RESUMO
Galaxy clusters are the most massive virialized structures in the Universe and are formed through the gravitational accretion of matter over cosmic time1. The discovery2 of an evolved galaxy cluster at redshift z = 2, corresponding to a look-back time of 10.4 billion years, provides an opportunity to study its properties. The galaxy cluster XLSSC 122 was originally detected as a faint, extended X-ray source in the XMM Large Scale Structure survey and was revealed to be coincident with a compact over-density of galaxies2 with photometric redshifts of 1.9 ± 0.2. Subsequent observations3 at millimetre wavelengths detected a Sunyaev-Zel'dovich decrement along the line of sight to XLSSC 122, thus confirming the existence of hot intracluster gas, while deep imaging spectroscopy from the European Space Agency's X-ray Multi-Mirror Mission (XMM-Newton) revealed4 an extended, X-ray-bright gaseous atmosphere with a virial temperature of 60 million Kelvin, enriched with metals to the same extent as are local clusters. Here we report optical spectroscopic observations of XLSSC 122 and identify 37 member galaxies at a mean redshift of 1.98, corresponding to a look-back time of 10.4 billion years. We use photometry to determine a mean, dust-free stellar age of 2.98 billion years, indicating that star formation commenced in these galaxies at a mean redshift of 12, when the Universe was only 370 million years old. The full range of inferred formation redshifts, including the effects of dust, covers the interval from 7 to 13. These observations confirm that XLSSC 122 is a remarkably mature galaxy cluster with both evolved stellar populations in the member galaxies and a hot, metal-rich gas composing the intracluster medium.
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Progressive fibrosis of the interstitium is the dominant final pathway in renal destruction in native and transplanted kidneys. Over time, the continuum of molecular events following immunological and nonimmunological insults lead to interstitial fibrosis and tubular atrophy and culminate in kidney failure. We hypothesize that these insults trigger changes in DNA methylation (DNAm) patterns, which in turn could exacerbate injury and slow down the regeneration processes, leading to fibrosis development and graft dysfunction. Herein, we analyzed biopsy samples from kidney allografts collected 24 months posttransplantation and used an integrative multi-omics approach to understand the underlying molecular mechanisms. The role of DNAm and microRNAs on the graft gene expression was evaluated. Enrichment analyses of differentially methylated CpG sites were performed using GenomeRunner. CpGs were strongly enriched in regions that were variably methylated among tissues, implying high tissue specificity in their regulatory impact. Corresponding to this methylation pattern, gene expression data were related to immune response (activated state) and nephrogenesis (inhibited state). Preimplantation biopsies showed similar DNAm patterns to normal allograft biopsies at 2 years posttransplantation. Our findings demonstrate for the first time a relationship among epigenetic modifications and development of interstitial fibrosis, graft function, and inter-individual variation on long-term outcomes.
Assuntos
Atrofia/patologia , Metilação de DNA , Fibrose/patologia , Rejeição de Enxerto/genética , Falência Renal Crônica/patologia , Transplante de Rim/métodos , Túbulos Renais/patologia , Adulto , Atrofia/metabolismo , Biomarcadores/metabolismo , Estudos de Coortes , Progressão da Doença , Feminino , Fibrose/metabolismo , Seguimentos , Perfilação da Expressão Gênica , Taxa de Filtração Glomerular , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/genética , Falência Renal Crônica/cirurgia , Testes de Função Renal , Túbulos Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Transplante HomólogoRESUMO
There is no literature on the use of belatacept for sensitized patients or regrafts in kidney transplantation. We present our initial experience in high immunologic risk kidney transplant recipients who were converted from tacrolimus to belatacept for presumed acute calcineurin inhibitor (CNI) toxicity and/or interstitial fibrosis/tubular atrophy. Six (mean age = 40 years) patients were switched from tacrolimus to belatacept at a median of 4 months posttransplant. Renal function improved significantly from a peak mean estimated glomerular filtration rate (eGFR) of 23.8 ± 12.9 mL/min/1.73 m(2) prior to the switch to an eGFR of 42 ± 12.5 mL/min/1.73 m(2) (p = 0.03) at a mean follow-up of 16.5 months postconversion. No new rejection episodes were diagnosed despite a prior history of rejection in 2/6 (33%) patients. Surveillance biopsies performed in 5/6 patients did not show subclinical rejection. No development of donor-specific antibodies (DSA) was noted. In this preliminary investigation, we report improved kidney function without a concurrent increase in risk of rejection and DSA in six sensitized patients converted from tacrolimus to belatacept. Improvement in renal function was noted even in patients with chronic allograft fibrosis without evidence of acute CNI toxicity. Further studies with protocol biopsies are needed to ensure safety and wider applicability of this approach.
Assuntos
Abatacepte/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Complicações Pós-Operatórias/induzido quimicamente , Insuficiência Renal/induzido quimicamente , Tacrolimo/efeitos adversos , Adulto , Idoso , Aloenxertos/efeitos dos fármacos , Aloenxertos/fisiopatologia , Feminino , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Transplante Homólogo , Resultado do TratamentoRESUMO
The molecular basis of calcineurin inhibitor toxicity (CNIT) in kidney transplantation (KT) and its contribution to chronic allograft dysfunction (CAD) with interstitial fibrosis (IF) and tubular atrophy (TA) were evaluated by: (1) identifying specific CNIT molecular pathways that associate with allograft injury (cross-sectional study) and (2) assessing the contribution of the identified CNIT signature in the progression to CAD with IF/TA (longitudinal study). Kidney biopsies from well-selected transplant recipients with histological diagnosis of CNIT (n = 14), acute rejection (n = 13) and CAD with IF/TA (n = 10) were evaluated. Normal allografts (n = 18) were used as controls. To test CNIT contribution to CAD progression, an independent set of biopsies (n = 122) from 61 KT patients collected at 3 and ~12 months post-KT (range = 9-18) were evaluated. Patients were classified based on 2-year post-KT graft function and histological findings as progressors (n = 30) or nonprogressors to CAD (n = 31). Molecular signatures characterizing CNIT samples were identified. Patients classified as progressors showed an overlap of 7% and 22% with the CNIT signature at 3 and at ~12 months post-KT, respectively, while the overlap was <1% and 1% in nonprogressor patients, showing CNIT at the molecular level as a nonimmunological factor involved in the progression to CAD.
Assuntos
Biomarcadores/sangue , Inibidores de Calcineurina/efeitos adversos , Perfilação da Expressão Gênica , Rejeição de Enxerto/classificação , Falência Renal Crônica/cirurgia , Transplante de Rim , Adulto , Aloenxertos , Área Sob a Curva , Estudos Transversais , Progressão da Doença , Feminino , Seguimentos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/genética , Humanos , Falência Renal Crônica/complicações , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Complicações Pós-Operatórias , Prognóstico , Estudos ProspectivosRESUMO
Despite the advances in immunosuppression, renal allograft attrition over time remains unabated due to chronic allograft dysfunction (CAD) with interstitial fibrosis (IF) and tubular atrophy (TA). We aimed to evaluate microRNA (miRNA) signatures in CAD with IF/TA and appraise correlation with paired urine samples and potential utility in prospective evaluation of graft function. MiRNA signatures were established between CAD with IF/TA versus normal allografts by microarray. Validation of the microarray results and prospective evaluation of urine samples was performed using real-time quantitative-PCR (RT-qPCR). Fifty-six miRNAs were identified in samples with CAD-IF/TA. Five miRNAs were selected for further validation based on array fold change, p-value and in silico predicted mRNA targets. We confirmed the differential expression of these five miRNAs by RT-qPCR using an independent set of samples. Differential expression was detected for miR-142-3p, miR-204, miR-107 and miR-211 (p < 0.001) and miR-32 (p < 0.05). Furthermore, differential expression of miR-142-3p (p < 0.01), miR-204 (p < 0.01) and miR-211 (p < 0.05) was also observed between patient groups in urine samples. A characteristic miRNA signature for IF/TA that correlates with paired urine samples was identified. These results support the potential use of miRNAs as noninvasive markers of IF/TA and for monitoring graft function.
Assuntos
Rejeição de Enxerto , Transplante de Rim , MicroRNAs/genética , Urina , Adulto , Sequência de Bases , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real , Transplante HomólogoRESUMO
Learning occurs in a particular place and time. In most learning situations, information about the training context is encoded along with the task demands and solution. However, the extent to which context contributes to the acquisition and expression of a particular learned response is unclear. In the present paper we examined two fundamental issues underlying the importance of context information and its role in expression of discrimination learning and reversal learning. Rats were trained on a stimulus-response (S-R) habit task designed for the eight-arm radial maze and after reaching a set criterion different context manipulations were performed. Results from Section 2.2.1 revealed that although rats detected a change in context, the learning was not context specific. Results from Section 2.2.2 showed that S-R reversal learning was enhanced when animals were reversed in a context that was different from the one used during original training. Animals that were reversed in a different context showed a renewal effect to the initial S-R when brought back to the original training context.
Assuntos
Aprendizagem por Associação , Atenção , Aprendizagem por Discriminação , Habituação Psicofisiológica , Rememoração Mental , Orientação , Reversão de Aprendizagem , Animais , Condicionamento Operante , Aprendizagem em Labirinto , Ratos , Ratos Long-Evans , Meio SocialRESUMO
The presence of copper and iron in metal-doped wool has been shown previously to be associated with the production of free radicals and yellowing in photo-irradiated wool. In this study, the yellowness and trace metal content of 700 wool samples was measured to determine if photoyellowing, catalysed by metals, is a major determinant of the colour of fleece wool. Iron and copper content did not positively correlate with yellowness and yellower wool tended to have lower levels of these metals. Instead, a strong positive correlation of yellowness with the calcium, manganese and magnesium content was observed in yellow wools. High levels of calcium and magnesium is consistent with biofilm formation by Pseudomonas bacteria that have previously been associated with non-scourable staining of wool.
Assuntos
Cor , Oligoelementos/análise , Lã/química , Animais , Biofilmes , Pseudomonas/crescimento & desenvolvimento , OvinosRESUMO
Supermassive black holes (SMBHs; mass is greater than or approximately 10(5) times that of the Sun) are known to exist at the center of most galaxies with sufficient stellar mass. In the local universe, it is possible to infer their properties from the surrounding stars or gas. However, at high redshifts we require active, continuous accretion to infer the presence of the SMBHs, which often comes in the form of long-term accretion in active galactic nuclei. SMBHs can also capture and tidally disrupt stars orbiting nearby, resulting in bright flares from otherwise quiescent black holes. Here, we report on a ~200-second x-ray quasi-periodicity around a previously dormant SMBH located in the center of a galaxy at redshift z = 0.3534. This result may open the possibility of probing general relativity beyond our local universe.
RESUMO
The objective of the present randomized, open-label, naturalistic 8-week study was to compare the efficacy and safety of treatment with clonazepam (N = 63) and paroxetine (N = 57) in patients with panic disorder with or without agoraphobia. Efficacy assessment included number of panic attacks and clinician ratings of the global severity of panic disorders with the clinical global impression (CGI) improvement (CGI-I) and CGI severity (CGI-S) scales. Most patients were females (69.8 and 68.4% in the clonazepam and paroxetine groups, respectively) and age (mean ± SD) was 35.9 ± 9.6 years for the clonazepam group and 33.7 ± 8.8 years for the paroxetine group. Treatment with clonazepam versus paroxetine resulted in fewer weekly panic attacks at week 4 (0.1 vs 0.5, respectively; P < 0.01), and greater clinical improvements at week 8 (CGI-I: 1.6 vs 2.9; P = 0.04). Anxiety severity was significantly reduced with clonazepam versus paroxetine at weeks 1 and 2, with no difference in panic disorder severity. Patients treated with clonazepam had fewer adverse events than patients treated with paroxetine (73 vs 95%; P = 0.001). The most common adverse events were drowsiness/fatigue (57%), memory/concentration difficulties (24%), and sexual dysfunction (11%) in the clonazepam group and drowsiness/fatigue (81%), sexual dysfunction (70%), and nausea/vomiting (61%) in the paroxetine group. This naturalistic study confirms the efficacy and tolerability of clonazepam and paroxetine in the acute treatment of patients with panic disorder.
Assuntos
Agorafobia/tratamento farmacológico , Clonazepam/uso terapêutico , Transtorno de Pânico/tratamento farmacológico , Paroxetina/uso terapêutico , Adolescente , Adulto , Clonazepam/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paroxetina/efeitos adversos , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Adulto JovemAssuntos
Antígenos de Diferenciação/genética , Antígenos CD28/genética , Doença Celíaca/genética , Predisposição Genética para Doença/genética , Imunoconjugados , Abatacepte , Antígenos CD , Antígeno CTLA-4 , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genéticaAssuntos
Transplante de Rim/fisiologia , Emprego , Feminino , Seguimentos , Nível de Saúde , Humanos , Transplante de Rim/mortalidade , Transplante de Rim/reabilitação , Masculino , Prontuários Médicos , Morbidade , Complicações Pós-Operatórias/epidemiologia , Gravidez , Estudos Retrospectivos , Inquéritos e Questionários , Fatores de TempoRESUMO
The objective of the present randomized, open-label, naturalistic 8-week study was to compare the efficacy and safety of treatment with clonazepam (N = 63) and paroxetine (N = 57) in patients with panic disorder with or without agoraphobia. Efficacy assessment included number of panic attacks and clinician ratings of the global severity of panic disorders with the clinical global impression (CGI) improvement (CGI-I) and CGI severity (CGI-S) scales. Most patients were females (69.8 and 68.4 percent in the clonazepam and paroxetine groups, respectively) and age (mean ± SD) was 35.9 ± 9.6 years for the clonazepam group and 33.7 ± 8.8 years for the paroxetine group. Treatment with clonazepam versus paroxetine resulted in fewer weekly panic attacks at week 4 (0.1 vs 0.5, respectively; P < 0.01), and greater clinical improvements at week 8 (CGI-I: 1.6 vs 2.9; P = 0.04). Anxiety severity was significantly reduced with clonazepam versus paroxetine at weeks 1 and 2, with no difference in panic disorder severity. Patients treated with clonazepam had fewer adverse events than patients treated with paroxetine (73 vs 95 percent; P = 0.001). The most common adverse events were drowsiness/fatigue (57 percent), memory/concentration difficulties (24 percent), and sexual dysfunction (11 percent) in the clonazepam group and drowsiness/fatigue (81 percent), sexual dysfunction (70 percent), and nausea/vomiting (61 percent) in the paroxetine group. This naturalistic study confirms the efficacy and tolerability of clonazepam and paroxetine in the acute treatment of patients with panic disorder.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Agorafobia/tratamento farmacológico , Clonazepam/uso terapêutico , Transtorno de Pânico/tratamento farmacológico , Paroxetina/uso terapêutico , Clonazepam/efeitos adversos , Escalas de Graduação Psiquiátrica , Paroxetina/efeitos adversos , Resultado do TratamentoRESUMO
Increased awareness of the high prevalence of celiac disease and the degree of underdiagnosis has led to calls for routine screening in certain groups. The potential consequences of underdiagnosis have been the subject of several studies. Where there is a delay in diagnosis, there may be an increased risk of associated autoimmune diseases. Alternatively, there may be marked neurological complications, or fetal growth retardation where pregnancy preceeds diagnosis. Once a diagnosis is obtained, treatment may become easier with further evidence that oats are well tolerated by most people with celiac disease. Screening will be facilitated by the development of highly sensitive and specific enzyme-linked immunosorbent assays for tissue transglutaminase. Further insights into the genetics of the condition have been gained with the discovery of a new human leukocyte antigen susceptibility type, plus a possible non-human-leukocyte antigen susceptibility gene.
RESUMO
Celiac disease, or gluten-sensitive enteropathy, is a small intestinal disorder which affects up to 1:250 people in the United States. Disease development has a strong genetic component, with a sibling relative risk (lambda(s)) of 30. One susceptibility locus is the MHC region, with a particular association with the HLA-DQ alleles DQA1*0501 and DQB1*0201. However, haplotype sharing studies suggest that genes within the MHC complex contribute no more than 40% to the sibling familial risk of disease. This means that the stronger genetic risk is likely to be conferred by a small number of non-HLA-linked genes. Genome-wide linkage studies, plus linkage and association studies of candidate loci have been used to try to identify these genes. However, these studies have either failed to detect loci, or produced inconsistent results. Such difficulties in identifying susceptibility genes are encountered when investigating any complex genetic disorder. Information from the Human Genome Project, coupled with new technology for high throughput single nucleotide polymorphism typing may help to identify the non-HLA determinants of celiac disease in the future.
Assuntos
Doença Celíaca/genética , Doença Celíaca/imunologia , Mapeamento Cromossômico , Ligação Genética , Antígenos HLA/genética , Humanos , Complexo Principal de Histocompatibilidade , Fatores de RiscoRESUMO
A man temporarily developed an organic personality change, psychosis and epilepsy after a frontal lobe operation for a subarachnoid haemorrhage. While affected, he set fire to his house. The arson is thought to have been a direct result of a seizure. The case and its legal management are discussed.
Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Epilepsia do Lobo Temporal/complicações , Piromania/etiologia , Complicações Pós-Operatórias/psicologia , Hemorragia Subaracnóidea/cirurgia , Adulto , Carbamazepina/uso terapêutico , Epilepsia do Lobo Temporal/tratamento farmacológico , Lobo Frontal/cirurgia , Humanos , MasculinoRESUMO
We review the significance of the Widal agglutination test in the diagnosis of typhoid fever. Over 100 years since its introduction as a serologic means of detecting the presence of typhoid fever, the Widal test continues to be plagued with controversies involving the quality of the antigens used and interpretation of the result, particularly in endemic areas. Areas of concern with clinical and laboratory significance discussed in this review include: the techniques of test performance, interpretation of results, limitation of the value of the test results in endemic typhoid areas, the quality of the antigens used, and alternative diagnostic tests.
Assuntos
Testes de Hemaglutinação/métodos , Febre Tifoide/diagnóstico , Antígenos de Bactérias , Humanos , Salmonella paratyphi A/imunologia , Salmonella typhi/imunologia , Sensibilidade e EspecificidadeRESUMO
Deferoxamine is widely used in the diagnosis and treatment of aluminum toxicity and has a characteristic combination of side effects, including a poorly defined worsening of existing neurologic symptoms. However, to date, no measurement of cerebrospinal fluid (CSF) aluminum concentrations after deferoxamine exist. We report the case of a patient who developed acute neurological deterioration in conjunction with sepsis and elevated serum aluminum levels shortly after renal transplantation. Simultaneous values for blood and CSF aluminum were measured in response to deferoxamine and hemodialysis. The increase in CSF aluminum levels appears to parallel that seen in serum after deferoxamine. We hypothesize that this elevation in CSF aluminum may account for the observed neurologic deterioration after deferoxamine and postulate various pathophysiologic mechanisms that might be involved.
Assuntos
Alumínio/líquido cefalorraquidiano , Encefalopatias/induzido quimicamente , Desferroxamina/efeitos adversos , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Adulto , Alumínio/efeitos adversos , Encefalopatias/tratamento farmacológico , Desferroxamina/uso terapêutico , Feminino , Humanos , Transplante de RimRESUMO
We reviewed 16,621 blood chemistry samples taken over a 12-week period; 34 patients with severe hypophosphatemia (serum phosphate level less than or equal to 1.0 mg/dl) were identified, for an incidence of 0.24%. The most common causes of severe hypophosphatemia (SH) in this population were infusion of dextrose solutions (73%), nutritional recovery syndrome (50%), phosphate-binding antacids (50%), and alcohol withdrawal (32%). In general, the patients were normophosphatemic at the time of hospitalization, and SH occurred early in the hospital course. All of the patients responded to the drop in serum phosphate by renal conservation of phosphate (Tm PO4/GFR less than 1.0 mg/dl GFR). Patients required small doses of phosphate to achieve a serum level above 2.0 mg/dl, with 50% of the population receiving less than 25 mmol of replacement therapy. Regardless of the route or amount of replacement therapy given, the course of SH was typically short and without sequelae.
Assuntos
Fosfatos/sangue , Adulto , Idoso , Antiácidos/efeitos adversos , Etanol/efeitos adversos , Feminino , Glucose/efeitos adversos , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Distúrbios Nutricionais/complicações , Estudos Prospectivos , Síndrome de Abstinência a Substâncias/complicaçõesRESUMO
BACKGROUND: Partial reinnervation of cardiac sympathetic nerves has been observed after heart transplantation; we hypothesized that parasympathetic control to the heart after transplantation may return as well. To test this hypothesis, we examined heart rate responses produced by two cardiovascular reflexes whose efferent limbs are subserved by vagal fibers to the heart: (1) trigeminal reflex (simulated diving reflex) and (2) arterial baroreflex with phenylephrine injection. METHODS AND RESULTS: An "early" group (n=31, <24 months after transplantation) and a "late group" (n=27, >45 months after transplantation) were studied and compared with a control group with intact cardiac innervation (n=32) and a renal transplant group with similar transplant immunosuppressive regimen (n=11). For trigeminal reflex testing, responses of the donor sinus node (DSN) (sinus node controlling heart rate) and recipient sinus node (RSN) in the innervated remnant right atrium in cardiac transplant patients were compared with heart rate responses in the control groups. For arterial baroreflex testing, baroreflex gains for the DSN and RSN in the cardiac transplant groups were compared with those of the control group. With engagement of the trigeminal reflex, the DSN rate of both transplant groups changed minimally (early, 1.2+/-1.2 bpm; late, 1.8+/-2.5 bpm) compared with the expected decrease in control subjects (-19.8+/-3.0 bpm) and renal transplant patients (-23.9+/-4.9 bpm) (P<.001 versus cardiac transplants). Changes in the RSN rate of both cardiac transplant groups (early, -13.0+/-4.0 bpm; late, -10.0+/-3.7 bpm) were similar to the control groups. Arterial baroreflex gains for the DSN were also depressed (early, 0.1+/-0.2 ms/mm Hg; late, 0.2+/-0.2 ms/mm Hg) compared with control (14.9+/-1.8 ms/mm Hg) and RSN (early, 9.9+/-1.3 ms/mm Hg; late, 10.9+/-1.3 ms/mm Hg; P<.001 versus DSN transplant). CONCLUSIONS: These data suggest that parasympathetic influences on donor heart rate are absent in the majority of patients up to 96 months after cardiac transplantation.
Assuntos
Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/fisiologia , Transplante de Coração , Sistema Nervoso Parassimpático/fisiopatologia , Adulto , Idoso , Artérias/fisiopatologia , Barorreflexo/fisiologia , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Reflexo/fisiologia , Fatores de Tempo , Nervo Trigêmeo/fisiopatologiaRESUMO
Coeliac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically predisposed individuals. Patients with CD have an increased prevalence of other autoimmune disorders, including type 1 diabetes (T1D) and Graves' disease (GD). CD shares with these conditions certain HLA susceptibility alleles. A number of studies have also shown association of autoimmune diseases, including CD, with the CD28-cytotoxic T lymphocyte antigen 4 (CTLA4)-inducible costimulator (ICOS) region of chromosome 2q33, but until recently the precise causal variant has remained unknown. Recently, it was shown that, in GD, CT60 (+6230G>A), a single nucleotide polymorphism (SNP) at the end of the CTLA4 transcript, is associated with an alteration in the ratio of splice forms of the CTLA4 gene and that this ratio affects disease susceptibility. A similar but weaker association was found with T1D. There is also an independent association of GD and T1D with the SNP MH30 (-23 327G>C), which possibly affects promoter region function. Hypothesizing that CT60 and MH30 may be causal variants in other autoimmune disorders, we investigated these SNPs in CD using 149 family trios and 100 unrelated/unaffected controls. No association was detected with either SNP using both the transmission disequilibrium test (TDT) and case-control methods. Our study appears to have good power to detect moderate genetic effects, but possibly these SNPs exert too weak an effect on risk of CD to have been detected in our sample. Alternatively, the previously noted association of CD with the CTLA4 gene region may be due to different causal variants. Unlike T1D and GD, CD is not a true autoimmune disease, and CD has different associations at the CTLA4 exon 1 SNP +49G>A from all other autoimmune disorders. MH30, CT60, and other SNPs in the region may still warrant further investigation in other CD samples.