3B). The data reveal that the individual CGD cells up-regulate the transcription of the iNOS gene (NOS2) beyond WT cells in both neutrophil and macrophages upon challenge. The response of bone marrow-derived dendritic cells (BMDCs) from unchallenged WT and CGD mice to GlyAg alone was also tested. At 24 h, mRNA and cell extracts were isolated and analyzed by qPCR and Western blot respectively. We found that

iNOS transcription was increased by nearly ten-fold over WT in response to GlyAg (Fig. 3C) and this difference was readily apparent at the protein level HER2 inhibitor (Fig. 3D). These data demonstrate that GlyAg-stimulated CGD cells up-regulate the iNOS gene to a significantly greater extent than WT cells in neutrophils, macrophages, and BMDCs, and this difference accounts for the increased NO produced in the peritoneal cavity upon challenge (Fig. 2A). Given that GlyAg-induced abscess formation is dependent on NO-dependent processing, presentation on MHCII, and subsequent CD4+ T-cell activation 20, we examined

the CGD effect on the amount of GlyAg processing. CGD and WT APCs were incubated for 48 h with radiolabeled GlyAg, then intracellular GlyAg was analyzed for changes in molecular mass as a measure of processing. Greater amounts of the MHCII-presentable low molecular weight form of GlyAg were found in CGD cells compared with WT (Fig. 4A, arrow), demonstrating that increases in NO correlates with greater processed GlyAg available for this website MHCII presentation. Next, to determine if the increased

NO production and antigen processing seen in CGD mice would lead to aberrant T-cell activation, syngeneic APCs and CD4+ T cells were cultured and stimulated with GlyAg and analyzed for IFN-γ by ELISA. We found that the CGD T cells responded earlier and more robustly than WT T cells, with strong IFN-γ production by day 3 in CGD assays (Fig. 4B). The relationship between NO production and T-cell response was further demonstrated by comparing Demeclocycline the T-cell responses from WT, CGD, and iNOS−/− animals at day 3. IFN-γ production was modest for WT, heightened for CGD, and reduced for iNOS−/− cells (Fig. 4C), showing a direct correlation between NO concentration and T-cell response amplitude. To differentiate between greater individual cell responses and a greater number of cells responding, we challenged WT and CGD animals with GlyAg and compared the number of CD4+ T cells expressing CD69, an early activation marker (Fig. 4D). At 24 h, the number of CD4+CD69+ cells without GlyAg challenge was indistinguishable between WT and CGD animals (12.3 and 11.4% respectively), while in vivo stimulation with GlyAg yielded ∼4% increases in CD69+ T cells in both backgrounds (Fig. 4D). Since responding CD4+ T cells have been previously localized to the abscess wall following GlyAg challenge 24, we also performed immunohistochemistry on abscess cryosections.

1b). We also examined the kinetics of iNOS expression in BCG-infected macrophages with IL-17A pre-treatment by qPCR and Western blot analysis. From qPCR analysis, we observed that the expression level of iNOS mRNA in BCG-infected macrophages was enhanced by IL-17A over a time course of 24 hr (Fig. 1c). Similar observations could be obtained using Western blot analysis. The production of iNOS protein in BCG-infected macrophages was enhanced by IL-17A as early as 3 hr post-infection and the enhancing effect continued to 12 hr post-infection (Fig. 1d).

At 24 hr post-infection, we observed that the protein levels of iNOS were comparable between BCG-infected macrophages with or without IL-17A pre-treatment. Interleukin-17A alone did not induce detectable level of iNOS protein in Romidepsin macrophages at all time-points being tested (Fig. 1d). Taken together, our data suggest that IL-17A is able to enhance NO production in macrophages by up-regulating iNOS expression during BCG infection. Signalling pathways of MAPK, including JNK, ERK1/2 and p38 MAPK, are activated in macrophages in response to mycobacterial infection, mTOR inhibitor leading to production of pro-inflammatory cytokines.[19, 21, 23] The

expression of iNOS has also been shown to be regulated by those MAPK pathways.[15, 24] To investigate whether IL-17A pre-treatment affects BCG-activated MAPK pathways, we analysed the phosphorylations of various MAPKs. We pre-treated the macrophages with IL-17A for 24 hr, Tyrosine-protein kinase BLK followed by BCG infection for 60, 90, 120 and 150 min. Total cell lysates were harvested for Western blot analysis of phosphorylation of JNK, p38 MAPK

and ERK1/2. Our results showed that phosphorylation of JNK, p38 MAPK and ERK1/2 in macrophages was strongly induced by BCG at 60 and 90 min post-infection (Fig. 2a, lane 2 and lane 6) and became diminished at 120 and 150 min post-infection (Fig. 2a, lane 10 and lane 14). The levels of phosphorylated JNK at 60 min post-infection were found to be similar between BCG-infected macrophages with or without IL-17A pre-treatment (Fig. 2a, lane 2 versus lane 3). However, we observed that in the presence of IL-17A, the BCG-induced phosphorylation of JNK was enhanced at 90, 120 and 150 min (Fig. 2a, lane 7, land 11 and lane 15, respectively). The data suggest that IL-17A is able to prolong BCG-induced phosphorylation of JNK. On the other hand, IL-17A had no effects on BCG-activated ERK1/2 and p38 MAPK at all time-points being tested (Fig. 2a). For verification that JNK was involved in the enhancement of BCG-induced NO production by IL-17A, we blocked the activation of the JNK pathway by using SP600125, which is a reversible ATP competitive inhibitor specific to JNK.[25] Previous studies reported by other groups have shown that the JNK inhibitor SP600125 is able to suppress NO production in macrophages being stimulated by Toll-like receptor agonists including BCG and lipopolysaccharide.

Indeed, in that study the virus, inoculated through the intraperitoneal route, was cleared rapidly from the thymus but led to a significant increase in CD4-CD8- thymic T cells preceeding the onset of hyperglycaemia. CV-B4 infection of the thymus has been described in human tissue in vitro, and in mice in vivo and in vitro, and the infection results in the disturbance of T cell differentiation/maturation processes [71–76]. The role of alterations

in T lymphocyte subsets in the development of T1D cannot be excluded in so far as they have been observed Proteasome inhibitor already in NOD mice [77], in BB rats [78] and also in diabetic patients [79,80]. Whether enterovirus-induced disturbances of thymic cells can play a role in T1D pathogenesis by impairing T cell differentiation and/or central self-tolerance establishment should be investigated further in experimental models in vitro and/or in vivo. For a clearer understanding of the complex interplay between enterovirus and the thymus in the viral pathogenesis of T1D, the link remains to be made between thymus infection and the development of selleck chemicals the disease in human

beings. Interestingly, in a recent study macrophages infected with an enterovirus (poliovirus) were evidenced in thymus of some patients with myasthenia gravis, suggesting a viral contribution to the intrathymic alterations leading to the disease [81]. Furthermore, CV-A and CV-B have already been found in human perinatal and neonatal thymus in favour of vertical transmission of the viral infection [82,83]. Whether enteroviruses are present in the thymus of patients with T1D or patients in the preclinical stages of the disease merits further study. In T1D, the tolerance of immune system

towards β cells is disturbed at the peripheral level through Treg dysfunction [57]. A disturbance of tolerance at the central level through the infection of thymus with enteroviruses cannot be discarded, and could play a role in the pathogenesis of T1D (see Fig. 2). The potential role of thymus dysfunction in the pathogenesis of T1D opens the possibility of targeting this organ for preventive and therapeutic strategies. Indeed, there are increasing promising insights towards intrathymic manipulation. On the basis of the filipin close homology and cross-tolerance between insulin, the primary T1D autoantigen and Igf2, the dominant thymic self-antigen of the insulin family, a novel type of vaccination, so-called ‘negative/tolerogenic selfvaccination’, is currently being developed for the prevention and cure of T1D [84]. Conversely, intrathymic manipulation also offers a potential way of enhancing the ability of T cells to control infection by increasing the numbers of positively selected thymocytes able to recognize a given molecule of the corresponding infectious agent.

vulnificus components with pattern recognition receptors (PRRs) (Espat et al., 1996; Powell et al., 1997, 2003; Shin et al., 2002; Lu et al., 2009). Recent studies showed that recombinant-produced V. vulnificus lipoprotein (Ilpa) and flagellar filament protein (FlaB) are recognized by Toll-like receptor 2 (TLR2) and TLR5, respectively (Lee et al., 2006; Goo et al., 2007). TLRs are a family of PRRs that are among the first line of host defense (Takeda & Akira, 2005; Gerold et al., 2007). Upon recognition of agonists, TLRs associate with central adapter

molecules such as myeloid differentiation factor 88 (MyD88). This interaction initiates a signaling cascade that results in production of TNFα and other proinflammatory cytokines. Although Mitomycin C price TLR signaling is usually essential for activating an effective host immune response, it also plays a lead role in induction of the systemic inflammatory response that causes septic shock (Leaver et al., 2007). Thus, TLRs have attracted attention as HM781-36B targets for treatment of sepsis. However, blockade of harmful TLR signaling requires knowledge of the TLR repertoire activated by a pathogen and the effect of TLR signaling on the host response and the outcome of infection (Gao et al., 2008). In addition to TLR2 and TLR5 agonists, V. vulnificus synthesizes lipopolysaccharide, which elicits a proinflammatory

cytokine response (e.g. TNFα secretion and cytokine mRNA expression) from human peripheral blood monocytes (Powell et al., 1997). Many Gram-negative bacteria activate TLR signaling due to recognition of their lipopolysaccharide via TLR4 (Takeda & Akira, 2005; Gerold et al., 2007). However, there was no information concerning whether V. vulnificus activates TLR4.

The goal of this study was to investigate the role of TLR4 in the host response to V. vulnificus using mice that are genetically deficient for this receptor. Wild-type (WT) male C57BL/6 mice were purchased from the Jackson Laboratory (Bar Harbor, ME). Homozygous TLR4 knockout (KO) (Hoshino et al., 1999) and MyD88 KO (Adachi crotamiton et al., 1998) mice that had been backcrossed for eight generations to WT mice were obtained via S. Akira (Osaka, Japan). Homozygous TNFα KO mice generated on a C57BL/6 background were obtained via L. Old (New York, NY). All mice were housed under specific pathogen-free conditions. MyD88 KO mice were reared without antibiotics and received sterile water and food. Animal procedures were approved by the University of North Carolina at Chapel Hill (UNC-CH) Institutional Animal Care and Use Committee. Vibrio vulnificus type strain ATCC 27562, a clinical (blood) isolate, was purchased from Remel (Lake Charles, LA) and grown in Bacto heart infusion (HI) broth (Becton Dickinson and Co., Sparks, MD) or on HI agar. Stocks were prepared by addition of glycerol (10% final concentration) to broth cultures and stored at −70 °C. Inactivated V.

[3, 8] TAMs generally fail to express pro-inflammatory cytokines for T helper type 1 (Th1) responses but are excellent producers of immunosuppressive cytokines for Th2 responses.[4] As TAMs generally exhibit low antigen-presenting and co-stimulating capacity, they ordinarily fail to activate T-cell-mediated adaptive immunity.[4, 7] Therefore, unlike M1 macrophages, which are highly microbicidal and tumoricidal, the M2-like TAMs are immunosuppressive

and facilitate tumour progression.[4, 7] Experimental and epidemiological studies demonstrated that TAMs play an important selleck products role in tumour growth, angiogenesis, metastasis, matrix remodelling and immune evasion in various human and animal tumours.[5, 7-10] Recently, TAMs are ‘accused’ for their

chemo-resistance and radio-protective effects in mouse tumour models, because an increased density of TAMs is associated with poor efficacy in chemotherapy,[11, 12] and radiotherapy-induced macrophage aggregation is paralleled by decreased radiocurability.[13-15] Clinical studies also revealed connections between the state of TAMs and poor outcomes of human tumours. The density, activation and histological location of TAMs can be used to predict patients’ survival time in different types of cancer.[16-20] For instance, an increased number of TAMs was selleck chemical correlated with a shortened progress-free survival in classical Hodgkin lymphoma.[16] Besides, Kurahara et al.[18] observed that a larger number of M2-polarized TAMs correlated with increased CHIR-99021 solubility dmso density of lymphatic vessels, high incidence of lymph node metastasis and a poor prognosis in patients with pancreatic cancer. Therefore, TAMs are now considered as a promising target for tumour therapy, and reduction of their tumour-promoting activities has become a hot study area.[21] Generally, the approaches to targeting TAMs are by following

two routes: decreasing the quantity of TAMs in tumour tissue or shifting TAMs from tumour-promoting to tumoricidal status. Although the clinical application of a TAM-targeted approach is still far from clear, a number of experimental studies have collectively shown the effect of this approach on faster tumour rejection and better therapeutic outcome,[22-26] which sheds inspirational light on further clinical studies. In this review, we will discuss current TAM-targeted strategies for anti-tumour therapy. Since the functions of TAMs largely depend on their accumulation and activation in tumour tissues, TAM-targeted anti-tumour approaches are principally based on: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1 tumoricidal activity of TAMs; and (iv) blocking M2 tumour-promoting activity of TAMs. These strategies are summarized in Fig. 1. Some tumour-released and stroma-released cytokines and chemokines facilitate the recruitment of macrophages to tumour tissues.

Longer differentiation, free of activation signals, might be required for the acquisition of a migratory phenotype in response to later activation; however, such differentiation pattern may not occur in inflamed tissues. Persistent macrophage and DC activation by TLR ligands leads to particularly

powerful inhibitory mechanisms blocking further activation by the same or heterologous stimuli 9. There are several inhibitory factors induced in response to TLR stimulation; it is still unclear, however, how these factors contribute to tolerance for further activation. Some pathways have been connected, like miR146a and IL-10 might both contribute to decreased IRAK1 Dabrafenib expression 11, 21, but the present view supports several coexisting inhibitory pathways in activated DCs and macrophages. Whether these pathways are redundant, additive or synergistic Olaparib solubility dmso or act in different conditions or time frames is yet to be understood. Since DCs developing from monocyte precursors in the inflamed tissues might be particularly affected by the constant presence

of microbial compounds and inflammatory mediators, we decided to study which inhibitory pathways are activated in MoDCs in the presence of early and persistent TLR4 stimulation. We set up an assay distinguishing a timely separated role for the different inhibitory molecules and showed that the LPS-induced SOCS1, STAT3, SLAM, miR146a and IL-10 molecules possessed an immediate effect decreasing the activation induced IL-12 production. None of these molecules, however, played an essential role in the establishment of tolerance to further activation signals. The short-term influence of the tested inhibitory signaling components was probably a consequence of the transient increase in their gene expression or the presence of other, more

efficient inhibitory pathways. Although not tested here, it is also possible that certain Guanylate cyclase 2C inhibitory factors could modulate the expression of particular genes in DCs, thereby inducing a qualitative tuning of cellular functions. Contrary to these pathways, IRAK-1 downregulation, occurring in MoDCs receiving early activation through TLR4 during differentiation, might alone be sufficient to inhibit further activation through TLR molecules, as demonstrated by the strong inhibitory effect of a siRNA induced IRAK-1 downregulation on IL-12 secretion. Previously, SOCS1 has been implicated in establishing tolerance in MoDCs that developed in the presence of TLR4, TLR2 or TLR3 ligands through inhibiting GM-CSF receptor signaling and thereby preventing DC differentiation 11. A blockade of the DC differentiation pathway as a consequence of TLR stimulation on monocyte precursors has also been indicated by other studies, in case of human MoDCs in vitro 27 and in monocytes entering the skin in response to Gram-negative bacteria 28.

We previously reported that adoptive transfer of in vitro-differentiated ovalbumin (OVA)-specific Th1 and Th2 cells conferred airway inflammation and airway hyperresponsiveness (AHR) to unprimed recipients 13. In atopic asthma, Th2 immune responses might have a critical role in the development of allergen-induced airway eosinophilic inflammation and AHR 14, 15. Therefore,

the suppression of Th2 responses could be a potential target of immunotherapy for atopic asthma. We previously demonstrated that administration of anti-CD44 mAbs inhibits the development of airway inflammation and AHR in an Ascaris suum antigen-induced murine model of pulmonary eosinophilia 16. Furthermore, we reported that Ponatinib solubility dmso treatment with anti-CD44 mAb reduces the number of T1/ST2+CD4+ T cells in the airway of mice immunized and challenged with Dermatophagoides farinae (Derf) 17. Both Th1 and Th2 cells, however, express CD44 and use CD44 for their rolling on, and adhesion to, the intestinal endothelium 18. Recently, Nagarkatti et al.

reported that CD44 deficiency enhances the development of Th2 effectors in response to sheep red blood cells and chicken OVA 12. Thus, the contribution of CD44 to Th1- and Th2-mediated allergic inflammation remains unclear. In the present study, to directly clarify the role of CD44 in the development of asthma, airway inflammation see more and AHR were evaluated in a murine model of Derf-induced allergic asthma using CD44-deficient Exoribonuclease (CD44KO) mice. To further validate the role of CD44 expressed on CD4+ T cells in the induction of airway inflammation and AHR, antigen-sensitized splenic CD4+ T cells from CD44KO mice were transferred into unprimed mice. Finally, to clarify the selective contribution of CD44 among T-cell

subsets, we analyzed the effect of anti-CD44 mAb on the accumulation of in vitro-differentiated OVA-specific Th1 and Th2 cells in the airway in OVA-challenged mice. To investigate the contribution of CD44 in the development of asthma, we evaluated Derf-induced AHR and airway inflammation in the CD44KO mice compared with WT C57BL/6 mice in a murine model of allergic asthma. Two groups of mice were sensitized with either Derf in PBS or PBS alone, by intraperitoneal administration, according to the procedures described in Materials and Methods. AHR was evaluated 24 h after intranasal challenge with Derf by double-flow plethysmography. Derf challenge induced a significant increase in airway reactivity to methacholine in comparison with PBS-treated controls in WT mice (p=0.0002, Fig. 1A). Unlike in WT mice, AHR to methacholine after antigen challenge was not observed in CD44KO mice, and the degree of airway reactivity to methacholine was similar to that of PBS-exposed mice (p=0.5004, Fig. 1A). The number of inflammatory cells in the BALF was evaluated 24 h after intranasal antigen challenge.

We found that GATA-3 interacts with MTA-2. GATA-3 and MTA-2 bound to several regions of the Th2 cytokine locus mutually exclusively in Th1 and Th2 cells, and they antagonized the regulation of the il4 gene. However, this antagonism did not occur in the regulation of ifng gene expression. Instead, both GATA-3 and MTA-2 bound to the ifng promoter preferentially in Th2 cells. Surprisingly, within one and the same Th2 cell, GATA-3

and MTA-2 associated in the ifng locus, but not in the Th2 cytokine locus. The reason for this discrepancy is not clear and may be a consequence of a contribution Z-VAD-FMK concentration of other differentially recruited proteins, the identity of which is currently not clear. MTA-2 knockout (KO) mice have been shown to undergo abnormal T-cell activation and proliferation, and to develop lupus-like autoimmune disease.22 The Th2 polarized cells from MTA-2 KO mice have been shown to produce increased amounts of both IL-4 and IFN-γ compared with those from wild-type mouse, but Th1 polarized cells from MTA-2 KO mice have been shown to produce comparable amounts of find more these cytokines. This result

suggests that MTA-2 have inhibitory effects on the expression of IL-4 and IFN-γ in Th2 cells. This is consistent with our findings that MTA-2 inhibits the expression of both il4 and ifng genes, and that GATA-3 and MTA-2 antagonize the regulation of Th2 cytokine genes. GATA-3 has been shown to interact with several transcription factors, including repressor of GATA (ROG), friend of GATA (FOG), MAD homologue

3 (Smad), spleen focus forming virus proviral integration oncogene spi1 (PU.1), T-box protein expression T cells (T-bet), Selleckchem Hydroxychloroquine lymphoid enhancer factor 1 (LEF-1), and Pias1. The over-expression of ROG suppresses GATA-3-dependent transactivation and Th2 cell differentiation.26 Forced expression of FOG-1 significantly repressed the transcriptional activity of GATA-3, the production of Th2 cytokines, and the differentiation of Th2 cells in vitro.27 PU.1 suppresses Th2 cytokine production from the Th2 cells through the inhibition of GATA-3 binding to the HSVa enhancer.28 T-bet mediates the inhibitory effect on il5 promoter activity by interacting with GATA-3.29 High-mobility group (HMG) box type transcription factor, lymphoid enhancer factor 1 (LEF-1) has been shown to interact with GATA-3 and suppress the function of GATA-3.30 Transcriptional co-regulator Pias1 has also been found to interact with GATA-3, and increase its transcriptional activity.31 In this study, we identified MTA-2 as a new partner of GATA-3, a transcriptional co-factor which is involved in chromatin remodelling. Hence, this study may provide a clue to search for a possible mechanism of GATA-3-mediated transcriptional regulation and chromatin remodelling.

16 ml or 7.7 ml flow chambers. The flow rate (F) was adjusted to a very low rate of 1.3 ml h−1 resulting in an exchange rate of up to 180 and 6.25 times chamber volumes per 24 hours in the small and large chambers, respectively. The results of culture at a very low flow rate were markedly different from cultures in micro well plates. Low flow rates may better mimic the in vivo situation and thus may be of higher relevance for the clinical setting.

Under these conditions, a general resistance of fungal biofilms against anidulafungin cannot be confirmed. Strains of C. albicans and C. glabrata showed very uniform results whereas the C. parapsilosis group and C. lusitaniae varied from high susceptibility to resistance. Species differentiation of the C. parapsilosis group LY294002 nmr Cobimetinib manufacturer appears to be appropriate in clinical microbiological diagnostics. For the majority of the tested Candida species, anidualafungin was more effective than voriconazole. For the species C. lusitaniae and C. guilliermondii susceptibility testing should be considered prior to clinical use of echinocandin antifungals. “
“A biofilm composed of various microorganisms including Candida is found on denture surfaces and is likely to be involved in the etiology of denture-induced

stomatitis. The purpose of this study was to examine the role of hydrophobic interactions in candidal adherence to acrylic surfaces, particularly that of the hyphal form of Candida albicans. Candida clinical isolates were used. Acrylic plates coated with carrageenan and hydrocolloid (Hitachi chemical, Tokyo, Japan) were used as a hydrophilic substratum. A microbial suspension was placed on each acrylic plate and incubated. All plates were washed

very in phosphate-buffered saline containing CaCl2 and MgCl2 [PBS (+)] and cells still adhering to the acrylic surface were collected by 0.25% trypsin treatment. Cell-surface hydrophobicity was estimated using a modification of the technique used to measure adherence to hydrocarbons. When the acrylic plates were coated with hydrophilic materials, the adherence of hydrophobic clinical isolates of Candida and the hydrophobic hyphal C. albicans decreased, whereas the adherence of non-hydrophobic Candida was not affected or increased. We suggest that hydrophilic coating of denture surfaces could be a potent method for reduction of the adherence of relatively hydrophobic fungal cells, particularly hyphal C. albicans, which causes denture stomatitis and related infections. “
“This study was to develop a real-time florescence quantitative PCR (RT-FQ-PCR) assay to measure virulence-associated DEAD-box RNA helicase (VAD1) mRNA from Cryptococcus neoformans and evaluate its potential use in diagnosis and follow-up treatment of C. neoformans meningitis (CNM). Cryptococcus neoformans was detected using RT-FQ-PCR, ink staining, fungal culturing and C. neoformans antigen detection in CNM compared with a normal control.

Further comparison of thyroid function in patients with different genotypes showed that the frequency of the G-allele was significantly higher among hypothyroid patients (P < 0·05). Interestingly, among 25 hypothyroid patients BAY 80-6946 supplier with both elevated thyroid peroxidase antibody and thyroglobulin antibody concentrations, 14 presented with the AG genotype and 11 with the GG genotype, while no AA genotype was found in this group. Evaluating the independent effect of different genetic and non-genetic factors on thyroid function with multiple regression analysis, we established a strong contribution

of thyroid peroxidase antibodies (P < 0·0002) and an insignificant contribution of thyroglobulin antibodies, CT60 genotype, age, family history and smoking. After elimination of the thyroid autoantibody effect, the contribution of the CT60 genotype reached the level of significance (P < 0·05). This study of patients with two different forms of thyroid

autoimmune disease, HT and PPT, demonstrates a strong contribution of CT60 CTLA-4 SNP to thyroid autoantibody production. The significant increase of thyroid peroxidase antibody concentration and slight increase of thyroglobulin antibody concentration found in patients carrying the polymorphous CT60 CTLA-4 allele is consistent with our previous report on HT patients, where exon 1 and promoter CTLA-4 polymorphisms were studied [6]. Exon 1 SNP has also been shown to influence higher thyroid MK-8669 autoantibody production in Graves’ disease [9]. Nevertheless, no data are available in the literature on association of Casein kinase 1 CT60 SNP with thyroid autoantibody production. Similarly, the data on genetic susceptibility in PPT are scarce in spite of the relatively high prevalence of 8% in the postpartum period [10]. A few earlier reports suggested an association with human leucocyte antigen (HLA) status, which was not confirmed afterwards [11]. The first report referring to the CTLA-4 gene in PPT

was published a decade ago, describing no association between PPT and microsatellite CTLA-4 polymorphism [12]. The second report was our recent case–control study, where we were not able to demonstrate a link between CT60 CTLA-4 SNP and PPT [13]. However, the strong influence of thyroid peroxidase antibodies on development, thyroid function and prognosis of PPT was reported, as patients with higher thyroid peroxidase antibodies in the postpartum period developed PPT more often, presented with hypothyroidism more often and developed permanent hypothyroidism more often [2,11,14,15]. The current study also showed that thyroid peroxidase antibody concentrations were significantly higher in the hypothyroid form of PPT and the frequency of patients positive for thyroid autoantibodies was also significantly higher among hypothyroid patients.