Comparison of anti-spike IgG, anti-spike IgA levels and neutralizing antibody activity induced by CoronaVac and BNT162b2 vaccines in patients with inflammatory rheumatic diseases receiving immunosuppressive therapy.

BACKGROUND: The importance of COVID-19 vaccination for patients on immunosuppressive (IS) medication has increased due to the high risk of severe disease or mortality. Different vaccines have varying efficacy rates against symptomatic COVID-19, ranging from 46.8% to 95%. The objective of this study was to examine the differences in anti-Spike IgG, anti-Spike IgA, and neutralizing antibody (NAb) activity between the inactive CoronaVac vaccine and the mRNA-based BNT162b2 vaccine in IS patients. METHOD: A total of 441 volunteers, including 104 IS patients, 263 healthy controls (HC), who received two doses of CoronaVac or BNT162b2, and 74 unvaccinated patients with a history of SARS-CoV-2 infection, were included in the study. Anti-spike IgG, IgA, and NAb activity were investigated. RESULTS: Immunogenicity with BNT162b2 was higher than with CoronaVac, but in IS groups, it was lower than HC (CoronaVac-IS: 79.3%, CoronaVac-HC: 96.5%, p < 0.001; BNT162b2-IS: 91.3%, BNT162b2-HC: 100%, p = 0.005). With CoronaVac, anti-Spike IgG levels were significantly lower than BNT162b2 (CoronaVac-IS: 234.5AU/mL, CoronaVac-HC: 457.85AU/mL; BNT162b2-IS: 5311.2AU/mL, BNT162b2-HC: 8842.8AU/mL). NAb activity in the BNT162b2 group was significantly higher. NAb and anti-Spike IgG levels were found to be correlated. Among the IS group, a significantly lower response to the vaccines was observed when using rituximab. IgA levels were found to be lower with CoronaVac. CONCLUSIONS: Although immunogenicity was lower in IS patients, an acceptable response was obtained with both vaccines, and significantly higher anti-Spike IgG, anti-Spike IgA, and NAb activity levels were obtained with BNT162b2.

Hemodynamic Instability during Thyroidectomy in Graves' Disease.

BACKGROUND: The aim of this study was to investigate the changes in vital signs and hemodynamic status that occur in patients during the intraoperative course of thyroidectomy in Graves' Disease (GD). METHODS: A total of 71 patients were included in the study. Patients were directed to surgery when they had large goiters with compressive symptoms or suspicious nodules, were pregnant or lactating, were unresponsive or intolerant to antithyroid drugs (ATDs), or expressed a preference to have surgery. All patients scheduled for operations underwent surgery while in the euthyroid state. RESULTS: Hemodynamic instability was observed in 18 patients during thyroidectomy. Disease duration, sample weight, and thyroid-stimulating hormone receptor antibodies (TRAb) levels were found to be effective on hemodynamic instability. Logistic regression analysis revealed an 11-fold increase in the instability risk in patients with a period of disease shorter than 21 months (P = 0.037). A TRAb value >11.5 increased the risk by 235fold (p < 0.001). CONCLUSION: High levels of TRAb values and new onset of disease with shorter periods of ATDs use may be risk factors for hemodynamic instability during thyroidectomy. Patients with larger thyroid glands are at greater risk for instability during surgery. Those risks should be taken into account during surgery, and the surgical and anesthetic management of the patient should be made more carefully in concordance with the anesthesia team.

The association between P selectin glycoprotein ligand 1 gene variable number of tandem repeats polymorphism and risk of thrombosis in Behçet's disease.

OBJECTIVES: Behçet's disease (BD) has been recognized as an unclassified type of vasculitis with an accompanying tendency to thrombosis. No disease-specific pathology has been demonstrated so far to explain the prothrombotic state, and this predisposition is considered to be associated with endothelial activation/dysfunction. P-selectin glycoprotein ligand-1 (PSGL-1) variable number of tandem repeat (VNTR) polymorphism has an impact on the protein length, and heterozygosity affect of the PSGL-1 to P-selectin interaction, which has been found to be associated with an increased risk of thrombosis in patients with antiphospholipid syndrome. We aimed to analyze the association of PSGL-1 gene polymorphism, in a group of BD patients with and without thrombosis. METHODS: The study group consisted of 136 BD patients (112 male, 24 female) with thrombosis, 120 BD patients without thrombosis (54 male, 66 female) during at least 5 years disease course, and 190 healthy controls (103 male, 87 female) All patients fulfilled the International Study Group criteria for classification of BD. Genotyping for the PSGL-1 gene exon 2 VNTR polymorphism was carried out with the amplification of genomic DNA and running of the polymerase chain reaction product on agarose gel electrophoresis. RESULTS: The frequency of heterozygous genotypes (AB+AC+BC) was greater in BD patients with thrombosis compared to BD patients without thrombosis (33.1% vs. 20.8%, P = 0.028, odds ratio = 1.85). However, the increased frequency of heterozygous genotypes in BD patients with thrombosis did not reach a statistically significant level compared to healthy controls (33.1% vs. 32.6%). CONCLUSIONS: PSGL-1 VNTR polymorphism may have limited contribution to the thrombotic tendency in patients with BD.

Natural Killer Cell Subsets and Their Functional Activity in Behçet's Disease.

BACKGROUND: Behçet's disease (BD) is a rare, chronic autoinflammatory disorder of unknown origin. Natural killer (NK) cells are one of the major immunoregulatory cell groups of the innate immune system, but their role in BD pathogenesis is not well documented. OBJECTIVES: We aimed to investigate the role of NK cell subsets and their cytokine secretion and cytotoxic activity in patients with BD. PATIENTS AND METHODS: The study group consisted of BD patients who had only mucocutaneous involvement, and they were compared with healthy subjects. BD patients were divided into two groups according to their frequencies of oral ulcerations. NK cell cytotoxicity was determined using CD107a expression and a CFSE-based cytotoxicity test. Expression of NK cell receptors and surface markers and the intracellular IL-5, IL-10, IL-17, and IFN-γ levels in CD16+ NK cells were assessed by flow cytometry. RESULTS: Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells. CONCLUSION: Increases in NK1/NK2 ratio and CD16+IFN-γ+ NK1 cells might support the idea of a biased IFN-γ dominant immune response in the mucocutaneous involvement of BD pathogenesis. Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells.

Low frequency of HLA-B27 in ankylosing spondylitis and its relationship with clinical findings in patients from Turkey.

OBJECTIVE: Human leukocyte antigen B27 (HLA-B27) is strongly associated with ankylosing spondylitis (AS). However, the association between clinical findings and HLA-B27 vary in terms of geographic area. This study aimed to determine the frequency of HLA-B27 positivity and its relationship with clinical findings. MATERIAL AND METHODS: All subjects fulfilling the modified New York diagnosis criteria for AS enrolled in study. The demographic data and histories of the patients were collected retrospectively from patient files. Polymerase chain reaction-based HLA-B27 analysis of all cases was performed. RESULTS: The male to female ratio was 2.5, and mean age of disease onset was 28.3 years. HLA-B27 positivity was detected in 115 patients (70%). Although there was no significant connection between the clinical findings and HLA-B27 positivity, there was a positive relationship between the presence of syndesmophytes and HLA-B27 positivity (p=0.044). The number of patients treated with anti-tumor necrosis factor was higher in the HLA-B27-positive group; however, the difference was not significant (39.1% and 28.9%, respectively). More patients were treated with anti-tumor necrosis factor in the HLA-B27-positive group than in the HLA-B27-negative group; however, the difference was not significant (39.1% and 28.9%, respectively). CONCLUSION: Compared with northern Europe, HLA-B27-positive rate of patients with AS has been shown to be lower in Turkey. Except for the presence of syndesmophytes, there was not a statistically significant relationship between HLA-B27 positivity and clinical and radiologic findings.

High-resolution computed tomography and rheumatoid arthritis: semi-quantitative evaluation of lung damage and its correlation with clinical and functional abnormalities.

BACKGROUND: We aimed to establish risk factors for radiological lung damage associated with rheumatoid arthritis (RA) and determine whether clinical findings and pulmonary function test were correlated with Warrick score calculated on the basis of high-resolution computed tomography or not. METHODS: One hundred thirty RA patients who were followed at rheumatology outpatient clinic were included through retrospective screening. To evaluate radiological involvement, the semi-quantitative evaluation proposed by Warrick was used to assign a score for each lesion based on the severity and extent of the pulmonary damage. In addition to the total score, indices for alveolitis and fibrosis were created. The correlations between each score and clinical and functional parameters were tested for all patients. RESULTS: We showed that age was an independent explanatory variable of radiological lung damage. Percentage of predicted lung diffusion capacity for carbon monoxide (DLco) below 75 % and presence of respiratory symptoms were found to contribute more to radiological lung damage. Warrick score was positively correlated with age at study onset (r = 0.43, p < 0.001). In addition, a negative correlation was found between Warrick score and DLco % predicted (r = -0.357, p = 0.001). Alveolitis index was negatively correlated with DLco % predicted (r = -0.321, p = 0.003). CONCLUSIONS: It is considered that this semi-quantitative method may have added value in early diagnosis, appropriate treatment decisions and follow-up when taken into account together with risk factors associated with pulmonary damage in RA.

Sinus node dysfunction in adult systemic lupus erythematosus flare: A case report.

Cardiac involvement can affect up to 50% of the systemic lupus erythematosus (SLE) patients but conduction system disturbances in SLE are less commonly described. For an early detection of this complication in the acute phase of SLE a whole cardiovascular examination and periodic electrocardiographic monitoring are recommended. We describe a patient who was diagnosed with flare up of lupus activity manifesting as sinus node dysfunction presenting as profound sinus bradycardia. She was successfully treated with high-dose methylprednisolone therapy.

IL-22-secreting Th22 and IFN-γ-secreting Th17 cells in Behçet's disease.

OBJECTIVE: Behçet's disease (BD) is a systemic inflammatory disease with unknown etiology. Studies have shown that some T helper (Th) 1-associated cytokines have role in the inflammation of BD. The CD4(+) Th cells can be differentiated into Th1, Th2, Th17 and Th22 secrete different cytokines to regulate immune system. In this study, cytokine secretion of Th subsets in BD was investigated. METHODS: The study group consisted of 26 BD patients with mucocutaneous involvement and 12 healthy subjects. Lymphocyte subpopulations, IL-5, IL-10, IL-17, IL-22 and IFN-γ secretion of CD4(+) T and Foxp3(+) Treg cells were determined by flow cytometry. RESULTS: Compared with healthy subjects, Th1 (IL-17A(-)IL-22(-)IFN-γ(+)), Th22 (IL-17A(-)IL-22(+)IFN-γ) and IL-17A(+)IFN-γ(+)-secreting cells were significantly increased, and the percentage of Treg cells were dramatically reduced in BD patients. The frequency of recurrent oral ulcers was associated with increased Th22 cells. CONCLUSIONS: Our study describes an association between Th22 cell subset and IL-17A(+) IFNγ(+)-secreting cells with mucocutaneous BD. These findings revealed that reduced levels of Tregs and increased levels of Th1 and Th22 cells as well as Th17/Th1 cells might be associated with the pathogenesis of BD.

MEFV gene variations in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to investigate the frequency of familial Mediterranean fever (FMF)-associated MEFV gene variations in patients with systemic lupus erythematosus (SLE). METHODS: The study group comprised 190 SLE patients and 101 healthy controls of Turkish origin with no clinical features of FMF. All individuals were genotyped for the four most common MEFV gene variations (M694V, M680I, V726A and E148Q) by PCR-restriction fragment length polymorphism analysis. RESULTS: The frequency of carrying any of the four MEFV gene variations under study was 15 % in patients with SLE and 10 % in the healthy controls (p = 0.23). After the exclusion of the less penetrant E148Q variation, re-analysis for the three penetrant mutations revealed a significant association between exon 10 variations and pericarditis [p = 0.038, odds ratio (OR) 3.5, 95 % confidence interval (CI) 1.0-12.1], and pleural effusion (p = 0.043, OR 5.2, 95 % CI 0.8-30.9). No significant association was detected between the MEFV gene variations and a higher acute phase response. CONCLUSIONS: The MEFV gene variations analyzed in our study do not seem to increase the overall susceptibility to SLE and do not have any strong association with its clinical manifestations. The possibility of a modest effect of penetrant exon 10 MEFV variants on the development of serosal effusions needs to be explored in a larger series of patients.

MEFV gene variations in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to investigate the frequency of familial Mediterranean fever (FMF)-associated MEFV gene variations in patients with systemic lupus erythematosus (SLE). METHODS: The study group comprised 190 SLE patients and 101 healthy controls of Turkish origin with no clinical features of FMF. All individuals were genotyped for the four most common MEFV gene variations (M694V, M680I, V726A and E148Q) by PCR-restriction fragment length polymorphism analysis. RESULTS: The frequency of carrying any of the four MEFV gene variations under study was 15 % in patients with SLE and 10 % in the healthy controls (p = 0.23). After the exclusion of the less penetrant E148Q variation, re-analysis for the three penetrant mutations revealed a significant association between exon 10 variations and pericarditis [p = 0.038, odds ratio (OR) 3.5, 95 % confidence interval (CI) 1.0-12.1], and pleural effusion (p = 0.043, OR 5.2, 95 % CI 0.8-30.9). No significant association was detected between the MEFV gene variations and a higher acute phase response. CONCLUSIONS: The MEFV gene variations analyzed in our study do not seem to increase the overall susceptibility to SLE and do not have any strong association with its clinical manifestations. The possibility of a modest effect of penetrant exon 10 MEFV variants on the development of serosal effusions needs to be explored in a larger series of patients.

The association of TNFRSF1A gene and MEFV gene mutations with adult onset Still's disease.

Adult onset Still's disease (ASD) is a systemic inflammatory disorder of unknown etiology. ASD is characterized by fever with unknown etiology, rash, arthritis, and involvement of several organ systems. FMF and TRAPS are two important autoinflammatory diseases which characterized with recurrent inflammatory attacks. We aimed in this study to investigate the MEFV gene and TNFRSF1A gene variations in ASD. Twenty consecutive Turkish ASD patients (14 female and 6 male; mean age 38.45 ± 14; mean disease duration 3.3 ± 2.3; mean age of the disease onset 35.1 ± 14.4) and 103 healthy controls of Turkish origin were analyzed. All ASD patients were genotyped for the 4 MEFV mutations (M694V, E148Q, V726A, M680I) and TNFRSF1A gene exon 2-3 and exon 4-5 by using sequence analysis. The healthy controls are genotyped using PCR-RFLP method for intron 4 variation. The results of MEFV gene mutations screening show an increase in the MEFV mutation rate in ASD group, but it was not significantly different (p = 0.442, OR 1.64, 95 % CI 0.409-6.589). T-C polymorphism (rs1800692) was the only variation in the intron 4 of TNFRSF1A gene that we observed at the ASD patients. The frequency of TT genotype was 15 %, TC: 45 %, and CC: 40 % in ASD patients and the frequencies were 22, 41, and 37 % in healthy controls, respectively. When we analyzed the allele difference between both groups, there was no difference (p = 0.54, OR 1.24, 0.619-2.496-2.654). The variations in MEFV may have role in ASD pathogenesis. Our findings suggest that there is no significant association between ASD and TNFRSF1A variations.

Behçet's disease: immunological relevance with arthritis of ankylosing spondylitis.

Behçet's disease (BD) is a multi-system inflammatory disorder, in which cytokine balance is polarized to Th1. In this study, the cell surface molecule expression, Th1/Th2, inflammatory cytokine levels in blood, and synovial fluid of CD3(+) T lymphocytes in BD were investigated. The study group consisted of 10 BD, 10 ankylosing spondylitis (AS) patients with peripheral arthritis, and 10 healthy subjects. Expression of cell surface molecules, intracellular IL-2, IL-5, IL-8, IL-10, IL-12, IFN-γ, and TNF-α levels in CD3(+) T lymphocytes were determined by flow cytometry in synovial and peripheral blood mononuclear cells (PBMCs). Synovial and plasma cytokine levels were measured by ELISA and CBA. In PBMCs, CD4, CD25, HLA-DR expression and intracellular IL-12, and TNF-α levels of CD3(+) T lymphocytes were statistically increased in BD patients compared to healthy subjects. Compare to AS patients, CD25 and HLA-DR surface expression and intracellular IFN-γ and TNF-α levels in T cells were significantly elevated in BD patients. In BD patients, there was an increase in IL-8 secretion; however, in AS patients, both Th1- and Th2-type cytokines were increased compare to healthy subjects. Intracellular cytokine expression did not show any difference in BD patients; however, IL-12 content of synovial fluid was significantly increased compared to AS patients. Our findings revealed that Th1 polarization occurred in both peripheral blood and synovial fluid of BD patients with arthritis. It is found no difference between synovial fluid analysis of BD and AS patients, showing the similarities in the pathogenesis of both diseases.

A novel TNFRSF1 gene mutation in a Turkish family: a report of three cases.

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autosomal dominantly inherited rare autoinflammatory disease. It is caused by mutations in exons 2-3 and 4-5 of the tumor necrosing factor receptor superfamily 1A (TNFRSF1A) gene on chromosome 12p13.2. TNFRSF1A gene encodes the 55-kDa receptor for tumor necrosis factor. Attacks are associated with abdominal pain, myalgia, erythematous skin rash, conjunctivitis, and periorbital edema. Until now, more than 80 mutations have been identified. We herein report three patients with TRAPS of Turkish origin. The patients were followed up in our outpatient clinic in Kocaeli University Division of Rheumatology. Because of their TRAPS associated clinical features, we isolated genomic DNA from whole blood and sequenced the exon 2-3 and 4-5 third exon of TNFRSF1A gene after amplification with appropriate primers. One of the patients with TRAPS was 47-year-old female, who described recurrent attacks of fever, urticarial rash, conjunctivitis, arthralgia, myalgia, abdominal pain, thoracic pain, headache, fatigue, and elevated acute phase response since her childhood. With the sequencing of the TNFRSF1A gene, we identified heterozygous C29R mutation, which has not been reported before in any TRAPS patient. The other patients are her sons with similar findings and age 29 and 26. They were heterozygous for C29R mutation in TNFRSF1A gene too. We report novel C29R mutation in three TRAPS patients of Turkish origin, in which the main clinical features are recurrent fever attacks, erythematous skin rash, conjunctivitis, myalgia, and arthralgia. Treatment with steroids resolved the symptoms and lesions.

A genome-wide analysis of lentivector integration sites using targeted sequence capture and next generation sequencing technology.

One application of next-generation sequencing (NGS) is the targeted resequencing of interested genes which has not been used in viral integration site analysis of gene therapy applications. Here, we combined targeted sequence capture array and next generation sequencing to address the whole genome profiling of viral integration sites. Human 293T and K562 cells were transduced with a HIV-1 derived vector. A custom made DNA probe sets targeted pLVTHM vector used to capture lentiviral vector/human genome junctions. The captured DNA was sequenced using GS FLX platform. Seven thousand four hundred and eighty four human genome sequences flanking the long terminal repeats (LTR) of pLVTHM fragment sequences matched with an identity of at least 98% and minimum 50 bp criteria in both cells. In total, 203 unique integration sites were identified. The integrations in both cell lines were totally distant from the CpG islands and from the transcription start sites and preferentially located in introns. A comparison between the two cell lines showed that the lentiviral-transduced DNA does not have the same preferred regions in the two different cell lines.

Association of familial Mediterranean fever-related MEFV variations with ankylosing spondylitis.

OBJECTIVE: The pathogenesis of ankylosing spondylitis (AS) has a strong genetic contribution. Familial Mediterranean fever (FMF) is an autosomal recessively inherited autoinflammatory disorder caused by MEFV gene missense variations, and a clinical association between FMF and AS has been reported previously. The aim of this study was to analyze the association of common MEFV variations (M694V, M680I, V726A, and E148Q) with AS in a group of Turkish patients. METHODS: The study group comprised 193 patients with AS and 103 matched healthy control subjects. All individuals were genotyped for 4 MEFV variations and HLA-B27 using genomic DNA, and association of the variations with the clinical and laboratory features of the patients was analyzed. RESULTS: The MEFV missense variations were significantly more frequent in patients with AS (22.3%) compared with healthy control subjects (9.7%; odds ratio [OR] 2.67, 95% confidence interval [95% CI] 1.28-5.56). This difference was more prominent for exon 10 variations (M694V, V726A, M680I) (OR 3.75, 95% CI 1.41-9.97), especially for the most-penetrant variation M694V (OR 4.73, 95% CI 1.39-16.12). MEFV variations were more frequent in HLA-B27-negative patients with AS, and the difference was statistically significant in patients carrying exon 10 variants. CONCLUSION: FMF-related MEFV variations are associated with AS, and these variations may contribute to the pathogenesis of AS, especially in populations in which the prevalence of FMF is high.

Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease.

Behçet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behçet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behçet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 x 10(-8)). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 10(-9), OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production.

Low-dose natural human interferon-alpha lozenges in the treatment of Behçet's syndrome.

OBJECTIVES: There had been evidence that low-dose local IFN could be beneficial in the management of recurrent oral ulcers (OUs). We investigated the efficacy and collected initial data on the safety of low-dose natural human IFN-alpha administered by the oral mucosal route in Behçet's syndrome (BS) in a placebo controlled, double blind study. METHODS: Eighty-four (59 males and 25 females) patients with BS with mainly skin mucosa disease and a history of recurrent OU for > or = 1 year were studied. When they had at least two OUs with a total diameter of > or = 4 mm, they were randomly allocated to (i) 2000 IFN-alpha IU/day, (ii) 1000 IFN-alpha IU/day and (iii) placebo groups. Subjects were monitored weekly over an initial 4 weeks and bi-weekly for an additional 8 weeks of treatment. OU were counted and measured at each study visit. The primary efficacy end point was the difference in the total ulcer burden at Week 0 compared with that at Week 12. RESULTS: Out of the 84 patients enrolled, 72 completed the trial. There were no statistically significant differences between the treatment arms in terms of the primary endpoint. CONCLUSIONS: Low-dose natural human IFN-alpha did not have beneficial effects on reducing the total ulcer burden among BS patients from Turkey. The study also showed that counting the number of ulcers rather than measuring the size would be adequate in future studies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00483184, http://www.clinicaltrials.gov/ct2/results?term=NCT00483184.

No association of the TLR2 gene Arg753Gln polymorphism with rheumatic heart disease and Behçet's disease.

Behçet's disease (BD) is a multisystem inflammatory disorder of unknown etiology, and infections with different microorganisms including streptococci have been claimed as triggers of inflammatory attacks in BD pathogenesis. Toll-like receptor 2 (TLR2) has been known to recognize several microbial antigens including that of streptococci, and TLR2 gene Arg753Gln polymorphism has been reported to be strongly associated with acute rheumatic fever with an odds ratio of 100. This study aimed to investigate the TLR2 gene Arg753Gln polymorphism in a group of patients with BD and rheumatic heart disease (RHD) and to analyze the role of genotyping errors resulting from duplicated gene segments. The study group consisted of 211 patients with BD, 95 patients with RHD, and 94 matched Turkish healthy controls. Because of the duplicated exon 3 in 23-kb upstream of the TLR2 gene, genotyping for the Arg753Gln polymorphism with polymerase chain reaction-restriction fragment length polymorphism method was carried out using a new set of primers and PstI restriction enzyme. TLR2 gene Gln753 allele was observed in two of 211 (1.0%) patients with BD, five of 95 (5.3%) patients with RHD, and two of 94 (2.1%) healthy controls. All patients and controls were found to be heterozygous for Arg753Gln polymorphism, except one patient with BD, who was homozygous for Gln753. Although a slight increase of heterozygosity was noted in patients with RHD, no statistically significant difference was observed in the distribution of Arg753Gln polymorphism in BD and RHD compared to healthy controls. In conclusion, TLR2 gene Arg753Gln polymorphism is not associated with BD nor with RHD; and a duplicated region of the TLR2 exon 3 located 23-kb upstream of the polymorphic region may explain contradictory association findings described so far.

Prevalence and virological features of occult hepatitis B virus infection in female sex workers who work uncontrolled in Turkey.

BACKGROUND: There is little information about the prevalence of occult hepatitis B virus infection (OHBVI). We have investigated the prevalence and virological features of OHBVI among female sex workers (FSWs) in Istanbul. METHODS: Hepatitis B surface antigen (HBsAg) was tested in FSWs who work uncontrolled and were admitted to Venereal Diseases Hospital. HBV DNA and anti-HBs were investigated in all the HBsAg-negative cases. Hepatitis B envelope (HBe) antigen, anti-HBe, anti-hepatitis B core (HBc) antigen, HBV genotype, S gene and precore (PC)/basic core promoter (BCP) mutations were determined in HBV DNA-positive sera. RESULTS: Two hundred and eighty-six volunteers were enrolled and 32.5% (n=93) of them had anti-HBs positivity. HBV DNA (range 30-209 copy/ml) was positive in 11 anti-HBs-negative and two anti-HBs-positive cases. The prevalence of OHBVI was 4.5% (13/286). Anti-HBc was positive in 77% (10/13) of those with OHBVI and anti-HBe positivity was 53.8% (7/13). Only genotype D was present in all occult HBV-infected cases. One PC (G1896A) and one BCP (T1762/A1764) mutation was found, but S gene mutation was not detected in any of the samples. CONCLUSION: In this population, OHBVI may have a negligible role in the horizontal transmission because of a very low viral load, and PC and core promoter mutations are very rare.