Joseph V. Califano

Evidence of a Substantial Genetic Basis for IgG2 Levels in Families with Aggressive Periodontitis

IgG2 is elevated in localized but not in generalized aggressive periodontitis (AgP). Exposure to pathogenic bacteria is essential for disease. Immune responses are dominated by IgG2 reactive with bacterial surface carbohydrates. We used variance component analyses to assess IgG2 heritability and determine whether genes that influence IgG2 are the same genes that influence disease susceptibility. We studied 17 Caucasian and 43 African American families with two or more localized or generalized AgP-affected members (274 subjects with IgG2 measurements). Only 16% of the variance in IgG2 was attributable to age, race, and smoking. Even with the addition of localized AgP, the model still explained only 19% of IgG2 variance. By contrast, heritability of IgG2 levels was estimated to be 38% and highly significant (P = 0.0006), demonstrating a substantial genetic basis. Bi-trait variance component analyses of IgG2 and quantitative measures of AgP indicate that different genes appear to control IgG2 levels and disease susceptibility.

Antibody of the IgG2 Subclass, Actinobacillus actinomycetemcomitans, and Early-Onset Periodontitis*

Susceptibility to early-onset periodontitis (EOP) appears to be attributable to a gene inherited in an autosomal dominant pattern. This explains why EOP clusters in families and why about half of the family members develop periodontal disease early in life. Manifestation of EOP is variable, with some patients having a localized form restricted to first molars and incisors (LJP) and others with a severe generalized form of periodontitis (SP). The extent and severity of disease is less in patients who are seropositive for Actinobacillus actinomycetemcomitans than in seronegative patients, and this relationship prompted the hypothesis that anti-A. actinomycetemcomitans helps limit disease. The dominant antibody is an IgG2 reactive with the serotypespecific carbohydrate. The incidence of the LJP form of EOP is about 10 times higher in blacks than in whites. Interestingly, blacks have higher levels of serum IgG2, a higher frequency of anti-A. actinomycetemcomitans antibody, and higher serum titers of IgG2 anti-A. actinomycetemcomitans which may help explain why the disease is localized. Studies in progress suggest that smoking reduces serum IgG2 levels in SP patients and is associated with more severe periodontal destruction. In marked contrast, IgG2 does not appear to be reduced in LJP patients who smoke, and smoking does not appear to increase periodontal destruction. We think that IgG2 anti-A. actinomycetemcomitans is playing a role in limiting the extent and severity of disease in patients genetically susceptible to EOP. J Periodontol 1996;67:317-322.

Characterization of Porphyromonas gingivalis Insertion Sequence-Like Element ISPg5

ABSTRACT Porphyromonas gingivalis, a black-pigmented, gram-negative anaerobe, is found in periodontitis lesions, and its presence in subgingival plaque significantly increases the risk for periodontitis. In contrast to many bacterial pathogens, P. gingivalis strains display considerable variability, which is likely due to genetic exchange and intragenomic changes. To explore the latter possibility, we have studied the occurrence of insertion sequence (IS)-like elements in P. gingivalis W83 by utilizing a convenient and rapid method of capturing IS-like sequences and through analysis of the genome sequence of P. gingivalis strain W83. We adapted the method of Matsutani et al. (S. Matsutani, H. Ohtsubo, Y. Maeda, and E. Ohtsubo, J. Mol. Biol. 196:445–455, 1987) to isolate and clone rapidly annealing DNA sequences characteristic of repetitive regions within a genome. We show that in P. gingivalis strain W83, such sequences include (i) nucleotide sequence with homology to tRNA genes, (ii) a previously described IS element, and (iii) a novel IS-like element. Analysis of the P. gingivalis genome sequence for the distribution of the least used tetranucleotide, CTAG, identified regions in many of the initial 218 contigs which contained CTAG clusters. Examination of these CTAG clusters led to the discovery of 11 copies of the same novel IS-like element identified by the repeated sequence capture method of Matsutani et al. This new 1,512-bp IS-like element, designated ISPg5, has features of the IS3 family of IS elements. When a recombinant plasmid containing much of ISPg5 was used in Southern analysis of several P. gingivalis strains, including clinical isolates, diversity among strains was apparent. This suggests that ISPg5 and other IS elements may contribute to strain diversity and can be used for strain fingerprinting.

HIV infection and tooth loss

OBJECTIVES The objective of this study was to determine the relationship between HIV infection and tooth loss. Based on periodontal reports, we hypothesize HIV+ patients experience greater tooth loss than systemically healthy patients. STUDY DESIGN This was a retrospective cross-sectional chart study involving 193 HIV+ patients and 192 controls matched on age, race, gender, and smoking status. The relationships between tooth loss and age, race, gender, smoking, CD4+ cell count, and viral load were determined. This study used a 2-year follow-up/maintenance period and was conducted during the era of highly active antiretroviral therapy (HAART). RESULTS Tooth loss between groups was not significantly different at any time point: (1) before dental treatment; (2) after initial periodontal and restorative treatment; and (3) following a 2-year maintenance period. Age, race, and smoking were risk factors for tooth loss. Among HIV+ individuals, CD4+ cell count and viral load did not influence tooth loss. CONCLUSIONS HIV infection, in the era of HAART, does not appear to be a risk factor for tooth loss. We also did not find any association between tooth loss and indices of HIV disease progression.

Radiographic Considerations for the Regional Anatomy in the Posterior Mandible

BACKGROUND Previous studies of the inferior alveolar nerve have used cadaveric specimens in small patient groups. The purpose of this study was to describe the anatomy in the posterior mandible with respect to the inferior alveolar nerve (IAN) using computed tomography (CT) images in a large patient population. We hypothesize that CT scans are an important component of a thorough treatment plan for minimizing risk to the IAN and optimizing surgical outcomes. METHODS CT scans of 195 patients (62 males and 133 females; age range: 22 to 88 years) were evaluated retrospectively. With the aid of computer software, cross-sectional images were examined at 5-mm increments distal to the mental foramen to the ascending ramus. Four measurements were made at each cross-sectional image. The distances from the IAN to the: 1) alveolar crest (CN); 2) buccal cortical plate (BN); 3) lingual cortical plate (LN); and 4) inferior border (IN) were measured. RESULTS Most measurements for males and females were significantly different. Mean values were as follows (males/females): CN, 13.85 ± 0.43/11.98 ± 0.40 mm (P <0.01); BN, 4.98 ± 0.15/4.47 ± 0.11 mm (P <0.01); LN, 2.93 ± 0.12/3.19 ± 0.10 mm (P <0.10); and IN, 7.76 ± 0.16/7.00 ± 0.15 mm (P <0.01). The 95% confidence intervals indicated that many patients had limited bone volume in the buccal shelf or ascending ramus. CONCLUSION Given the high degree of variability in mandibular bone volume surrounding the IAN and the position of the IAN, the use of CT scans should be considered for surgical procedures in the posterior mandible when there is risk of injury to the IAN.