Increased serum PCSK9, a potential biomarker to screen for periodontitis, and decreased total bilirubin associated with probing depth in a Japanese community survey.

BACKGROUND AND OBJECTIVES: Previous reports suggest that several serum biomarkers play roles in the pathogenesis, inflammatory response, and oxidative stress in periodontitis caused by bacterial infections, linking chronic periodontitis to atherosclerotic vascular disease (ASVD). The aim of this preliminary study was to investigate, in a Japanese cross-sectional community survey, potential serum biomarkers of periodontitis that are associated with ASVD and chronic periodontitis. MATERIAL AND METHODS: The study cohort included a total of 108 male subjects who underwent annual health examinations. Serum biomarkers (high-sensitivity C-reactive protein [hs-CRP], proprotein convertase subtilisin/kexin type 9 [PCSK9], interleukin-6, tumor necrosis factor-α, soluble CD14, myeloperoxidase, matrix metalloproteinase-3, adiponectin, total bilirubin [TBIL], and serum lipids) were analyzed to determine their association (if any) with periodontal parameters. Aortic stiffness was evaluated using the brachial-ankle aortic pulse wave velocity (PWV) index and the cardio-ankle vascular index (CAVI). RESULTS: The concentrations of PCSK9 and hs-CRP were increased (P = .001 and .042, respectively), and the concentration of TBIL was decreased (P = .046), in subjects with periodontal disease (determined as a probing depth of ≥4 mm in at least one site) compared with periodontally healthy subjects. The ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol and the concentrations of triglycerides, remnant-like particles-cholesterol, and oxidized LDL were elevated in subjects with periodontal disease compared with periodontally healthy subjects (P = .038, .007, .002, and .049, respectively). Multivariate regression analyses indicated that the number of sites with a pocket depth of ≥4 mm was associated with the concentration of PCSK9 and inversely associated with the concentration of TBIL independently (standardized ß = .243, P = .040; standardized ß = -.443, P = .0002; respectively). Analysis of receiver operating characteristic curves of PCSK9 indicated moderate accuracy for predicting the presence of disease sites (probing depth ≥ 4 mm) (area under the curve = 0.740). No significance in the values of PWV and CAVI was observed between subjects with periodontal disease and periodontally healthy subjects. CONCLUSION: In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters. Moreover, PCSK9 could be a candidate biomarker for diagnosing chronic periodontitis, and may also have potential to evaluate the risk for periodontitis to cause ASVD. Longitudinal studies of larger populations are necessary to confirm the exact association of periodontitis with increased serum PCSK9 and decreased TBIL.

Synovial mesenchymal stem cells from osteo- or rheumatoid arthritis joints exhibit good potential for cartilage repair using a scaffold-free tissue engineering approach.

OBJECTIVE: To assess whether synovial mesenchymal stem cells (SMSCs) from patients with osteoarthritis (OA) or rheumatoid arthritis (RA) can be used as an alternative cell source for cartilage repair using allogenic tissue engineered construct (TEC). METHODS: Twenty-five patients (17 female, average age 61.8 years) were divided according to their pathology (control trauma group; N = 6, OA group; N = 6) and RA patients were subdivided into two groups to evaluate the impact of biologics in accordance with whether treated with biologics [Bio(+)RA; N = 7] or not [Bio(-)RA; N = 6]. We compared the following characteristics among these groups: (1) The cell proliferation capacity of SMSCs; (2) The influence of passage number on features of SMSCs; (3) The weight and volume of TEC from the same number of SMSCs; (4) Inflammatory cytokine gene expressions levels of TEC; (5) The chondrogenic potential of TEC; and (6) Osteochondral repair using TEC in athymic nude rats. RESULTS: SMSCs from the four groups exhibited equivalent features in the above evaluation items. In in vivo studies, the TEC-treated repair tissues for all groups exhibited significantly better outcomes than those for the untreated group and no significant differences among the four TEC groups. CONCLUSION: SMSCs from OA or RA patients are no less appropriate for repairing cartilage than those from trauma patients and thus, may be an effective source for allogenic cell-based cartilage repair.

Relationships between IL-6 gene polymorphism, low BMD and periodontitis in postmenopausal women.

OBJECTIVE: IL-6 plays critical roles in bone resorption and the pathogenesis of periodontitis in both inflammation and alveolar bone loss. A negative correlation was observed between periodontitis and truncal bone mineral density (BMD) in postmenopausal women. The C allele carriers of a genetic polymorphism IL-6-572G/C have higher levels of serum IL-6 compared to G allele carriers. We investigated the possible effect of IL-6-572G/C polymorphism on the relationship between low BMD and periodontitis in postmenopausal women. SUBJECTS AND METHODS: A total of 300 postmenopausal Japanese women who lived in Yokogoshi area of Niigata City, Japan, participated in this study. Genomic DNA was extracted from peripheral blood. The IL-6-572G/C genotypes were determined by the restriction fragment length polymorphism method. Bone mineral density (BMD) of right femoral neck and serum bone metabolism markers were measured. Low BMD was defined to have the BMD<80% of the mean for young adults. Periodontal parameters at two sites per tooth were measured. RESULTS: Serum osteocalcin levels were significantly lower in the IL-6-572G/G genotype (p=0.025). In the -572G allele non-carriers, percentages of PPD≥4mm sites were significantly higher in low BMD group compared with the healthy control group (p=0.021). Logistic regression analysis revealed low BMD to be associated with periodontitis (Odds ratio=1.736, p=0.027) after adjusted with IL-6-572G carriage, age, serum albumin level. CONCLUSIONS: IL-6-572G/C polymorphism was not an independent risk factor of low BMD or periodontitis, but may affect the relationship between the two diseases in postmenopausal Japanese women.

Theoretical analysis of magnetically propelled microrobots in the cardiovascular system.

The field of medical microrobotics is rapidly progressing; however, it is particularly challenging to control microrobots inside blood vessels. In this paper, the magnetic propulsion of a microrobot in pulsating flow is investigated. Regarding this task, the advantages of a reduced blood flow velocity are examined. The required magnetic field gradient in relation to the size of the microrobot is theoretically analyzed and compared to that for propulsion during reduced blood flow velocity. Quantitative and qualitative advantages together with the practical challenges are discussed.

Peroxisome proliferator-activated receptor (PPAR) γ polymorphism, vitamin D, bone mineral density and periodontitis in postmenopausal women.

OBJECTIVES: PPARg regulates bone metabolism and inflammation. Our previous study suggested PPARg Pro12Ala polymorphism to represent a susceptibility factor for periodontitis in pregnant Japanese women. Several recent papers have drawn attention to a possible link between low bone mineral density (BMD) and periodontitis in postmenopausal women. Since the pathogenesis for both involve bone remodeling, they might share common risk factors such as gene polymorphisms and vitamin D level. The present study investigated possible associations between the PPARgPro12Ala polymorphism, periodontitis, BMD and serum 25(OH)D in postmenopausal Japanese women. MATERIALS AND METHODS: PPARgPro12Ala genotypes of 359 women were determined by PCR-RFLP. BMD and periodontal parameters of each woman were measured. Serum 25(OH)D levels were determined by radioimmunoassay. RESULTS: PPARgPro12Ala polymorphism was not associated with periodontitis or BMD as an independent factor. Serum 25(OH)D was significantly higher in Ala allele carriers compared to non-carriers. Only in the Ala allele carriers, positive correlations were found between mean clinical attachment level and BMD, between BMD and 25(OH)D, and between percentage of sites with probing depth ≥ 4 mm and 25(OH)D. CONCLUSIONS: PPARgPro12Ala polymorphism was not independently associated with periodontitis or BMD. However, the polymorphism might be a modulator of the relationship between the two conditions in postmenopausal Japanese women.

FcγRIIB-nt645+25A/G gene polymorphism and periodontitis in Japanese women with preeclampsia.

FcγRIIB contains a unique immunoreceptor tyrosine-based inhibition motif (ITIM) and functions as a negative feedback regulator of leucocyte activation and antibody production. We have previously reported FcγRIIB-nt645+25A/G gene polymorphism to be associated with prevalence and severity of periodontitis, FcγRIIB expression level on peripheral B lymphocytes and the serum IgG level against periodontopathic bacteria. Previous studies have reported maternal periodontal disease to be associated with an increased risk for preeclampsia. Therefore, FcγRIIB-nt645+25A/G gene polymorphism may be associated with preeclampsia by affecting immune response to periodontopathic bacteria in pregnant women. To elucidate whether FcγRIIB-nt645+25A/G gene polymorphism has associations with preeclampsia and/or periodontitis in pregnant Japanese women, a case-control study was carried out on women with preeclampsia (n = 13) and without preeclampsia (n = 106). Maternal periodontal parameters and bacterial data of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in subgingival plaque were collected within 5 days of delivery. FcγR genotypes of each woman were determined using the genomic DNA isolated from peripheral blood. Serum IgG levels specific for each bacteria were determined. There was a significant association between FcγRIIB-nt645+25A/G polymorphism and preeclampsia (P = 0.013). The frequency of the FcγRIIB-nt645+25AA genotype was higher in the preeclampsia group compared with the nonpreeclampsia group (P = 0.007). The DNA level of A. actinomycetemcomitans from subgingival plaque was shown to be higher in the preeclampsia group (P = 0.017). In conclusion, maternal FcγRIIB-nt645+25A/G polymorphism and subgingival DNA level of A. actinomycetemcomitans were significantly associated with the prevalence of preeclampsia in a limited number of Japanese women independently with periodontal infection. Further investigations should be performed to confirm this association in a larger population and to determine the biological process of the association.

Association of the FcγRIIB-nt645+25A/G polymorphism with the expression level of the FcγRIIb receptor, the antibody response to Porphyromonas gingivalis and the severity of periodontitis.

BACKGROUND AND OBJECTIVE: Human FcγRIIb is an immunoglobulin G (IgG) receptor that inhibits the activation of B lymphocytes through cross-linking with the B-cell receptor via immune complexes. This function acts as a negative regulator of antibody production. Our previous studies have demonstrated the gene polymorphisms in FcγRIIb to be associated with periodontitis. In this study, we presented a polymorphism--FcγRIIB-nt645+25A/G (rs2125685)--in intron 4 and analyzed its functional relevance to periodontitis. We examined whether the FcγRIIB-nt645+25A/G polymorphism is associated with periodontal parameters, the IgG response to the periodontopathic bacterium Porphyromonas gingivalis and/or the expression level of FcγRIIb on peripheral B lymphocytes. MATERIAL AND METHODS: Thirty-two patients with chronic periodontitis were genotyped with nested PCR and by direct sequencing of genome DNA. The levels of serum IgG and of specific IgG subclasses for P. gingivalis sonicate and for the recombinant 40-kDa outer membrane protein (OMP) were determined. The expression levels of FcγRIIb on peripheral B lymphocytes from 19 healthy donors were measured by flow cytometry. RESULTS: Patients with the FcγRIIB-nt645+25AA genotype showed significantly higher mean clinical attachment levels compared to patients with the FcγRIIB-nt645+25GG genotype (p = 0.003) and a significantly lower IgG response to P. gingivalis sonicate and to the 40-kDa OMP. The expression levels of FcγRIIb protein on the cell surface in peripheral B lymphocytes were higher in healthy donors with the FcγRIIB-nt645+25AA genotype than in those with the FcγRIIB-nt645+25GG genotype (p = 0.03). CONCLUSION: The higher expression levels of FcγRIIb in subjects with the FcγRIIB-nt645+25AA genotype may induce a lower level of production of IgG against P. gingivalis and therefore more severe periodontitis.

FcγRIIB polymorphisms, periodontitis and preterm birth in Japanese pregnant women.

BACKGROUND AND OBJECTIVE: Recently, numerous studies have investigated the association of preterm birth with periodontitis. FcγRIIb is a human low-affinity receptor for immunoglobulin G (IgG). We have previously demonstrated single nucleotide polymorphisms (SNPs) of FcγRIIb to be associated with periodontitis and the serum-specific IgG level against periodontopathic bacteria. In this study, we investigated whether FcγRIIB gene polymorphisms were associated with periodontitis and/or pregnancy outcome. MATERIAL AND METHODS: We assessed the periodontal conditions of 122 Japanese pregnant women within 5 d of delivery, and polymorphisms in FcγRIIB and in other Fcγ receptors were detected from the genomic DNA. Using clinical and genomic data, we analyzed the relationship between periodontitis, preterm birth and Fcγ receptor polymorphisms. RESULTS: A significant difference was observed in the distribution of FcγRIIB-nt645+25A/G (rs2125685) between preterm and term birth groups, with a higher prevalence of nt645+25AA in the preterm birth group (p = 0.032). Additionally, the FcγRIIB-nt645+25GG carrier showed significantly higher results for the prevalence of periodontitis (p = 0.048), mean pocket depth (p = 0.021), mean clinical attachment level (p = 0.010), percentage of sites with pocket depth ≥ 4 mm (p = 0.005) and percentage of sites with clinical attachment level ≥ 3 mm (p = 0.007) than the AA carrier. An association between preterm birth and periodontitis was not observed in this study. CONCLUSION: These findings suggest that FcγRIIB-nt645+25AA carriers are more likely to experience preterm birth than FcγRIIB-nt645+25AG and GG carriers. Also, women with FcγRIIB-nt645+25G exhibited a greater tendency to have periodontitis than those with nt645+25A.

Electromagnetic drive of microrobot geometrically constrained in blood vessel.

We propose new electromagnetic actuation of a microrobot by utilizing geometric constraints in a blood vessel. In our concept, a microrobot travels in a vascular network while keeping the contact to the vascular wall. In the paper, forces working on the microrobot are modeled in two dimensions, and conditions to propel the microrobot while pushing it against the vascular wall are described. The design of the microrobot composed of three permanent magnets is also presented. The feasibility of the 2D actuation of the microrobot was confirmed using an experimental setup composed of four pairs of coils generating both uniform magnetic fields and uniform magnetic field gradients. Finally, the model was extended to 3D in order to investigate 3D actuation of the microrobot.

Microsurgical skill assessment: toward skill-based surgical robotic control.

A surgical skill assessment system was developed to quantify microsurgical skills. Infrared optical makers, an inertial measurement unit, and strain gauges were mounted on tweezers to record surgical tasks. In preliminary experiments, the tool tip trajectory, acceleration, and applied force were measured and microsurgery videos were evaluated by three expert surgeons. The preliminary results indicated the feasibility of the system by showing the significant difference between unskilled and skilled surgeons.

Lower antibody response to Porphyromonas gingivalis associated with immunoglobulin G Fcgamma receptor IIB polymorphism.

BACKGROUND AND OBJECTIVE: Human FcgammaRIIB is one of the receptors for immunoglobulin G (IgG) and suppresses the activation of B lymphocytes through cross-linking with the B cell receptor via immune complexes. This function of FcgammaRIIB is essential for the negative regulation of antibody production. Our previous study has demonstrated the gene polymorphism FcgammaRIIB-I232T to be associated with periodontitis. The polymorphism FcgammaRIIB-232T has been reported to inhibit B-cell antigen receptor signaling more effectively compared to FcgammaRIIB-232I, while other groups concluded that FcgammaRIIB-232T had no ability to inhibit activatory receptors. In this study, we examined whether FcgammaRIIB-I232T polymorphism would change the IgG antibody response to the periodontopathic bacteria Porphyromonas gingivalis. MATERIAL AND METHODS: Forty-seven patients with periodontitis were genotyped with the direct sequencing of genome DNA. Serum IgG and specific IgG subclass levels for the sonicate of P. gingivalis and the recombinant 40 kDa outer membrane protein (OMP) were determined. RESULTS: No significant difference in the total IgG level and IgG response to P. gingivalis sonicate were observed between sera from FcgammaRIIB-232T carriers and non-carriers. The FcgammaRIIB-232T carriers revealed a significantly lower IgG(2) response to P. gingivalis 40 kDa OMP compared to non-carriers (p = 0.04, Mann-Whitney U-test). Lower responses of FcgammaRIIB-232T carriers were also observed in specific IgG and IgG(1) levels. The FcgammaRIIB-232T carriers revealed a low level of IgG(2) response to P. gingivalis 40 kDa OMP, even with a high average probing pocket depth. CONCLUSION: These results suggest that association of the FcgammaRIIB-232T allele with periodontitis might be related to the lower levels of antibody response to P. gingivalis.

Control of fracture reduction robot using force/torque measurement.

We have developed a surgical robotic system for femoral fracture reduction employing indirect traction. Indirect traction in fracture reduction is a generally used surgical method for preventing complications such as bone splits caused by high stress on bones. For traction, a patient's foot is gripped by a jig and pulled to the distal side. Indirect traction has the advantage of distributing bone stress by utilizing a strong traction force; however, this procedure does not accurately control the proper positioning of fractured fragments when a surgical robot is used. The human leg has knee and an ankle joints, and thus robotic motion presents problems in not being able to directly propagate reduction motion to a fractured femoral fragment, rendering control of bone position difficult. We propose a control method for fracture reduction robots using external force/torque measurements of the human leg to achieve precise fracture reduction. Results showed that the proposed method reduced repositioning error from 6.8 mm and 15.9 degrees to 0.7 mm and 5.3 degrees, respectively.

The FcgammaRIIa polymorphism influences production of interleukin-1 by mononuclear cells.

The functional bi-allelic polymorphism of immunoglobulin G (IgG) Fc receptor (FcgammaR) IIa influences the efficiency of human IgG2 binding. Our previous study showed that the high affinity FcgammaRIIa genotype (-H/H131) was associated with periodontitis risk. As interleukin-1 (IL-1) is one of the major causes of periodontal tissue destruction, it is hypothesized that the FcgammaRIIa-H/H131cross-linking could induce an increased IL-1 release by mononuclear cells. In this study, we evaluated the intracellular expressions of IL-1beta in CD14 positive cells upon stimulation with human IgG2 by flow cytometry. FcgammaRIIa-H/H131 subjects exhibited a higher percentage of IL-1beta-producing cells than FcgammaRIIa-R/H131 and -R/R131 subjects (P < 0.05). These results support the concept that FcgammaRIIa genotype may affect IL-1beta production, possibly leading to interindividual differences in periodontitis risk.

Quantitative evaluation of the effect of visually-induced motion sickness using causal coherence function between blood pressure and heart rate.

To evaluate the effect of visually-induced motion sickness on the human, blood pressure variability (BP) and heart rate variability (HR) of 51 normal subjects watching a 15min-long video image taken by a vibrating handy camera were analyzed. Not only coherence function (K/sup 2/) between BP and HR but also two causal coherence functions: K/sup 2//sub BP-->HR/ from BP to HR and K/sup 2//sub HR-->BP/ from HR to BP were introduced to divide causal linearity of the cardiovascular system regarded as a closed-loop system. K/sup 2/ represents total linearity of the system. K/sup 2//sub BP-->HR/ and K/sup 2//sub HR-->BP/ correspond to the baroreflex system and the mechanical hemodynamics, respectively. The results revealed that K/sup 2//sub BP-->HR/ at the Mayer wave-band (around 0.1 Hz) of the subjects prone to motion sickness decreased gradually and was significantly lower than that of the subjects not prone to in later scenes. This result has never been obtained from conventional methods dealing with a cardiovascular system as an open-loop system.

FcgammaRIIB gene polymorphisms in Japanese periodontitis patients.

Human type II low-affinity receptor for immunoglobulin G (FcgammaRII) constitutes a clustered gene family consisting of FcgammaRIIA, IIB and IIC genes. FcgammaRIIB is unique in its ability to transmit inhibitory signals in B cells via immunoreceptor tyrosine-based inhibitory motif (ITIM). B-cell activation and subsequent elevated production of IgG are the immunopathological features of inflammatory disease such as periodontitis. To determine whether an association with periodontitis susceptibility exists, genetic polymorphisms of FcgammaRIIB were examined in Japanese patients with aggressive periodontitis (AGP) and chronic periodontitis (CP), and in the race-matched healthy controls (HCs). A significant difference was observed in the distribution of FcgammaRIIB-232I/T allele (exon 5) between the AGP and HC groups, with enrichment of the 232T in the AGP group (P=0.006). In addition, the FcgammaRIIB-nt 646-184A/G allele (intron 4) distribution was significantly different between the CP and HC groups, with enrichment of the nt 646-184A in the CP group (P=0.011). These results document the association of FcgammaRIIB gene polymorphisms with susceptibility to periodontitis in the Japanese.

The Fc gamma receptor genotype as a severity factor for chronic periodontitis in Japanese patients.

BACKGROUND: Functional polymorphisms of immunoglobulin G (IgG) Fc receptors (Fc gamma R) have been shown to be associated with generalized aggressive periodontitis (GAgP) or recurrence of chronic periodontitis (CP) in Japanese patients. The purpose of this study was to evaluate whether Fc gamma R polymorphisms are also associated with severity of CP. METHODS: Fifty Japanese non-smoking patients with severe CP and 39 Japanese non-smoking patients with moderate CP were identified according to established clinical criteria, including measurements of probing depth (PD), clinical attachment level (CAL), and alveolar bone loss (BL). Fc gamma R genotypes for 3 bi-allelic polymorphisms (Fc gamma RIIa-R/H131, Fc gamma RIIIa-158V/F, Fc gamma RIIIb-NA1/NA2) were determined in these CP patients and 64 race-matched, non-smoking healthy controls by means of allele-specific polymerase chain reactions. RESULTS: There was a significant over-representation of Fc gamma RIIIa-158V allele in severe CP patients compared to moderate CP patients (odds ratio 2.03, 95% confidence interval [CI] 1.03-4.01, chi 2 = 4.86, P = 0.028). In addition, we found a strong association between CP severity and Fc gamma R composite genotype comprising Fc gamma RIIIa-158V plus Fc gamma RIIIb-NA2 (severe CP versus moderate CP: odds ratio 4.69, 95% CI 1.52-15.10, chi 2 = 9.35, P = 0.002; severe CP versus healthy controls: odds ratio 4.10, 95% CI 1.62-10.59, chi 2 = 11.13, P = 0.0009). Moreover, CP patients positive for the composite genotype exhibited more severe signs of periodontitis than composite genotype-negative individuals (positive versus negative; mean PD: 3.8 mm versus 3.2 mm, P = 0.005; mean CAL: 4.5 mm versus 3.7 mm, P = 0.005; mean % BL: 37.6% versus 29.9%, P = 0.008). CONCLUSION: Our results document the Fc gamma RIIIa-158V allele and possibly Fc gamma RIIIb-NA2 to be associated with severity of CP in Japanese patients.

Elevated mRNA expression for supervillin and vascular endothelial growth factor in human neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis.

Differential gene expression was examined in human neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis (P. gingivalis-LPS) using RNA fingerprinting by arbitrarily primed polymerase chain reaction (RAP-PCR). LPS from Escherichia coli (E. coli-LPS) was used as control. More than 200 differently expressed transcripts were found in 8 subjects showing differential regulation at the transcriptional level. Densitometric analyses revealed that 42-100 genes were upregulated, while 53-116 genes were downregulated by P. gingivalis-LPS compared with E. coli-LPS. The results of sequencing identification showed the presence of supervillin (SVIL) and vascular endothelial growth factor (VEGF) genes in the clones which were upregulated by P. gingivalis-LPS. Consequently, semiquantitative analyses proved that the level of mRNA for SVIL and VEGF were significantly higher in P. gingivalis-LPS-stimulated neutrophils than in other bacterial (E. coli, Actinobacillus actinomycetemcomitans, Prevotella intermedia) LPS- or synthetic lipid A-stimulated neutrophils. Our findings suggest that an elevated mRNA expression for SVIL could be associated with impaired function of neutrophils when stimulated by P. gingivalis-LPS. Further, the VEGF mRNA over-expression might be related to the pathogenesis of P. gingivalis-associated periodontitis. The RAP-PCR technique used in this study enabled us to identify a number of P. gingivalis-LPS regulated genes which hitherto have not been reported.

Evidence for a novel polymorphism affecting both N-linked glycosylation and ligand binding of the IgG receptor IIIB (CD16).

Immunoglobulin G Fc receptor IIIb (FcgammaRIIIb) is constitutively expressed on neutrophils, and has three allelic forms: FcgammaRIIIb-NA1, FcgammaRIIIb-NA2, and FcgammaRIIIb-SH. We identified two Japanese subjects in whom an A to G substitution at nt 221 changes asparagine (N) to serine (S) at amino acid position 45 in the FcgammaRIIIb-NA2 gene. FcgammaRIIIb-NA2-specific monoclonal antibodies (GRM1 and PEN1) did not bind to mutant neutrophils, which lack an N-linked glycosylation site. Furthermore, IgG3-mediated neutrophil phagocytosis by mutant was slightly increased as compared to wild-type donors (Note).

Increased frequency of FcgammaRIIIb-NA1 allele in periodontitis-resistant subjects in an elderly Japanese population.

Many elderly people show minimum periodontal tissue destruction, which might be partly due to genetic advantages in host immune response against periodontopathic bacteria. The human IgG Fc receptor IIIb on neutrophils bears a NA1-NA2 polymorphism. The FcgammaRIIIb-NA1 displays a more efficient interaction with IgG1- and IgG3-opsonized bacteria, compared with the FcgammaRIIIb-NA2. We investigated a 70-year-old Japanese population (n = 599) to determine whether the FcgammaRIIIb polymorphism was associated with resistance to periodontitis. Among subjects with > or = 20 teeth present, periodontitis-resistant (n = 46) and periodontitis-susceptible groups (n = 73) were selected based on the percentage of sites with > or = 4 mm probing attachment loss in the entire dentition. The FcgammaRIIIb-NA1 allotype was overrepresented in the periodontitis-resistant group, compared with the periodontitis-susceptible group (chi2 = 4.89, p = 0.03, odds ratio = 1.87, 95% CI, 1.07 to 3.28). This suggests that FcgammaRIIIb-NA1 may be associated with resistance to periodontitis.

Effective in vitro clearance of Porphyromonas gingivalis by Fc alpha receptor I (CD89) on gingival crevicular neutrophils.

Porphyromonas gingivalis has been implicated as a causative pathogen in periodontitis. Immunotherapeutic approaches have recently been suggested to aid in the clearance of P. gingivalis from disease sites. Because antibody-Fc receptor (FcR) interactions play a role in the effector functions of polymorphonuclear neutrophils (PMN), we evaluated which FcR on PMN from gingival crevicular fluid (GCF) serves as an optimal target molecule for FcR-directed immunotherapy. GCF PMN and peripheral blood (PB) PMN from adult periodontitis patients were analyzed for their immunoglobulin G (IgG) and IgA FcR (Fc gamma R and Fc alpha R, respectively) expression and function by studying IgG- and IgA-mediated elimination of P. gingivalis. GCF PMN exhibited higher Fc alpha RI and Fc gamma RI levels and lower Fc gamma RIIa and Fc gamma RIIIb levels than PB PMN. Functional studies revealed that GCF PMN exhibited less of a capacity to phagocytose and kill IgG1-opsonized P. gingivalis than PB PMN. IgA1-mediated phagocytosis and killing capacity was, however, comparable between GCF PMN and PB PMN. In summary, these in vitro results document that Fc alpha RI represents a candidate target for FcR-directed immunotherapy for the clearance of P. gingivalis.