Objective. Human low-affinity Fc␥ receptors (Fc␥R) constitute a clustered gene family located on chromosome 1q23, that consists of Fc␥RIIA, IIB, IIC, IIIA, and IIIB genes. Fc␥RIIB is unique in its ability to transmit inhibitory signals, and recent animal studies demonstrated a role for Fc␥RIIB deficiency in the development of autoimmunity. Genetic variants of Fc␥RIIA, IIIA, and IIIB and their association with systemic lupus erythematosus (SLE) have been extensively studied in various populations, but the results were inconsistent. To examine the possibility that another susceptibility gene of primary significance exists within the Fc␥R region, we screened for polymorphisms of the human FCGR2B gene, and examined whether these polymorphisms are associated with SLE.Methods. Variation screening of FCGR2B was performed by direct sequencing and polymerase chain reaction (PCR)-single-strand conformation polymorphism methods using complementary DNA samples. Genotyping of the detected polymorphism was done using genomic DNA, with a specific genotyping system based on nested PCR and hybridization probing. Association with SLE was analyzed in 193 Japanese patients with SLE and 303 healthy individuals. In addition, the same groups of patients and controls were genotyped for the previously known polymorphisms of FCGR2A, FCGR3A, and FCGR3B. Results. We detected a single-nucleotide polymorphism in FCGR2B, (c.695T>C), coding for a nonsynonymous substitution, Ile232Thr (I232T), within the transmembrane domain. The frequency of the 232T/T genotype was significantly increased in SLE patients compared with healthy individuals. When the same patients and controls were also genotyped for FCGR2A-131R/H, FCGR3A-176V/F, and FCGR3B-NA1/2 polymorphisms, FCGR3A-176F/F showed significant association. Two-locus analyses suggested that both FCGR2B and FCGR3A may contribute to SLE susceptibility, while the previously reported association of FCGR3B was considered to be secondary and derived from strong linkage disequilibrium with FCGR2B.Conclusion. These results demonstrate the association of a new polymorphism of FCGR2B (I232T) with susceptibility to SLE in the Japanese.Results of genome-wide linkage studies have suggested that the chromosomal region 1q23 is one of the strongest candidate regions for human systemic lupus erythematosus (SLE) (1,2), as well as its syntenic region in murine lupus (3). Three Fc␥ receptor type II

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While nasopharyngeal sampling is the gold standard for the detection of Streptococcus pneumoniae carriage, historically seen, saliva sampling also seems highly sensitive for pneumococcal detection. We investigated S. pneumoniae carriage in saliva from fifty schoolchildren by conventional and molecular methods. Saliva was first culture-enriched for pneumococci, after which, DNA was extracted from all bacterial growth and tested by quantitative-PCR (qPCR) for pneumococcus-specific genes lytA and piaA. Next, serotype composition of the samples was determined by serotype-specific qPCRs, conventional-PCRs (cPCR) and sequencing of cPCR amplicons. Although only 2 (4%) of 50 samples were positive by conventional diagnostic culture, 44 (88%) were positive for pneumococci by qPCR. In total, we detected the presence of at least 81 pneumococcal strains representing 20 serotypes in samples from 44 carriers with 23 carriers (52%) positive for multiple (up to 6) serotypes. The number of serotypes detected per sample correlated with pneumococcal abundance. This study shows that saliva could be used as a tool for future pneumococcal surveillance studies. Furthermore, high rates of pneumococcal carriage and co-carriage of multiple pneumococcal strains together with a large number of serotypes in circulation suggests a ubiquitous presence of S. pneumoniae in saliva of school-aged children. Our results also suggest that factors promoting pneumococcal carriage within individual hosts may weaken competitive interactions between S. pneumoniae strains.

Both IgG and IgA Abs have been implicated in host defense against bacterial infections, although their relative contributions remain unclear. We generated a unique panel of human chimeric Abs of all human IgG and IgA subclasses with identical V genes against porin A, a major subcapsular protein Ag of Neisseria meningitidis and a vaccine candidate. Chimeric Abs were produced in baby hamster kidney cells, and IgA-producing clones were cotransfected with human J chain and/or human secretory component. Although IgG (isotypes IgG1–3) mediated efficient complement-dependent lysis, IgA was unable to. However, IgA proved equally active to IgG in stimulating polymorphonuclear leukocyte respiratory burst. Remarkably, although porin-specific monomeric, dimeric, and polymeric IgA triggered efficient phagocytosis, secretory IgA did not. These studies reveal unique and nonoverlapping roles for IgG and IgA Abs in defense against meningococcal infections.

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Objective Fc receptors for IgG (FcγR) play a prominent role in the clearance of immune complexes in systemic lupus erythematosus (SLE). Polymorphisms of FcγR have been proposed as genetic factors that influence susceptibility to SLE. We analyzed 3 functional FcγR polymorphisms in a strictly Caucasian population of SLE patients, and determined the influence of these polymorphisms on the clearance of immune complexes in vivo. Methods Genomic DNA was isolated from 230 Caucasian patients with SLE and 154 controls. Amplification of FcγR‐genomic regions in allotype‐specific polymerase chain reactions was used to distinguish the genotypes. In addition, we analyzed the FcγR genotypes of 13 patients with SLE who participated in a study determining the half‐life of IgG‐coated erythrocytes in the blood. Results We found a strong trend toward skewing of FcγRIIa, with an enrichment of the homozygous FcγRIIa‐R/R131 genotype in patients compared with controls. We did not find a correlation between this genotype and the development of lupus nephritis. However, we established that the half‐life of IgG‐coated erythrocytes in the blood was prolonged in patients expressing the FcγRIIa‐R/R131 genotype. The homozygous FcγRIIIa‐F/F158 genotype was found more frequently in patients with arthritis and/or serositis. Conclusion In Caucasian populations, the R/H polymorphism of FcγRIIa is a minor determinant in susceptibility to SLE, whereas the V/F polymorphism of FcγRIIIa is associated with a set of disease manifestations. Notably, the R/H polymorphism of FcγRIIa affects the clearance of immune complexes in vivo, which may influence the course of a disease such as SLE.

Despite a strict control program for methicillin-resistant Staphylococcus aureus (MRSA) in human medicine in the Netherlands, MRSA was cultured from exudative epidermitis lesions of 4 piglets on a breeding farm, 20 pigs on a supplier farm, and 2 workers on these farms. The MRSA strains were indistinguishable, suggesting direct transmission.

Human IgG receptors (FcgammaR) display considerable heterogeneity, and are crucial immune response modulating molecules. FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB display functional biallelic polymorphisms. FcgammaR polymorphisms have been found associated with susceptibility to infectious and autoimmune diseases. Linked transmission of FcgammaR alleles was studied by determining the distribution of FcgammaRIIA-FcgammaRIIIA-FcgammaRIIIB genotype combinations in 514 Dutch Caucasian, and 149 Japanese blood donors. The structure of the FcgammaR locus was studied by radiation hybrid mapping of FcgammaRIA, FcgammaRIIA, FcgammaRIIB, FcgammaRIIIA, FcgammaRIIIB, and adjacent genes from the pentraxin family. In addition, crossing-over frequencies within the FcgammaR locus were determined in 63 Dutch Caucasian families, encompassing 183 individuals. FcgammaRII and FcgammaRIII subclasses were mapped in close proximity (0.47-3.14 cR). Accordingly, crossing-over frequencies within the FcgammaRII-III locus in Dutch families were low. Analysis of combined FcgammaR genotypes strongly suggested non-random distribution of FcgammaRIIA-FcgammaRIIIA-, and FcgammaRIIIA-FcgammaRIIIB genotypes in Dutch donors (P<0.001 and P<0.00001, respectively), and of FcgammaRIIA-FcgammaRIIIb genotypes in Japanese blood donors (P<0.02). Frequencies of FcgammaRII-FcgammaRIII haplotypes differed significantly between Dutch and Japanese (P<0.00001). This study provides important information for the interpretation of studies reporting associations of FcgammaR alleles with disease, and underscores the apparent differences in FcgammaR heterogeneity between ethnic groups.