Multiplex gene expression profile in inflamed mucosa of patients with Crohn’s disease ileal localization: A pilot study

Table 1 Clinical characteristics of patients with ileal Crohn’s disease

Patient	Pt1	Pt2	Pt3	Pt4	Pt5	Pt6	Pt7	Pt8	Pt9	Pt10	Pt11	Pt12	Pt13	Pt14
Localization	L1	L1	L1	L1	L1	L1	L3	L1	L3	L1	L3-L4	L1	L3	L1
of CDa
Age of CD	57	15	53	55	25	31	39	42	16	24	19	18	46	30
onset (yr)
Surgery / relapse	1st	1st	Relapse	1st	Relapse	Relapse	Relapse	1st	Relapse	Relapse	Relapse	Relapse	Relapse	1st
	surgery	surgery		surgery				surgery						surgery
Disease behaviorb	B2	B2, B3	B2	B3	B2, B4	B2	B3	B2	B2	B2	B2	B2	B3	B2
Therapyc	C, F, I, B	F, C	C	No	F, C, I	C, F, I	I, B	F, C	C, I, F, B	C	F, C, B	F, C, I	C, F, B, I	F, C, I
Smoking statusd	No	Cur	No	No	10月10日	No	No	20/30	10月10日	Cur	10月20日	No	No	No
		20/15.5								10
Genotype	wt	R702	wt	hzG881R	wt	wt	wt	wt	hzG881R	R702	No seq	No seq	wt	wt

Localization of Crohn Disease: L1: terminal ileum; L2: colon; L3: ileum colon; L4: upper G (gastrointestinal); Disease behavior: B1: non-stricturing, non-penetrating; B2: stricturing; B3: penetrating; B4: perianal disease. Therapy: M: mesalazine; I: immunosuppressant; B: biologics; C: corticosteroids; Ab: antibiotics. Smoking status: No: non-smoker; Ex: ex-smoker; Cur: current smoker, no. cigs per day / no. yr. MIM: Mendelian inheritance in Man. 1: Transport across epithelia; 2: Immune response; 3: Antimicrobial activity; 4: Different physiological activities.

Table 2 Panel of the 24 genes investigated

Symbol	Complete name	Group	Accession number	mim	Gene product function (s)	Ref.
HPRT1	Hypoxanthine phosphoribosyltransferase 1	Low expression housekeeping gene	M26434	308000	It plays a central role in the generation of purine nucleotides, chosen as a low expression housekeeping gene	[39]
ACTB	Actin betaprovided	High expression housekeeping gene	M28424	102630	Is involved in the cell motility, structure, and integrity	[40]
SLC40A1	Solute carrier family 40 (iron-regulated transporter), member1	1	AF215636	604653	Exports iron from duodenal epithelial cells	[41]
ABCB1	ATP-binding cassette, sub-family B (MDR/TAP), member1	1	M14758	171050	Transports various molecules across extra- and intra-cellular membranes. It belongs to a protein sub-family involved in multidrug resistance	[42]
SLC22A5	Solute carrier family 22 (organic cation/carnitine transporter), member 5	1	AF057164	603377	Transports several small organic cations in the liver, kidney, intestine. It is involved in elimination of drugs and environmental toxins	[43]
SLC22A4	Solute carrier family 22 (organic cation/ergothioneine transporter), member 4	1	AB007448	604190	Polyspecific transporter of organic cations in the liver, kidney, intestine, and involved in the elimination of these molecules.	[44]
CCR6	Chemokine (C-C motif) receptor6	2	U68030	601835	Induces B-lineage maturation and antigen-driven B-cell differentiation	[45]
IL17A	Interleukin 17A	2	U32659	603149	Produced by Th17-type CD4+ cells. Regulates the activities of NF-kB and mitogen-activated protein kinases	[26]
IL17F	Interleukin 17F	2	AF384857	606496	Produced by Th17-type CD4+ cells. Stimulates the production of other cytokines, including IL6,IL8.It also inhibits angiogenesis by endothelial	[46]
					cells.
STAT3	Signal transducer and activator of transcription 3 (acute-phase response factor)	2-4	BC014482	102582	Activates transcription of cell growth and apoptosis’ genes asresponses to inflammation	[22,47]
MICA	MHC class I polypeptide-related sequence A	2	L14848	600169	Acts as a stress-induced antigen broadly recognized by intestinal intra-epithelial gamma delta T cells.	[48,49]
MYD88	Myeloid differentiation primary response gene (88)	2	U84408	602170	Acts as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling	[50]
					pathways
IL23R	Interleukin 23 receptor	2	AF461422	607562	Expressed on Th17 cells. Involvedin the IL23A signaling pathways with the receptor molecule IL12RB1/IL12Rbeta1.	[20]
JAK2	Janus kinase 2	2	3717	147796	Is involved in cytokine receptor signaling pathways and is required for responses to gamma interferon	[51]
IFNG	Interferon, gamma	2	3458	147570	It encodes a cytokine with antiviral,immunoregulatory and anti-tumor properties and activates macrophages	[52]
CAMP	Cathelicidin antimicrobial peptide	3	BC055089	600474	It is an antimicrobial protein (defensin)	[53]
CARD15	Nucleotide-binding oligomerization domain containing 2	2	AF178930	605956	Induces immune response to intracellular bacterial by recognizing the muramyl dipeptide (MDP)	[54]
DEFB4	Defensin, beta 4A	3	AJ314835	602215	Acts as an antibiotic peptide locally regulated by inflammation.	[55,56]
HAMP	Hepcidin antimicrobialpeptide	1/2/3	AF309489	606464	It is involved in iron transport, antimicrobial, defence and inflammatory responses	[57,58]
LRRK2	Leucine-rich repeat kinase 2	3/4	AK026776	609007	It is involved in autophagy and implicated in clearance of intracellular bacteria.	[59,60]
TNFSF15	Tumor necrosis facto (ligand) superfamily, member 15	4	AF039390	604052	Induces apoptosis in endothelial cells	[61]
CARD14	Caspase recruitment domain family, member 14	4	AF322642	607211	Regulates the molecular scaffolding process and activates NF-kappa B	[62,63]
ATG16L1	ATG16 autophagy related 16-like 1	4	AK000897	610767	Induces autophagy processes involved in degradation of cell organelles	[64]
ESR1	Estrogen receptor 1	4	X03635	133430	Involved in the metabolic pathway of the hormones and in several diseases including osteoporosis	[65]
BMP2	Bone morphogenetic protein 2	4	650	112261	Induces bone and cartilage formation	[66]
DLG5	Discs, large homolog 5	4	U61843	604090	It encodes for scaffolding molecules involved in cell-cell contact and in the maintenance of epithelial cell integrity. Its products are also involved in the transmission of extracellular signals	[67]

MIM: Mendelian Inheritance in Man. 1: Transport across epithelia; 2: Immune response; 3: Antimicrobial activity; 4: Different physiological activities.