Immunoglobulin subtype-coated bacteria are correlated with the disease activity of inflammatory bowel disease.

Immune response involving various immunoglobulin (Ig) isotypes and subtypes to microbiome is involved in the pathogenesis and disease activity of inflammatory bowel diseases (IBDs). To clarify the presence of Ig-coated bacteria in the intestine and its association with disease activity in ulcerative colitis (UC) and Crohn's disease (CD), we extracted and classified Ig-coated bacteria from fecal samples of 42 patients with IBD and 12 healthy controls (HCs) using flow cytometry and 16S ribosomal RNA sequence analysis. The percentage of bacteria coated with IgA and IgM was higher in patients with IBD than in HCs, and IgG-coated bacteria were found only in patients with IBD. Moreover, the percentages of bacteria coated with IgG1, IgG2, IgG3, and IgM in UC samples and IgG3, IgG4, and IgM in CD samples were correlated with disease activities. The proportions of Bacteroides ovatus and Streptococcus increased during the active phase of CD. Hence, the detailed analysis of Ig-coated bacteria and Ig subtypes using flow cytometry could aid in developing useful indicators of disease activity and identifying more disease-related bacteria, which could become novel treatment targets for IBDs.

Localized intestinal AL amyloidosis detected as bright green using autofluorescence endoscopy.

Amyloidosis is classifiable as systemic, with amyloid deposition in organs throughout the body, or localized, involving only one organ. Amyloidosis localized in the intestinal tract is rare. This report describes three cases of localized AL amyloidosis in the intestinal tract and presents their clinical characteristics, endoscopic findings, and prognoses. All three cases were asymptomatic, and were found accidentally during endoscopy for closer examination after a positive fecal occult blood test. Endoscopic findings included patchy redness and meandering dilated vessels of the lesion. Using autofluorescence (AFI) endoscopy, the lesion of amyloid deposition was enhanced as bright green. We used fluorescence microscopy to observe unstained specimens obtained from an amyloid deposition site with excitation light. Autofluorescence was detected with the broad excitation wavelength at amyloid deposition lesion sites of the specimen. Results revealed that AL amyloid has autofluorescence that engenders its detection by AFI endoscopy as bright green. In none of the three cases was systemic amyloidosis or organ failure observed. The long-term course of all the cases was favorable.

N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells.

PPM [metal-dependent protein phosphatase, formerly called PP2C (protein phosphatase 2C)] family members play essential roles in regulating a variety of signalling pathways. While searching for protein phosphatase(s) that act on AMPK (AMP-activated protein kinase), we found that PPM1A and PPM1B are N-myristoylated and that this modification is essential for their ability to dephosphorylate the α subunit of AMPK (AMPKα) in cells. N-Myristoylation was also required for two other functions of PPM1A and PPM1B in cells. Although a non-myristoylated mutation (G2A) of PPM1A and PPM1B prevented membrane association, this relocalization did not likely cause the decreased activity towards AMPKα. In in vitro experiments, the G2A mutants exhibited reduced activities towards AMPKα, but much higher specific activity against an artificial substrate, PNPP (p-nitrophenyl phosphate), compared with the wild-type counterparts. Taken together, the results of the present study suggest that N-myristoylation of PPM1A and PPM1B plays a key role in recognition of their physiological substrates in cells.