Humoral immune responses to Porphymmonas gingivalis and Actinobacillus actinomycetemcomitans in adult periodontitis and rapidly progressive periodontitis

The relationships between various forms of periodontal disease and the avidities of serum antibodies of all 3 immunoglobulin (Ig) classes (IgG, IgM and IgA) to Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans were investigated. Twenty-four patients with untreated adult periodontitis and twelve untreated patients diagnosed as suffering from the early-onset form of periodontitis, rapidly progressive periodontitis, were studied. The latter group were matched for age and sex to healthy controls. Antibody litres were measured and avidity (expressed as molarity) was further assayed using the thiocyanate elution method. Avidity has previously been shown to relate to the biological function of antibody. IgM avidities to P. gingivalis were lower in the rapidly progressive periodontitis group than in the adult periodontitis group (0.54 M vs 0.74 M). IgG avidities tended to be lower in the former than in the latter group (0.58 M vs 0.92 M). In accordance with other workers, seropositivily was defined as an immunoglobulin titre more than twice the median level of control sera. Only 2 of the rapidly progressive periodontitis group were seropositive. Interestingly, the seronegative rapidly progressive periodontitis patients were significantly different (0.53 M vs 0.92 M). The data that patients with various forms of periodontal disease appear to produce antibodies of differing avidity to P. gingivalis suggest that the quality of the humoral immune response to suspected periodontopathogens may have a bearing on the aetiology of periodontal disease.     

Delayed expansion of a restricted T cell repertoire by low-density TCR ligands

The role of TCR ligand density (i.e. the number of antigen-MHC complexes) in modulating the diversity of a T cell response selected from a pool of naive precursors remains largely undefined. By measuring early-activation markers up-regulation and proliferation following stimulation with staphylococcal enterotoxin A (SEA), we demonstrate that decreasing the ligand dose below an optimal concentration leads to the delayed activation of a restricted set of TCRVbeta-bearing T cells, with the specific, non-stochastic exclusion of some TCRVbeta+ T cells from the activated pool. Our results suggest that the failure of these TCRVbeta-bearing T cells to reach the activation threshold at sub-optimal ligand concentration is due to the inefficiency of TCR engagement, as measured by TCR internalization, and does not correlate with the relative precursor frequency in the non-immune repertoire. Moreover, even at SEA concentrations that lead to the simultaneous proliferation of all SEA-reactive T cells, we observe marked differences in the ability to secrete cytokines among the different responsive TCRVbeta-bearing T cells. Altogether, our results indicate that the development of a T cell response to a scarce display of ligand significantly narrows TCR repertoire diversity by mechanisms that involve focusing of the repertoire on the expansion of those T cells with the highest avidity of TCR engagement.     

Avidity and titer of immunoglobulin G subclasses to Porphymmonas gingivalis in adult periodontitis patients

The relative avidity and titer of antibodies representing the 4 immunoglobulin G (IgG) subclasses (IgG1-4) reactive with Porphyromonas gingivalis, P. gingivalis-lipopolysaccharide (-LPS), streptokinase (SK) and tetanus toxoid (TT) in the sera of patients having adult periodontitis and of healthy controls were measured. Patient antibody titers to P. gingivalis and P. gingivalis-LPS were found to be significantly elevated for IgG, IgG1 (no P. gingivalis-LPS antibodies) and IgG2. The predominant antibody response to P. gingivalis and P. gingivalis-LPS occurred in the IgG2 subclass. When the relative avidity of the antibodies to P. gingivalis and P. gingivalis-LPS were examined, no significant differences between control and patient sera could be identified. However, anti-P. gingivalis and P. gingivalis-LPS antibodies were found to possess significantly lower relative avidity than either SK or TT antibodies. The IgG1 subclass antibodies to P. gingivalis, SK and TT all appeared to be of high relative avidity. In contrast, anti-P. gingivalis and P. gingivalis-LPS of the IgG2 subclass were of significantly lower relative avidity. Since the predominant humoral response to P. gingivalis occurs in the IgG2 subclass, the low relative avidity of these antibodies predominates in measurements of whole serum activity.     

Non-invasive detection and quantification of acute myocardial infarction in rabbits using mono-[123I]iodohypericin microSPECT.

AIMS: Mono-[(123)I]iodohypericin ([(123)I]MIH) has been reported to have high avidity for necrosis. In the present study, by using rabbit models of acute myocardial infarction, we explored the suitability of [(123)I]MIH micro single photon emission computed tomography (microSPECT) for non-invasive visualization of myocardial infarcts in comparison with [(13)N]ammonia micro positron emission tomography (microPET) imaging, postmortem histomorphometry, and [(123)I]MIH autoradiography. METHODS AND RESULTS: Fourteen rabbits were divided into four groups. The left circumflex coronary artery was permanently occluded in group A (n = 3), reperfused by releasing the ligature after 15 min in group B (n = 3) or 90 min in group C (n = 6), or not occluded in group D (n = 2). Animals received [(13)N]ammonia microPET perfusion imaging 18 h after infarct induction followed by microSPECT imaging at 2-3.5, 9-11, and 22-24 h post injection (p.i.) of [(123)I]MIH. The cardiac images were assembled into polar maps for assessment of tracer uptake. Animals were sacrificed and the excised heart was sliced for autoradiography, triphenyl tetrazolium chloride, and haematoxylin-eosin staining. Using [(123)I]MIH microSPECT, infarcts were well delineated at 9 h p.i. Mean microSPECT infarct size was 38.8 and 32.7% of left ventricular area for groups A and C, respectively, whereas group B showed low uptake of [(123)I]MIH. Highest mean infarct/viable tissue activity ratio of 61/1 was obtained by autoradiography in group C animals at 24 h p.i. CONCLUSION: The study indicates the suitability of [(123)I]MIH for in vivo visualization of myocardial infarcts.     

Structural aspects of cross-reactivity and its relation toantibody affinity

In the context of IgE/allergen interactions, affinity is largely determined by the stability of the allergen-IgE complex: a low affinity is usually equated with a rapid dissociation of the complex. Regular solid-phase assays are not well suited for affinity estimates because of multivalency effects, unstirred layer effects and invisible antibodies. Elution of IgE bound to solid-phase coupled allergen might be a good measure of intrinsic affinity, provided that reassociation of antibodies is prevented by a high concentration of soluble allergen. Allergen-mediated IgE-dependent triggering of a mast cell is presumably a two-step process. During the first step, the allergen is bound to a cell-bound IgE antibody and dragged over the cell surface. The second step is the interaction between this cell-bound allergen and another IgE antibody. The hypothesis is that the affinity requirements for the first step are higher than for the second. The implication is that a mast cell can be triggered by a single high-affinity antibody in combination with one or more low-affinity antibodies.     

风疹病毒特异性IgG抗体亲和力测定的临床意义

目的区分风疹病毒原发性感染、继发性感染的病毒活化或再感染。方法对12 y以下患儿的风疹病毒IgG抗体(RV-IgG)阳性血清,采用尿素变性酶联免疫吸附实验(ELISA法)测定RV-IgG抗体亲和力指数(AI)。结果1~12 y的患儿中,只有4.8%(3/63)的病例有低亲和力抗体(AI<30%)。1 y以内患儿中高达56.2%(18/32)的病例有低亲和力抗体,明显高于1~12 y患儿。1 y以内患儿中,1~3 mo和4~6 mo患儿低亲和力抗体比例低(分别为36.4%和44.4%),而7~12mo患儿有83.3%为低亲和力抗体。结论RV的早期感染大都发生在1y以内。IgG抗体亲和力测定是鉴别初次感染和体内病毒活化及再感染的有效方法。     

Use of SAG2A recombinant Toxoplasma gondii surface antigen as a diagnostic marker for human acute toxoplasmosis: analysis of titers and avidity of IgG and IgG1 antibodies

We evaluated the reactivity of IgG and IgG1 antibodies by immunoassays in sera from patients with acute and chronic phases of toxoplasmosis against 2 recombinant antigens, SAG2A (full molecule) and SAG2ADelta (truncated molecule from the epitope recognized by A4D12 monoclonal antibody [mAb]), in comparison with soluble Toxoplasma antigen (STAg). Results demonstrated higher IgG reactivity in acute sera with both STAg and SAG2A than in chronic phase sera, and this difference was more evident for IgG1 antibodies to SAG2A. Low reactivity to SAG2ADelta was found in sera from both phases. ELISA-IgG-SAG2A showed high sensitivity (95%) and specificity (100%). ELISA-IgG1-SAG2A sensitivity was significantly higher (90%) for acute than for chronic (67%) phases. ELISA-IgG avidity using STAg demonstrated high performance for characterizing sera with high avidity (>60%), whereas the ELISA-IgG1 avidity-SAG2A immunoassay was the best to define chronic phase infection. It can be concluded that SAG2A is an antigen that may be used as a diagnostic tool to characterize the acute phase Toxoplasma gondii infection. Also, the epitope recognized by A4D12 mAb may be critical for the recognition of this molecule.     

Complete modification of TCR specificity and repertoire selection does not perturb a CD8+ T cell immunodominance hierarchy

Understanding T cell immunodominance hierarchies is fundamental to the development of cellular-based vaccines and immunotherapy. A combination of influenza virus infection in C57BL/6J mice and reverse genetics is used here to dissect the role of T cell antigen receptor (TCR) repertoire in the immunodominant D^bNP₃₆₆CD8⁺ T cell response. Infection with an engineered virus (NPM6A) containing a single alanine (A) mutation at the critical p6 NP_366–374 residue induced a noncross-reactive CD8⁺ T cell response characterized by a novel, narrower TCR repertoire per individual mouse that was nonetheless equivalent in magnitude to that generated after WT virus challenge. Although of lower overall avidity, the levels of both cytotoxic T lymphocyte activity and cytokine production were comparable with those seen for the native response. Importantly, the overdominance profile characteristic of secondary D^bNP₃₆₆-specific clonal expansions was retained for the NPM6A mutant. The primary determinants of immunodominance in this endogenous, non-TCR-transgenic model of viral immunity are thus independent of TCR repertoire composition and diversity. These findings both highlight the importance of effective antigen dose for T cell vaccination and/or immunotherapy and demonstrate the feasibility of priming the memory T cell compartment with engineered viruses to protect against commonly selected mutants viral (or tumor) escape mutants.     

经验性131I治疗对甲状腺乳头状癌不摄碘肺转移患者价值存疑

背景与目的:甲状腺乳头状癌(papillary thyroid cancer,PTC)肺转移但131I全身显像(whole body scan,WBS)阴性的患者是否可从经验性131I治疗中获益仍存在争议.探究经验性131I治疗对PTC伴不摄碘性肺转移患者的必要性.方法:经筛选纳入回顾性分析2008年—2019年就诊于...