The clinical and immunological patterns of this unique chronic infectious disease clearly demonstrate a continuous scale of changes in histological lesions. Disease classification is defined within two poles (tuberculoid to lepromatous) with transitions between these clinical forms. While typical epithelioid

macrophages predominate at the paucibacillary tuberculoid pole of the disease, inactivated foamy macrophages predominate at the lepromatous end [1]. In lepromatous leprosy (LL), the lack of systemic inflammatory signals and corresponding local ones strongly indicates that a complex anti-inflammatory network is at work. In this regard, neuroendocrine system involvement, in conjunction with the existence of multiple suppressive pathways under the control of the innate and adaptive immune learn more response, has been reported [2-7]. We have suggested that IDO may play a role in a hitherto unknown suppressive mechanism in leprosy [6]. It has also been reported that accumulated oxidized host phospholipids in lepromatous macrophages downregulate the innate immune response [8]. Foamy macrophages seem to sustain intracellular mycobacteria in a physiological state similar to a nonreplicating

vegetative one [9]. In this context, Montoya et al. [10] demonstrated that lepromatous macrophages https://www.selleckchem.com/products/carfilzomib-pr-171.html exhibit a high expression of the cysteine-rich superfamily scavenger receptor (SRCR), which increases the phagocytic capacity of macrophages and leads to a reduction in bactericidal activity. CD163, a receptor only expressed in monocytes and macrophages, is a member of the class B SRCR superfamily with immunomodulatory Protein tyrosine phosphatase properties. Likewise, CD163 is a receptor of hemoglobin (Hb) and hemoglobin–haptoglobin (Hp, Hb–Hp) complexes. The metabolites resulting from intracellular Hb degradation exhibit potent antioxidative

and anti-inflammatory effects. It has been described that the binding of Hb to CD163 induces the release of IL-10 and other anti-inflammatory mediators from macrophages in vivo [11]. It has also been demonstrated that IL-10 enhances CD163 expression by creating a feedback arm of regulation [12, 13] and that the CD163 levels in plasma inversely correlate with the expression of CD163 in blood monocytes [14]. In addition, increased CD163 shedding seems to be associated with the immunosuppressive control of inflammation [15]. The role of CD163 as a bacterial sensor has also been proposed, raising the possibility that a different extracellular domain in this receptor is responsible for triggering proinflammatory cytokines, in contrast to what has been considered its traditional endocytic role [16]. Recent reports have demonstrated ongoing interaction between CD163 and IDO in bone marrow-derived dendritic cells (BMDCs), perhaps indicating that different CD163 signals lead to IDO expression [17].

GIFT showed that neutrophil-specific autoantibodies were produced by the patient, and the amount of autoantibody inversely correlated with the patient’s neutrophil counts.

The presence of an autoantibody to a novel antigen on immature myeloid cells or click here neutrophils is the likely the cause of severe neutropenia in this patient with KS. Kawasaki syndrome (KS) is an acute febrile illness that presents with systemic vasculitis and is associated with a high incidence of coronary artery abnormalities (CAA) [1, 2]. High-dose intravenous immunoglobulin (IVIG) therapy is effective and reduces the incidence of CAA [3]. Although haematological abnormalities, including leukocytosis, thrombocytosis and anaemia associated with KS, have been reported [4], there are only a few publications reporting severe neutropenia [5–7]. Neutropenia is defined as an absolute neutrophil count (ANC) of <1500/mm3, while severe neutropenia, observed in 1.0% of patients with KS [6], has an ANC of <500/mm3. Neutropenia was observed approximately 3–4 weeks after onset of KS [7]. Neutropenia during the subacute phase of KS has been ascribed to the transient inhibition of GM-CSF production [7], downregulation of inflammatory cytokines such

as interleukin (IL)-1β, IL-6 and tumour necrosis factor-α (neutrophil apoptosis inhibitors) [8, 9], the administration of aspirin www.selleckchem.com/products/ly2835219.html or IVIG therapy [10, 11] and the possible relation of Glutathione peroxidase the production of antibodies that bind to neutrophils [12]. However, the detailed mechanisms behind neutropenia in KS have not been fully elucidated. Here, we describe a patient with KS whose disease was complicated with severe transient neutropenia. Bone marrow examination revealed developmental arrest at the early myelocyte stage, and flow cytometric analysis showed the presence of autoantibodies that bound to immature CD13-positive myeloid cells. We speculated that this specific antibody bound to premature myeloid cells or peripheral neutrophils and contributed

to the transient severe neutropenia of the patient. The aim of this study was to clarify the mechanisms of neutropenia in KS, using a combination of the granulocyte immunofluorescence test (GIFT) and flow cytometry. Patient report.  A previously healthy 2-year-old boy was admitted to a neighbourhood hospital suffering with fever, lymphadenopathy and fatigue (Fig. 1). Laboratory findings revealed a white blood cell count (WBC) of 24,700/mm3 and C-reactive protein (CRP) of 19.8 mg/dl. He was diagnosed with bacterial lymphadenitis and treated with Panipenem/Betamipron (PAPM/BP). On the fifth day of illness, he developed a skin rash, reddening of lips and conjunctival injection and was then diagnosed with KS.

The chronic phase of Chagas disease is either asymptomatic or may lead to cardiac and digestive system pathology.

Chagas heart C59 wnt chemical structure disease is a potentially fatal dilated cardiomyopathy that develops in 30% of T. cruzi-infected individuals [2] and is responsible for the largest number of deaths among chagasic patients. Clinical treatment of chagasic cardiomyopathy-associated hypertension in chagasic patients includes sodium restriction and additional treatment with digitalis, diuretics or angiotensin-converting enzyme (ACE) inhibitors, such as captopril [3,4]. As true for other ACE inhibitors, captopril has also been reported to reduce heart inflammation and fibrosis [5]. ACE has a dual role in vascular homeostasis. Acting primarily in the renin–angiotensin system, ACE processes the inactive intermediate angiotensin I (Ang I), generating the vasopressor octapeptide angiotensin II (Ang II). Although Ang II may bind to different subtypes of G protein coupled

receptors, excessive formation of this agonist may increase intracellular volume, peripheral vascular resistance and blood pressure [5]. ACE inhibitors such as captopril exert their anti-hypertensive effects by inhibiting ACE-dependent formation of the vasopressor Ang II and by attenuating ACE (kininase II)-dependent degradation of bradykinin (BK) or CT99021 lysyl-bradykinin (LBK) [6]. Termed collectively as ‘kinins’, BK/LBK are short-lived peptides liberated from an internal moiety of high or low molecular weight kininogens by the action of specialized proteases of host [7] or microbial origin [8,9].

Once released, BK/LBK exert their vasodilating function by triggering endothelium BK2R, a constitutively expressed G-protein coupled receptor (GPCR) [10]. Alternatively, the released kinins Phosphatidylinositol diacylglycerol-lyase undergo processing by kininase I, generating arginine-truncated metabolites (des-Arg-kinin) that activate BK1R, an inducible subtype of kinin receptor up-regulated in inflamed tissues [11], while losing affinity for BK2R. Studies on cruzipain, a lysosomal cysteine protease characterized previously as a kinin-releasing enzyme of T. cruzi[12], provided the first evidence that pathogen uptake is driven by the activation of kinin receptors (BK2R and BK1R) [13,14]. Whether involving human endothelial cells or murine cardiomyocytes, these in vitro studies revealed that addition of captopril to the interaction medium potentiated parasite invasion via the kinin signalling pathway [13,14]. More recently, it was reported that BK/LBK induces the maturation of dendritic cells (DCs) through the signalling of BK2R [15,16]. Further underscoring the importance of kinins and ACE to pathogenic outcome, Monteiro and co-workers [17] demonstrated that ACE inhibitors (single-dose administration) potentiated paw oedema evoked by trypomastigotes through mechanisms involving co-operation between Toll-like receptor (TLR)-2 and BK2R.

We found that a clinically relevant concentration of rapamycin inhibits innate as well as adaptive immune functions of TLR-activated human PDC, but with two exceptions: (1) it enhances the ability of TLR-7-stimulated PDC to stimulate

CD4+ T cell proliferation by enhancing CD80 expression; and (2) it enhances the ability of TLR-7-stimulated PDC to induce CD4+FoxP3+ Treg, while it leaves their capacity to generate functional CD8+ Treg unaffected. Rapamycin inhibited IFN-α secretion by PDC effectively in the case of TLR-7 stimulation, but only Pictilisib a minor inhibitory effect was observed upon TLR-9 stimulation despite effective suppression of mTOR-signalling in TLR-9-stimulated PDC. This observation is of critical importance for emerging studies on rapamycin treatment of autoimmune diseases caused by chronic stimulation of IFN-α production by PDC, such as SLE and psoriasis [18, 28]. In these diseases, PDC are stimulated continuously by immune complexes comprising self-DNA and RNA.

While RNA complexes are sensed by TLR-7, DNA complexes are sensed by TLR-9 in the early endosomes, such as CpG-A[29]. Our results predict AZD0530 molecular weight that rapamycin treatment can ameliorate overproduction of IFN which is induced by self-RNA complexes, but not self-DNA-driven IFN production. Similarly, our findings suggest that rapamycin treatment may abrogate the early IFN-α response to RNA viruses which are sensed by TLR-7, such as influenza virus, respiratory syncytial virus (RSV) and hepatitis

C virus (HCV), thereby enhancing susceptibility to these viruses, but not to DNA-viruses sensed by TLR-9. Cao et al. [16] also reported that rapamycin, in second the same concentration as we used in the present study, inhibits CpG-A ODN 2336-induced IFN-α production by human PDC less efficiently compared to loxoribine-induced IFN-α production. Nevertheless, these authors reported a twofold inhibition, while we observed only 20% inhibition of CpG-A ODN 2336-induced IFN-α secretion. One explanation for this difference may be related to the use of different IFN-α ELISA kits with different sensitivities for IFN-α subtypes. The ELISA that we used detects the main subtypes IFN-α2a, IFN-α2b and IFN-α2c. In addition to its well-known immunosuppressive effects, recent studies revealed immunostimulatory effects of rapamycin, such as stimulation of proinflammatory cytokine production in myeloid cells [30] and promotion of CD8+ memory T cell differentiation [31, 32]. The data presented here add to the emerging contrasting effects of rapamycin on the immune system. Immunogenic functions of PDC that are inhibited by rapamycin include: proinflammatory cytokine production, IFN-α secretion induced by TRL-7 ligation and the capacity to stimulate proinflammatory cytokine production in allogeneic T cells. Conversely, rapamycin enhances the capacity of TLR-7-activated PDC to stimulate CD4+ T cell expansion, and inhibits the ability of TLR-engaged PDC to stimulate IL-10 secretion by T cells.

More than 95% of the cells were CD56+CD3- lymphocytes. Enriched NK cells were co-cultured with AFP (25 µg/ml, AFP-DCs) or Alb (25 µg/ml, Alb-DCs) pretreated DCs for 24 h. The cytolytic activity of NK cells co-cultured with AFP-DCs or Alb-DCs against target cells (K562, NK sensitive cells, or Huh7, human HCC cells) was assessed by 4-h 51Cr-releasing assay with or without the presence of neutralizing antibody of IL-12 (BD Pharmingen) or recombinant IL-12p70 protein (PeproTech), as described previously [14]. In some experiments,

a Transwell insert was also used to prevent direct contact of NK cells and DCs in co-culture systems, as described previously [14]. The statistical significance of differences between the two groups was determined by applying the Mann–Whitney U-test. We defined statistical significance as P < 0·05. We investigated the activity of NK cells co-cultured with Metformin AFP-DCs or Alb-DCs. NK cells from the same healthy volunteers were co-cultured with AFP-DCs or Alb-DCs for 24 h, and we evaluated the cytolytic activity of NK cells co-cultured with DCs against K562 cells as target cells with the 51Cr-releasing assay. The cytotoxicity of NK cells BMN 673 in vivo co-cultured with AFP-DCs against K562 cells was significantly lower than those with Alb-DCs (Fig. 1a). Similarly, the cytotoxicity of NK cells co-cultured with AFP-DCs against Huh7 cells was significantly lower than

that with Alb-DCs (Fig. 1b). We also evaluated the IFN-γ production from NK cells co-cultured with AFP-DCs or Alb-DCs by specific ELISA. IFN-γ production from NK cells co-cultured with AFP-DCs was significantly lower than that from NK cells co-cultured

with Alb-DCs (Fig. 1c). These results demonstrated that NK activity co-cultured with AFP-DCS was lower than that Bcl-2 inhibitor with Alb-DCs. Next, NK cells were cultured with AFP (AFP-NK cells) or Alb (Alb-NK cells) for 24 h, and we evaluated the cytolytic activity of AFP-NK and Alb-NK against K562 cells with the 51Cr-releasing assay. The cytotoxicity of AFP-NK cells was almost similar to that of Alb-NK cells, and the presence of DCs could enhance the cytotoxicity of NK cells (Fig. 2a). These results suggested that AFP does not directly impair NK cell function and that DCs play a critical role in activating NK cells. To examine whether this attenuation of NK cells was caused by the cytokine from DCs or by direct contact with DCs, NK cells were co-cultured with AFP-DCs or Alb-DCs in Transwell culture for 24 h. The cytotoxicity of NK cells co-cultured with AFP-DCs was lower than that with Alb-DCs, which was similar to the results without Transwell membrane (Fig. 2b). These results suggested that soluble factors derived from DCs played a role in activating NK cells. We next examined the function of AFP-DCs. We obtained DCs from eight healthy volunteers and cultured the DCs for 7 days in RPMI-1640 with AFP (AFP-DCs) or Alb (Alb-DCs). On day 6, we added LPS to induce DC maturation.

Probiotics are live bacteria that confer

a health benefit to the host when administrated in adequate amounts (WAO/WHO, 2002), and lactic acid bacteria (LAB) including lactobacilli and bifidobacteria are commonly used as probiotics. LAB exhibit a variety of immunomodulating effects, including preventive effects against various infections (Nomoto, 2005; Namba et al., 2010; Fukuda et al., 2011) and carcinogenesis (Reddy & Rivenson, 1993; Takagi et al., 2001) as well as antiallergic effects (Fujiwara et al., 2004; Xiao et al., 2006a ,b). Leyer et al. (2009) have reported that intake of the combination of probiotic strains reduced cold and influenza-like symptom incidence and duration in healthy children during the winter season. Several studies have demonstrated selleck chemicals llc that some strains of LAB protect against influenza virus (IFV) infection in a murine model and that the protective effects might be mediated

by the augmentation of secreted immunoglobulin A production and the enhancement of innate immunity in the host (Yasui et al., 1999, 2004; Hori et al., 2002; Maeda et al., 2009; Kawase et al., 2010; Kobayashi et al., 2010). Influenza is an acute viral respiratory disease caused by IFV, which attacks the host respiratory tract mucosa. IFV infection sometimes causes lethal pneumonia in the elderly and encephalopathy in children, which results in high morbidity and significant mortality. After IFV infection in the lung, viruses are initially detected and destroyed nonspecifically by innate

immune responses, in which macrophages SP600125 research buy and natural killer (NK) cells are involved, and if the viruses escape the early defense mechanisms, they are detected and eliminated specifically by adaptive immune responses (Tamura & Kurata, 2004). Following viral infection in the lung, alveolar macro-phages secrete various cytokines Y-27632 2HCl such as interleukin-12 (IL-12) that induce early NK cell-mediated interferon-γ (IFN-γ) production (Monteiro et al., 1998). The activated NK cells lyse virus-infected cells and contribute to the inhibition of early viral replication (Stein-Streilein & Guffee, 1986). In the adaptive immune response, secretory IgA and cytotoxic T lymphocytes specific for the viral antigen are induced and contribute to the recovery from viral infection (Wiley et al., 2001; Asahi et al., 2002). However, adaptive immunity requires several days for clonal expansion and the differentiation of naive lymphocytes into effector cells. Thus, as a method for preventing IFV infection, it would be crucial to enhance innate immunity that acts at the early stage of viral infection. Several studies have demonstrated that the strains of LAB that induce IL-12 elicit NK cell activities and IFN-γ production in an IL-12-dependent manner and enhance innate immunity (Ogawa et al., 2006; Shida et al., 2006a; Koizumi et al.

ITAMI NORITOMO1, UEMURA SUSUMU2, TSUNEYAMA KAZUSHI2, HAMADA HIROMI3, NAKAYAMA MASAAKI4 1Nikko Memorial Hospital, Kidney Center, Japan; 2Nikko Memorial Hospital, Dept. of Clinical Engineering, Japan; 3Nikko Memorial Hospital, Dept. of Surgery, Japan; 4Fukushima Medical University, Dept. of Nephrology, Japan Introduction: The beneficial effects of electrolyzed water hemodialysis such as a reduction in oxidative stress and inflammatory markers have been reported and improvements

in blood pressure and maintaining of cardiac function are expected. Presented is a comparative study on the cardiac function of maintenance hemodialysis patients who have undergone electrolyzed water hemodialysis for over two years. Methods: The subjects of our study were 19 maintenance hemodialysis

patients (6 male, 13 female) who had received electrolyzed water hemodialysis(EW-HD) SRT1720 for over two years at our hospital and in whom post-dialysis echocardiography was performed. Measured values were compared for the one year of standard hemodialysis(S-HD) prior to starting EW-HD, the first year of EW-HD(EW1st) and the second year of EW-HD(EW2nd). The measured values included: 1) Left ventricle mass index(LVMI), 2) Left ventricle ejection fraction(EF), 3) Left ventricle fractional shortening(FS), 4) Left ventricle diastolic performance(E/E’), and 5) Heart-lung ratio. Results: The values shown are the average ± standard deviation, with the critical rate calculated by Tukey’s test shown in parentheses. 1)  LVMI; S-HD: 103.0 ± 30.7 g/m2, EW1st: MLN2238 101.3 ± 31.5 g/m2, EW2nd: 100.5 ± 28.2 g/m2 Conclusion: These results suggest the possibility that electrolyzed water hemodialysis can contribute to maintaining cardiac function in maintenance hemodialysis Grape seed extract patients. CHOI JOON SEOK1, KIM HA YEON1, OAK CHAN YOUNG1, LEE SEUNG HYOUNG1, KANG

YONG UN1, KIM CHANG SEONG1, BAE EUN HUI1, MA SEONG KWON1, KWEON SUN SEOG2, KIM SOO WAN1 1Department of Internal Medicine, Chonnam National University Medical School, Gwangju; 2Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea Introduction: Hyponatremia is a common electrolyte disorder associated with tumor-related conditions. However, the clinical impact of hyponatremia in patients with colorectal cancer has not been evaluated. Methods: We retrospectively assessed 2944 patients who had been admitted to Chonnam National University Hwasun Hospital with a diagnosis of colorectal cancer. In order to determine the relationship between serum sodium level and 3-year mortality, we categorized the patients according to the sodium level as having normonatremia or mild, moderate, or severe hyponatremia. Results: Hyponatremia, defined as a serum sodium level of <135 mEq/L, was evident in 27.6% of patients during hospitalization.

All three patients who received these surgical interventions reached full recovery from fungal

pleural infections (two due to Aspergillus spp.). In summary, drainage with chest tubes and in some cases surgical (thoracoscopic) debridement is indicated in Aspergillus pleural empyema, which occurs mostly after pneumonectomies.[86-91] Aspergillus arthritis is a rare clinical disease most frequently present in immunocompromised patients. Knee and shoulder are the joints most frequently affected; however, the wrist and sacroiliac joint have also been reported. The infection of selleck chemical joints by Aspergillus spp. is caused mostly by haematogenous spread in disseminated IA; however, cases have been reported after medical injections into the joint.[57] Contamination and infection during surgery have also been reported in patients without underlying immunosuppression or other predisposing risk factors. Diagnostic imaging, such as magnetic resonance imaging which can show bone marrow oedema, should be performed early. Positron emission tomography-computed tomography may show uptake of 18-Fluoro-deoxiglucose (standard uptake value 9.0 against

the contralateral side 1.5) in the suspected joint, confirming the presence of articular and extra-articular inflammation. Clinical presentation consists of pain, swelling and instability in the affected joint. Drainage Sorafenib price should be performed to gain synovial fluid for diagnostic methods. While debridement SSR128129E and drainage are indicated in Aspergillus arthritis, joint replacement can only be recommended in selected cases.[92-94, 94-100] Steinfeld et al. [99] reported of two cases of Aspergillus arthritis of the knee that were managed by surgical intervention after the poor response to antifungal therapy alone. Arthroscopic debridement with a motorised shaver was performed and both patients showed good response. In immunocompetent patients with Aspergillus arthritis, antifungal therapy without surgical intervention has been reported to result in full recovery.[96]

In Aspergillus prosthetic joint infection change of prosthesis may help to save the extremity.[100, 101] Aspergillus skin and soft-tissue infections primarily occur in immunocompromised patients. However, primary cutaneous aspergillosis has recently also been reported on a tattoo in an immunocompetent patient who underwent home tattooing.[102] In immunocompromised patients, IA can manifest in skin and soft tissue, either as primary cutaneous Aspergillus infection or as secondary cutaneous manifestations of an underlying disseminated Aspergillus infection. Primary cutaneous aspergillosis mostly arises around intravenous line site, burns, bruises or surgical wounds, which represent potential ports of entry in patients with neutropenia.

An in vitro study demonstrated that BMP-2, BMP-6, BMP-7, selleck inhibitor and BMP-15, not activin-A and GDF-9, decreased PCSK 6 gene expression in human

GC. FSH induced PCSK 6 mRNA in the presence of activin-A or GDF-9. GDF-3, which is an inhibitor of BMP cytokines, also induced PCSK 6 mRNA expression. PCSK 6, which is a critical factor to produce BMP cytokines, was suppressed with BMP stimulation in human GC, suggesting the presence of a negative feedback system in the follicular development process. “
“Schistosomiasis is the second most important parasitic disease in the world in terms of public health impact. Globally, it is estimated that the disease affects over 200 million people and is responsible for 200,000 deaths each year. The three major schistosomes infecting humans are Schistosoma mansoni, S. japonicum, and S. haematobium. Much immunological

research Bortezomib cell line has focused on schistosomiasis because of the pathological effects of the disease, which include liver fibrosis and bladder dysfunction. This unit covers a wide range of aspects with respect to maintaining the life cycles of these parasites, including preparation of schistosome egg antigen, maintenance of intermediate snail hosts, infection of the definitive and intermediate hosts, and others. The unit primarily focuses on S. mansoni, but also includes coverage of S. japonicum and S. haematobium life cycles. Curr. Protoc. Immunol. 103:19.1.1-19.1.58. © 2013 by John Wiley & Sons, Inc. “
“Lactic acid is the predominant acid present in the vagina. We evaluated the consequences of lactic acid, at physiological levels present in the vagina, on cytokine responses of peripheral blood mononuclear cells (PBMCs) obtained from 10 individuals in the presence or absence of bacterial lipopolysaccharide. Preincubation of PBMCs in 15 mM lactic acid before the addition of lipopolysaccharide resulted in a 246% mean increase in interleukin-23 (IL-23) secretion over that released in the presence of lipopolysaccharide alone (P=0.0068). The lipopolysaccharide-induced production of tumor necrosis factor-α,

IL-6, IL-10 PRKD3 and IL-12 was unaffected by lactic acid. IL-23 stimulation was not observed if the lactic acid was neutralized before its addition to the culture medium or if hydrochloric acid was substituted for lactic acid. In the absence of lipopolysaccharide, lactic acid did not stimulate the production of IL-23 or any of the other cytokines. The increase in IL-23 production was proportional to the lactic acid concentration over a 15–60 mM range. We conclude that at body sites characterized by lactic acid accumulation, such as in the human vagina, exposure to gram-negative bacteria results in selective IL-23 production, leading to a subsequent preferential stimulation of the Th17 T lymphocyte pathway.

This interpretation is further supported because, overall, these commensal bacterial species are detected in substantially larger quantities in both healthy and periodontitis patients compared to the oral burden with the pathogens [7,30–33]. Thus, it would

be predicted that if the level of antibody responses were a function of the magnitude of antigenic challenge (i.e. the portion of the bioburden due to a particular species), the antibody response to the commensal bacteria should be substantially more robust than the response to the periodontal pathogens. Stratifying the patients into disease severity AZD1152-HQPA groups based upon mean pocket depth demonstrated that only the sum of antibody responses to the periodontal pathogens increased significantly with selleck screening library severity of periodontal disease, while the response to the commensals was similar across the disease

groups. Additionally, comparing the antibody responses to the pathogens and commensals in the disease-stratified patients showed that in the most diseased patients the antibody levels to the pathogens were greater than antibody to the commensal bacteria. Comparison of the antibody levels to the individual bacterial species in disease-stratified groups demonstrated that among the pathogens, P. gingivalis was the only species that increased significantly with severity of disease. Therefore, in this adult population, antibody to P. gingivalis appears to provide a distinct marker of the current periodontal status, which is L-gulonolactone oxidase also a reflection of past disease experience in the patients. P. gingivalis has been implicated strongly as a periodontal pathogen, and it is biologically

plausible that it might elicit a disproportionate antibody response. Examination of antibody levels, disease and smoking using correlation analysis provided some additional observations. Minimal correlation was noted between antibody levels BOP. While the extent of inflammation is generally related to the severity and extent of periodontitis, one explanation in this population could lie in the fact that all subjects in the study are current smokers. Smoking reduces BOP because the nicotine in cigarettes causes vasoconstriction in the gingiva, so this may alter the relationship between immune response capacity and the extent of BOP [34]. Vasoconstriction also prevents white blood cells, and thus stimulation of IgG antibody production, from the microbial challenge in the gingiva. One might anticipate a different relationship in non-smoking subjects. This would be supported by existing literature describing differences in antibody levels in periodontitis versus control subjects that varied depending upon the smoking status of the subjects [35,36].