Relative avidity of serum antibodies to putative periodontopathogens in periodontal disease

ELISA was used to determine both the avidity and titre of IgG, IgA and IgM antibodies to the gram-negative anaerobe. Porphyromonas gingivalis, in twenty periodontitis patients enrolled in a longitudinal study of attachment loss and eleven non-periodontitis affected subjects. The avidity and titre of IgG antibodies to Actinobacillus Actinomycetemcomitans were also examined. A cross-sectional analysis of the longitudinal patients at baseline and non-periodontally affected controls confirmed earlier findings that IgG and IgA antibody titres to P. gingivalis were higher in periodontitis patients than in individuals who were not periodontally affected. In this cross-sectional analysis, IgG antibody avidities to P. gingivalis were not found to be significantly higher in periodontitis than in control subjects (p = 0.065). However, indications of the potential prognostic value of antibody avidity was demonstrated by the higher IgM avidities to P. gingivalis in patients who did not experience attachment loss during the three-month monitoring period than in those who did (p=0.0005).     

Macaca nemestrina: a non-human primate model for studies of periodontal disease

The non-human primate Macaca nemestrina was evaluated for use as a potential model in periodontal research by study of 16 animals. Using one incisor, premolar, and molar per quadrant, we measured supragingival plaque, severity of gingival inflammation, and pocket depth, and analyzed the subgingival flora. Serum IgG titers and avidities to antigens of Porphyromonas gingivalis (Pg) and Actinobacillus actinomycetemcomitans (Aa) were also assessed. Ten animals were between 13 and 24 years old, and six were between 4 and 5 years old. While mean gingival inflammation scores were significantly higher for older than for for younger animals (2.2 vs 1.8, p < 0.05), mean plaque index scores and mean probing depths did not differ significantly. The animals harbored a subgingival microflora considered to be pathogenic for humans including Aa, Pg, Bacteroides forsythus, Prevotella intermedia I and II, Campylobacter recta and Fusobacterium nucleatum . Aa, however, was found only in the younger animals. All of the animals had serum IgG antibodies reactive with antigens of Pg and Aa, and titers for Pg but not for Aa were significantly higher in the older relative to the younger animals (t test p < 0.02). In contrast, antibody avidity did not significantly differ between the two groups. A combined clinical assessment index based on maximum probing depth, gingival index score, and tooth loss was used to assess the overall disease severity. Titers were positively associated with disease severity (Spearman's rank correlation 0.57, p=0.02). We conclude that M. nemestrina harbors a subgingival microflora considered to be pathogenic for humans, manifest serum IgG antibodies to antigens of Pg and Aa, and exhibits clinical features of periodontitis comparable to those seen in humans. This species appears, therefore, to be a useful model for investigating periodontal microbial-host interactions, including the immune response.     

Elevated serum IgG titer and avidity to Actinobacillus actinomycetemcomitans serotype c in Japanese periodontitis patients

AIM: The purpose of this study was to characterize serum antibody responses to different serotypes of Actinobacillus actinomycetemcomitans strains in various forms of periodontitis and to determine whether any specific type of A. actinomycetemcomitans was associated with any specific form of periodontitis in a Japanese population. METHODS: Sonicated whole cell and autoclaved serotype antigens of A. actinomycetemcomitans were used. Serum IgG titer and avidity to A. actinomycetemcomitans were measured by enzyme-linked immunoabsorbant assay (ELISA) and ammonium thiocyanate-dissociation ELISA, respectively, in 46 aggressive periodontitis patients (8 localized, 38 generalized), 28 chronic periodontitis patients, and 18 periodontally healthy subjects. The presence of A. actinomycetemcomitans in plaque and saliva samples was determined using polymerase chain reaction. RESULTS: Generalized aggressive and chronic periodontitis patients exhibited significantly higher IgG titers than healthy subjects to both sonicated and autoclaved antigens of serotype c strains, while IgG titer to serotype b (Y4) was significantly higher in localized aggressive periodontitis patients compared to healthy subjects. No A. actinomycetemcomitans was detected in localized aggressive periodontitis patients. A. actinomycetemcomitans-positive patients exhibited significantly higher IgG titer and avidity to serotype c than A. actinomycetemcomitans-negative patients. In A. actinomycetemcomitans-positive patients, a significantly positive correlation was observed between antibody titer and avidity to serotype c. A. actinomycetemcomitans-positive patients with generalized aggressive periodontitis showed lower IgG avidities to serotype c than those with chronic periodontitis, though no statistically significant difference was found. CONCLUSION: A. actinomycetemcomitans serotype c may play a significant role in chronic and generalized aggressive periodontitis, while A. actinomycetemcomitans serotype b may be associated with localized aggressive periodontitis in a Japanese population.     

Quadrant root planing versus same-day full-mouth root planing

OBJECTIVES: The aim of this study was to determine whether same-day full-mouth scaling and root planing (FM-SRP) and quadrant scaling and root planing (Q-SRP) resulted in variations in the systemic humoral immune response dynamics (antibody titres and avidity) during active treatment and 3 and 6 months post-therapy. MATERIALS AND METHODS: Forty patients with chronic periodontitis were recruited into this study. Subjects were randomised into two groups and received either scaling and root planing quadrant by quadrant at 2-weekly intervals (Q-SRP group) or same-day full-mouth scaling and root planing (FM-SRP group). Clinical measurements and serum samples were obtained at baseline and approximately 6 weeks after the last clinical intervention (R1) and 6 months after the initiation of therapy (R2). Furthermore, serum samples were obtained from each patient undergoing therapy (Q-SRP and FM-SRP) at 3 bi-weekly instances so as to determine the short-term effects of each session of scaling and root planing on the dynamics of the humoral immune response. Serum antibody titre was assayed by enzyme-linked immunosorbent assay (ELISA) and antibody avidity was measured by thiocyanate dissociation against five putative periodontal pathogens: Porphyromonas gingivalis; Actinobacillus actinomycetemcomitans; Prevotella intermedia; Treponema denticola and Bacteroides forsythus. RESULTS: Both therapies resulted in similar antibody titre reductions against the majority of the organisms tested and although there was a distinct trend for antibody avidity to increase following therapy, this was not found to be statistically significant, reflecting marked inter-individual variation. In addition, no evidence emerged from this study to support increased antibody titres following the active phases of both treatment approaches due to an inoculation effect. Nevertheless, significant short-term increases in antibody avidity to most test bacteria were noted for both treatment strategies. CONCLUSION: Both therapies were associated with a reduction in antibody titres and an increase in the binding ability or avidity of antibodies, but there was a marked inter-subject variability and statistical significance was reached for only some of the test bacteria. No significant differences in the humoral antibody dynamics were found between the two treatment approaches.     

Changes in subgingival microflora and humoral immune response following periodontal therapy

OBJECTIVES: To investigate the effect of scaling and root planing (SRP) on the microflora and humoral immune response in adult periodontitis. MATERIALS & METHODS: Clinical measurements, subgingival plaque samples, gingival crevicular fluid and sera were taken from 4 sites in 28 adult periodontitis patients before and after SRP. Polymerase chain reaction was used to determine the presence of A. actinomycetemcomitans, P. gingivalis, B. forsythus, P. intermedia, and T. denticola. ELISA was used to investigate the systemic and local antibody titres to these organisms, and thiocyanate dissociation for the determination of serum antibody avidity. RESULTS: SRP produced a good clinical improvement. On a subject basis there was little significant change in the microflora. However, on a site basis, there were significant reductions in P. intermedia, B. forsythus and T. denticola. There was little change in systemic and local antibody titres following SRP, although there was a significant reduction in antibody avidity to P. gingivalis and P. intermedia CONCLUSION: Post-therapy clinical improvement was associated with a reduction in bacterial prevalence, but statistical significance was only reached at a site level and this microbial reduction was not significant for all organisms. No significant post-therapy effects on the humoral immune response were noted other than a reduced antibody avidity to P. gingivalis and P. intermedia. The lack of a clear pattern in the humoral immune response may reflect a failure of the host response to produce adequate levels of biologically functional antibodies, and complex interactions between the subgingival flora and the host response.     

弓形体IgG抗体亲和力指数在胎儿宫内感染中的临床意义

【目的】探讨弓形体（toxoplasma，TOX）IgG抗体亲和力指数，判断弓形体感染孕妇宫内感染的概率。【方法】ELISA法检测中晚期孕妇弓形体特异性抗体IgM和IgG，并对150例TOX—IgM或TOX—IgG阳性孕妇的胎儿或新生儿脐血进行TOX—IgM检测；采用尿素变性试验检测弓形体感染孕妇TOX-IgG抗体亲和力指数（avidityindex，AI）。【结果】孕妇弓形体IgM抗体阳性和IgG抗体阴性58例；弓形体IgM和IgG抗体阳性22例；弓形体IgM抗体阴性和IgG抗体阳性70例。胎儿或新生儿IgM阳性44例。原发性感染宫内感染率高于继发性感染（P〈0．05），活动性感染宫内感染率高于非活动性（P〈0．01），AI≤30％宫内感染率高于AI〉30％（P〈0．01）。【结论]IgG抗体亲和力指数AI≤30％结合IgM阳性有助于提高判断弓形体宫内感染的发生率。     

Increases in HPV-16/18 antibody avidity and HPV-specific memory B-cell response in mid-adult aged men post-dose three of the quadrivalent HPV vaccine

Strong quantitative and functional antibody responses to the quadrivalent human papillomavirus (HPV) vaccine were reported in mid-adult aged men, but there are limited data on the avidity of the antibody response and the memory B-cell response following vaccination. Although circulating antibodies induced by vaccination are believed to be the main mediators of protection against infection, evaluation of avidity of antibodies and memory B cell responses are critical for a better understanding of the vaccine immunogenicity mechanisms. Both the modified enzyme-linked immunosorbent assay (ELISA) and the enzyme-linked immunosorbent spot (ELISpot) assay are tools to measure the humoral and cellular immune responses post vaccination to characterize vaccine immunogenicity. The avidity of HPV-16 and HPV-18 specific IgG in the serum of mid-adult aged men (N = 126) who received three quadrivalent HPV vaccine doses was examined using a modified ELISA. HPV-16 memory B-cell responses were assessed via ELISpot at month 0 (prior to vaccination) and 1-month post-dose three of the vaccine (month 7). The quadrivalent vaccine induced an increase in HPV-16 and HPV-18 antibody avidity at month 7. HPV-18 avidity levels moderately correlated with anti-HPV-18 antibody titers, but no association was observed for HPV-16 antibody titers and avidity levels. The HPV-16-specific memory B-cell response was induced following three vaccine doses, however, no association with anti-HPV-16 antibody avidity was observed. Three doses of quadrivalent HPV vaccine increased antibody affinity maturation for HPV-16/18 and increased the frequency of anti-HPV-16 memory B-cells in mid-adult aged men.     

Serum autoantibodies directed against transglutaminase‐2 have a low avidity compared with alloantibodies against gliadin in coeliac disease

Coeliac disease is characterized by intolerance to gliadin and related gluten components present in wheat, barley and rye. Coeliac disease patients harbour antibodies directed against alloantigens such as gliadin, but also against the autoantigen transglutaminase‐2 (TG2). The type and quality of antibody responses provides insight into the underlying immune activation processes. Therefore, in this study we have analysed the avidity of the antibody response directed against the autoantigen TG2 and compared this with antibody responses against the alloantigens gliadin and Escherichia coli. We observed that the immunoglobulin (Ig)A autoantibody response directed against TG2 is of low avidity compared with the IgA response against the alloantigens gliadin and E. coli in the same patients; the same was true for IgG, both in IgA‐deficient and in ‐sufficient coeliac patients. The observed avidities appear not to be related to disease stage, antibody levels, age or duration of exposure to gluten. In conclusion, in coeliac disease there is a clear difference in avidity of the antibody responses directed against the auto‐ and alloantigens, indicating different regulation or site of initiation of these responses.     

Skewed B cell receptor repertoire and reduced antibody avidity in patients with DOCK8 deficiency

DOCK8 immunodeficiency syndrome (DIDS) is a combined immunodeficiency characterized by recurrent viral infections, severe atopy and early onset malignancy. Immunological abnormalities include lymphopenia, CD8⁺ T‐cell cytoskeleton dysfunction, defective B cell memory and variable serum immunoglobulin levels. Here, we analyse the B cell receptor repertoire (BCR) characteristics and antibody avidity of four DIDS patients, attempt to understand the dysregulated humoral immunity in DIDS patients with a normal antibody titre and suggest a scientific basis for intravenous immunoglobulin (IVIG) replacement therapy for these patients. We analysed BCR characteristics, including somatic hypermutation (SHM) frequency, using deep sequencing of multiplex PCR products derived from BCR heavy chain CDR3 regions from DIDS patients and controls. The antibody avidity of human tetanus and hemophilus influenza B antibodies was determined by ELISA using thiocyanate elution. IVIG replacement treatment and infection conditions were investigated retrospectively. We found skewing of the BCR repertoire and decreased antibody avidity in patients with DIDS. DIDS patients had fewer negatively charged amino acids than healthy controls. The SHM frequency of the IGHV3 gene was lower in patients with DIDS. Patients received regular IVIG therapy, resulting in fewer and less severe infections. We conclude that although IgG levels are normal in most DIDS patients, IVIG replacement therapy is still necessary.     

影响分化型甲状腺癌肺转移患者预后的临床因素

目的:探讨影响分化型甲状腺癌（DTC）肺转移患者预后的临床因素。方法:回顾性分析西安交通大学第一附属医院2011年至2017年间接受放射性碘治疗的DTC肺转移患者。根据随访患者影像学检查结果、无进展生存率（PFS）和癌症特异性生存率评估其肺转移病灶碘摄取能力和血清甲状腺球蛋白（Tg）水平对预后的影响。结果:最终63例患者被纳入分析。在中位随访35个月（5~91个月）后，多变量分析结果提示肺转移灶摄碘阴性，但Tg分泌阳性是DTC肺转移的独立预后因素，其是导致较短PFS的独立危险因素（P=0.032）。结论:肺转移灶摄碘阴性，但Tg分泌阳性是预测DTC肺转移不良结局最重要的预后因素。