Comorbidity data were collected and a modified patient symptom module was completed. Fifty-five patients who were managed without dialysis were reviewed and the symptom burden recorded was high. Using a tool that may lead to assessing more effective symptom treatments, revealed the extent of symptom burden in conservatively managed ESKD. It is also important to emphasize that a conservative, non-dialysis approach to ESKD management should not be a vacuum, but in fact can provide an intensive programme

of multidisciplinary care and support. It also provides the patient and their family with the confidence that there will be no reduction in medical and nursing care.60 A study from Hong Kong assessed and compared the quality of life and symptom burden between patients on haemodialysis SCH 900776 cell line and peritoneal dialysis with palliative care ESKD patients with an eGFR <15 mL/min.22 This prospective observational study included 179 patients, 134 who had dialysis and 45 who undertook palliative care. Those that received palliative care had greater comorbidity and were older. There was no significant difference in symptom burden between groups and the quality of life was significantly reduced in both groups. In this setting there was little difference in symptoms

and quality of life whether they had dialysis GSK126 cell line or palliative care. The palliative care process needs to consider acknowledging and dealing with this grieving both in the patient, their family and health-care providers. A study conducted by Badger exploring factors impacting on end-of-life transitions in critical care found two key areas of concern for nurses.61 These were the ‘complex emotions and frank indecisiveness expressed by patients’ families. Grief and loss are issues intertwined throughout Dimethyl sulfoxide the course of CKD and ESKD management.62 Although grief is clearly associated with death, it is also evident and experienced much earlier in the trajectory of an illness and is even felt immediately a new high impact diagnosis is realized. Clinicians may avoid discussing end-of-life decisions with patients for fear of causing undue anxiety.63 This is despite the patients desire to address the issues. Cultural differences in the

approach to end-of-life decisions, advanced care planning and withdrawal from dialysis have been addressed by Davison and Holley.43 Non-Western cultures, significantly represented in the Australian population, may have very different understandings of the medical system, health and disease. These cultural sensitivities need to be taken into account when discussing palliative care and end-of-life decisions. Several studies have indicated that the beliefs and values of health professionals have a clear impact on the integration of palliative care into the management of ESKD patients. Twohig and Byock64 found that the focus of care remained on cure and prolongation of life and that ethical cultural and legal issues impact on the clinical decision to withdraw or withhold dialysis.

In terms of staging of patients during stratification in trial enrolment, we may need to take lessons from new insights emerging from studies on disease tissue (via the Network for Pancreatic Organ Donors with Diabetes; nPOD [10]) and Phase III clinical trials failing to reach end-points [12, 13]. Both of these imply that type 1 diabetes may be a very heterogeneous disease, manifesting differently in different patient groups and geographical locations. selleck screening library An intriguing example is that of abatacept, which appeared to worsen clinical outcome in African American subjects [14]. In addition, the average age at disease onset of patients

enrolled on the Indian subcontinent into the teplizumab Phase III study was 44 years [13], an age of disease onset that would usually be considered at the very upper limit. With the exception of oral insulin [15] and proinsulin peptide immunotherapy [16], immunological parameters have not generally been used in selection or randomization of patients in clinical trials.

Lessons from the islet transplantation setting, in which baseline immune correlates determine clinical outcome [17-19], may be of use here and it is conceivable that incorporating immune correlates into trial design may improve the chance of detecting click here therapeutic efficacy and indicate subpopulations of patients with particular benefit, lack of efficacy or even adverse responses to certain immune intervention strategies [7]. While common beliefs

advocate a combination of drugs for intervention (Table 5), it is important to scrutinize potential adverse interference, as may have played a role in the recent trial combining low-dose interleukin (IL)-2 and rapamycin, in Fenbendazole which each of the separate constituents could have yielded clinical benefit [20]. Preclinical studies should be used carefully to identify those showing the desired synergy or any concerns in relation to the single components of combinations (i.e. accelerated disease, see below). Biological agents have proved to be immensely valuable in the treatment of autoimmune disease, and type 1 diabetes is no exception to this therapeutic track. Biologics targeting lymphocytes or co-stimulation events generally invoke immune suppression rather than modulation. This was perhaps most evident in case of the rituximab intervention study, in which patients were vaccinated under the treatment umbrella in a rare attempt to understand the mechanism of action of anti-CD20 immunotherapy. Indeed, rituximab blunted the induction of immune responses against a neoantigen, whereas after revaccination 1 year later (3 months after cessation of rituximab therapy) vigorous responses to the same neoantigen were established that did not differ from placebo-treated patients [21].

The Fli-1+/− MRL/lpr mice receiving BM from WT MRL/lpr mice also had improved disease development compared to WT MRL/lpr mice that received BM from WT MRL/lpr mice. These findings indicate that the impact of Fli-1 on disease development in MRL/lpr mice is complex, and involves both haematopoietic cell and non-haematopoietic cell mediated mechanisms Fli-1+/− MRL/lpr mice were generated as described previously [13]. WT MRL/lpr mice were purchased from the Jackson

Laboratory (Bar Harbor, ME, USA). Fli-1+/− MRL/lpr mice used in this study were back-crossed with WT MRL/lpr mice for 12 generations. The major histocompatibility complex (MHC) locus for MRL/lpr Fli-1+/− mice was the same PF-02341066 in vivo as in WT MRL/lpr mice. Two groups of mice, WT MRL/lpr and Fli-1+/− MRL/lpr, were generated by breeding Fli-1+/− MRL/lpr mice with WT MRL/lpr mice. Mice were examined twice-weekly for external disease manifestations such as skin rash, ear necrosis and lymph node enlargement. All mice were housed under pathogen-free selleck inhibitor conditions at the animal facility of the Ralph H. Johnson Veterans Affairs Medical Center. Four groups of 10-week-old MRL/lpr mice (10–12 mice/group) were irradiated with fractionated irradiation (5 Gy X2; 4-h interval). Three

h after final irradiation each mouse in the four groups received 1 million BM cells by tail vein injection. In group 1, WT MRL/lpr mice received BM from Fli-1+/− MRL/lpr mice (Fli-1+/− WT). In group 2, Fli-1+/− MRL/lpr mice

received BM from WT MRL/lpr mice (WT Fli-1+/−). In group 3, WT MRL/lpr mice received BM from WT MRL/lpr mice (WT WT). In group 4, Fli-1+/− MRL/lpr mice received BM from Fli-1+/− MRL/lpr mice (Fli-1+/− Fli-1+/−). BM cells collected from donor mice at the age of 8 weeks. To monitor the efficiency of irradiation, eight WT MRL/lpr mice were irradiated as above without receiving BM transplantation. This total body irradiation was performed using a 6 × 106 eV linear accelerator (Clinac 600, Varian, Palo Alto, CA, USA). BM cells were flushed from femurs using Alpha modified Eagle’s medium (MEM) without deoxyribosides and ribosides, supplemented with 0·1% bovine serum albumin (BSA), penicillin and streptomycin (MP Biomedicals, Aurora, OH, USA). The sex of BM cell donors was mismatched ZD1839 chemical structure to receivers to determine the efficiency of BM transplantation. All irradiated mice were treated with 1 mg/ml neomycin sulphate for 3 weeks while in recovery from the BM transplantation. Sera were collected from the four groups of mice 12 weeks after BM transplantation at 4-week intervals. Mice were killed at 24 weeks after BM transplantation for assessment of renal disease. BM transplantation was performed in another four groups of mice (10–12 mice/group, equal female and male) as described above, and these mice were used to assess the impact of different BM transplantation on survival.

Here, we used a new murine model of K. pneumoniae infection to investigate the functions of Cav1 in host defense. K. pneumoniae is a capsulate gram-negative bacterium, and the third most commonly isolated microorganism in blood cultures from sepsis patients [[12]]. Due to emerging antibiotic resistance, K. pneumoniae infection remains a see more major health threat [[13, 14]]. Therefore, a better understanding of its molecular pathogenesis

is necessary. Here, we sought to define the host defenses generated against K. pneumoniae using cav1 KO mice. We demonstrated that Cav1 deficiency led to a more severe disease phenotype in mice due to a dysregulated cytokine profile. Additionally, our results suggest that this phenotype depends on Akt-STAT5 cross-talk, involving the β-catenin−GSK3β signaling BMS-777607 clinical trial system. To determine the role of Cav1 in K. pneumoniae infection, we intranasally introduced this bacterium (2 × 105 CFU/mouse) to cav1 KO and WT mice (with otherwise similar genetic backgrounds). We used

KO mice within 4 months after birth as pulmonary abnormalities are known to occur after 6–12 months of age. This high inoculum was implemented to evaluate acute infection within 72 h [[12, 15]]. As shown in Fig. 1A, the cav1 KO mice rapidly succumbed to K. pneumoniae pneumonia with 66.7% mortality within 24 h and 100% mortality by 48 h. In contrast, the WT mice were profoundly resistant and showed significantly greater survival than the cav1 KO group (Log-rank test, p = 0.029). These findings indicate that Cav1 significantly contributes to the resilience of these animals against K. pneumoniae infection. To compare the host responses to K. pneumoniae in cav1 KO and WT mice, bacterial

burdens in the lungs and other organs were determined. Animals were challenged with 2 × 105 CFU/mouse of K. pneumoniae and sacrificed at 24 h (5 mice/group). After BAL (bronchoalveolar lavage) procedures to remove free bacteria, the lungs were aseptically removed and homogenized in order to quantify bacterial burdens. Cav1 ZD1839 concentration KO mice showed significantly increased CFUs of K. pneumoniae in the lung tissue and alveolar macrophages (AMs) when compared with WT mice (Fig. 1B and C showing CFU per gram lung or per 1000 AMs; p < 0.001, one-way ANOVA). To better understand the role of Cav1, we also investigated bacterial burdens at an early time point (8 h postinfection) (4 mice/group), and our results showed that CFUs in BAL cells and in lung homogenates were also significantly increased in Cav1 KO mice as compared with WT mice (Fig. 1D and E). To determine lung injury caused by K. pneumoniae infection, the levels of polymorphonuclear neutrophils in BAL cells and lungs from both cav1 KO and WT mice were assayed. The proportion of neutrophils in the BAL fluid was significantly elevated in cav1 KO mice after 24 h K. pneumoniae infection (Fig. 2A).

Intriguingly, the closest insect ortholog of the intracellular sensors RIG-I and MDA5 is Dicer-2 and virus infection in Drosophila initiates a specific transcriptional response, including the induction of the antiviral effector Vago, whose expression is dependent selleckchem upon Dicer-2 [32]. This suggests that Dicer-2-driven signaling contributes to the induction of a specific set of antiviral effectors during infection. The spectrum of Dicer-2-dependent downstream signaling events, and whether this function of Dicer-2 is conserved in shrimp and

other invertebrates, has yet to be elucidated. One potential mechanism to explain the nonspecific immunity triggered by dsRNA in shrimp is that the detection

of dsRNA, either by Dicer-2 or an additional sensor (Fig. 1B), triggers a feed-forward loop, whereby the RNAi machinery itself is transcriptionally upregulated, thus setting up a cellular environment that is poised to attack and degrade additional foreign nucleic acids. A recent study found that injection of dsRNA leads to the specific upregulation of Ago2 and Sid-1 mRNA in the shrimp Litopenaeus vannamei [28]. Moreover, WSSV infection induced Dicer-2 mRNA in Litopenaeus vannamei [33]. Recent work in our laboratory has shown that virus infection of Drosophila induces the upregulation of the RNAi pathway components Dicer-2 and Ars2 [34]. However, the viral PAMPs involved in inducing this response are not likely dsRNA, since the transcriptional upregulation see more O-methylated flavonoid of antiviral effectors occurs prior to viral replication. The shrimp Ars2 ortholog was recently identified and cloned [35]; it will therefore be important to investigate whether Ars2 and additional members of the RNA-silencing pathways in shrimp are regulated by infection. Although vsiRNAs are produced in an infected cell, whether these small RNAs or other viral RNA species, such as dsRNA, are released from infected cells

remains unknown. It is possible that the release of nucleic acids from infected cells alerts neighboring cells or even distant cells to the presence of infection. Accordingly, a local infection could lead to systemic antiviral defenses. This would also present opportunities for synergies between sequence-specific responses, which act cell-autonomously, and sequence-independent responses, which generate a nonautonomous anti-viral state. Studies in Drosophila have demonstrated that systemic RNAi can suppress viral replication [36]. Further exploration of these possibilities will likely reveal additional aspects of immunity to viral pathogens, but altogether will reinforce the fact that the initiation of antiviral immunity in response to the detection of viral PAMPs, including dsRNA, is a defense strategy conserved through evolution.

In a recent study, Warren et al.14 sequenced the TCR repertoire, and successfully obtained more than one billion TSA HDAC chemical structure raw reads from a single blood sample, which is the deepest immune receptor sequencing to date, with a yield of about 200 million TCR-β nucleotide sequences. There are other sequencing machines available, each with its own advantages and disadvantages. We concentrate on the two machines mentioned above, as they are the only machines used so far in sequencing the immunological repertoire.

Other machines include the SOLiD sequencer (Life Technologies, Grand Island, NY), Helicos (Cambridge, MA), PacBio (Menlo Park, CA), and IonTorrent (Life Technologies, Grand Island, NY).11,15,16 The task at hand, for unbiased Rep-Seq protocols, is to isolate the relevant sequences, from the source B and T cells. These sequences are then sequenced by an NGS machine. To determine relative abundance of different sequences within the repertoire, a

proper account for each of the source sequences is made. Any biased amplification of some of the sequences will leave us with a skewed view of the repertoire. If, for example, one of the sequences in the process is favoured for amplification in one of the stages of the protocol, then we are left unable to discriminate such amplification from actual dominance of the clone in the repertoire. Causes for amplification are therefore an extremely sensitive issue in Rep-Seq and different groups provide different solutions (see below). Upon isolation of the appropriate genetic material (RNA/DNA, B cells/T cells), Rep-Seq requires ABT-263 purchase the ‘lifting’ of the relevant immunoglobulin coding region. This is mostly done through a PCR-based amplification step. This amplification involves DNA primers with complementarities to the target regions. The standard technique uses multiple sets of primers, which are usually compatible with germline V

and J segments17–22 (Fig. 2a). It is impossible to design primers for all the numerous gene segments; for this reason Phloretin primers are designed for families of genes or consensus sequences so that most gene segments are detected.23 A common primer should be designed to recognize the highest consensus region, whereas unique or family primers should recognize the least consensus region within a segment. In addition, specific tags can be added to the primers; for example, to identify from which sample a sequence was amplified.21 However, using a multiplex PCR amplification system, a strong bias is expected towards specific V and J segments, and so observed sequence relative abundances may not accurately reflect real amounts. To deal with these issues, 5′ rapid amplification of cDNA ends (5′-RACE) has been used (see refs 14,24,25; Fig. 1b). The group of Daniel Douek at the National Institutes of Health (Bethesda, MD) have recently established their own 5′ RACE protocol.

g. DC-LAMP-modified mRNA is used – also class II epitopes. In addition, there is the potential to include functional molecules selleck to program a next generation of “designer” DC. We are, for example, currently testing in a comparative trial “GM-CSF-IL-4” MoDC transfected with mRNA (but after rather than before maturation) coding for three antigenswith

or without an E/L selectin fusion molecule, designed to bring about migration of DC upon i.v. injection from the blood to the lymph nodes and, thereby, achieve stronger T-cell responses with a more diversified homing pattern 84. This would be a major advantage because limited migration even of mature DC from skin injection sites to draining lymph nodes remains a major

limitation, notably as intranodal injection has proven unreliable 85 and pre-conditioning of the injection site in contrast to mice does not enhance DC migration in man (de Vries, personal communication). Interestingly, in our current trial intravenous (but not intracutaneous) injection of DC led to some cases of clinical regressions, and should thus be explored despite a previous comparative trial pointing to the inferiority Maraviroc cell line of the i.v. route 45. We are also exploring DC transfected after maturation with an optimized CD40L mRNA, which results in DC that induce highly proliferative, inflammatory CTL in vitro63, 64. Within the DC-THERA Network of Excellence (www.dc–thera.org), another novel “designer” DC type is currently being compared to other DC, the so-called Tri-Mix DC (generated by transfecting immature GM-CSF+IL-4 DC with mRNA coding for CD70, CD40L, and a constitutively

active TLR4) 86. There are many other possibilities to enhance the stimulatory capacity of DC for T or also NK cells, either by introducing other advantageous molecules via mRNA or silencing inhibitory ones by siRNA transfection (e.g. SOCS1) 87. Loading DC with Clomifene dying tumor cells has proven promising in clinical trials 88, particularly with autologous tumor cells and “only” cocktail-matured DC 89, 90. The workup of the patients treated by C.W. Schmidt’s group 89, 90 using a laborious yet highly informative strategy 4 has shown that the vaccine-induced immune responses are dominated by highly individualized responses to shared and neoantigens generated by somatic point mutations (Thomas Wölfel, personal communication) in congruence with previous observations in select melanoma patients 3, 4. The mRNA transfection approach allows for exploring the total antigenic repertoire of tumors without limitations imposed by availability of tumor tissue, as even a few cells can provide sufficient amounts of mRNA for PCR amplification 81. An alternative approach yet to be tested is to take advantage of the increasing knowledge on the cancer genomes, and to use mRNA-transfected DC to specifically target oncogenic driver mutations 91.

We would like to thank Trevor Darby for provision of control C2 non-polarized RNA samples. The authors and their work are supported by SFI grant numbers: 02/CE/B124 and 07/CE/B1368. The authors have Sorafenib mw no conflicting financial interests. Figure S1. Evaluation of PRR expression in non polarised C2, polarised C2 and polarised C2-M epithelia-I, CD302 (a), CD302 (b), NLRP3 (c) NLRP11 (D), NOD1(e), NLRC5 (f), CLEC4A (g) and MYD88 (h) expression was measured by qRT-PCR. Figure S2. Evaluation of PRR expression in non polarised C2, polarised C2 and polarised C2-M epithelia-II, RIPK2 (a), TLR1 (b), TLR2 (c) TLR3 (d), TLR5 (e), TLR6 (f), TLR7 (g) and TLR8 (h) expression was measured by qRT-PCR. Figure S3. Commensal

bacteria induce CCL20 and CLDN4 gene expression in polarised C2 cells. Figure S4. Co-localisation and translocation of commensal bacteria in murine Peyer’s patch M cells. Figure S5. Pathway analysis of gene expression profiles of C2-M cells incubated with commensal bacteria. Figure S6. The effect of commensal bacteria on gene expression of microarray identified gene candidates in polarised C2 cells. Table S1. List of PCR primers and probes used in this study. Table S2. List of PCR primers used in the PRR gene expression screen BAY 80-6946 order used in this study. Table S3. List of genes present in each data set corresponding to Fig. 2. “
“Surrogate markers for monitoring immuno-virological

discordant responders, in addition to plasma viral load and CD4 cells, are still lacking. We assessed the diagnostic utility of CD38 expression on CD8 T cell assay, alone or in association with lymphocyte proliferation to mycotic antigens, in evaluating antiretroviral response. 28 vertically HIV-infected youths, 21 HAART- and seven 2 nucleotide reverse transcriptase inhibitors-treated, were enrolled in a retrospective study. Responders (57.1%) and non-responders (42.9%) to stable antiretroviral

therapy for a minimum of 6 months, on the basis of viral load and CD4 T cells, comprehensively evaluated by CD38 expression on CD8 T lymphocytes [measured as CD38 antibody bound per CD8 T cell (CD38 ABC) and %CD38+ of total CD8 Edoxaban T cells (%CD38/CD8)] and lymphocyte proliferation to P. jiroveci, C. albicans, C. neoformans, A. fumigatus at a single time point after treatment, were selected. CD38 expression ≥2401 CD38 ABC and ≥85% CD38/CD8 cut-off points, accurately discriminates responders versus non-responders, both measures resulting in 75.0% (CI 42.8–94.5) sensitivity (identification of non-responder) and 93.8% (CI 69.8–99.8) specificity (identification of responder), when considered as single assays. The association ‘≥2401 CD38 ABC or ≥85% CD38/CD8’ improved sensitivity to 83.3% (CI 51.6–97.9), while the association ‘<2401 CD38ABC (or <85% CD38/CD8) and lymphoproliferative response positive to ≥2 tested organisms’ improved specificity to 100% (CI 79.4–100).

The lesion ITF2357 exhibited low intensity on T1-weighted MRI and high intensity on T2-weighted images, with surrounding parenchymal edema. The mass exhibited gadolinium enhancement with

dural tail signs. Moreover, multiple foci of linear enhancement spreading through the sulci and into the nearby brain parenchyma were evident. At 1 month after parturition, en bloc removal of the mass, the attached dura mater and adjacent brain tissue was performed. Histologically, the mass located in the subdural space was composed of a mixture of B- and T-lymphocytes and plasma cells. Within the mass, multiple small lobules of meningothelial cells showing immunoreactivity for epithelial membrane antigen and vimentin were observed. The inflammatory cells had also infiltrated the subarachnoid and Virchow-Robin spaces, Antiinfection Compound Library screening and the dura

mater. The cerebral cortex showed ischemic changes, but no tumor cell invasion. On the basis of these histological features, the lesion appeared to be LPM with an inconspicuous meningothelial component and extensive inflammatory infiltration. This case appears to provide useful information on the pathogenesis of this variant. “
“Evidence suggests that sex hormones may play a role in the tumorigenesis of meningiomas, and studies have demonstrated the expression of hormone receptors in these tumors. Aromatase expression has been detected in several normal tissues, including neurons in the CNS, and tumor tissues. We aim to assess the expression of aromatase (ARO) and of progesterone receptor (PR), estrogen receptor (ER) and androgen receptor (AR) in both normal and neoplastic meningeal cells. A cross-sectional study was conducted with 126 patients diagnosed with meningioma (97 women and 29 men; mean age, 53.6 years) submitted to neurosurgery at Hospital São José, Complexo Hospitalar Santa Casa de Porto Alegre, southern Brazil. Control sections of normal meningeal cells, 19 patients, were obtained by evaluating the arachnoid tissue present in the

arachnoid cyst resected material. Immunohistochemistry was applied to assess ARO, PR, ER and AR. Aromatase expression was Carnitine palmitoyltransferase II detected in 100% of the control patients and in 0% of the patients with meningioma. ER was present in 24.6% of the meningiomas and in 0% of the controls, AR in 18.3% of the meningiomas and in 0% of the controls, and PR in 60.3% of the meningiomas and in 47.4% of the controls. A positive association was observed between the presence of AR and ER (OR 3.7; P = 0.01) in meningiomas. There were no significant differences in the presence of hormone receptors between meningioma histological subtypes. PR expression in women with meningioma was significantly higher than that found in men (OR 2.3; P = 0.08).

Nuclear factor-erythroid 2-related factor 2 (Nrf2) is one Gemcitabine price of the most important cellular defense mechanisms against oxidative stress. NAD(P)H quinine oxidoreductase (NQO1), was the well-studied Nrf2 target genes that are up-regulated through the antioxidant response element regulatory element in response to oxidative stress. The aims of the research was investigated

the effects of Zn deficiency on diabetes-induced renal oxidative damage, inflammation and fibrosis, and the relation with Nrf2 and NQO1. Methods: Type 1 diabetes was induced in FVB mice with multiple low doses of streptozotocin. Once hyperglycemia was established, diabetic and age matched control mice were treated with and without Zn chelator, N, N, N′, N′-tetrakis (2-pyridylemethyl) ethylenediamine (TPEN) at 5 mg/kg daily for 4 months. Renal oxidative damage, inflammation

and fibrosis mice were examined by histopathological observation, Naphthol AS-D Chloroacetate esterase assay, immunofluorescent staining, and Western blotting assay. Human renal tubular HK 11 cells were treated by TPEN and Zn, the expression of Nrf2 and NQO1 were examined by immunofluorescent and Western bloting assay. Results: Chronic treatment with TPEN significantly JNK inhibitor for decreased renal Zn levels in both diabetic and control mice. Compared to group with diabetes or TPEN alone, Diabetes/TPEN group showed a significant decrease in Nrf2 expression along with significant increases of renal oxidative damage (protein nitration and lipid oxidation), renal inflammation [infiltrated inflammatory cells and expression of plasminogen activator inhibitor-1(PAI-1) ], and renal fibrosis [PAS staining and expression of profibrotic mediator connective tissue growth factor (CTGF)]. Mechanistic study with human renal tubular HK 11 cells showed that TPEN removal of intracellular Zn decreased

Nrf2 and NQO1 expression, which could be significantly attenuated by Zn supplementation. Conclusion: These results indicated that Zn deficiency significantly enhanced diabetes-induced renal oxidative damage, inflammation and structural remodeling through downregulation of Nrf2 expression and function. CHOI SOO Y1, LIM SUN W2, YOO EUN J1, SANADA SATORU3, LEE HWAN H1, KWON MI J1, LEE-KWON WHASEON1, KWON HYUG M1,3 1UNIST; 2Catholic University of Korea; 3University of Maryland Introduction: We reported previously that, in patients with ∼30 years of type 1 diabetes, proteinuria was associated with ∼50% higher activity of the TonEBP transcription factor in monocytes (1).