory infection with tendency for persistent infections, in 867 Finnish military recruits. IgG seropositivity in arrival and departure serum samples during 6-12 months of military service was considered as persistence of antibodies and a possible prolonged or chronic infection. The -174C allele was significantly associated with IgG seropositivity (P = 0.0002) and the persistence of IgG antibodies (P = 0.0002) as well as with slightly elevated C-reactive protein (CRP) levels (P = 0.003). In addition, the association was stronger when persistent C. pneumoniae antibodies were present together with elevated CRP than when either of them was positive alone (OR; 95% CI: 3.45; 2.00-5.98 and 1.41; 1.00-1.99, respectively). Our data suggest that IL-6 -174 G/C polymorphism is associated with persistence of C. pneumoniae antibodies and may be linked to the chronic or prolonged infection with systemic low-grade inflammation.

Chlamydia pneumoniae infection is associated with elevated body mass index in young men.

Chlamydia pneumoniae infection is said to be associated with obesity. We studied the association between C. pneumoniae infection and inflammation and increased BMI in 891 Finnish military recruits. IgG seropositivity in arrival and departure serum samples during 6-12 months of military service was considered as persistence of antibodies and a possible indication of chronic infection. Persistently high C-reactive protein (CRP) level (elevated on arrival and departure) (OR 2.2, 95% CI 1.3-3.9), and persistent C. pneumoniae antibodies (OR 2.1, 95% CI 1.5-2.8) were significant risk factors for overweight (BMI 25 kg/m2). In addition, those who had persistent antibodies and persistently elevated CRP levels, or those who had either of them, had a significantly higher BMI (kg/m2) compared to those who had neither of them (25.8 vs. 24.6 vs. 23.5, respectively; P<0.001). These results provide new information about the association between possible chronic C. pneumoniae infection and obesity in young men.

Effects of CD14, TLR2, TLR4, LPB, and IL-6 gene polymorphisms on Chlamydia pneumoniae growth in human macrophages in vitro.

Chlamydia pneumoniae is an obligate intracellular gram-negative bacterium, which causes respiratory infections in humans. It can infect various cell types, e.g. vascular endothelial cells, smooth muscle cells and monocyte-derived macrophages in vitro. The susceptibility of macrophages from healthy individuals to C. pneumoniae infection is highly variable. In this study, we evaluated the effects of innate immunity genes CD14 -260 C>T, TLR2 Arg753Gln, TLR4 Asp299Gly, LBP Phe436Leu and IL6 -174 G>C polymorphisms on C. pneumoniae growth in human macrophages in vitro. The growth of C. pneumoniae was highest in CD14 -260 C>T TT genotype cells and the difference to CC and CT genotypes was statistically significant (P = 0.032 and 0.022 respectively). The G-allele of the IL6 -174 G>C polymorphism had a positive influence on chlamydial growth; the difference was statistically significant only between CC and GC genotypes (P = 0.018). TLR2 Arg 753Gln, TLR4 Asp299Gly, LBP Phe436Leu polymorphisms showed no effect on chlamydial growth.

Susceptibility of human monocyte-macrophages to Chlamydia pneumoniae infection in vitro is highly variable and associated with levels of soluble CD14 and C. pneumoniae IgA and human HSP-IgG antibodies in serum.

Chlamydia pneumoniae, an intracellular microbe, causes respiratory infections and may participate in the development of atherosclerosis. It is able to survive and multiply in macrophages. The susceptibility of monocyte-macrophages from healthy individuals to C. pneumoniae infection in vitro was studied. Intracellular growth of C. pneumoniae, as an indicator of susceptibility to infection, was compared to serum levels of C-reactive protein, soluble CD14 (sCD14), human heat shock protein (HSP)-IgG, human HSP-IgA, C. pneumoniae IgG and IgA antibodies. The production of C. pneumoniae in infected macrophages was highly variable, ranging from 0 to 638 chlamydial genomes per human genome. Chlamydia pneumoniae production associated positively with serum C. pneumoniae IgA (titre: > or =10) and hHSP-IgG and negatively with sCD14 concentration. The association between sCD14 concentration, C. pneumoniae IgA and human HSP-IgG antibodies and C. pneumoniae production was statistically significant only among males. Age and gender did not correlate with the production. We hypothesize that persons whose macrophages cannot restrict the growth of C. pneumoniae are more prone to chronic infection by this agent.

Acute Chlamydia pneumoniae infections in asthmatic and non-asthmatic military conscripts during a non-epidemic period.

Chlamydia pneumoniae respiratory tract infections were studied in 512 male military conscripts (123 asthmatic and 389 non-asthmatic) taking part in 180-day service between July 2004 and July 2005 in Kajaani, Finland. Respiratory tract infections requiring a medical consultation were analysed prospectively. At baseline, at end of service, and during each episode of respiratory infection, blood samples were obtained for measurement of C. pneumoniae antibodies. Data concerning the clinical features of each infection episode were collected. Serological evidence of acute C. pneumoniae infection was found in 34 of the 512 conscripts with antibody data available, including 9.8% of the asthmatic subjects and 5.7% of the non-asthmatic subjects (p 0.111). A serological diagnosis could be made for 25 clinical episodes in 24 conscripts. The spectrum of respiratory tract infections included 13 episodes of mild upper respiratory tract infection and seven episodes of sinusitis, with five episodes involving asthma exacerbation. Two of three pneumonias were primary infections. Primary infections were diagnosed in five subjects, and re-infection/reactivation in 19 subjects, with the latter comprising 12 non-asthmatic subjects and seven asthmatic subjects (p 0.180). Prolonged infections were present in six asthmatic subjects and one non-asthmatic subject (p 0.001). A wide variety of respiratory tract infections, ranging from common cold to pneumonia, were associated with serologically confirmed C. pneumoniae infections. Infections were often mild, with common cold and sinusitis being the most common manifestations. Acute, rapidly resolved C. pneumoniae infections were equally common among asthmatic subjects and non-asthmatic subjects, whereas prolonged infections were more common among subjects with asthma.

Helper cells (Leu-3a+) carry the specificity of nickel sensitivity reaction in vitro in humans.

Suppressor and helper T-cell functions were studied in nickel (6.25 micrograms/ml)-induced 7-day blast transformation reaction in vitro. This was done in cocultures of 5 pairs of HLA-identical siblings; one of the siblings was nickel-sensitive and the other healthy. Suppressor and helper cells were isolated by panning, using monoclonal antibodies Leu-2a and Leu-3a. Helper cells from the nickel-sensitive siblings were obligatory for the blast transformation reaction to occur. Helper cells from the healthy sibling were not able to elicit blast transformation. Suppressor cells from nickel-sensitive and healthy subjects did not functionally differ from each other in their ability to support nickel-induced blast transformation, but the presence of suppressor cells was essential for the blast transformation reaction to occur. Proportional amounts of suppressor, helper, and Ia-antigen (Leu-10 positive)-bearing cells and monocytes (Leu-3M positive) were determined by avidin-biotin-peroxidase complex immunoperoxidase method before culturing the cells and on the seventh day of nickel-induced blast transformation culture. This was done in 6 pairs of unrelated nickel-sensitive and healthy subjects. Amounts of neither suppressor cells nor monocytes increased during the culture. Helper cells increased in both groups (p less than 0.0025). Ia-antigen bearing cells increased only in the cultures of nickel-sensitive subjects (p less than 0.0025). In conclusion, helper T cells seem to carry the specificity of nickel-induced blast transformation reaction, but suppressor T cells are also needed. Unresponsiveness to nickel is not due to specific suppressor T cells.

Inhibition of in vitro nickel sulfate reaction by anti-HLA-D/DR antisera. Lack of demonstrable suppressor cells in peripheral blood in nickel unresponsiveness in man.

A nickel sulfate induced lymphocyte blast transformation reaction in vitro was specifically inhibited by anti-HLA-D/DR antisera, which indicates the requirement of HLA-D/DR antigens in cellular cooperation. Macrophages are effective antigen presenting cells in the in vitro nickel reaction and this step could be the site of an HLA-antigen function in the recognition of "self." It was shown that macrophages of an HLA identical, healthy sibling could offer proper "help" to macrophage-depleted lymphocytes of the nickel allergic subject in evoking a nickel reaction. Thus, in this respect, the function of macrophages in nickel allergy is not different from that in a nickel-unresponsive state. The nickel unresponsiveness in healthy subjects is probably not due to specific suppressor cells because HLA identical lymphocytes from the healthy siblings could not suppress the nickel induced blast transformation of the nickel allergic siblings. This suggests that a deletion of sensitized clones in the periphery is the more probable mechanism of unresponsiveness in healthy subjects.

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.

The frequency of QAP2.1 is increased in psoriasis vulgaris patients but no unusual linkage between QAP/DQA1 or QBP/DQB1.

Psoriasis vulgaris is a chronic skin disease with a genetic and immunological background. We have previously defined the two most frequent risk haplotypes in Finns: A2,B13,Cw6,DR7,DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201. The aim of this study was to further examine whether the flanking regions, URRs of DQ (QAP and QBP) and TAP1 and TAP2 genes are involved in susceptibility to psoriasis. The frequency of QAP2.1 was increased in psoriatics as compared with controls (Pc = 3.6 x 10(-2), RR = 5.0), and the frequency of QAP4.1 was decreased in psoriasis patients (Pc = 4.2 x 10(-2)). The frequency of the phenotype combination Val/Ile at position 379 of TAP2 was decreased in patients (Pc = 1 x 10(-2)). The allele and phenotype frequencies of TAP1 and TAP2 genes were not different between these groups. Haplotypes A2, B13,Cw6,DR7,DQA1*0201,QAP2.1 and A1,B17,Cw6, DR7,DQA1*0201,QAP2.1 are the two most frequent HLA marker haplotypes for psoriasis vulgaris in Finns, Cw6, DR7, DQA1*0201 and QAP2.1 being the most important single alleles for the risk of this disease.

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).

Candida immunity in patients undergoing surgical treatment for heart valve disease.

The appearance of Candida antigen (Latex agglutination method), Candida antibodies (indirect immunofluorescence) and positive fungal cultures as well as the lymphocyte transformation response to Candida antigen "in vitro" was studied in a series of 37 successive patients before and after heart valve replacement. The Candida antigen test was positive preoperatively in 11/36 (31%) and postoperatively in 14/36 (39%) of the patients and in 2/200 (1%) of the controls (blood donors). The differences in the frequencies of positive tests between the patient group and the control group are significant (p less than 0.001). The lymphocyte response to Oidiomycin (Candida albicans) preoperatively was greater than the mean control value in 6/11 (54.5%) of the patients showing a positive Candida antigen test, but only in 4/25 (16.0%) of the patients who were Candida antigen negative. The total number of lymphocytes and the number of ANAE positive (T) cells as well as the lymphocyte response to Oidiomycin (OID), tuberculoprotein (PPD) and phytohaemagglutinin (PHA) decreased markedly postoperatively. Candida antibody titres were positive (greater than or equal to 1:128) in 3/37 (8%) of the postoperative patients and in 2/84 (2.4%) of the controls. This difference is not significant. Positive Candida antibody titres were found postoperatively in 15/37 (41%) of the patients, which is a significantly higher frequency than that seen preoperatively (p less than 0.005). More positive fungal cultures from throat specimens (p less than 0.005) were found in the patient group before surgery than in the control group (hospital personnel). After surgery the number of positive fungal cultures in these cases decreased (p less than 0.001) due to the use of oral antifungal prophylaxis with nystatin tablets.(ABSTRACT TRUNCATED AT 250 WORDS)

The specificity of a nickel sulphate reaction in vitro: a family study and a study of chromium-allergic subjects.

In vitro PPD and nickel sulphate lymphocyte blast transformation reactions were performed in ten families with one or more allergic nickel contact dermatitis patients. The healthy family members did not have an inherited ability to react to nickel in vitro. Their nickel stimulation response was significantly lower (P less than 0.005) than that among the allergic subjects. In the families studied, atopic members did not have higher nickel reactions than nonatopic subjects. Thus, the in vitro nickel reaction is not connected to atopy. This is further confirmed by the fact that the percentage of atopic subjects (19%) in these families is not higher than the percentage in the general population. In addition, six unrelated chromium-allergic patients were tested, and their lymphocytes did not cross-react with nickel sulphate in vitro. These results indicate that the in vitro nickel blast transformation reaction is specific to clinical nickel allergy in about 90% of nickel dermatitis patients.

Lymphocyte transformation in nickel allergy: amplification of T-lymphocyte responses to nickel sulphate by macrophages in vitro.

The cell-mediated immunity of thirty-four nickel contact dermatitis patients was evaluated by performing lymphocyte stimulations with NiSO4 (1.25 and 6.25 microgram/ml) and tuberculin (PPD), phytohaemagglutinin-P, pokeweed mitogen, and concanavalin A. Twenty-six of the patients were nonatopic and eight atopic. Forty-nine healthy subjects served as controls. Nickel sulphate stimulation was significantly increased (P < 0.005) in the allergic subjects, whereas PPD stimulation was decreased (P = 0.01). The responses to the other mitogens did not differ significantly between the control subjects and the patients. The lymphocyte transformation reaction to nickel sulphate was shown to occur in T cells and to be enhanced by the helper function of macrophages.

Dermatophytes in northern Finland in 1982-90.

The epidemiology of human dermatophytes was studied in northern Finland in 1982-90. The samples were analysed at the Department of Medical Microbiology, University of Oulu. The total number of samples was 17,822, of which 3185 (18%) were positive. The annual number of samples and positive cultures remained relatively constant. Trichophyton rubrum was the most common species being isolated from 2101 samples (66% of all positive cultures), while Trichophyton mentagrophytes was isolated from 815 samples (26%) and Epidermophyton floccosum from 193 samples (6%). T. verrucosum caused an epidemic among cattle keepers in 1987-90, causing 47 infections. Microsporum canis, T. terrestre and T. violaceum were rare. The same species affected both children and adults. There was a tendency towards a decrease in tinea in the groin and a slight increase in tinea pedis. T. rubrum and T. mentagrophytes occurred most frequently in patients aged 41-45 years and as foot infections. E. floccosum usually affected the toe web and the groin in patients aged 21-25 years, more often infecting men. Fifty-four per cent of all positive samples came from men and 46% from women.

Gold sensitivity blast transformation.

A 36-year-old female patient developed eczema from wearing gold jewelry. Epicutaneous skin tests were performed with gold leaf, potassium dicyanoaurate, gold sodium thiosulphate, gold chloride, sodium chloroaurate and potassium bromoaurate. The test was positive with gold sodium thiosulphate only. Blast transformation was induced with all the gold salts except sodium chloroaurate, and the positive responses seemed to be dose-dependent. In vitro gold salt-induced reactions are useful in the diagnosis of allergic contact dermatitis.

Optimal conditions for the opsonophagocytosis test with Streptococcus pneumoniae serotypes 3, 6A, 7F and 19F and human granulocytes.

There are great variations in test systems used to measure pneumococcal opsonophagocytosis; therefore, in the present study, a detailed analysis of the human granulocyte opsonophagocytosis test with pneumococci was made. Variables affecting the test were evaluated. These were the amount of bacteria, the amount of antipneumococcal antibody and complement in the test. Correlation between phagocytosis percentage (percentage of cells taking part in the phagocytosis) and phagocytosis index (mean amount of bacteria phagocytosed per cell) was shown. The conclusion is that, after precise test-adjustment, weak phagocytosis is better detected by phagocytosis percentage and high phagocytosis activity is best shown by phagocytosis index.

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.

Lack of association of T cell receptor beta-chain constant region polymorphism with insulin-dependent diabetes mellitus in Finland.

Allelic polymorphism in the T cell receptor constant beta-chain gene region has been reported to be associated with autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). The present analysis of 164 children and adolescents with IDDM and 193 controls for BqlII polymorphism using a TcR-C beta cDNA probe revealed two allelic restriction fragments with sizes of 10.5 kb (U) and 9.6 kb (L). No particular association was observed between the RFLP genotypes and IDDM (UU 27% versus 31%; UL 53% versus 52%; and LL 20% versus 17%, in diabetic subjects and controls, respectively), nor were any differences found between patients with various HLA risk antigens. The frequency of heterozygotes was 52% in 63 DR3-positive diabetic subjects and 53% in 73 DR3-negative ones. The results do not support any involvement of the TcR constant region genes in susceptibility to IDDM.