Prevalence of periodontitis in individuals with human leukocyte antigens (HLA) A9, B15, A2, and B5.

OBJECTIVE: Human leukocyte antigens (HLA) have been associated with periodontitis. Previous studies revealed HLA-A9 and HLA-B15 as potential susceptibility factors, while HLA-A2 and HLA-B5 might have protective effects. The aim of the study was to verify these associations in a group of HLA-typed blood donors with previously unknown periodontal status. MATERIALS AND METHODS: In four German centers, 140 blood donors with known HLA class I status were enrolled and allocated to the following five groups: HLA-A9 (N = 24), HLA-B15 (N = 20), HLA-A2 (N = 30), HLA-B5 (N = 26), and controls (N = 40). Periodontal examination included the measurement of probing depths (PDs), clinical attachment level (CAL), bleeding on probing (BOP), and community periodontal index of treatment needs (CPITN). RESULTS: Carriers with HLA-A9 and HLA-B15 had higher values of mean PD (P < 0.0001), CAL (P < 0.0001), and BOP (P < 0.002) as well as sites with PD and CAL with ≥4 and ≥6 mm (P < 0.0003), respectively, than controls. Multiple regression analyses revealed HLA-A9, HLA-B15, and smoking as risk indicators for moderate to severe (CPITN 3-4; odds ratio (OR): 66.7, 15.3, and 5.1) and severe (CPITN 4; OR: 6.6, 7.4, and 3.8) periodontitis. HLA-A2 and HLA-B5 did not show any relevant associations. CONCLUSION: The present data support a role of HLA-A9 and HLA-B15 as susceptibility factors for periodontitis, whereas HLA-A2 and HLA-B5 could not be confirmed as resistance factors. CLINICAL RELEVANCE: Both HLA antigens A9 and B15 are potential candidates for periodontal risk assessment.

Individual composition of human leukocyte antigens and periodontopathogens in the background of periodontitis.

BACKGROUND: Human leukocyte antigens (HLAs) are a basic precondition to induce the immune response to pathogens. Therefore, this study evaluates associations among periodontitis, five key periodontopathic bacteria, and HLAs to test their impact together with additional risk factors in multivariate analyses. METHODS: Eighty-five patients with generalized aggressive periodontitis (GAgP) and 71 patients with generalized chronic periodontitis (CP) were compared to 88 periodontitis-free controls. HLA Class I and II typing was performed by polymerase chain reaction (PCR) with sequence-specific primers. Subgingival plaque specimens were detected by PCR with sequence-specific oligonucleotides. Risk-factor analyses were performed with respect to the cofactors age, sex, smoking, and plaque level by logistic regression. RESULTS: In the total patient group (GAgP + CP), the adjusted odds ratio (OR) of periodontitis was decreased in cases who were carriers of HLA-B*57 (OR = 0.259, 95% confidence interval [CI] = 0.086 to 0.782), HLA-DQB1*08 (OR = 0.404, 95% CI = 0.187 to 0.871), or the combination HLA-DRB1*04;DRB4*;DQB1*0302 (OR = 0.407, 95% CI = 0.185 to 0.895). Moreover, individuals who expressed HLA-DRB1*04 (OR = 0.36, 95% CI = 0.148 to 0.886) or HLA-DRB1*04;DRB4*;DQB1*0302 (OR = 0.29, 95% CI = 0.092 to 0.884) had a decreased colonization risk with Aggregatibacter actinomycetemcomitans. CONCLUSIONS: Certain HLA markers were negatively associated to the manifestation of a generalized periodontitis and/or the individual colonization of A. actinomycetemcomitans. The underlying mechanisms have to be investigated in future studies.

Interferon-gamma and interleukin-12 gene polymorphisms and their relation to aggressive and chronic periodontitis and key periodontal pathogens.

BACKGROUND: The gene polymorphisms interferon-gamma (IFN-gamma) 874 T/A and interleukin (IL)-12 1188 A/C have been associated with the altered production of cytokines. Therefore, they might be indicative of the occurrence of chronic periodontitis (CP) or aggressive periodontitis (AgP) and the prevalence of key periodontal pathogens. For this purpose, we analyzed these polymorphisms in subjects with generalized AgP or generalized CP. Moreover, we assessed the relationship between these polymorphisms and five periodontopathic bacteria. METHODS: A total of 124 unrelated German white subjects with periodontitis (AgP=72 and CP=52) and 74 periodontitis-free subjects were studied. Gene polymorphisms were determined by polymerase chain reaction with sequence-specific primers. Subgingival bacteria were molecular biologically analyzed using multiplex polymerase chain reaction and reverse hybridization. The distributions of alleles and genotypes were calculated by the chi(2) test with Yates correction. Risk factor analyses were carried out by logistic regression considering established confounders for periodontitis. RESULTS: Allele and genotype frequencies of both investigated polymorphisms were not significantly different between subjects with periodontitis and periodontitis-free controls. However, in the total study group, IL-12 AA-positive subjects had a significantly higher bleeding index than individuals who expressed IL-12 CC (68.2% versus 50.0%, P=0.025). Moreover, IFN-gamma AA carriers had a decreased odds ratio (OR) for the individual presence of Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) (OR=0.39, P=0.012) after adjustment for age, gender, smoking, and probing depth. IFN-gamma TA predisposed an individual to infection with Prevotella intermedia (OR=2.15, P=0.019). CONCLUSION: Although a relationship between the bleeding index and the presence of bacteria was shown, IFN-gamma and IL-12 polymorphisms are not suitable diagnostic features for AgP and CP.

Genetic markers of tumour necrosis factor alpha in aggressive and chronic periodontitis.

AIM: Tumour necrosis factor alpha (TNFalpha) plays an important role in the pathogenesis of periodontitis. TNFalpha production is influenced by gene polymorphisms. The aim of this study was to evaluate links between genetic variants and chronic/aggressive periodontitis in a multivariate model. SUBJECTS: One hundred and twenty-three periodontitis patients (chronic: n=54, aggressive: n=69) and 52 healthy controls without periodontitis were included in the study. MATERIAL AND METHODS: Single nucleotide polymorphisms (SNPs) c.-308G>A, c.-238G>A and haplotypes were analysed by a polymerase chain reaction with sequence-specific primers (PCR-SSP). The clinical investigation included smoking status, plaque and bleeding indexes, pocket depth and attachment loss. RESULTS: Prevotella intermedia occurred more frequently in individuals positive for the -308GG/-238GG haplotype combination (Odds Ratio=2, 95% Confidence interval: 1.1-3.7, p=0.037, 1-beta=61%). In binary logistic regression analyses, this TNFalpha haplotype could not be shown to be associated with periodontitis considering smoking, age, gender and approximal plaque index or subgingival bacterial colonization as confounding factors. CONCLUSIONS: Although the genetic background of TNFalpha could be shown to be associated with subgingival colonization with P. Intermedia, there is no evidence that it is an independent risk factor for periodontitis in multivariate models.

Human leukocyte antigen polymorphism in chronic and aggressive periodontitis among Caucasians: a meta-analysis.

AIM: Multiple studies have reported associations between periodontitis and particular human leukocyte antigens (HLA). Because associations are inconsistent, we conducted a systematic literature review and a meta-analysis focusing on Caucasian case-control studies. MATERIAL AND METHODS: A literature search reporting on the distribution of HLA class I and II phenotypes in Caucasian patients with chronic periodontitis (CP) and aggressive periodontitis (AP) was performed. Data sources included electronic databases and bibliographies of published articles. Screening and data abstraction were conducted independently by different reviewers. RESULTS: Out of 174 publications, 12 studies were considered to be suitable for meta-analysis. In patients with CP, no significant HLA associations were found. Patients with AP showed a positive association with HLA-A9 [odds ratio=2.59 (95% confidence interval 1.36-4.83), p=0.004] and HLA-B15 [1.90 (1.15-3.16), p=0.01] as well as a negative association with HLA-A2 [0.72 (0.56-0.94), p=0.01] and -B5 [0.49 (0.30-0.79), p=0.004]. On grouping all patients into one periodontitis group (AP+CP), the same deviations were confirmed with higher statistical significance. For HLA-A9 and -B15, significant heterogeneity was found between the studies. No significant associations were found with HLA class II antigens. CONCLUSIONS: HLA-A9 and -B15 seem to represent susceptibility factors for AP whereas HLA-A2 and -B5 are potential protective factors against periodontitis among Caucasians.

Are there common human leucocyte antigen associations in juvenile idiopathic arthritis and periodontitis?

AIM: The aim of this study was to evaluate common human leucocyte antigen (HLA) associations in patients with juvenile idiopathic arthritis (N=110), in patients with generalized aggressive periodontitis (N=50) and in patients with chronic periodontitis (N=102) in comparison to healthy controls (no periodontitis, no arthritis N=102). MATERIAL AND METHODS: HLA-class I and II markers were determined using microlymphocytotoxicity test and polymerase chain reaction with sequence specific primers. Statistical analyses were carried out by chi(2)-test and Yates' correction. If n<5 Fisher's exact test was performed. In the arthritis group the influence of HLA on attachment loss was determined by using backwards logistic regression considering age, gender, smoking, plaque level, and the duration of the disease. RESULTS: In comparison with the controls HLA-DRB3(*) occurred more frequently in both females suffering from juvenile idiopathic arthritis (74.58%versus 54.54%, p=0.024) and females suffering from chronic periodontitis (73.02%versus 54.54%, p=0.035). Furthermore, among patients with juvenile idiopathic arthritis an increased odds ratio (OR) for attachment loss was found in subjects who expressed HLA-A(*)01 (OR=4.6, p=0.014) or HLA-A(*)01:DRB3(*) (OR=4.3, p=0.031). CONCLUSION: HLA-DRB3(*) could be a common putative risk indicator for juvenile idiopathic arthritis and chronic periodontitis among females.

Is there a relationship between juvenile idiopathic arthritis and periodontitis?

AIM: The aim was to compare the prevalence of periodontal conditions in patients with juvenile idiopathic arthritis (JIA) (n=78, age 14.4 years) with those revealed in a healthy control group (n=75, age 15.5 years). MATERIAL AND METHODS: In both groups, the approximal plaque index (API), the modified sulcular bleeding index (SBI), and the clinical attachment loss (CAL) were determined. Laboratory parameters for JIA activity included the capsule-reactive protein (CRP) and the immunoglobulins A, G, M. RESULTS: JIA patients had a significantly higher API (64.6%versus 49.9%, p=0.004) and slightly higher mean percentages of sites with CAL>3.5 mm (0.58%versus 0.22%, p=0.041). There was no significant difference in the prevalence of patients and controls who had sites with CAL >3.5 mm (25.6%versus 17.3%, p=0.212). The mean CAL was slightly greater (0.2 mm; p=0.030) in patients with CRP> or =5.0 mg/l compared with patients with CRP<5.0 mg/l. Patients who took non-steroidal anti-inflammatory drugs (NSAIDs) had a significantly decreased SBI (26.2%versus 51.1%, p=0.019). CONCLUSION: After adjustment for microbial plaque, JIA is not a risk factor for periodontitis.

Meningioma: is there an association with human leukocyte antigens?

The expression of human leukocyte antigen (HLA) alleles plays an important role in the development and recurrence of benign and malignant diseases. Association of single HLA alleles or haplotypes with neoplastic processes has been investigated previously, and correlation between HLA and solid tumors, such as head and neck cancers or uterine cervical squamous epithelial lesions, were reported. However, there is no published data on the influence of the HLA system on the development of symptomatic cerebral meningioma, a mostly benign intracranial tumor of mesenchymal origin in adults. The present investigation is comparing the frequency of single HLA alleles and haplotypes in 81 adult Caucasian patients with symptomatic central nervous system meningiomas to that of 157 area- and race-matched healthy controls. Both standard serological and molecular genetic (PCR) techniques were used for HLA typing. Our results suggest an association between single HLA alleles and occurrence of clinically symptomatic meningioma. Patients with HLA-A*02 had a 2.5-fold increased risk of meningioma (P = 0.02), and those with HLA-DQB1*05 had a 1.8-fold increased risk of meningioma (P = 0.05). Conversely, HLA-A*01, -B*08, and -DRB1*03 were associated with a 0.4-, 0.5-, and 0.5-fold, respectively, decreased risk of meningioma (P = 0.008, P = 0.05, and P = 0.04). Moreover, the occurrence rate of combinations and estimated haplotypes containing these HLA alleles was strikingly different in meningioma patients compared with controls: significantly increased for the haplotypes HLA-A*02:DRB1*04 (P = 0.02, relative risk = 2.5) and HLA-A*02:DRB1*04:DQB1*0302,DQB1*05 (P = 0.03, RR = 7.5), and significantly decreased for the haplotype HLA-A*01:B*08:DRB1*03 (P = 0.01, relative risk = 0.2). In conclusion, these data suggest that some single HLA alleles and haplotypes may protect from or predispose to developing symptomatic central nervous system meningioma during adult life. These associations may be indicative of the involvement of the immune system in the host antitumor surveillance, recognition, and destruction of de novo arising human tumor cells.

Central MHC genes affect IgA levels in the human: reciprocal effects in IgA deficiency and IgA nephropathy.

This study investigates the hypothesis that alternative alleles of one or more genes in the central major histocompatibility complex (MHC) predispose carriers to IgA deficiency (IgAD) or IgA Nephropathy (IgAN). Australian caucasian IgAD, IgAN patients, and controls were typed at HLA loci, single nucleotide polymorphisms, and microsatellites in the MHC. Alleles of the D6S273 microsatellite exhibited strong associations with IgAD and IgAN. D6S273*129 and *139 were more frequent in IgAD and less frequent in IgAN patients than controls. The reverse was true for D6S273*133 and *131. Alleles of other microsatellites exhibited weak associations with IgAD or IgAN. D6S273*129 is found on the 65.1 ancestral haplotype [HLA-B14(65),DR1], which has been reported to be increased in IgAD, but the majority of IgAD patients with D6S273*129 did not have other alleles of the haplotype. D6S273*139 is characteristic of the 8.1 ancestral haplotype (HLA-A1,B8,DR3), which was common in IgAD and rare in IgAN patients. Further studies of the 8.1 haplotype in Australian, German and Spanish caucasian subjects revealed that HLA-DR3, in the absence of -B8, is not associated with IgAD. However -B8 is associated with IgAD in the absence of -DR3, consistent with a susceptibility locus in the central MHC. Provisional mapping within this region is discussed.