Decreased regulatory T‐cells and CD4+/CD8+ ratio correlate with disease onset and progression in patients with generalized vitiligo

The aim of present study was to evaluate CD4⁺/CD8⁺ ratio and CD4⁺CD25^hiFoxP3⁺ Tregs in GV patients with reference to their effect on disease onset and progression. Flow cytometry was used for determination of CD4⁺/CD8⁺ ratio and Tregs in 82 patients and 50 controls. CD8⁺ T‐cell counts were significantly higher in GV patients as compared with controls (p = 0.003). Active GV patients showed higher CD8⁺ T‐cell counts compared with stable GV patients (p = 0.001). The CD4⁺/CD8⁺ ratio decreased significantly in patients as compared with controls (p = 0.001). Moreover, the ratio in active GV patients significantly lowered as compared with stable GV patients (p = 0.002). Significant decrease in Treg cell percentage and counts in GV patients was observed compared with controls (p = 0.009, p = 0.008) with significant reduction in FoxP3 expression (p = 0.024). Treg cell percentage and counts were significantly decreased in active GV patients compared with stable GV patients (p = 0.007, p = 0.002). Our results suggest that an imbalance of CD4⁺/CD8⁺ ratio and natural Tregs in frequency and function might be involved in the T‐cell mediated pathogenesis of GV and its progression.     

Polymorphic variant at the IL2 region is associated with type 1 diabetes and may affect serum levels of interleukin-2

Polymorphic variants at the interleukin-2 (IL2) locus affect the risk of several autoimmune disorders. Our aim was to evaluate the association of the four IL2 polymorphisms (rs6822844, rs6534349, rs2069762 and rs3136534) with type 1 diabetes (T1D) in the Polish population, and to correlate them with the serum interleukin-2 levels. 543 unrelated T1D patients and 706 healthy control subjects were enrolled. The minor T allele at rs6822844 was significantly less frequent in T1D compared to controls (p = 0.002; OR 0.71; 95 % CI 0.571–0.880). Likewise, the frequency of the TT genotype was decreased among the affected individuals (p = 0.007). In healthy subjects, stratification according to the rs6822844 genotype revealed significant differences in circulating interleukin-2 (p = 0.037) with the highest levels in TT protective genotypes. Three other IL2 polymorphisms did not display significant differences in allele and genotype distribution. In conclusion, the rs6822844 variant is associated with T1D and may play a functional role, or reflect the influence of another causative genetic variant in linkage disequilibrium.     

Serum selenium versus lymphocyte subsets and markers of disease progression and inflammatory response in human immunodeficiency virus-1 infection

Serum selenium levels were determined cross-sectionally in 57 HIV-infected patients who were classified according to the Centers for Disease Control (CDC) 1993 classification system. Mean serum selenium levels were lower in CDC stage II (58.7±12.2 μg/L;p<0.01;n=18) and stage III (47.6±11.3 μg/L;p<0.01;n=19) HIV-infected patients, than in healthy subjects (80.6±9.6 μg/L;n=48) and stage I patients (73.6±16.5 μg/L;n=20). Serum selenium levels were positively correlated with CD4 count, CD4/8 ratio, hematocrit, and serum albumin (r=0.42;r=0.39;r=0.48; andr=0.45;p<0.01, respectively) and inversely with serum levels of thymidine kinase (r=−0.49;p<0.01;n=49) and β2-microglobulin (r=−0.46;p<0.001;n=49). In addition, serum selenium levels in 20 randomly selected AIDS-free individuals (CDC I:n=10; CDC II:n=10) were inversely correlated with serum concentrations of interleukin-8 (IL-8) and soluble tumor necrosis factor receptors (sTNFR) types I and II. There was no correlation with serum immuneglobulin A and total serum protein levels. The results show that the progressive deprivation of serum selenium in HIV-infection is associated with loss of CD4⁺-cells and with increased levels of markers of disease progression and inflammatory response.     

Ozone therapy restores immune dysfunction in refractory idiopathic granulomatous mastitis as a novel potential therapeutic approach

Immunological dysfunction has been suggested to play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). We recently showed that ozone therapy was effective in patients with steroid-resistant IGM. This study assessed alterations in intracellular cytokine expression patterns in different T-lymphocyte subsets after ozone therapy in refractory IGM. Peripheral blood T lymphocyte subsets (CD8⁺, CD4⁺, CD4⁺CD25⁺CD127⁻) were analyzed via flow-cytometry for intracellular cytokine expressions IFN-γ, TNF-α, IL-10, and TGF-β before and after completion of 4-month systemic ozone therapy. Ozone therapy significantly increased the CD4⁺IFN-γ⁺ (p = 0.032), CD4⁺TNF-α⁺ (p = 0.028), and the CD8⁺TNF-α⁺ (p = 0.012) T cells. In contrast, significant decreases in CD4⁺ IL-10⁺ (p = 0.047) and CD8⁺IL-10⁺ T cells (p = 0.022) and CD4⁺CD25⁺CD127^−//low Treg cells secreting TGF-β (p = 0.005) were found after ozone therapy. When patients were analyzed according to the response to ozone therapy, patients with a complete remission were more likely to have increased CD3⁻CD16⁺CD56⁺ natural killer cells (p = 0.0027) and decreased CD19⁺ B lymphocytes (p = 0.046) following ozone therapy. Our results suggest that ozone therapy stimulated a T-helper-1 response associated with IFN-γ production and downregulation of TGF-β expression in CD4⁺CD25⁺CD127⁻ Treg cells. These alterations in the immune system following ozone therapy can improve wound healing and restore immune dysfunction in patients with refractory IGM.     

Difference of immune cell infiltration between stable and unstable carotid artery atherosclerosis

Atherosclerotic plaque instability contributes to ischaemic stroke and myocardial infarction. This study is to compare the abundance and difference of immune cell subtypes within unstable atherosclerotic tissues. CIBERSORT was used to speculate the proportions of 22 immune cell types based on a microarray of atherosclerotic carotid artery samples. R software was utilized to illustrate the bar plot, heat map and vioplot. The immune cell landscape in atherosclerosis was diverse, dominated by M2 macrophages, M0 macrophages, resting CD4 memory T cells and CD8 T cells. There was a significant difference in resting CD4 memory T cells (p = 0.032), T cells follicular helper (p = 0.033), M0 (p = 0.047) and M2 macrophages (p = 0.012) between stable and unstable atherosclerotic plaques. Compared with stable atherosclerotic plaques, unstable atherosclerotic plaques had a higher percentage of M2 macrophages. Moreover, correlation analysis indicated that the percentage of naïve CD4 T cells was strongly correlated with that of gamma delta T cells (r = 0.93, p < 0.001), while memory B cells were correlated with plasma cells (r = 0.85, p < 0.001). In summary, our study explored the abundance and difference of specific immune cell subgroups at unstable plaques, which would aid new immunotherapies for atherosclerosis.     

Peripheral Blood T Cell Dynamics Predict Relapse in Multiple Sclerosis Patients on Fingolimod

Background

Fingolimod efficiently reduces multiple sclerosis (MS) relapse by inhibiting lymphocyte egress from lymph nodes through down-modulation of sphingosine 1-phosphate (S1P) receptors. We aimed to clarify the alterations in peripheral blood T cell subsets associated with MS relapse on fingolimod.

Methods/Principal Findings

Blood samples successively collected from 23 relapsing-remitting MS patients before and during fingolimod therapy (0.5 mg/day) for 12 months and 18 healthy controls (HCs) were analysed for T cell subsets by flow cytometry. In MS patients, the percentages of central memory T (CCR7⁺CD45RO⁺) cells (TCM) and naïve T (CCR7⁺CD45RO^-) cells decreased significantly, while those of effector memory T (CCR7^-CD45RA^-) and suppressor precursor T (CD28^-) cells increased in both CD4⁺T and CD8⁺T cells from 2 weeks to 12 months during fingolimod therapy. The percentages of regulatory T (CD4⁺CD25^highCD127^low) cells in CD4⁺T cells and CCR7^-CD45RA⁺T cells in CD8⁺T cells also increased significantly. Eight relapsed patients demonstrated greater percentages of CD4⁺TCM than 15 non-relapsed patients at 3 and 6 months (p=0.0051 and p=0.0088, respectively). The IL17-, IL9-, and IL4-producing CD4⁺T cell percentages were significantly higher at pre-treatment in MS patients compared with HCs (p<0.01 for all), while the IL17-producing CD4⁺T cell percentages tended to show a transient increase at 2 weeks of fingolimod therapy (p^corr=0.0834).

Conclusions

The CD4⁺TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.     

Exhaled pentane as a possible marker for survival and lipid peroxidation during radiotherapy for lung cancer—a pilot study

To examine lipid peroxidation during radiotherapy (RT), exhaled pentane samples were collected from 11 lung cancer patients before RT and 30 and 120 min after the start of RT on days 1, 4 and 5 and at 30 and 40 Grays, if possible. Exhaled pentane samples were collected once from 30 healthy controls. Serum thiobarbituric-acid-reactive substances (TBARS) and conjugated dienes (CD) were obtained from patients on each exhaled air collection day. Lung cancer patients had higher exhaled pentane levels than controls (1.73 ng/L vs 0.83 ng/L, p=0.017). Exhaled pentane levels tended to decrease during the first RT day (p=0.075) and levels of CD decreased during the first week of RT (p=0.014). Higher pre-treatment pentane levels predicted better survival (p=0.003). Elevated exhaled pentane levels before RT may be due to the lipid peroxidation burden associated with cancer. The decrease of lipid peroxidation markers during RT may be attributable to enhanced antioxidant defense mechanisms.     

CTLA4 is differentially associated with autoimmune diseases in the Dutch population

Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) is an important negative regulator of T-cell response and its genetic association with type 1 diabetes (T1D) has recently been demonstrated. The frequent co-association of autoimmune diseases (AID) and the implication from multiple genome scans that the CTLA4 gene region is a general autoimmune region, led us to study the role of CTLA4 in independent cohorts of T1D, coeliac disease (CD) and rheumatoid arthritis (RA) patients. We present independent data that confirm the association of CTLA4 in Dutch patients with juvenile onset T1D and show differential association of CTLA4 with CD and RA. The CTLA4 gene polymorphisms were tested for association in 350 T1D, 310 CD, 520 RA patients and 900 controls. In addition, 218 families were tested by the transmission disequilibrium test (TDT). T1D patients showed the highest association with the MH30*G: −1147*C: +49*G: CT60*G: JO37_3*G (haplotype 2) in both a case/control cohort (P=0.002, OR=1.42) and by TDT (P=0.02, OR=1.43). In contrast, this haplotype showed no association in the RA and CD cohorts. However, we observed an increased frequency of the MH30*G: −1147*T: +49*A: CT60*G: JO37_3*A (haplotype 3) in the CD patients diagnosed at a young age (OR=1.6, P=0.026, P _c=0.052). Furthermore, when T1D and CD patients were stratified based on the HLA risk, the T1D susceptible CTLA4 haplotype 2 was over-represented in the high HLA-risk T1D and CD groups. In conclusion, we confirmed association between CTLA4 haplotype 2 and T1D in the Dutch population. Association with another CTLA4 haplotype (haplotype 3) was confirmed for CD, but only in those patients who had an early age of expression. No effect was found between RA and CTLA4. The association of the CTLA4 haplotype 2 with the high-risk HLA genotype in T1D and CD, which share DQ2 as the one of high-risk alleles, might provide a clue to understanding the common genetic background of AID.Electronic Supplementary Material Supplementary material is available for this article at An erratum to this article can be found at     

Lymphocyte subsets and T(h)1/T(h)2 immune responses in patients with adenocarcinoma of the oesophagus or oesophagogastric junction: relation to pTNM stage and clinical outcome

Introduction Recent studies have indicated that the cytokines produced by CD4⁺ T helper type 1 (T_h1) and type 2 (T_h2) cells are critically important in antitumour immunity and perhaps clinical outcome. From this perspective, we investigated the immunocompetence of patients with previously untreated cancer of the oesophagus or oesophagogastric junction (OGJ) in relation to stage of disease and postoperative survival.Methods Blood samples were taken prior to surgery from 32 patients with adenocarcinoma of the oesophagus or OGJ. Ten healthy volunteers served as normal controls. T-cell and monocyte subpopulations were determined using flow cytometry. Monocyte as well as T_h1- and T_h2-lymphocyte cytokine levels were assessed in stimulated whole blood cultures.Results Absolute T-cell and monocyte (subset) counts as well as monocyte cytokine levels were similar among patients and controls. Production of T_h1-type cytokines was higher in patients than in controls (IFN-, p=0.01; IL-2, p=0.05), whereas T_h2-type cytokine levels were comparable (IL-4, p=0.5; IL-13, p=0.3). T-cell CD4⁺/CD8⁺ ratios decreased as pTNM stage worsened (stage I/II vs stage III/IV, p=0.009). Of all measured immunological parameters, only IL-2 production significantly affected both overall survival (p=0.015) and disease-free survival (p=0.0062). High IL-2 levels corresponded with a favourable prognosis.Conclusions Patients awaiting surgery for adenocarcinoma of the oesophagus or oesophagogastric junction demonstrated a shift in the T_h1/T_h2 balance—in favour of T_h1—compared with healthy volunteers. The ability of T cells to produce IL-2 was related to survival indicating a crucial role of T_h1-type cells in antitumour immunosurveillance.     

Factors regulating circulating vascular endothelial growth factor (VEGF): Association with bone mineral density (BMD) in post-menopausal osteoporosis

Vascular endothelial growth factor (VEGF) plays an important role in bone health. We investigated the factors which influence circulating VEGF and their association with bone mineral density (BMD). Two hundred and fifty two post-menopausal women aged 64.5 [9.2] years were studied. BMD was determined at the lumbar spine (LS), femoral neck (FN) and total hip (TH). Serum oestradiol and VEGF were measured. Subjects were genotyped for two polymorphic variants in the 5′ untranslated region of the VEGF gene; G(634)C and C(936)T. Positive correlations were seen between circulating VEGF and BMI (r = 0.2, p < 0.02) and oestradiol (r = 0.25, p < 0.001). Following multi-linear regression analysis, serum VEGF was associated with the G(634) polymorphism (p = 0.08) and dietary calcium intake (p = 0.02). The association with calcium intake may be mediated by PTH as suggested by the in vitro studies. Following correction for confounders, there was no association between circulating VEGF and BMD at any site. Both VEGF polymorphisms were significant predictors of LS BMD G(634)C: p = 0.017 and C(936)T: p = 0.05. Circulating VEGF may be influenced by genetic, environmental and endocrine factors. Polymorphic variants in the VEGF gene are associated with spine BMD. Further larger studies are needed.     

The Changes of Lipid Metabolism in Advanced Renal Cell Carcinoma Patients Treated with Everolimus: A New Pharmacodynamic Marker?

Background

Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between the baseline values and treatmentrelated modifications of total serum cholesterol (C), triglycerides (T), body mass index (BMI), fasting blood glucose level (FBG) and blood pressure (BP) levels and the outcome of patients treated with everolimus for mRCC.

Methods

177 patients were included in this retrospective analysis. Time to progression (TTP), clinical benefit (CB) and overall survival (OS) were evaluated.

Results

Basal BMI was significantly higher in patients who experienced a CB (p=0,0145). C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001). Median TTP was significantly longer in patients with T raise compared to patients without T (10 vs 6, p=0.030), C (8 vs 5, p=0.042) and C+T raise (10.9 vs 5.0, p=0.003). At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005). T raise (21.0 vs 14.0, p=0.002) and C+T increase (21.0 vs 14.0, p=0.006) were correlated with improved OS but were not significant at multivariate analysis.

Conclusion

C+T raise is an early predictor for everolimus efficacy for patients with mRCC.     

Seasonal occurrence and reproduction of Hypnea charoides (Rhodophyta) in Tung Ping Chau,N.T., Hong Kong SAR,China

Seasonal occurrence and reproduction in populations of Hypnea charoides Lamouroux were investigated along two coastal shores, A Ma Wan and Lung Lok Shui, in Tung Ping Chau, N. T., Hong Kong SAR, China, from 1996 to 1999. Annual growth of these populations was initiated in early winter (November–December) and ended in late spring (April–May). Mean length of H. charoides in A Ma Wan was significantly negatively correlated with photoperiod (r=−0.359, n=38, p<0.05) and seawater temperature (r=−0.669, n=38, p<0.05). Vegetative plants were dominant but relatively high abundance in tetrasporic plants was observed at the end of each growing season. Percentage occurrence of tetrasporic plants was significantly positively correlated with seawater temperature in samples collected at −1 m CD (r=0.635, n=19, p<0.05), −2 m CD (r=0.690, n=13, p<0.05) and from drifted populations (r=0.705, n=17, p<0.05), suggesting that increase in seawater temperature might induce tetrasporogenesis of H. charoides in A Ma Wan. Plants in Lung Lok Shui were mostly vegetative but 100% tetrasporic samples were collected at −1 m CD during an unusual growth period in October 1998. High abundance of tetrasporic plants was also observed at a depth of −10 m CD on 9 April 1998 (97.5%) and 22-April 1999 (90%). Significantly negative correlation was found in percentage occurrence of vegetative plants at −10 m CD with photoperiod (r=−0.553, n=14, p<0.05) and seawater temperature (r=−0.855, n=8, p<0.05). Dominance of vegetative and tetrasporic plants and rarity of cystocarpic plants in both A Ma Wan and Lung Lok Shui suggested that the life span of H. charoides might be very short and/or majority of the plants underwent apomeiosis to complete their life cycles in Tung Ping Chau.

     

Emperipolesis mediated by CD8+ T cells correlates with biliary epithelia cell injury in primary biliary cholangitis

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell‐in‐cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty‐six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early‐stage PBC (stages I and II, n = 39) and late‐stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin‐eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3⁺ and CD8⁺ T cells correlated with the advancement of emperipolesis (R² = 0.318, P < .001; R² = 0.060, P < .05). The cell numbers of TUNEL‐positive BECs and double staining for CK19 and Ki67 showed a significant positive correlation with emperipolesis degree (R² = 0.236, P < .001; R² = 0.267, P < .001). We conclude that emperipolesis mediated by CD8⁺ T cells appears to be relevant to apoptosis of BEC and thus may aggravate the further injury of interlobular bile ducts.     

Expression of the proliferation-associated nuclear protein MIB-1 and its relationship with microvascular density in bone marrow biopsies of patients with myelodysplastic syndromes

The myelodysplastic syndromes (MDS) are a group of disorders characterized by dysplastic hemopoiesis and an increased risk of leukemic transformation. The process of angiogenesis has been implicated in the pathogenesis and evolution of MDS. In this study the proliferative activity and extent of angiogenesis was examined in bone marrow samples from 54 patients with MDS in relation to clinicopathologic features. Cellular proliferation and microvascular density (MVD) were examined immunohistochemically, using the monoclonal antibody MIB-1 (Ki-67) and an anti-CD34 monoclonal antibody respectively. Serum concentrations of interleukin-6 (IL-6) were measured by ELISA. The results showed that the MIB-1 Labeling Index (MIB-1 LI), MVD and IL-6 increased significantly with advancing severity of disease. Among the MDS-FAB subtypes, MIB-1 LI, MVD and IL-6 were significantly higher in RAEB-t, RAEB and CMML in comparison to RA and RARS (p < 0.0001 in all cases). Similarly, MIB-1 and MVD were increased in patients with score 3 in comparison to scores 0 and 1 in the IPSS system (p < 0.05). All parameters studied were significantly higher in patients versus controls. We conclude that cellular proliferative activity and angiogenesis are associated with disease progression in MDS patients.     

Role of IL1A rs1800587, IL1B rs1143627 and IL1RN rs2234677 Genotype Regarding Development of Chronic Lumbar Radicular Pain; a Prospective One-Year Study

Previous studies indicate that lumbar radicular pain following disc herniation may be associated with release of several pro-inflammatory mediators, including interleukin-1 (IL1). In the present study, we examined how genetic variability in IL1A (rs1800587 C>T), IL1B (rs1143627 T>C) and IL1RN (rs2234677 G>A) influenced the clinical outcome the first year after disc herniation. Patients (n = 258) with lumbar radicular pain due to disc herniation were recruited from two hospitals in Norway. Pain and disability were measured by visual analogue scale (VAS) and Oswestry Disability Index (ODI) over a 12 month period. The result showed that patients with the IL1A T allele, in combination with the IL1RN A allele had more pain and a slower recovery than other patients (VAS p = 0.049, ODI p = 0.059 rmANOVA; VAS p = 0.003, ODI p = 0.050 one-way ANOVA at 12 months). However, regarding the IL1B/IL1RN genotype, no clear effect on recovery was observed (VAS p = 0.175, ODI p = 0.055 rmANOVA; VAS p = 0.105, ODI p = 0.214 one-way ANOVA at 12 months). The data suggest that the IL1A T/IL1RN A genotype, but not the IL1B T/IL1RN A genotype, may increase the risk of a chronic outcome in patients following disc herniation.     

Interferon gamma gene +874A/T polymorphism and intracellular interferon gamma expression in pulmonary tuberculosis

We investigated whether IFN-γ gene +874(A/T) polymorphism influences intracellular interferon gamma expression in T-cell subsets of normal healthy subjects (NHS) and pulmonary tuberculosis patients (PTB). Peripheral blood mononuclear cells were stimulated with live Mycobacterium tuberculosis (MTB) and the intracellular IFN-γ expression was studied using flow cytometry. Genotyping of IFN-γ gene +874(A/T) was done using allele specific polymerase chain reaction. Significantly increased IFN-γ expressing CD3+CD4+ and CD3+CD8+ T cells were observed in NHS with AA genotype compared to TT genotype in unstimulated (p = 0.0308 and p = 0.0157) and MTB stimulated (p = 0.0494 and p = 0.0287) cultures and this difference was not observed in PTB patients. The present study suggests that the variant genotypes of IFN-γ (+874) may be associated with altered expression of IFN-γ at the intracellular level and play an immunoregulatory role at the site of M. tuberculosis infection.     

Assessment of Treg/Th17 axis role in immunopathogenesis of chronic injuries of mustard lung disease

Purpose: Sulfur mustard (SM) lung is a heterogeneous disease associated with abnormal inflammatory immune responses. The Th17/Treg axis imbalance is associated with the pathogenesis of chronic inflammatory pulmonary disease. We aimed to determine the distribution of different Th17 and Treg cells in patients with SM lung and chronic obstructive pulmonary disease (COPD) and evaluate the clinical implications in this homeostasis. Methods: In this analytical cross-sectional study, CD4?⁺?Foxp3^+?Treg and CD4⁺?IL-17^+?Th17 cells were measured in peripheral blood mononuclear cells (PBMCs) and transbronchial biopsy (TBB) samples of 15 SM-exposed patients, 12 COPD and 13 healthy controls (HCs). The potential correlation between the ratio of Th17/Tregs and lung function was evaluated with multivariate logistic regression (MLR) analysis. Results: The frequency of CD4?⁺?FoxP3⁺?Tregs and CD4?⁺?IL-17⁺?Th17 was increased ～1.7-fold (8.71/4.95) and ～2.7-fold (1.028/0.371) respectively, in the PBMC of SM patients compared with the health controls (p?<?0.001). The results indicated that there were increases in the frequency of Th17 and Tregs cells in the patients with COPD versus the HC, that is, ～2.6-fold (0.987/0.371) and ～1.4-fold (7.12/4.95), respectively; but they did not reach to SM level (p?≥?0.05). Moreover, in the TBB samples, the CD4?⁺?IL-17^+?Th17 and CD4⁺?FoxP3^+?Tregs numbers were significantly higher in SM and COPD patients than HC (p?<?0.05). The Th17 and Treg cells were inversely correlated with forced expiratory volume in 1s (FEV1%) (r?=??0.351, p =?0.001; r?=??0.344, p?=?0.021) and FEV1/FVC (r?=??0.44, p?=?0.001; r?=??0.302, p?=?0.011), respectively. Instead, positive correlations were found between Treg/Th17 ratios and forced FEV1%pred (r?=?0.156, p?=?0.007), as well as FEV1/FVC ratio (r?=?0.334, p?=?0.006). Conclusions: The imbalance of Th17/Treg has a key role in immunopathogenesis of chronic phase of mustard lung disease.     

A potential role of TNFR gene polymorphisms in autoimmune thyroid diseases in the Tunisian population

Autoimmune thyroid diseases (AITDs) including Graves disease (GD) and autoimmune hypothyroidism (AH) are associated with TNF genes polymorphisms. TNF molecules bind to TNFRI and TNFRII. No genetic association was reported between TNFR and AITDs. In this study, we have analysed two polymorphisms in TNFRI gene (TNFRI+36A/G SNP and a microsatellite (GT)₁₇ (GA)_n) and one polymorphism in TNFRII gene (TNFRII +676 T/G). All these polymorphisms were studied in a large Tunisian family with high prevalence of AITDs, and on a case-control sample of 91 GD patients and 165 controls. The present study was undertaken to investigate the genetic association of these polymorphisms with AITDs development. We reported the implication of TNFRIA3 allele in AITDs pathogenesis in familial and case control studies, respectively (χ² = 4.13, p = 0.042; χ² = 9.26, p_c = 0.005). In addition, Case-control study has revealed for the first time that TNFRII+676G allele was associated with GD (χ² = 11.53; p = 0.0007). Two TNFRI haplotypes were found to be associated with GD: TNFRI+36G-A8, TNFRI+36A-A3 (χ² = 88.07; p = 6.32 × 10⁻²¹, χ² = 16.78; p = 4.2 × 10⁻⁵, respectively). Our data showed that TNFRI polymorphisms have an important role in AITDs pathogenesis in both familial and case-control samples and that TNFRII was rather implicated in GD development in the Tunisian population.