Implications of the Colonic Deposition of Free Hemoglobin-α Chain

Myers, Jeremy N.; Schaffer, Michael; Korolkova, Olga Y.; Williams, Amanda D.; Gangula, Pandu R.; M’Koma, Amosy E.

doi:10.1097/mib.0000000000000144

Cited by 24 publications

(35 citation statements)

References 127 publications

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“…Five colon tissue protein extracts and staining of HD5 per disease by immunohistochemistry (IHC) was done as previously described. 24 Quantification of HD5 staining was analyzed manually by microscopy and automatically quantified using Nikon's Eclipse Ti microscope with built-in NEARAS [ 24 , 25 ].…”

Section: Methodsmentioning

confidence: 99%

Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease

et al. 2017

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Inability to distinguish Crohn's colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately. Four patients groups were assessed via whole-transcriptome microarray, qPCR, Western blot, and immunohistochemistry for differential expression of Human α-Defensin-5. In addition, immunohistochemistry for Paneth cells and Lysozyme, a Paneth cell marker, was also performed. Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn's colitis, p< 0.0001. Among patients with indeterminate colitis, Human α-Defensin-5 is a reliable differentiator with a positive predictive value of 96 percent. We also observed abundant ectopic crypt Paneth cells in all colectomy tissue samples of Crohn's colitis patients. In a retrospective study, we show that Human α-Defensin-5 could be used in indeterminate colitis patients to determine if they have either ulcerative colitis (low levels of Human α-Defensin-5) or Crohn's colitis (high levels of Human α-Defensin-5). Twenty of 67 patients (30 percent) who underwent restorative proctocolectomy for definitive ulcerative colitis were clinically changed to de novo Crohn's disease. These patients were profiled by Human α-Defensin-5 immunohistochemistry. All patients tested strongly positive. In addition, we observed by both hematoxylin and eosin and Lysozyme staining, a large number of ectopic Paneth cells in the colonic crypt of Crohn's colitis patient samples. Our experiments are the first to show that Human α-Defensin-5 is a potential candidate biomarker to molecularly differentiate Crohn's colitis from ulcerative colitis, to our knowledge. These data give us both a potential diagnostic marker in Human α-Defensin-5 and insight to develop future mechanistic studies to better understand crypt biology in Crohn's colitis.

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Section: Methodsmentioning

confidence: 99%

Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease

et al. 2017

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“…Previous studies have demonstrated that nitrergic neurons are degenerated in colitis (Onori et al, 2005; Sung et al, 2006). Recent studies from our laboratory indicate that nNOS, as well as antioxidants (NRF2 regulated-Phase II enzymes) protein expression are down-regulated in diseased colon specimens (Myers et al, 2014; Gangula et al, 2017). Furthermore, our previous studies demonstrated that polybacterial infection led to a decrease in nNOS, NRF2 and antioxidants protein expression in the colon tissues (Gangula et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Identification of Specific Oral and Gut Pathogens in Full Thickness Colon of Colitis Patients: Implications for Colon Motility

Dinakaran¹,

Mandape²,

Shuba³

et al. 2019

Front. Microbiol.

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Impaired colon motility is one of the leading problems associated with inflammatory bowel disease (IBD). An expanding body of evidence supports the role of microbiome in normal gut function and in progression of IBD. The objective of this work is to determine whether diseased full thickness colon specimens, including the neuromuscular region (critical for colon motility function), contain specific oral and gut pathogens. In addition, we compared the differences in colon microbiome between Caucasians (CA) and African Americans (AA). Thirty-nine human full thickness colon (diseased colon and adjacent healthy colon) specimens were collected from Crohn's Colitis (CC) or Ulcerative Colitis (UC) patients while they underwent elective colon surgeries. We isolated and analyzed bacterial ribosomal RNA (rRNA) from colon specimens by amplicon sequencing of the 16S rRNA gene region. The microbiome proportions were quantified into Operational Taxonomic Units (OTUs) by analysis with Quantitative Insights Into Microbial ecology (QIIME) platform. Two hundred twenty-eight different bacterial species were identified by QIIME analysis. However, we could only decipher the species name of fifty-three bacteria. Our results show that proportion of non-detrimental bacteria in CC or UC colon samples were altered compared to adjacent healthy colon specimens. We further show, for the first time in full thickness colon specimens, that microbiome of CC and UC diseased specimens is dominated by putative oral pathogens belonging to the Phyla Firmicutes (Streptococcus, Staphylococcus, Peptostreptococcus), and Fusobacteria (Fusobacterium). In addition, we have identified patterns of differences in microbiome levels between CA and AA specimens with potential implications for health disparities research. Overall, our results suggest a significant association between oral and gut microbes in the modulation of colon motility in colitis patients.

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“…Although not yet described in the intestine, non-erythroid hemoglobin expression has been reported in various cell types where it exerts antimicrobial activity and plays a role in oxidative and nitrosative stresses [ 53 ]. Considering the hematologic abnormalities associated with the development of NEC [ 1 , 2 ], future investigation of hemoglobin is needed in light of a recent study that reported a toxic effect of α-hemoglobin on colonic epithelial cells [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling in necrotizing enterocolitis reveals pathways common to those reported in Crohn’s disease

Tremblay

Thibault

Ferretti³

et al. 2015

BMC Med Genomics

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BackgroundNecrotizing enterocolitis (NEC) is the most frequent life-threatening gastrointestinal disease experienced by premature infants in neonatal intensive care units. The challenge for neonatologists is to detect early clinical manifestations of NEC. One strategy would be to identify specific markers that could be used as early diagnostic tools to identify preterm infants most at risk of developing NEC or in the event of a diagnostic dilemma of suspected disease. As a first step in this direction, we sought to determine the specific gene expression profile of NEC.MethodsDeep sequencing (RNA-Seq) was used to establish the gene expression profiles in ileal samples obtained from preterm infants diagnosed with NEC and non-NEC conditions. Data were analyzed with Ingenuity Pathway Analysis and ToppCluster softwares.ResultsData analysis indicated that the most significant functional pathways over-represented in NEC neonates were associated with immune functions, such as altered T and B cell signaling, B cell development, and the role of pattern recognition receptors for bacteria and viruses. Among the genes that were strongly modulated in neonates with NEC, we observed a significant degree of similarity when compared with those reported in Crohn’s disease, a chronic inflammatory bowel disease.ConclusionsGene expression profile analysis revealed a predominantly altered immune response in the intestine of NEC neonates. Moreover, comparative analysis between NEC and Crohn’s disease gene expression repertoires revealed a surprisingly high degree of similarity between these two conditions suggesting a new avenue for identifying NEC biomarkers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-016-0166-9) contains supplementary material, which is available to authorized users.

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Implications of the Colonic Deposition of Free Hemoglobin-α Chain

Cited by 24 publications

References 127 publications

Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease

Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease

Identification of Specific Oral and Gut Pathogens in Full Thickness Colon of Colitis Patients: Implications for Colon Motility

Gene expression profiling in necrotizing enterocolitis reveals pathways common to those reported in Crohn’s disease

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