Sylvi Silvennoinen-Kassinen

Cold temperature and low humidity are associated with increased occurrence of respiratory tract infections.

OBJECTIVE The association between cold exposure and acute respiratory tract infections (RTIs) has remained unclear. The study examined whether the development of RTIs is potentiated by cold exposure and lowered humidity in a northern population. METHODS A population study where diagnosed RTI episodes, outdoor temperature and humidity among conscripts (n=892) were analysed. RESULTS Altogether 643 RTI episodes were diagnosed during the follow-up period. Five hundred and ninety-five episodes were upper (URTI) and 87 lower (LRTI) RTIs. The mean average daily temperature preceding any RTIs was -3.7+/-10.6; for URTI and LRTI they were -4.1+/-10.6 degrees C and -1.1+/-10.0 degrees C, respectively. Temperature was associated with common cold (p=0.017), pharyngitis (p=0.011) and LRTI (p=0.048). Absolute humidity was associated with URTI (p<0.001). A 1 degrees C decrease in temperature increased the estimated risk for URTI by 4.3% (p<0.0001), for common cold by 2.1% (p=0.004), for pharyngitis by 2.8% (p=0.019) and for LRTI by 2.1% (p=0.039). A decrease of 1g/m(-3) in absolute humidity increased the estimated risk for URTI by 10.0% (p<0.001) and for pharyngitis by 10.8% (p=0.023). The average outdoor temperature decreased during the preceding three days of the onset of any RTIs, URTI, LRTI or common cold. The temperature for the preceding 14 days also showed a linear decrease for any RTI, URTI or common cold. Absolute humidity decreased linearly during the preceding three days before the onset of common cold, and during the preceding 14 days for all RTIs, common cold and LRTI. CONCLUSIONS Cold temperature and low humidity were associated with increased occurrence of RTIs, and a decrease in temperature and humidity preceded the onset of the infections.

The Association Between C-Reactive Protein Levels and Depression: Results from the Northern Finland 1966 Birth Cohort Study

BACKGROUND To investigate whether depressive episodes (previous, current single, and recurrent) are associated in both genders with highly sensitive C-reactive protein (hs-CRP) levels, earlier recommended for risk assessment of cardiovascular disease. The impact of the severity of current single and recurrent depressive episodes on this putative association was also investigated. METHODS The genetically homogeneous Northern Finland 1966 Birth Cohort was followed until age 31, when, in a cross-sectional setting (n = 5269), the highly sensitive enzyme immunoassay (hs-EIA) method was used to measure CRP concentration. Depressive episodes were defined through mailed questionnaires, including Hopkins Symptom Checklist-25 (HSCL-25) and information on self-reported, doctor-diagnosed depression. RESULTS After adjusting for confounders, logistic regression analyses showed that in male subjects, elevated hs-CRP levels (> or =1.0 mg/L) increased the probability for severe current and recurrent depressive episodes 1.7-fold and 3.1-fold, respectively. Correspondingly, an hs-CRP level of >3.0 mg/L increased the probability for recurrent depression up to 4.1-fold. In female subjects, no statistically significant associations were found. CONCLUSIONS Our results support the hypothesis that an activation of systemic inflammatory processes may contribute to the pathophysiology of severe depression in men. Further investigations are needed regarding the impact of our findings on diagnostic/treatment strategies concerning severe and, especially recurrent, depression in men.

Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to respiratory tract infections in young men.

BACKGROUND Mannose-binding lectin (MBL) is an important component of innate immunity, and its deficiency is associated with susceptibility to recurrent infections. METHODS This exploratory study investigated the association of serum MBL concentrations and MBL2 gene polymorphisms with respiratory tract infections in young men. We genotyped 6 single-nucleotide polymorphisms (SNPs) in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (variant alleles B, C, and D and wild-type allele A) of the MBL2 gene by real-time polymerase chain reaction and measured serum MBL concentrations in 111 Finnish military recruits with asthma and 362 without. RESULTS An MBL level below the median concentration was a significant risk factor for infections (asthma status-adjusted odds ratio [OR], 2.5 [95% confidence interval {CI}, 1.4-4.5]). Among the 6 SNPs, there was a significant association between the promoter Y/Y genotype and infections (OR, 2.3 [95% CI, 1.2-4.4]) and a borderline significant association between exon 1 variant alleles and infections (OR, 1.7 [95% CI, 0.9-3.1]), after adjustment for asthma status. CONCLUSION These preliminary results suggest, for the first time, an association between MBL level and respiratory tract infections in young men and a possible association between infections and MBL2 polymorphisms.

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.

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=9.3×10−6) and DR7 (P=3.9×10−5). 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=1.5×10−4) was found, and this was in accordance with a slightly decreased frequency of DQA1*0501 (P=3.1×10−2), which was usually linked with this haplotype. These results stimulate the search 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=7.5×10−7, relative risk 24.4, aetiological factor 0.29).

Characterization of nickel-specific T cell clones

Nickel is the major cause of metal‐induced allergic dermatitis. Twelve nickel‐specific T cell clones were used to investigate the cellular immune reactions occurring in nickel sensitivity. The selection between the alternative T cell receptors α and βγδ and two alternative Vβ genes (Vβ5 and Vβ8) were studied to see if nickel induces a selective pressure for clones bearing particular genes. Cell surface markers were studied by monoclonal antibodies and flow cytometry. Soluble mediators were measured by an ELISA method.

Pneumococcal carriage is more common in asthmatic than in non-asthmatic young men.

Introduction:  The aim was to investigate the prevalence of oropharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis and beta‐haemolytic streptococci among asthmatic and non‐asthmatic young Finnish men and to identify putative risk factors.

Long-lasting allergic patch test reaction caused by gold

Allergic contact dermatitis caused by gold is rare, and only isolated cases have been reported. Patch Jesting with gold may cause a long‐lasing reaction. The purpose of this study is to describe a well‐studied case of gold allergy caused by denial gold crowns. A gold‐sensitized patient and a non‐sensitized control subject were examined using patch tests, immunohistochemistry. electron microscopy and blast transformation reactions. Sodium thiosulfate, auranofin and sodium thiomalate gave positive patch test reactions. Immunohistochemistry and electron microscopy were performed from biopsies taken from allergic patch lest reactions caused by gold sodium thiosulfate 1 day and 17 days after applying the patches, from normal skin and from a 17‐day‐old allergic patch test reaction caused by ammonium persulfate. Down‐regulation had taken place by 17 days in the allergic ammonium persulfate reaction, but not in the 17‐day allergic gold lest reaction. The patient reacted to all but one of the gold‐induced blast transformation tests, sodium chloroaurate being non‐inductive. The non‐sensitized control subject did not exhibit any reactions. In conclusion, gold sodium thiosulfate, gold sodium thiomalate and auranofin can be used as patch test substances for gold allergy, though long‐lasting allergic patch test reactions may develop. In vitro gold salt induced blast transformation is an alternative test for gold allergy. The slow down‐regulation of the allergic patch test reactions needs to be studied further.

Mononuclear cell subsets in the nickel-allergic reaction in vitro and in vivo

Nickel is the major cause of metal-induced contact allergy. To understand the mechanism of its immune reaction, we studied changes in lymphocyte surface markers during nickel challenge in both allergic and healthy subjects using an in vitro nickel reaction in which the lymphocytes of allergic subjects divide when they are stimulated with nickel sulfate. The lymphocytes were labeled with monoclonal antibodies (MAbs) to cell-surface antigens and studied by flow cytometry. Mononuclear cells from the nickel reaction in vivo were studied from skin biopsy specimens using MAbs and avidin-biotin immunohistochemistry. Nickel-induced lymphoblast transformation occurred in vitro only in cells from nickel-allergic subjects. CD4+ cells and CD45RO+ cells were overrepresented among the lymphoblasts of nickel-sensitive subjects, whereas CD8+ and CD8+CD11b+ and CD4+CD45R+ cells were underrepresented. The lymphoblasts contained T cells with the following activation markers: CD25, HLA-DR, CD26, CD71, Ki-67, and activation-associated antigen detected by the MAb, M21C5, but they were CD30-. CD16+ cells were overrepresented among the lymphoblasts. Nickel-reacting T cells used predominantly the T cell receptor, alpha beta-heterodimer, but no preferential selection of either V beta 5, V beta 6, or V beta 8 was observed. The phenotypes of nickel-reacting cells from cutaneous biopsy specimens were in agreement with the in vitro results.

Pneumococcal carriage is more common in asthmatic than in non-asthmatic young men

Introduction:  The aim was to investigate the prevalence of oropharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis and beta‐haemolytic streptococci among asthmatic and non‐asthmatic young Finnish men and to identify putative risk factors.