Expression of triggering receptor on myeloid cell 1 and histocompatibility complex molecules in sepsis and major abdominal surgery

AIM： To evaluate the surface expression of triggering receptor on myeloid cell 1 （TREM-1）, class Ⅱ major histocompatibility complex molecules （HLA-DR）, and the expression of the splicing variant （svTREH-1） of TREM-1 in septic patients and those subjected to major abdominal surgery. METHODS： Using flow cytometry, we examined the surface expression of TREM-1 and HLA-DR in peripheral blood monocytes from 11 septic patients, 7 elective gastrointestinal surgical patients, and 10 healthy volunteers, svTREM-1 levels were analyzed by RT-PCR. RESULTS： Basal expression of TREM-1 and HLA- DR in healthy volunteers was 35.91±14.75 MFI and 75.8±18.3%, respectively. In septic patients, TREM-1 expression was 59.9±23.9 MFI and HLA-DR expression was 44.39±20.25%, with a significant difference between healthy and septic groups （P〈0.05） for both molecules. In the surgical patients, TREM-1 and HLA-DR expressions were 56.8±20.85 HFI and 71±13.8% before surgery and 72.65±29.92 MFI and 72.82±22.55% after surgery. TREM-1 expression was significantly different （P = 0.0087） between the samples before and after surgery and svTREM-1 expression was 0.8590± 0.1451 MF1, 0.8820±0.1460 MF1, and 2.210±0.7873 MF1 in the healthy, surgical （after surgery） and septic groups, respectively. There was a significant difference （P = 0.048） in svTREM-1 expression between the healthy and surgical groups and the septic group. CONCLUSION： TREM-1 expression is increased during systemic inflammatory conditions such as sepsis and the postoperative phase. Simultaneous low expression of HLA-DR molecules correlates with the severity of illness and increases susceptibility to infection. Additionally, TREM-1 expression is distinctly different in surgical patients at different stages of the inflammatory response before and after surgery. Thus, surface TREM-1 appears to be an endogenous signal during the course of the inflammatory response, svTREM-1 expression is significantly increased during sepsis, appearing to be an indicator of severity of illness. Together, these data indicate that TREM-1 may play an important role in establishing and amplifying the systemic inflammatory response. TREM-1, HLA-DR, and svTREM-1 expression analysis can provide useful diagnostic and prognostic indicators during SIRS, CARS, and sepsis.

Low prevalence of germline hMSH6 mutations in colorectal cancer families from Spain

AIM: To investigate the prevalence and penetrance of hMSH6 mutations in Spanish HNPCC families that was negative for mutation in hMLH1 or hMSH2.METHODS: We used PCR-based DGGE assay and direct Sequencing to screen for hMSH6 gene in 91 HNPCC families.RESULTS: we have identified 10 families with germ-line mutations in the DNA sequence. These mutations included two intronic variation, three missense mutation, one nonsense mutation, and four silent mutations. Among the 10 germ-line mutations identified in the Spanish cohort,8 were novel, perhaps, suggesting different mutational spectra in the Spanish population. Detailed pedigrees were constructed for the three families with a possible pathogenic hMSH6 mutation. The two silent mutations H388H and L758L, detected in a person affected of colorectal cancer at age 29, produce loss of the wild-type allele in the tumor sample. Immunohistochemical analysis showed that expression of MSH6 protein was lost only in the tumors from the carriers of V878A and Q263X mutations.CONCLUSION: Altogether, our results indicate that disease-causing germ-line mutations of hMSH6 are very less frequent in Spanish HNPCC families.

Current status of the genetic susceptibility in attenuated adenomatous polyposis

Adenomatous polyposis(AP)is classified according to cumulative adenoma number in classical AP(CAP)and attenuated AP(AAP).Genetic susceptibility is the major risk factor in CAP due to mutations in the known high predisposition genes APC and MUTYH.However,the contribution of genetic susceptibility to AAP is lower and less understood.New predisposition genes have been recently proposed,and some of them have been validated,but their scarcity hinders accurate risk estimations and prevalence calculations.AAP is a heterogeneous condition in terms of severity,clinical features and heritability.Therefore,clinicians do not have strong discriminating criteria for the recommendation of the genetic study of known predisposition genes,and the detection rate is low.Elucidation and knowledge of new AAP high predisposition genes are of great importance to offer accurate genetic counseling to the patient and family members.This review aims to update the genetic knowledge of AAP,and to expound the difficulties involved in the genetic analysis of a highly heterogeneous condition such as AAP.