The lack of association between CD14 genotypes and IgE as well as atopic outcomes in this large German study population seems to indicate that CD14 genotypes may not directly be involved in the development of allergies during childhood.

The collectin surfactant protein-D (SP-D) plays a significant role in innate immunity. Epidemiological studies described associations between single nucleotide polymorphisms (SNPs) of the human gene coding surfactant protein-D (SFTPD) and infectious pulmonary diseases. Studies on twins indicated very strong genetic dependence for serum levels of SP-D. The aim of this study was to determine the genetic influence of sequence variations within the SFTPD gene on the constitutional serum SP-D levels. We sequenced the 5' untranslated region (5'UTR), the coding region and the 3' region of the SFTPD gene of 32 randomly selected blood donors. Six validated SNPs were genotyped with sequence-specific probes (TaqMan 7000) in 290 German blood donors. Serum SP-D levels were analysed by ELISA, and the association of SFTPD haplotype estimates with the quantitative phenotype serum SP-D level was determined. One single SFTPD haplotype (allele frequency 13.53%) revealed a negative association with serum SP-D levels (P<0.0001). This was confirmed in a second prospectively collected group of blood donors (n=160, P=0.0034). The discovery of a frequent negative variant of the SFTPD gene provides a basis for genetic analysis of the function of SP-D in the resistance against pulmonary infections and inflammatory disorders in humans.

Interleukin (IL)-4 exerts its biological effects through binding to the IL-4 receptor (IL4R) complex, plays a central role in stimulating B-cell differentiation, and is crucial for the development of T helper 2 cells. Recently, a soluble form of the human IL4R alpha chain (sIL4R alpha), which is produced by alternate mRNA splicing of exon 8, was discovered. sIL4R is thought to play an important role in either enhancing or inhibiting IL-4 signalling. We analyzed the 5' promoter region of the human IL4R alpha-chain gene (IL4RA) of healthy volunteers by DNA sequencing and found three novel single-nucleotide polymorphisms (SNPs; T-890C, T-1914C, C-3223T) and one novel short tandem repeat [(CAAAA)(5-7)-3600]. The two common promoter region SNPs T-1914C and C-3223T as well as six known coding SNPs in the IL4RA gene were genotyped in healthy blood donors by PCR with sequence-specific primers; total sIL4R levels were measured by ELISA. Results revealed a highly significant association of the -3223T variant with lowered sIL4R levels (two-tailed t-test, P=0.0002). Results remained highly significant after Bonferroni adjustment for multiple comparisons (P=0.0017). Moreover, the C-3223T variant was found to be in strong linkage disequilibrium with the extracellular 150V variant (P<0.001), which was recently described to be associated with atopic asthma in a Japanese population. Since this novel IL4RA promoter region SNP is common (allele frequency 29.8%), we conclude that it may be of importance for the genetic regulation of the IL-4 signalling pathway.

Aim: Deficiency in collectins is discussed as a risk factor for pulmonary and systemic infections in children and adults. The objective of this study was to determine serum concentrations of surfactant protein D (SP‐D) and mannose‐binding lectin (MBL) in preterm and term infants at birth. Methods: 47 preterm infants below 32 wk gestational age (GA) and 19 healthy, term newborn infants at birth have been included in the study, and SP‐D as well as MBL concentrations have been determined in umbilical cord blood samples using sandwich ELISA technique. In addition, SP‐D concentrations were assessed in tracheal aspirates (TA) of 24 mechanically ventilated preterms and in infants without pulmonary complications before elective surgery. Results: MBL serum concentrations were significantly lower in preterms <32 wk GA (756.7 ng/ml; 14.6–11 184 ng/ml) compared to term newborns (3168.9 ng/ml; 282.3–7679.5 ng/ml; p=0.005; median and range, respectively). Serum SP‐D concentrations were significantly decreased in preterms between 28 and 32 wk GA (1.4 ng/ml; 0–4.6 ng/ml; n=26) compared to term infants (2.2 ng/ml; 1.2–3.3 ng/ml; p=0.05) and were found to positively correlate with history of antenatal corticosteroids and chorioamnionitis. SP‐D concentrations in TA were increased in preterm infants between 28 and 32 wk GA with respiratory distress syndrome (RDS) (25.0 ng/ml; 0.9–44.7 ng/ml; n=12) compared to control subjects (6.6 ng/ml; 0.5–30.4 ng/ml; n=12) in contrast to extremely immature infants <28 wk GA suffering from RDS (4.4 ng/ml; 0.8–78.4 ng/ml; n=12). Conclusion: In preterm infants, significant changes occur in collectin umbilical cord blood concentrations and pulmonary SP‐D levels. Functional aspects of these findings need to be addressed further.

Evidence from in vitro studies suggests that immunosuppressive drugs interfere with key functions of dendritic cells (DCs), but the in vivo relevance of these findings is elusive. We prospectively analyzed the major DC precursor subsets in the blood of kidney transplant recipients on long-term immunosuppression (> or =1 year). A total of 87 patients were compared to 87 age- and sex-matched controls. Total DC numbers and the precursor subsets, myeloid type 1 DCs, myeloid type 2 DCs (mDC1, mDC2) and plasmacytoid DCs (pDCs) were identified by four color flow cytometry. Long-term immunosuppression was associated with significant reduction of all major DC subsets in comparison to healthy controls (mDC1 p < 0.001; mDC2 p < 0.0001; two-tailed Mann-Whitney U-test) with the strongest negative impact on pDCs (p < 0.00001). In contrast, total leukocyte numbers were not significantly affected. Analysis of the relative impact of different agents revealed a significant impact of prednisolone on pDCs (p = 0.009) and mDCs2 (p = 0.006). The functional relevance of pDC deficiency was confirmed independently by Interferon-alpha analysis after Toll-like receptor 7 (p < or = 0.001) and 9 (p < 0.05) stimulation. These results indicate for the first time a profound negative impact of long-term immunosuppression on major DC subsets in kidney transplant recipients. DC deficiency may have important implications with respect to viral infections and tumor development.