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Aims: To examine the feasibility and validity of obtaining International Classification of Primary Care (ICPC)-coded diagnoses of diabetes mellitus (DM) from general practice electronic health records for case definition in epidemiological studies, as alternatives to self-reported DM.Methods: The Netherlands Epidemiology of Obesity study is a population-based cohort study of 6671 persons aged 45-65 years at baseline, included between 2008 & minus;2012. Data from electronic health records were collected between 2012 & minus;2014. We defined a reference standard using diagnoses, prescriptions and consultation notes and investigated its agreement with ICPC-coded diagnoses of DM and self-reported DM.Results: After a median follow-up of 1.8 years, data from 6442 (97%) participants were collected. With the reference standard, 506 participants (79/1000 person-years) were classified with prevalent DM at baseline and 131 participants (11/1000 person-years) were classified with incident DM during follow-up. The agreement of prevalent DM between self-report and the reference standard was 98% (kappa 0.86), the agreement between ICPC-coded diagnoses and the reference standard was 99% (kappa 0.95). The agreement of incident DM between ICPC-coded diagnoses and the reference standard was >99% (kappa 0.92).Conclusions: ICPC-coded diagnoses of DM from general practice electronic health records are a feasible and valid alternative to self-reported diagnoses of DM.(c) 2020 The Author(s). Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Objective: The aim of this study was to examine the relations between intakes of total, saturated, mono-unsaturated, poly-unsaturated and trans fatty acids (SFA, MUFA, PUFA and TFA), and their dietary sources (dairy, meat and plant) with markers of type 2 diabetes risk. Subjects/Methods: This was a cross-sectional analysis of baseline data of 5675 non-diabetic, middle-aged participants of the Netherlands Epidemiology of Obesity (NEO) study. Associations between habitual dietary intake and fasting and postprandial blood glucose and insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), HOMA of β-cell function (HOMA-B) and Disposition Index were assessed through multivariable linear regression models with adjustments for demographic, lifestyle and dietary factors. Results: Mean (s.d.) intakes in percent of energy (En%) were 34.4 (5.8) for total fatty acids, 12.4 (2.9) for SFA, 12.2 (2.4) for MUFA, 6.9 (1.9) for PUFA and 0.6 (0.2) for TFA. As compared with carbohydrates, only SFA was weakly inversely associated with fasting insulin, HOMA-IR and HOMA-B. When stratified by dietary source, all fatty acids from meat were positively associated with fasting insulin-total fatty acidsmeat (per 5 En%: 10.0%; 95% confidence interval: 4.0, 16.3), SFAmeat (per 1 En%: 3.7%; 0.4, 7.2), MUFAmeat (per 1 En%: 5.0%; 2.0, 8.1), PUFAmeat (per 1 En%: 17.3%; 6.0, 29.7) and TFAmeat (per 0.1 En%: 10.5%; 3.2, 18.3). Similarly, all fatty acids from meat were positively associated with HOMA-IR and HOMA-B and inversely with Disposition Index. Conclusions: Our study suggests that the relations between fatty acid intakes and markers of type 2 diabetes risk may depend on the dietary sources of the fatty acids. More epidemiological studies on diet and cardiometabolic disease are needed, addressing possible interactions between nutrients and their dietary sources.

Aims To assess the intended intensity of Type 2 diabetes care and the factors associated with that intensity of care after the annual monitoring visit in which a new person-centred diabetes consultation model including shared decision making was used. Methods We conducted an observational study in 1284 people from 47 general practices and six hospital outpatient clinics. Intensity of care (more, no/minimal change, less) was based on monitoring frequency and referral to other care providers. We used multivariable analyses to determine the factors that were independently associated with intensity of care. Care providers also reported three factors which, in their opinion, determined the intensity of care. Results After the consultation, 22.8% of people chose more intensive care, 70.6% chose no/minimal change and 6.6% chose less intensive care. Whether care became more intensive vs not/minimally changed was associated with a high educational level (odds ratio 1.65, CI 1.07 to 2.53; P=0.023), concern about illness (odds ratio 1.08; CI 1.00 to 1.17; P=0.045), goal-setting (odds ratio 6.53, CI 3.79 to 11.27; P

Simultaneous pancreas-kidney (SPK) transplantation is an important treatment option for patients with type 1 diabetes (T1D) and end-stage renal disease (ESRD). Due to complications, in up to 10% of patients, allograft pancreatectomy is necessary shortly after transplantation. Usually the donor pancreas is discarded. Here, we report on a novel procedure to rescue endocrine tissue after allograft pancreatectomy. A 39-year-old woman with T1D and ESRD who had undergone SPK transplantation required emergency allograft pancreatectomy due to bleeding at the vascular anastomosis. Islets were isolated from the removed pancreas allograft, and almost 480 000 islet equivalents were infused into the portal vein. The patient recovered fully. After 3 months, near-normal mixed meal test (fasting glucose 7.0 mmol/L, 2-hour glucose 7.5 mmol/L, maximal stimulated C-peptide 3.25 nmol/L, without insulin use in the preceding 36 hours) was achieved. Glycated hemoglobin while taking a low dose of long-acting insulin was 32.7 mmol/mol hemoglobin (5.3%). When a donor pancreas is lost after transplantation, rescue β cell therapy by islet alloautotransplantation enables optimal use of scarce donor pancreata to optimize glycemic control without additional HLA alloantigen exposure.

Pancreatic islet transplantation is performed in a select group of patients with type 1 diabetes mellitus. Immunosuppressive regimens play an important role in long-term islet function. We aimed to investigate the efficacy of islet transplantation in patients with type 1 diabetes and a previous kidney transplantation using an alemtuzumab-based induction regimen and triple maintenance immunosuppression. Patients with type 1 diabetes, who had received a kidney transplant previously, were treated with alemtuzumab as induction therapy for their first islet transplantation and basiliximab induction therapy for subsequent islet transplantations. Maintenance immunosuppression consisted of triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone). Thirteen patients (age 50.9 ± 9.2 years, duration of diabetes 35 ± 9 years) received a total of 22 islet transplantations. One- and 2-year insulin independence was 62% and 42%, respectively; graft function was 100% and 92%, respectively. HbA1c dropped from 57.2 ± 13.1 (7.4 ± 1.2%) to 44.5 ± 11.8 mmol/molHb (6.2 ± 0.9%) (p = 0.003) after 2 years. Six of 13 patients suffered from severe hypoglycemia before islet transplantation. After transplantation, severe hypoglycemia was restricted to the only patient who lost graft function. Creatinine clearance was unchanged. Islet-after-kidney transplantation in patients with type 1 diabetes using an alemtuzumab-based induction regimen leads to considerable islet allograft function and improvement in glycemic control.

In clinical islet transplantation, allogeneic islets of Langerhans are transplanted into the portal vein of patients with type 1 diabetes, enabling the restoration of normoglycemia. After intra-hepatic transplantation several factors are involved in the decay in islet mass and function mainly caused by an immediate blood mediated inflammatory response, lack of vascularization, and allo- and autoimmunity. Bioengineered scaffolds can potentially provide an alternative extra-hepatic transplantation site for islets by improving nutrient diffusion and blood supply to the scaffold. This would ultimately result in enhanced islet viability and functionality compared to conventional intra portal transplantation. In this regard, the biomaterial choice, the three-dimensional (3D) shape and scaffold porosity are key parameters for an optimal construct design and, ultimately, transplantation outcome. We used 3D bioplotting for the fabrication of a 3D alginate-based porous scaffold as an extra-hepatic islet delivery system. In 3D-plotted alginate scaffolds the surface to volume ratio, and thus oxygen and nutrient transport, is increased compared to conventional bulk hydrogels. Several alginate mixtures have been tested for INS1E ?-cell viability. Alginate/gelatin mixtures resulted in high plotting performances, and satisfactory handling properties. INS1E ?-cells, human and mouse islets were successfully embedded in 3D-plotted constructs without affecting their morphology and viability, while preventing their aggregation. 3D plotted scaffolds could help in creating an alternative extra-hepatic transplantation site. In contrast to microcapsule embedding, in 3D plotted scaffold islets are confined in one location and blood vessels can grow into the pores of the construct, in closer contact to the embedded tissue. Once revascularization has occurred, the functionality is fully restored upon degradation of the scaffold.

Summary We present in this paper a test for inductive reasoning (TIR), which consists of two versions that can be used to assess the inductive reasoning development of third-grade pupils in primary education. The test versions can also be used in combination with a training program for inductive reasoning. Two experiments using samples of 954 and 145 pupils were carried out to investigate the psychometric properties of the tests, including validity. Item response theory (IRT) analyses revealed that the scores on the two TIR tests gave meaningful inductive reasoning summaries. This was supported by analyses of the convergent and divergent validity of the TIR tests. IRT analyses were used to equate the two TIR test versions such that the scores can be compared on a common scale. Possible explanations for the misfit of items that were deleted from the TIR tests are discussed.

The results of two evaluation studies with respect to a programme for enhancing inductive reasoning ability of third grade students are presented. The programme is a classroom version of the German programme 'Denktraining für Kinder 1' (Cognitive training for children; Klauer, 1989). In the first formative evaluation study, two experimental groups with 30 students in total and one control group with 9 students were involved. Observations during the lessons, and teachers' reports showed that teachers were able to implement the programme. Both experimental groups significantly outperformed the control group on a posttest immediately after the programme and on a follow-up test 3 1/2 months later. Further analyses of the data revealed tentative evidence of the superiority of a direct teaching method. In the second summative evaluation study, the same programme was applied to a larger sample (experimental groups: n = 99 in total; and control groups: n = 232 in total) of third grade students. On the basis of Study 1, the programme instructions were slightly changed. The experimental groups scored significantly higher on a posttest three months after completion of the programme. Copyright 1998 Academic Press.

Simultaneous pancreas-kidney transplantation (SPK) is an advanced treatment option for type 1 diabetes mellitus (DM) patients with microvascular disease including nephropathy. Sidestreamdarkfield (SDF) imaging has emerged as a noninvasive tool to visualize the human microcirculation. This study assessed the effect of SPK in diabetic nephropathy (DN) patients on microvascular alterations using SDF and correlated this with markers for endothelial dysfunction. Microvascular morphology was visualized using SDF of the oral mucosa in DN (n = 26) and SPK patients (n = 38), healthy controls (n = 20), DM1 patients (n = 15, DM ≥ 40 mL/min) and DN patients with a kidney transplant (KTx, n = 15). Furthermore, 21 DN patients were studied longitudinally up to 12 months after SPK. Circulating levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and soluble thrombomodulin (sTM) were measured using ELISA. Capillary tortuosity in the DN (1.83 ± 0.42) and DM ≥ 40 mL/min (1.55 ± 0.1) group was increased and showed reversal after SPK (1.31 ± 0.3, p < 0.001), but not after KTx (1.64 ± 0.1). sTM levels were increased in DN patients and reduced in SPK and KTx recipients (p < 0.05), while the Ang-2/Ang-1 ratio was normalized after SPK and not after KTx alone (from 0.16 ± 0.04 to 0.08 ± 0.02, p < 0.05). Interestingly, in the longitudinal study, reversal of capillary tortuosity and decrease in Ang-2/Ang-1 ratio and sTM was observed within 12 months after SPK. SPK is effective in reversing the systemic microvascular structural abnormalities in DN patients in the first year after transplantation.

Islet amyloid polypeptide ("amylin") is the major protein component of amyloid deposits in pancreatic islets of type 2 (non-insulin-dependent) diabetic patients. Islet amyloid polypeptide consists of 37 amino acids, is co-produced and co-secreted with insulin from islet beta-cells, can act as a hormone in regulation of carbohydrate metabolism, and is implicated in the pathogenesis of islet amyloid formation and of type 2 diabetes mellitus. Rat islet amyloid polypeptide differs from human islet amyloid polypeptide particularly in the region of amino acids 25-28, which is important for amyloid fibril formation. In rat and mouse, diabetes-associated islet amyloid does not develop. To study the genetic organization and biosynthesis of islet amyloid polypeptide, we have isolated and analyzed the human and rat islet amyloid polypeptide gene and corresponding cDNAs. Both genes contain 3 exons, encoding precursor proteins of 89 amino acids and 93 amino acids, respectively. Apart from a putative signal sequence, these precursors contain amino- and carboxy-terminal flanking peptides in addition to the mature islet amyloid polypeptide. To understand regulation of islet amyloid polypeptide gene expression, we have identified several potential cis-acting transcriptional control elements that influence beta-cell-specific islet amyloid polypeptide gene expression. Using antisera raised against synthetic human islet amyloid polypeptide we developed a specific and sensitive radioimmunoassay to measure levels of islet amyloid polypeptide in plasma and tissue extracts. Also antisera raised against the flanking peptides will be used in studying human islet amyloid polypeptide biosynthesis. Elevated plasma islet amyloid polypeptide levels have been demonstrated in some diabetic, glucose-intolerant, and obese individuals, as well as in rodent models of diabetes and obesity. To examine the potential role of islet amyloid polypeptide overproduction in the pathogenesis of islet amyloid formation and type 2 diabetes, we generated transgenic mice that overproduce either the amyloidogenic human islet amyloid polypeptide or the nonamyloidogenic rat islet amyloid polypeptide in their islet beta-cells. Despite moderately to highly (up to 15-fold) elevated plasma islet amyloid polypeptide levels, no marked hyperglycemia, hyperinsulinemia or obesity was observed. This suggests that chronic overproduction of islet amyloid polypeptide "per se" does not cause insulin resistance. No islet amyloid deposits were detected in mice up to 63 weeks of age, but in every mouse producing human islet amyloid polypeptide (as in man), accumulation of islet amyloid polypeptide was observed in beta-cell lysosomal bodies. This may represent an initial phase in intracellular amyloid fibril formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Mammalian cells exhibit increased sensitivity to hyperthermic temperatures of 38-42 degrees C after an acute high-temperature heat shock; this phenomenon is known as thermo-sensitization or the step-down heating effect. In order to determine whether the increase of heat shock mRNA after heat stress can be thermosensitized, we studied the induction of the mRNA of HSP68 and of HSP84 after application of step-down heating (SDH) in Reuber H35 rat hepatoma cells. SDH consisted of a pretreatment of 30 min at 41.5, 42.5 or 43.5 degrees C, followed by a continuous incubation at a lower hyperthermic temperature (40 or 41 degrees C). After mild pretreatment (30 min at 41.5 degrees C) the mRNA level of HSP68 was increased by subsequent incubation at 40 degrees C, although incubation at 40 degrees C alone had no effect. This increase was even more pronounced at 41 degrees C. An increase in the level of HSP84 mRNA was also observed after mild pretreatment (41.5 degrees C/30 min) followed by 41 degrees C post-incubation. Interestingly, an enhanced occurrence of thermotolerance was also observed upon application of mild step-down heating (42 degrees C/30 min-40 degrees C-43.5 degrees C/60 min). In contrast, cell cultures treated for 30 min at 43.5 degrees C (a temperature which induces an increase in HSP mRNA levels) showed an inhibited or delayed synthesis of HSP mRNA when post-treated at 40 or 41 degrees C. Under these conditions the development of thermotolerance did not take place either. With respect to the effect of step-down heating on HSP mRNA levels as well as on thermotolerance development, our data imply that a distinction should be made between 'mild' and 'severe' pretreatment temperature of the step-down heating protocol.

Objective— The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34 + cells is assumed to be indicative for the potential of these cells to support vascular maintenance and repair. However, in bone marrow and in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood, less than 0.5% of CD34 + cells co-express KDR. Therefore, we studied whether CD34 + /KDR + cells are generated in the peripheral circulation. Methods and Results— Using an ex vivo flow model, we show that activated platelets enable CD34 + cells to home to sites of vascular injury and that upon immobilization, KDR is translocated from an endosomal compartment to the cell-surface within 15 minutes. In patients with diabetes mellitus type 2, the percentage of circulating CD34 + co-expressing KDR was significantly elevated compared to age-matched controls. When treated with aspirin, the patients showed a 49% reduction in the generation of CD34 + /KDR + cells, indicating that the level of circulating CD34 + /KDR + cells also relates to in vivo platelet activation. Conclusion— Circulating CD34 + /KDR + are not mobilized from bone marrow as a predestined endothelial progenitor cell population but are mostly generated from circulating multipotent CD34 + cells at sites of vascular injury. Therefore, the number of circulating CD34 + /KDR + cells may serve as a marker for vascular injury.

GVHD remains a major problem in allo-SCT. We explored the presence of APC in skin biopsies of GVHD patients, using the IgG receptor CD64 expression as a hallmark for activated APC. By immunohistochemistry we demonstrated CD64 to be upregulated on host APC in skin biopsies of patients with acute GVHD and, less prominently, in chronic GVHD. Double staining for CD32 polymorphism revealed CD64-positive cells to be mainly of host origin. The majority of CD64-positive cells coexpressed CD68, indicating a macrophage phenotype. Given its very restricted cellular distribution, CD64 may represent an excellent target for APC-directed therapies in GVHD.

These authors contributed equally to this work.Because microvascular disease is one of the mostimportant drivers of diabetic complications, earlymonitoringofmicrovascularintegritymaybeofclinicalvalue. By assessing profiles of circulating microRNAs(miRNAs), known regulators of microvascular patho-physiology, in healthy controls anddiabetic nephropa-thy (DN) patients before and after simultaneouspancreas–kidney transplantation (SPK), we aimed toidentifydifferentiallyexpressedmiRNAsthatassociatewith microvascular impairment. Following a pilotstudy, we selected 13 candidate miRNAs and deter-mined their circulating levels in DN (n¼21), SPK-patients (n¼37), healthy controls (n¼19), type 1diabetes mellitus patients (n¼15) and DN patientswith a kidney transplant (n¼15). For validation ofselected miRNAs, 14 DN patients were studied longi-tudinallyup to12months afterSPK.Wedemonstrateda direct association of miR-25, -27a, -126, -130b, -132,-152, -181a, -223, -320, -326, -340, -574-3p and -660 withDN.Ofthose,miR-25,-27a,-130b,-132,-152,-320,-326,-340, -574-3p and -660 normalized after SPK. Impor-tantly, circulating levels of some of these miRNAstightlyassociatewithmicrovascularimpairmentastheyrelate to aberrant capillary tortuosity, angiopoietin-2/angiopoietin-1 ratios, circulating levels of soluble-thrombomodulin and insulin-like growth factor. Takentogether, circulating miRNA profiles associate withDN and systemic microvascular damage, and mightserve to identify individuals at risk of experiencingmicrovascularcomplications,aswellasgiveinsightintounderlying pathologies.Abbreviations:Ang-1,angiopoietin-1;Ang-2,angiopoie-tin-2; DM, diabetes mellitus; DN, diabetic nephropathy;IGF, insulin-like growth factor; KTx, kidney transplanta-tion; miRNA, microRNA; MTI, mean tortuosity index;SPK, simultaneous pancreas–kidney transplantation;SPKFU, simultaneous pancreas–kidney transplantationfollow-up; sTM, soluble thrombomodulinReceived 28 March 2014, revised 22 September 2014and accepted for publication 20 October 2014

Simultaneous kidney-pancreas transplantation is an established treatment for patients with type 1 diabetes and end-stage renal failure, even though restored beta cell function may become affected by recurrent islet autoimmunity or graft rejection. We characterised infiltrating lymphocytes isolated from a pancreatic graft with normal endocrine function in a kidney-pancreas recipient with type 1 diabetes.The pancreas graft was removed due to recurrent graft pancreatitis of unknown cause. Pancreas-infiltrating lymphocytes and peripheral blood mononuclear cells (PBMC) were isolated and characterised phenotypically and functionally.Compared with PBMC, pancreas-infiltrating lymphocytes exhibited a distinct activation/memory phenotype and T cell receptor profile that were indicative of selective infiltration of the pancreas. Islet autoreactive CD8(+) T cells could be detected in the pancreas and were increased in frequency compared with PBMC. Additionally, an augmentation of CD8(+) CD28(-) regulatory T cells was observed in the pancreas; these induced expression of the inhibitory receptor immunoglobulin-like transcript-3 on antigen-presenting cells in a donor HLA class I-specific manner.These data demonstrate the simultaneous presence of regulatory and effector T cells in the pancreas allograft of a recipient with type 1 diabetes. They also indicate that circulating islet autoreactive T cells may reflect immunological processes in pancreatic tissue, even though their frequency in the periphery may lead to underestimation of their presence in the pancreas. Additional specificities were also present in the pancreas that were undetectable in the circulation.

The use of antiretroviral combination therapy in HIV has been associated with lipodystrophy and several metabolic risk factors. We postulated that patients with HIV-lipodystrophy have impaired adipose tissue free fatty acid (FFA) trapping and, consequently, increased hepatic FFA delivery. We investigated FFA, hydroxybutyric acid (HBA; reflecting hepatic FFA oxidation), and triglyceride (TG) changes after a high fat meal in HIV-infected males with (LIPO; n = 26) and without (NONLIPO; n = 12) lipodystrophy and in healthy males (n = 35). Because defective peripheral FFA trapping has been associated with impaired action of complement component 3 (C3), we also determined postprandial C3 concentrations. The LIPO group had higher homeostasis model assessment scores compared with the other groups. Areas under the curve (AUCs) for FFA, HBA, and TG were higher in the LIPO group than in the NONLIPO group or the controls. No differences in TG-AUC, FFA-AUC, and HBA-AUC were observed between the NONLIPO group and controls. In HIV-infected patients, FFA-AUC and HBA-AUC were inversely related to sc adipose tissue area. Plasma C3 showed a postprandial increase in healthy controls, but not in the HIV-infected groups. C3 was not related to body fat distribution, postprandial FFA, or HBA. The present data suggest disturbed postprandial FFA metabolism in patients with HIV-lipodystrophy, most likely due to inadequate incorporation of FFA into TG in sc adipose tissue, but do not support a major role for C3 in these patients. The higher postprandial HBA levels reflect increased hepatic FFA delivery and may aggravate insulin resistance and dyslipidemia, leading to increased cardiovascular risk.

Aims/hypothesis. Patients with diabetes are characterised by endothelial dysfunction and cardiovascular mortality. In particular endothelium-derived nitric oxide has emerged as a first line mechanism against atherosclerosis. Hyperglycaemia causes oxygen radical stress but has also been associated with endothelial nitric oxide synthase uncoupling, both lead to decreased nitric oxide-availability. We recently showed that folate reverses eNOS uncoupling in vitro. Therefore we hypothesise that folate improves endothelial function in Type II (non-insulin-dependent) diabetes mellitus in vivo. Methods. Using forearm plethysmography, we evaluated the effect of local, intra-arterial administration of 5-methyltetrahydrofolate (5-MTHF, the active form of folic acid, 1 µg/100 ml FAV/min) on forearm blood flow in 23 patients with Type II diabetes and 21 control subjects, matched for age, sex, blood pressure, body mass index, weight and smoking habits. Serotonin as a stimulator of nitric oxide-dependent vasodilation and sodium nitroprusside as a stimulator of endothelium-independent vasodilation were infused. Results. Serotonin-induced vasodilation was blunted (53±30 vs 102±66 M/C%, p

Purpose: Cardiac Allograft Vasculopathy (CAV) after heart-transplantation is a major factor limiting the long-term patient survival. CAV is characterized by a concentric intima proliferation, which is induced by a mononuclear cell infiltrate (MNC). This process is often compared with a proliferative autoimmune disease in which IL-17 producing T-helper cells (Th17) play a central role. In this study the role of Th17 in the development of CAV was analyzed. Methods and Materials: Coronary arteries (CA) were obtained from CAV patients (n 6) and compared to CA from non-CAV patients (n 5). Q-PCR analysis was performed using a low density array on cDNA prepared from 5 microdissected areas: 1) luminal layer of the intima (LL), 2) smooth muscle cell layer of the intima, 3) tunica media, 4) adventitia (AD), and 5) lymphoid clusters outside the vessel. Genes (50) were selected for Th1/Th2/Th17 characterization. Positive gene expression by Q-PCR analysis was confirmed and localized by in situ hybridization and immunohistochemistry. Results: Tand B-cells were mainly detected in the LL and the AD of CAV and were absent in control CA. Cytokine expression in CAV was generally low, probably due to the immunosuppression. IFN, known to inhibit Th17, was however, significantly expressed, mainly in LL and AD of CAV but not in control CA. TGF, which induces Th17, was detected in both CAV and control CA, and was localized in macrophages. Th1 markers were abundantly present, but Th17 markers such as IL17, IL-23, and IL23R were weakly expressed or absent. Likewise, regulatory T-cells (FoxP3) were not detected in CAV and control CA, and Th2 markers only on a minority of MNC. Conclusions: In autoimmunity, a dichotomy between inducing Th17 and inhibiting regulatory T-cells has been described. In CAV, both are absent. This is suggestive of a different mechanism driving the proliferative response, possibly due to the low cytokine response under immunosuppression. Therefore, we suggest that the Th1-cells, which are predominant in the MNC, are responsible for the direct or indirect induction of the proliferative response.