A shared motif of hla-dpb1 affecting the susceptibility to pr3-anca positive granulomatosis with polyangiitis: comparative analysis of a Turkish cohort with matched healthy controls.

We aimed to analyse the distribution of HLA Class 2 genotypes which were reported among the genetic risk factors for ANCA-associated vasculitis (AAV) among Turkish patients in comparison with healthy subjects and previously reported data of AAV cohorts. Ninety-eight patients (F/M: 47/51 and mean age: 49 ± 1.14) were enrolled in the study and records of gender and birthplace-matched 196 healthy kidney donors were used as the control group. Patients were classified according to the clinical subgroups and ANCA serotypes (MPO-AAV, PR3-AAV). DNA was isolated from venous blood from all patients, and high-resolution HLA Class 2 genotyping was carried out by using NGS-Omixon Holotype HLA Kit. The frequencies of HLA-DQB1*03:03, - *06:04, and -DPB1*13:01, -*16:01 and -*66:01:00 alleles were significantly higher, and the frequencies of HLA-DQB1*02:02, -DPB1*02:01 and -*04:01 alleles were lower in the PR3-AAV subgroup (n = 53) compared to the controls. Comparison of amino acid sequences of the associated HLA-DPB1 alleles revealed the sequence of D-E-A-V in risk alleles replaced with the G-G-P-M sequence in protective alleles between 84 and 87th positions. Structural analysis of the HLA-DPB1*02:01 showed that this shared position is in the contact area between HLA-DP α and ß chains and within pocket 1 of the antigen-binding groove. First HLA genotyping analysis in Turkish AAV patients revealed a negative correlation between PR3-ANCA positivity and certain HLA-DPB1 alleles contradictory to the results reported from European cohorts. Known functional effects of D-E-A-V sequence on HLA-DPB1 support the importance of our finding, but further studies are needed to reveal its pathogenic mechanisms.

Nigella sativa (black seed) oil does not affect the T-helper 1 and T-helper 2 type cytokine production from splenic mononuclear cells in allergen sensitized mice.

Nigella sativa Linn. (Ranunculaceae) is known to have beneficial effects on a wide range of diseases including asthma. However, the mechanism of action in asthma and other allergic diseases is not entirely clear. The present study was planned to evaluate the effects of Nigella sativa on cytokine production of splenic mononuclear cells in ova-sensitized mice. Nineteen two-month-old BALB/c mice were given 0.3 mL of Nigella sativa oil by oro-eosophageal cannula once a day for a month. The control group consisting of 10 mice took 0.3 mL of 0.9% saline solution by the same route for the same period. In the third week of the study, all mice were sensitized by means of intraperitoneal injections of 20 microg of ovalbumin (OVA-Grade VI, Sigma). Ova injections were repeated three times with 7-day intervals. After another week, all mice were sacrificed by means of cervical dislocation. Then the splenic mononuclear cells (MNCs) of mice were cultured with OVA or Concavalin A (Con-A). From the culture supernatants, IL-4, IL-10 and IFN-gamma were assessed by means of ELISA. The cytokine production of splenic MNCs of mice that were given Nigella sativa for 30 days was not significantly different than those who took saline solution instead. In conclusion, Nigella sativa oil seems not to have an immunomodulatory effect on Th1 and Th2 cell responsiveness to allergen stimulation.

Sister chromatid exchanges in lymphocytes of nuclear medicine physicians.

OBJECTIVE: The aim of this study was to assess whether occupational exposure to chronic, low doses of Iodine 131 (I-131) and Technetium 99m (Tc-99m) may lead to genotoxicity. Medical personnel occupied in nuclear medicine departments are occupationally exposed to low doses of I-131 and Tc-99m. The determination of the frequency of sister chromatid exchanges (SCEs) and of cells with a high frequency of SCEs (HFC) is considered to be a sensitive indicator for detecting genotoxic potential of mutagenic and carcinogenic agents. Therefore, we examined peripheral lymphocytes from nuclear medicine physicians for the presence of both SCE and HFC. METHODS: Sixteen exposed nuclear medicine physicians (non-smokers) were compared to 16 physicians (non-smokers) who had not been exposed to chemical or physical mutagens in their usual working environment at the same hospital. RESULTS: A statistically significant difference was found between SCE frequencies and HFC percentages measured in lymphocytes from the exposed and control groups. CONCLUSIONS: The present observation on the effect of chronic low doses of I-131 and Tc-99m indicates the possibility of genotoxic implications of this type of occupational exposure. Hence, the personnel who work in nuclear medicine departments should carefully apply the radiation protection procedures and should minimize, as low as possible, radiation exposure to avoid possible genotoxic effects.