The long-term outcome of revision microdiscectomy for recurrent sciatica.

PURPOSE: To study the long-term outcome of revision microdiscectomy after classic microdiscectomy for lumbosacral radicular syndrome (LSRS). METHODS: Eighty-eight of 216 patients (41%) who underwent a revision microdiscectomy between 2007 and 2010 for MRI disc-related LSRS participated in this study. Questionnaires included visual analogue scores (VAS) for leg pain, RDQ, OLBD, RAND-36, and seven-point Likert scores for recovery, leg pain, and back pain. Any further lumbar re-revision operation(s) were recorded. RESULTS: Mean (SD) age was 59.8 (12.8), and median [IQR] time of follow-up was 10.0 years [9.0-11.0]. A favourable general perceived recovery was reported by 35 patients (40%). A favourable outcome with respect to perceived leg pain was present in 39 patients (45%), and 35 patients (41%) reported a favourable outcome concerning back pain. The median VAS for leg and back pain was worse in the unfavourable group (48.0/100 mm (IQR 16.0-71.0) vs. 3.0/100 mm (IQR 2.0-5.0) and 56.0/100 mm (IQR 27.0-74.0) vs. 4.0/100 mm (IQR 2.0-17.0), respectively; both p < 0.001). Re-revision operation occurred in 31 (35%) patients (24% same level same side); there was no significant difference in the rate of favourable outcome between patients with or without a re-revision operation. CONCLUSION: The long-term results after revision microdiscectomy for LSRS show an unfavourable outcome in the majority of patients and a high risk of re-revision microdiscectomy, with similar results. Based on also the disappointing results of alternative treatments, revision microdiscectomy for recurrent LSRS seems to still be a valid treatment. The results of our study may be useful to counsel patients in making appropriate treatment choices.

Subcutaneous administration, higher age and lower renal function are associated with erythrocyte methotrexate accumulation in Crohn's disease: a cross-sectional study.

BACKGROUND: Methotrexate is an immunomodulatory drug for patients with Crohn's disease. Erythrocyte MTX-polyglutamates (MTX-PG1-5) may be used for therapeutic drug monitoring (TDM) as MTX-PG is thought to mediate MTX's efficacy. Information on determinants of the concentration of MTX-PG in patients with Crohn's disease is lacking. We aim to identify clinical and biochemical determinants of the erythrocyte MTX-PG1-5 and MTX-PGtotal concentration in patients with Crohn's disease. METHODS: Adults with Crohn's disease on methotrexate treatment who visited the outpatient clinic of Amsterdam UMC were included. Erythrocyte MTX-PGs were measured by tandem mass spectrometry. RESULTS: Nineteen patients were included, with a median duration of MTX use of 77 months (range 7-202). Twelve patients received MTX monotherapy, whereas 7 patients were on concomitant TNF-α inhibitors. The mean dose of MTX was 15.5 mg (SD ± 2.8) and 12 (63%) patients used subcutaneous MTX. MTX-PG1-5 were successfully measured in 18 patients, showing substantial variability in concentrations of MTX-PGtotal and individual species. The median MTX-PGtotal was 117.1 nmol/L (range 46.4-258.7) with preferential accumulation of MTX-PG3 (43.1 nmol/L, range 15.3-96.1). Patients on subcutaneous compared to oral MTX had higher median MTX-PG(4,5) levels (55 versus 9 nmol/L, p = 0.01). Higher age (ß = 0.71) and lower estimated glomerular filtration rate (ß = - 0.52) were associated with a significantly higher MTX-PGtotal concentration (R2 = 0.60, p = 0.001). CONCLUSION: MTX-PG concentrations display a considerable inter-individual variability. Higher MTX-PG accumulation is associated with subcutaneous administration, higher age, and lower renal function in Crohn's disease patients.

The role of embryo contact and focal adhesions during maternal recognition of pregnancy.

Maternal recognition of pregnancy (MRP) in the mare is an unknown process. In a non-pregnant mare on day 14 post-ovulation (PO), prostaglandin F2α (PGF) is secreted by the endometrium causing regression of the corpus luteum. Prior to day 14, MRP must occur in order to attenuate secretion of PGF. The embryo is mobile throughout the uterus due to uterine contractions from day of entry to day 14. It is unknown what signaling is occurring. Literature stated that infusing oil or placing a glass marble into the equine uterus prolongs luteal lifespan and that in non-pregnant mares, serum exosomes contain miRNA that are targeting the focal adhesion (FA) pathway. The hypothesis of this study is embryo contact with endometrium causes a change in abundance of focal adhesion molecules (FA) in the endometrium leading to decrease in PGF secretion. Mares (n = 3/day) were utilized in a cross-over design with each mare serving as a pregnant and non-pregnant (non-mated) control on days 9 and 11 PO. Mares were randomly assigned to collection day and endometrial samples and embryos were collected on the specified day. Biopsy samples were divided into five pieces, four for culture for 24 hours and one immediately snap frozen. Endometrial biopsies for culture were placed in an incubator with one of four treatments: [1] an embryo in contact on the luminal side of the endometrium, [2] beads in contact on the luminal side of the endometrium, [3] peanut oil in contact on the luminal side of the endometrium or [4] the endometrium by itself. Biopsies and culture medium were frozen for further analysis. RNA and protein were isolated from biopsies for PCR and Western blot analysis for FA. PGF assays were performed on culture medium to determine concentration of PGF. Statistics were performed using SAS (P ≤ 0.05 indicated significance). The presence of beads on day 9 impacted samples from pregnant mares more than non-pregnant mares and had very little impact on day 11. Presence of oil decreased FA in samples from pregnant mares on day 9. On day 11, oil decreased FA abundance in samples from non-pregnant mares. Embryo contact caused multiple changes in RNA and protein abundance in endometrium from both pregnant and non-pregnant mares. The PGF secretion after 24 hours with each treatment was also determined. On day 9, there was no change in PGF secretion compared to any treatments. On day 11, presence of peanut oil increased PGF secretion in samples from non-pregnant mares. In samples from non-pregnant mares, presence of an embryo decreased PGF secretion compared to control samples from non-pregnant mares. Results revealed that while beads and peanut oil may impact abundance of FA RNA and protein in endometrial samples, it does not appear to impact PGF secretion. Conversely, embryo contact for 24 hours with endometrium from a non-pregnant mare causes a decrease in PGF secretion. These results suggest that it is not just contact of any substance/object causing attenuation of PGF secretion, but the embryo itself is necessary to decrease PGF secretion.

Web-based personalised information and support for patients with a neuroendocrine tumour: randomised controlled trial.

BACKGROUND: Patients with a neuroendocrine tumour (NET) frequently have physical and psychosocial complaints. Aim of this study is to determine whether a web-based, personalised information and support system (WINS) reduces distress and/or improves patients' perception of and satisfaction with information received. METHODS: Patients with NET, stratified for those newly diagnosed (< 6 months, n = 28) and with a longer history of disease (n = 74), were randomised between standard care (n = 49) and intervention, consisting of access to WINS (n = 53). Primary outcome was change of distress and satisfaction with perceived information measured with the distress thermometer and problem list and the QoL questionnaire (QLQ)-INFO25. The intervention group also completed a questionnaire based on the technical acceptance model (TAM). RESULTS: We observed no difference in distress slope and slope of median global score on perceived information and satisfaction between the intervention and control group. Interestingly, 55% of patients wished to receive more information at baseline. CONCLUSIONS: In a population of NET patients, access to WINS did not improve indicators for distress, perception of information and satisfaction with information received, more than standard care only. Despite the need for more information, the WINS does not have added value to the information and care provided by health care professionals. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02472678 ). Registered 6th Jan 2015. Retrospectively registered 1st May 2017.

HMGA2 is regulated by LIN28 and BRCA1 in human placental cells.

The chromatin associated transcription factor HMGA2 is a downstream target of let-7 miRNAs and binds to chromatin to regulate gene expression. Inhibition of let-7 miRNAs by RNA-binding proteins LIN28A and LIN28B is necessary during early embryogenesis to ensure stable expression of HMGA2. In addition to LIN28, HMGA2 is regulated by a BRCA1/ZNF350/CtIP repressor complex. In normal tissues, the BRCA1/ZNF350/CtIP complex binds to the HMGA2 promoter to prevent transcription. However, in many cancers the oncomiR miR-182 targets BRCA1, preventing BRCA1 translation and allowing for increased HMGA2. Little is known about the regulation of HMGA2 during early placental development; therefore, we hypothesized that both LIN28 and BRCA1 can regulate HMGA2 in placental cells. Using siRNA and CRISPR gene editing techniques, we found that knockdowns of both LIN28A and LIN28B increase HMGA2 levels in ACH-3P cells. These cells also demonstrated deficiencies in cell differentiation, seemingly differentiating solely towards the syncytiotrophoblast sublineage, secreting higher amounts of hCG, and displaying upregulated ERVW-1. Additionally, we found that a knockout of both LIN28A and LIN28B caused a significant increase of miR-182 and a decrease in BRCA1 allowing HMGA2 mRNA levels to increase and protein levels to remain the same. Using chromatin immunoprecipitation, we saw binding of the BRCA1 repressor complex to HMGA2. We also saw a decrease in binding to HMGA2's promoter in the LIN28A/B knockout cells. These findings suggest a novel role for BRCA1 during early human placental development.

Lymphoma development and survival in refractory coeliac disease type II: Histological response as prognostic factor.

BACKGROUND: Refractory coeliac disease type II (RCDII) frequently transforms into an enteropathy-associated T-cell lymphoma (EATL) and therefore requires intensive treatment. Current evaluated treatment strategies for RCDII include cladribine (2-CdA) and autologous stem cell transplantation (auSCT). OBJECTIVE: The purpose of this study was to evaluate long-term survival and define clear prognostic criteria for EATL development comparing two treatment strategies. METHODS: A total of 45 patients were retrospectively analysed. All patients received 2-CdA, after which they were either closely monitored (monotherapy, n = 30) or a step-up approach was used including auSCT (step-up therapy, n = 15). RESULTS: Ten patients (22%) ultimately developed EATL; nine of these had received monotherapy. Absence of histological remission after monotherapy was associated with EATL development (p = 0.010). Overall, 20 patients (44%) died with a median survival of 84 months. Overall survival (OS) within the monotherapy group was significantly worse in those without histological remission compared to those with complete histological remission(p = 0.030). The monotherapy group who achieved complete histological remission showed comparable EATL occurrence and OS as compared to the step-up therapy group (p = 0.80 and p = 0.14 respectively). CONCLUSION: Histological response is an accurate parameter to evaluate the effect of 2-CdA therapy and this parameter should be leading in the decisions whether or not to perform a step-up treatment approach in RCDII.

Outcome of Referrals for Non-Responsive Celiac Disease in a Tertiary Center: Low Incidence of Refractory Celiac Disease in the Netherlands.

OBJECTIVES: Refractory celiac disease (RCD) is a severe cause of non-responsive celiac disease (CD) due to its association with the enteropathy associated T-cell lymphoma (EATL). Conflicting data exist on the prevalence and the clinical manifestations of RCD type I (RCD I) and type II (RCD II). The aim of the current study was to provide insight in the incidence of RCD and in the distinction with other causes of non-responsive CD. METHODS: A total of 106 CD patients were referred to our tertiary referral center between January 2006 and December 2011 for evaluation of non-responsive CD. In addition, a questionnaire was sent to all 82 gastroenterology departments in the Netherlands to reveal whether a patient with RCD was currently being evaluated or had been treated between 2006 and 2012. RESULTS: During a 6 year period, a total of 31 patients were diagnosed with RCD (19 RCD I and 12 RCD II). The nationwide survey revealed 5 additional patients with RCD I and one patient with RCD II. This leads to an annual incidence of RCD of 0.83/10.000 CD patients. The remaining patients were diagnosed with involuntary gluten ingestion (21.7%), delayed mucosal recovery (11.3%), enteropathy associated T-cell lymphoma (7.5%) and autoimmune enteropathy (1.8%). CONCLUSIONS: This nationwide study reveals a low incidence of RCD in the Netherlands. Nevertheless, RCD is a clinically relevant disease entity in CD patients non-responsive to the gluten-free diet.

Expert clinical management of autoimmune hepatitis in the real world.

BACKGROUND: High-quality data on the management of autoimmune hepatitis (AIH) are scarce. Despite published guidelines, management of AIH is still expert based rather than evidence based. AIM: To survey expert hepatologists, asking each to describe their practices in the management of patients with AIH. METHODS: A survey questionnaire was distributed to members of the International AIH Group. The questionnaire consisted of four clinical scenarios on different presentations of AIH. RESULTS: Sixty surveys were sent, out of which 37 were returned. None reported budesonide as a first line induction agent for the acute presentation of AIH. Five (14%) participants reported using thiopurine S-methyltransferase measurements before commencement of thiopurine maintenance therapy. Thirteen (35%) routinely perform liver biopsy at 2 years of biochemical remission. If histological inflammatory activity is absent, four (11%) participants reduced azathioprine, whereas 10 (27%) attempted withdrawal altogether. Regarding the management of difficult-to-treat patients, mycophenolate mofetil is the most widely used second-line agent (n = ~450 in 28 centres), whereas tacrolimus (n = ~115 in 21 centres) and ciclosporin (n = ~112 in 18 centres) are less often reported. One centre reported considerable experience with infliximab, while rescue therapy with rituximab has been tried in seven centres. CONCLUSIONS: There is a wide variation in the management of patients with autoimmune hepatitis even among the most expert in the field. Although good quality evidence is lacking, there is considerable experience with second-line therapies. Future prospective studies should address these issues, so that we move from an expert- to an evidence- and personalised-based care in autoimmune hepatitis.

Novel variant of EATL evolving from mucosal γδ-T-cells in a patient with type I RCD.

OBJECTIVES: Enteropathy associated T-cell lymphoma (EATL) is a rare non-Hodgkin lymphoma that may complicate coeliac disease and typically occurs in patients with refractoriness to the gluten-free diet. The majority of these patients harbour a clonal expansion of intraepithelial lymphocytes (IELs) with an aberrant phenotype in the small intestine which are thus considered as the 'precursor' lymphoma cells. We describe a 51-year-old female patient with refractory coeliac disease (RCD) who developed an EATL with manifestations in the proximal small intestine and in a mesenteric lymph node that did not evolve from regular type 'aberrant' αß-T-cells but rather from a clonal expansion of γδ-T-cells. METHODS: Duodenal biopsies and lymphoma tissue from a patient with refractory coeliac disease whom developed an EATL were extensively studied by immunophenotypical, T-cell receptor immunogenetic and chromosomal analysis. RESULTS: Flow cytometric analysis of duodenal IELs revealed an unusual large clonal expansion of CD30 negative γδ-T-cells in a patient with RCD. When the patient clinically deteriorated 18 months later, a substantial part (30%) of this cell population did express CD30. In addition, identical immunogenetic aberrancies had developed in a prehepatic lymph node. CONCLUSIONS: We here report on a case of extraintestinal EATL that originated from a clonal γδ-IEL population rather than from aberrant IEL. This EATL displayed a distinctive pattern of immunophenotypical, T-cell receptor immunogenetic and chromosomal aberrancies as compared to classical EATL, defining this lymphoma as a novel variant of EATL.

Equine endometrial gene expression changes during and after maternal recognition of pregnancy.

The mechanism for maternal recognition of pregnancy (MRP) in horses is unknown. To maintain a pregnancy, a mobile conceptus must be recognized by the uterus before d 14 postovulation (PO). This recognition prevents endometrial secretion of PGF2α on d14 through 16, which would otherwise initiate luteolysis. The objective of this study was to evaluate gene expression in the endometrium of pregnant and nonpregnant mares during and after MRP to identify possible genes involved during this time. Twelve normally cycling mares were used in a crossover design and randomly assigned to a specific collection day. Endometrial samples were collected from a pregnant and nonpregnant (nonmated) mare on cycle d 12, 14, 16, and 18 (n = 3/d) PO. Microarray analysis comparing the endometrial gene expression in pregnant and nonpregnant mares revealed no differences at d 12. Ten genes were identified to have consistently higher or lower expression levels in the endometrium from pregnant versus nonpregnant mares on d 14, 16, and 18 (P < 0.001). The expression of these 10 genes was further analyzed with real-time PCR. d 14, 16, and 18 gene expression patterns were consistent with the microarray analysis, but on d 12, 4 of the 10 were identified as differentially expressed. Endometrial samples were then collected on d 13 PO (n = 3) and processed for western blot and immunohistochemical analysis of 2 proteins due to their reproductive significance. SPLA2 and DKK1 antibody specificity were confirmed via western blot analysis but were not different in samples from pregnant and nonpregnant mares (P = 0.114 and P = 0.514, respectively) and cellular localization was examined by immunohistochemical analysis. This is the first study to describe gene expression and cellular localization in the endometrium at the time of MRP for these genes and suggests that the uterus does not prepare to support a pregnancy until d 14. The function of these genes may be critical in the process of MRP.

[Coeliac disease and dentistry]. / Coeliakie en tandheelkunde.

Coeliac disease is a chronic autoimmune enteropathy, which is caused by exposure to dietary gluten in genetically pre-disposed individuals. -Approximately 0.5-1% of the Dutch population has coeliac disease, diag-nosed at both younger and older age. Treatment consists of a strict gluten-free diet. Symptoms can be diverse, including dental and oral manifestations. These dental and oral manifestations are often seen in patients with coeliac disease, although most of them are nonspecific. This is not the case for the symmetric enamel defects described by Aine and colleagues, which are very specific for coeliac disease. Early diagnosing of coeliac disease is important to prevent complications by (vitamin) deficiencies or rare (pre) malignant forms of coeliac disease. There seems to be a role for dentists in early diagnosing of coeliac disease.

Enteropathy-associated T-cell lymphoma: improving treatment strategies.

Enteropathy-associated T-cell lymphoma (EATL) is a rare and usually rapidly fatal intestinal T-cell non-Hodgkin lymphoma. It arises from intraepithelial lymphocytes and has a high association with coeliac disease. The high mortality of EATL is associated not only with the very aggressive and often chemotherapy-refractory nature of the lymphoma. The poor condition of patients due to prolonged and severe malnutrition compromises the ability to deliver chemotherapy. There are no standardized treatment protocols, and the optimal therapy for EATL remains unclear. The primary step of treatment consists of local debulking, preferably as early as possible after EATL diagnosis. Morbidity and mortality seem to rise with advanced stages of disease due to tumour size progression, worse nutritional status and a higher risk of emergency surgery due to perforation. Standard induction therapy for EATL is anthracycline-based chemotherapy, preferably resumed between 2 and 5 weeks after surgery (depending on clinical condition). Intensification of therapy using high-dose chemotherapy followed by consolidation with BEAM and autologous stem cell transplantation is associated with better outcome. Notably, this treatment strategy has only been applied in patients eligible for this aggressive regimen which might reflect selection bias. Unfortunately, prognosis of EATL remains poor; 5-year survival varies from 8 to 60% depending on the eligibility to receive additional steps of therapy. New treatment strategies are urgently needed for a better prognosis of this lethal complication of coeliac disease. Brentuximab vedotin (anti-CD30) might be promising when added to conventional chemotherapy and is suggested as upfront treatment in EATL.

Identification of heat shock protein 10 within the equine embryo, endometrium, and maternal peripheral blood mononuclear cells.

Early pregnancy factor has been identified as a 10-kDa extracellular homolog of heat shock protein 10 (Hsp10). Hsp10 has been detected during early pregnancy in serum of mice, sheep, pigs, horses, cows, and humans by the rosette inhibition test. Hsp10 has also been associated with several neoplastic and autoimmune diseases. The goal of the present study was to determine if Hsp10 could be detected in the early equine embryo through the use of immunohistochemistry and quantitative real-time PCR. Additionally, analysis of systemically harvested peripheral blood mononuclear cells (PBMCs) from both pregnant and nonpregnant mares was evaluated to determine expression levels of HSP10. Embryos were collected from Quarter Horse mares by uterine lavage at either 8 or 25 days after ovulation. Collection and separation of PBMCs occurred on Day 8 for both pregnant and nonpregnant mares. Immunohistochemistry revealed cytoplasmic localization of HSP10 throughout the single layer of ectodermal cells forming the trophoblast in Day-8 embryos. Day-25 embryos demonstrated intense localization focally along the apical border of ectodermal cells forming the trophoblast layer of the developing chorion. There was no nuclear staining in either embryonic population. Quantitative real-time PCR detected the presence of mRNA for HSP10 in both 8- and 25-day equine embryos. Day-25 embryos exhibited an elevated degree of expression (P = 0.006) compared with the 8-day embryos for HSP10. Endometrial samples did not display any significant difference in degree of expression for HSP10 (P = 0.10). Finally, PBMCs from pregnant mares demonstrated elevated (P = 0.03) expression of HSP10 compared to the nonpregnant mares on Day 8 of the estrous cycle. This study confirmed the presence of HSP10 protein and mRNA expression of HSP10 in equine embryos at two maturation stages. Additionally, the presence of increased gene expression within PBMCs of pregnant mares suggests communication, possibly leading to necessary immunomodulatory effects between the embryo and mare.

Optimal strategies to identify aberrant intra-epithelial lymphocytes in refractory coeliac disease.

INTRODUCTION: Different strategies have been developed to identify those refractory celiac disease (RCD) patients who are at risk to develop an enteropathy associated T-cell lymphoma (EATL). Flow cytometric analysis of intra-epithelial lymphocytes (IEL) with an aberrant phenotype is considered the golden standard but is not widely available. Immunohistochemistry (IHC) and T-cell receptor (TCR) rearrangement studies are commonly available but may lack sensitivity and specificity. Here, we compared the three different methods in the workup of patients suspected for RCD. METHODS: Duodenal biopsies from control patient (n = 5), RCD patients with moderately increased aberrant IEL populations (20-50 %: n = 14), and RCD patients with high numbers of aberrant IEL (>50 %: n = 5) as determined by flow cytometry were analysed by IHC and TCR-γ chain rearrangement analysis. Three pathologists scored the slides independently. RESULTS: Sensitivity of IHC and TCR-γ rearrangement analysis in RCD patients with high numbers of aberrant IELs was 100 and 71 %, respectively. RCD patients with aberrant cells between 25 and 50 % however, were missed by IHC and TCR in 50 and 57 % of cases, respectively. In addition, inter-rater reliability analysis of the IHC scoring revealed coder-pair Kappa coefficients between 0.28 and 0.85. CONCLUSION: Immunohistochemistry and to a lesser extent TCR-γ clonality analysis are sensitive in identifying patients with high numbers of aberrant IEL populations, yet miss half of RCD patients with moderately increased numbers. In addition, IHC has a high inter-observer variability. Therefore, patients suspected for RCD should undergo flow cytometric analysis of the duodenum.

Excreted/secreted Trichuris suis products reduce barrier function and suppress inflammatory cytokine production of intestinal epithelial cells.

The administration of helminths is considered a promising strategy for the treatment of autoimmune diseases due to their immunomodulatory properties. Currently, the application of the helminth Trichuris suis as a treatment for Crohn's disease is being studied in large multi-center clinical trials. The intestinal epithelium forms an efficient barrier between the intestinal lumen containing the microbial flora and helminths, and dendritic cells (DCs) present in the lamina propria that determine the TH response. Here, we investigated how excreted/secreted (E/S) products of T. suis affect the barrier function of intestinal epithelial cells (IECs) in order to reach the DCs and modulate the immune response. We show that T. suis E/S products reduce the barrier function and the expression of the tight junction proteins EMP-1 and claudin-4 in IEC CMT93/69 monolayers in a glycan-dependent manner. This resulted in an increased passage of soluble compounds to the basolateral side that affected DC function. In addition, T. suis E/S suppressed LPS-induced pro-inflammatory cytokine production by CMT93/69 cells, whereas the production of the TH2 response-inducing cytokine thymic stromal lymphopoietin (TSLP) was induced. Our studies indicate that T. suis E/S glycans affect the function of the intestinal epithelium in order to modulate DC function. Identification of the T. suis E/S glycans that modulate IEC and DC function may lead to a strategy to reduce symptoms of autoimmune and allergic immune diseases by orally administrated helminth-derived factors without the need of infection with live helminths.

Thiopurine treatment in patients with Crohn's disease leads to a selective reduction of an effector cytotoxic gene expression signature revealed by whole-genome expression profiling.

Crohn's disease (CD) is characterized by chronic inflammation of the gastrointestinal tract, as a result of aberrant activation of the innate immune system through TLR stimulation by bacterial products. The conventional immunosuppressive thiopurine derivatives (azathioprine and mercaptopurine) are used to treat CD. The effects of thiopurines on circulating immune cells and TLR responsiveness are unknown. To obtain a global view of affected gene expression of the immune system in CD patients and the treatment effect of thiopurine derivatives, we performed genome-wide transcriptome analysis on whole blood samples from 20 CD patients in remission, of which 10 patients received thiopurine treatment, compared to 16 healthy controls, before and after TLR4 stimulation with LPS. Several immune abnormalities were observed, including increased baseline interferon activity, while baseline expression of ribosomal genes was reduced. After LPS stimulation, CD patients showed reduced cytokine and chemokine expression. None of these effects were related to treatment. Strikingly, only one highly correlated set of 69 genes was affected by treatment, not influenced by LPS stimulation and consisted of genes reminiscent of effector cytotoxic NK cells. The most reduced cytotoxicity-related gene in CD was the cell surface marker CD160. Concordantly, we could demonstrate an in vivo reduction of circulating CD160(+)CD3(-)CD8(-) cells in CD patients after treatment with thiopurine derivatives in an independent cohort. In conclusion, using genome-wide profiling, we identified a disturbed immune activation status in peripheral blood cells from CD patients and a clear treatment effect of thiopurine derivatives selectively affecting effector cytotoxic CD160-positive cells.