Evaluation of the Th17 pathway in psoriasis and geographic tongue.

BACKGROUND: Psoriasis is a skin-articular disease with unclear etiopathogenesis. It has been suggested that the disease is immune-mediated by T-lymphocytes, predominantly Th17 cells. Similar to psoriasis, geographic tongue is an inflammatory disease with participation of Th17 cells and direct correlation with psoriasis. OBJECTIVE: To investigate and compare the inflammatory responses and the Th17 pathway in psoriasis and geographic tongue. METHODS: This was a cross-sectional study with 46 participants that were categorized into three groups: (A) patients with psoriasis vulgaris; (B) patients with geographic tongue and psoriasis; (C) patients with geographic tongue without psoriasis. All patients underwent physical examination, and a skin and oral biopsy for histopathological examination and immunohistochemical analysis with anti-IL6, anti-IL17, and anti-IL23 antibodies. RESULTS: Histological analysis of all lesions showed mononuclear inflammatory infiltrate. However, moderate intensity was prevalent for the patients with geographic tongue and psoriasis and geographic tongue groups. Immunopositivity for the antibodies anti-IL6, anti-IL17, and anti-IL23 revealed cytoplasmic staining, mainly basal and parabasal, in both psoriasis and geographic tongue. Regarding IL-6, in patients with geographic tongue and psoriasis cases the staining was stronger than in patients with geographic tongue without psoriasis cases. IL-17 evidenced more pronounced and extensive staining when compared to the other analyzed interleukins. IL-23 presented similar immunopositivity for both geographic tongue and psoriasis, demonstrating that the neutrophils recruited into the epithelium were stained. STUDY LIMITATION: This study was limited by the number of cases. CONCLUSION: The inflammatory process and immunostaining of IL-6, IL-17, and IL-23 were similar in geographic tongue and psoriasis, suggesting the existence of a type of geographic tongue that represents an oral manifestation of psoriasis.

Evaluation of the Th17 pathway in psoriasis and geographic tongue

Abstract Background: Psoriasis is a skin-articular disease with unclear etiopathogenesis. It has been suggested that the disease is immune-mediated by T-lymphocytes, predominantly Th17 cells. Similar to psoriasis, geographic tongue is an inflammatory disease with participation of Th17 cells and direct correlation with psoriasis. Objective: To investigate and compare the inflammatory responses and the Th17 pathway in psoriasis and geographic tongue. Methods: This was a cross-sectional study with 46 participants that were categorized into three groups: (A) patients with psoriasis vulgaris; (B) patients with geographic tongue and psoriasis; (C) patients with geographic tongue without psoriasis. All patients underwent physical examination, and a skin and oral biopsy for histopathological examination and immunohistochemical analysis with anti-IL6, anti-IL17, and anti-IL23 antibodies. Results: Histological analysis of all lesions showed mononuclear inflammatory infiltrate. However, moderate intensity was prevalent for the patients with geographic tongue and psoriasis and geographic tongue groups. Immunopositivity for the antibodies anti-IL6, anti-IL17, and anti-IL23 revealed cytoplasmic staining, mainly basal and parabasal, in both psoriasis and geographic tongue. Regarding IL-6, in patients with geographic tongue and psoriasis cases the staining was stronger than in patients with geographic tongue without psoriasis cases. IL-17 evidenced more pronounced and extensive staining when compared to the other analyzed interleukins. IL-23 presented similar immunopositivity for both geographic tongue and psoriasis, demonstrating that the neutrophils recruited into the epithelium were stained. Study limitation: This study was limited by the number of cases. Conclusion: The inflammatory process and immunostaining of IL-6, IL-17, and IL-23 were similar in geographic tongue and psoriasis, suggesting the existence of a type of geographic tongue that represents an oral manifestation of psoriasis.

Geographic tongue: assessment of peripheral nerve status, Langerhans cell, and HLA-DR expression.

OBJECTIVES: The objectives of this study were to determine whether geographic tongue (GT) is an antigen-driven condition by assessing Langerhans cell numbers and the expression of human leukocyte antigen (HLA)-DP, -DQ, and -DR in the epithelium of GT and to assess peripheral nerve status for any possible damage/injury association by quantifying neurite area in connective tissue in GT. STUDY DESIGN: Randomly selected samples of GT were examined by using routine immunoperoxidase staining methods to S100 protein, neurofilament, CD1a, and HLA class II. The Student t test and Mann-Whitney U test were used to assess statistical significance. RESULTS: Langerhans cell numbers were found to be increased in GT. HLA expression was also seen in Langerhans cells and inflammatory cells and in the spinous layer and parabasal epithelial cells in 2 samples of GT. Total nerve tissue, based on area measurements, was not significantly different between GT and control tissues. CONCLUSIONS: The increase in Langerhans cells suggests that GT is a condition that is likely driven by an unknown external antigen. Peripheral nerve damage was not apparent, suggesting that this is not a mechanism whereby patients with GT become symptomatic.

The prevalence of celiac disease in patients with geographic tongue.

BACKGROUND: Geographic tongue (GT) is a benign inflammatory condition usually involving the dorsal surface and lateral borders of the tongue. Numerous etiological factors of GT have been suggested, including immunological factors; genetic; atopic or allergic predisposition; emotional stress; and hormonal disturbances. GT may also coexist as one of the possible manifestations of celiac disease (CD). Therefore, the aim of this study was to investigate the prevalence of CD, positive serologic tests for CD screening, and HLA-DQ presence in patients with GT. METHODS: Tissue transglutaminase antibodies (anti-tTG), antibodies against gliadin (AGA), and human leukocyte antigen (HLA) typing were assessed for 60 GT patients and 60 healthy control subjects. The duodenal biopsy was performed in patients with positive serologic tests. RESULTS: We found that 9 (15%) GT patients were positive for IgA tTG, and in those patients histological changes consistent with CD were confirmed by duodenal biopsy. Only two of them reported the presence of gastrointestinal symptoms. There were statistically significant differences between the GT patients and control group for immunoglobulin (Ig) A tTG (P = 0.03), IgG tTG (P = 0.04), IgA AGA (P = 0.04), and IgG AGA (P = 0.02). CONCLUSION: The results of our study demonstrated the increased prevalence of CD in patients with GT. Therefore, the clinical oral examination should be considered a diagnostic tool, especially in atypical or silent forms of CD, since it may contribute to provide an early diagnosis.

A possible relationship of human leucocyte antigens with psoriasis vulgaris and geographic tongue.

BACKGROUND: Geographic tongue (GT) is the most frequent oral lesion in psoriatic patients (PP), and genetic involvement in these conditions has been described. The association of psoriasis with GT is still not clear, and the study of human leucocyte antigen (HLA) may help clarify this relation. OBJECTIVE: The aim of this study was to investigate the association of HLA alleles with psoriasis vulgaris and GT. METHODS: Fifty-eight Brazilian PP, 29 GT patients and 125 healthy controls individuals were selected. Information on demographic and clinical characteristics was collected. All patients underwent an oral examination and blood collection for HLA typing. RESULTS: HLA-A did not show significant differences in frequencies among the groups. HLA-B*57 allele was more frequently found in PP and was not found in GT. HLA-B*58 allele was more frequently found in GT. HLA-C*06 and -C*18 alleles were associated with psoriasis. No significant differences in HLA-DRB1 and HLA-DQB1 were observed. CONCLUSION: HLA-B*58 was associated with GT and HLA-B*57 was possibly associated with psoriasis. This suggested that some GT cases may represent true oral psoriasis and some may represent only GT. Therefore, it is necessary to make this distinction and increase our sample size to improve the correct diagnosis and treatment of these conditions.

Immunologic and psychologic parameters associated with geographic tongue.

OBJECTIVE: Several conditions have been associated with geographic tongue (GT). However, there is no consensus on the etiology of GT. The purpose of this study was to investigate whether immunologic and psychologic parameters are associated with diagnosis of GT. STUDY DESIGN: A case-control study was performed on 170 participants (85 with GT, 85 controls). Unstimulated whole saliva was collected, and tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) concentrations were measured. Anxiety level was measured using psychologic and physiologic testing instruments. An independent t test and a Pearson correlation analysis were performed with SPSS (α = .05). RESULTS: There was a significant difference between the 2 groups regarding the salivary concentrations of TNF-α (P = .008) and IL-6 (P = .001). The concentration of salivary cortisol and state and trait anxiety levels in the GT group were significantly higher than those in the control group (P = .001). CONCLUSIONS: Immunologic and psychologic parameters appear associated with GT and may constitute risk factors of this condition.

Neutrophil extracellular traps entrap and kill Borrelia burgdorferi sensu stricto spirochetes and are not affected by Ixodes ricinus tick saliva.

Lyme disease is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. They are transmitted mainly by Ixodes ricinus ticks. After a few hours of infestation, neutrophils massively infiltrate the bite site. They can kill Borrelia via phagocytosis, oxidative burst, and hydrolytic enzymes. However, factors in tick saliva promote propagation of the bacteria in the host even in the presence of a large number of neutrophils. The neutrophil extracellular trap (NET) consists in the extrusion of the neutrophil's own DNA, forming traps that can retain and kill bacteria. The production of reactive oxygen species is apparently associated with the onset of NETs (NETosis). In this article, we describe NET formation at the tick bite site in vivo in mice. We show that Borrelia burgdorferi sensu stricto spirochetes become trapped and killed by NETs in humans and that the bacteria do not seem to release significant nucleases to evade this process. Saliva from I. ricinus did not affect NET formation by human neutrophils or its stability. However, it greatly decreased neutrophil reactive oxygen species production, suggesting that a strong decrease of hydrogen peroxide does not affect NET formation. Finally, round bodies trapped in NETs were observed, some of them staining as live bacteria. This observation could help contribute to a better understanding of the early steps of Borrelia invasion and erythema migrans formation after tick bite.

Associations of HLA DR and DQ molecules with Lyme borreliosis in Latvian patients.

BACKGROUND: Many autoimmune diseases are associated with variants of HLA genes such as those encoding the MHC complex. This correlation is not absolute, but may help in understanding of the molecular mechanism of disease. The purpose of this study was to determine HLA-DR,-DQ alleles in Latvian patients with Lyme borreliosis and control (healthy) persons. Case patients and control subjects were similar in age, gender and ethnic heritage and differed only as regards the presence of Borrelia burgdorferi infection. The study included 25 patients with clinical stage - erythema migrans and 30 control (healthy) persons. HLA genotyping was performed by PCR with sequence-specific primers. RESULTS: The results show difference in HLA-DRB1 alleles distribution between patients and control subjects. The frequencies of HLA-DRB1 *04 (OR 11.24; p < 0.007) and HLA-DRB1 *17 (03) (OR 8.05; p < 0.033) were increased in the Lyme disease patients. And the frequency of allele DRB1*13 (OR 0.12; p < 0.017) was lower in Borreliosis patients and higher in control group. But, significant differences in frequencies of HLA-DQ alleles we did not detect. CONCLUSIONS: HLA predisposition to Lyme borreliosis appears not to be limited to HLA molecules, but some HLA-DR alleles also have a significant influence, and, may have implications in our understanding of pathogenesis of this disease. In particular, HLA-DRB1*04 and DRB1 *17 (03) may contribute to the Lyme borreliosis development in Latvian population.

Direct molecular detection and genotyping of Borrelia burgdorferi from whole blood of patients with early Lyme disease.

Direct molecular tests in blood for early Lyme disease can be insensitive due to low amount of circulating Borrelia burgdorferi DNA. To address this challenge, we have developed a sensitive strategy to both detect and genotype B. burgdorferi directly from whole blood collected during the initial patient visit. This strategy improved sensitivity by employing 1.25 mL of whole blood, a novel pre-enrichment of the entire specimen extract for Borrelia DNA prior to a multi-locus PCR and electrospray ionization mass spectrometry detection assay. We evaluated the assay on blood collected at the initial presentation from 21 endemic area patients who had both physician-diagnosed erythema migrans (EM) and positive two-tiered serology either at the initial visit or at a follow-up visit after three weeks of antibiotic therapy. Results of this DNA analysis showed detection of B. burgdorferi in 13 of 21 patients (62%). In most cases the new assay also provided the B. burgdorferi genotype. The combined results of our direct detection assay with initial physician visit serology resulted in the detection of early Lyme disease in 19 of 21 (90%) of patients at the initial visit. In 5 of 21 cases we demonstrate the ability to detect B. burgdorferi in early Lyme disease directly from whole blood specimens prior to seroconversion.

[Immunological mechanism of exfoliative tongue fur in children with asthma].

OBJECTIVE: To explore the immunological mechanism of exfoliative tongue fur in children with asthma. METHODS: Thirty-nine children with asthma, twenty-eight children with repetitive respiratory tract infection (non-asthma) and eleven healthy children were divided into five groups, which were asthma with exfoliative fur or with non-exfoliative fur groups, non-asthma with exfoliative fur or with non-exfoliative fur groups and normal control group. The concentrations of keratin 13 and bcl-2 in cells exfoliated from tongue fur were detected by immunohistochemical method. The expression levels of blood cell chemokine receptor-3 (CCR-3) and CD4(+) were examined by flow cytometry, and the levels of serum cortisol and IgE were detected by radioimmunoassay. RESULTS: The levels of blood CD4(+) and CCR-3 of children with asthma and exfoliative fur were higher than those in the asthma with non-exfoliative fur group and the normal control group (P<0.05). The serum level of cortisol in the groups of asthma with exfoliative fur and non-asthma with exfoliative fur were lower than that in the other groups (P<0.05). The serum levels of IgE in asthma with exfoliative fur or with non-exfoliative fur groups were higher than that in the other groups (P<0.05). Concentrations of keratin 13 in the cells exfoliated from tongue fur in the groups of asthma or non-asthma with exfoliative fur were lower than that of the other groups (P<0.05). There was no significant difference of expression level of bcl-2 in the cells exfoliated from tongue fur among these five groups. CONCLUSION: There is a reasonably close relationship between the formation of exfoliative tongue fur and the immune system such as low level of serum cortisol and high levels of blood CD4(+) and CCR-3, which may all promote the formation of exfoliative fur. The disability of keratinization and apoptosis of epithelial cells of tongue may also be one cause for its formation.

Hypersensitivity of the oral mucosa: clinics and pathology.

Hypersensitivity reactions of the oral mucosa comprise an array of clinical manifestations. Some of the reactions are difficult to differentiate from toxic reactions. Hypersensitivity reactions of type I, type III, and type IV are well known, although, especially for types I and III, they are rarely encountered. Type-I reactions are most frequently seen related to application of polymers in the oral cavity, such as orthodontic bonding and fissure sealant materials. There may also be systemic manifestations such as urticaria. Type-IV reactions may be seen related to most dental materials used, from amalgam and gold to polymers. These reactions appear as chronic reddening and/or ulceration of the oral mucosa. Lichenoid reactions have histopathological characteristics compatible with type-IV hypersensitivity reactions and are the most prevalent material-adverse reactions seen in the oral cavity. A special variety inside the lips with multiple papules and/or diffuse redness has recently been identified. This lesion comprises a serious treatment challenge. Skin patch tests, applying a series of dental materials in non-toxic concentrations on the skin, have been used to identify sensitization. However, the value of those tests can be questioned. Exacerbation of geographic stomatitis may be another form of hypersensitivity to dental materials.

Both psoriasis and benign migratory glossitis are associated with HLA-Cw6.

This study was undertaken to investigate human leucocyte antigen (HLA) associations with benign migratory glossitis and psoriasis in Brazilian patients and particularly to determine whether benign migratory glossitis is also associated with HLA-Cw6, the classical association observed in psoriasis. The results showed a highly significant association of Cw6 with both psoriasis and benign migratory glossitis, with this antigen being present in 59.1% of the patients with psoriasis, in 43.8% of the patients with benign migratory glossitis, and in only 12.6% of the controls. Other significant positive associations, although at a lower significance level, were with B13, both in psoriasis and in benign migratory glossitis, and with B17, only in psoriasis. To our knowledge, this is the first report on the association of Cw6 with benign migratory glossitis. We believe that this finding reinforces the concept of a pathogenetic relationship between benign migratory glossitis and psoriasis.

Histocompatibility antigens and geographic tongue.

The HLA-A, B and HLA-DR antigens were investigated in 50 unrelated Greek persons with geographic tongue and in 380 healthy control persons. An increased incidence of DR5 and DRW6 antigens was observed in the blood of persons with geographic tongue. Ten (20%) of them had the DRW6 antigen, and it was significantly increased compared with 29 (7.6%) of the controls (p < 0.01, RR = 3.32). Twenty-seven (54%) of the experimental group showed DR5 antigen compared with 136 (35.7%) of the controls (p < 0.025, RR = 2.18). On the contrary, only 12% (5) of the experimental group had the B51 antigen in comparison with the controls (26.3%) (p < 0.05, RR = 0.37). A decrease of the DR2 antigen was also found in the persons with geographic tongue (24%) in comparison with the controls (39.2%) (p < 0.05, RR = 0.58).

Benign migratory glossitis in patients with juvenile diabetes.

The prevalence of tissue type HLA-B15 has been shown to be higher in atopic patients with benign migratory glossitis and in patients with insulin-dependent diabetes mellitus than it is in the general population. Despite this apparent link, the possible relationship between benign migratory glossitis and insulin-dependent diabetes mellitus does not appear to have been investigated previously. This study of 87 diabetic patients and 105 age- and sex-matched nondiabetic control subjects revealed a fourfold increase in the prevalence of benign migratory glossitis in the diabetic group. These results suggest that benign migratory glossitis may be linked to diabetes mellitus and that further investigation of this association is warranted.

Antibodies of patients with Lyme disease to components of the Ixodes dammini spirochete.

Lyme disease is an inflammatory disorder of skin, joints, nervous system, and heart. The disease is associated with a preceding tick bite and is ameliorated by penicillin treatment. A spirochete (IDS) isolated from Ixodes dammini ticks has been implicated as the etiologic agent of Lyme disease. We examined the antibody responses of Lyme disease patients to IDS lysate components in order to further understand the pathogenesis of this disease. The components were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, reacted with patients' sera, and the bound IgG was detected with 125I-labeled protein A (western blot). We found that (a) Lyme disease patients had antibodies to IDS components (b) most patients studied had antibodies to two components with apparent subunit molecular weights of 41,000 and 60,000, and (c) the patients' antibody responses during illness and remission were specific, for the most part, for the IDS. In contrast to the findings with Lyme disease sera, sera from controls showed little reactivity with IDS components in either the western blots or a derivative solid-phase radioimmunoassay.

HLA antigens in geographic tongue.

HLA-A,B,C phenotyping was performed on 95 patients with geographic tongue to determine whether there is an increased frequency of any particular allele in this condition. An increased frequency of B15 was found in the patients when compared to normal controls. When the patients were divided into atopic and non-atopic groups there was an increased frequency of B15 and a decreased frequency of B40 in the atopic group compared to the controls. B40 was as decreased in the atopic group when compared to the non-atopic group. When the type I correction factor was applied to the probability values the differences in antigen frequencies in all cases became insignificant.