PMID- 30949171
OWN - NLM
STAT- MEDLINE
DCOM- 20200902
LR  - 20200902
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Decreased Ficolin-3-mediated Complement Lectin Pathway Activation and Alternative 
      Pathway Amplification During Bacterial Infections in Patients With Type 2 
      Diabetes Mellitus.
PG  - 509
LID - 10.3389/fimmu.2019.00509 [doi]
LID - 509
AB  - Bacterial infections are frequent and severe in patients with diabetes mellitus. 
      Whether diabetes per se induces functional alterations in the complement system 
      hampering activation during infection is unknown. We investigated key elements of 
      the complement system during bacterial infections in patients with type 2 
      diabetes mellitus (T2DM) and compared them to non-diabetic (ND) individuals. 
      Using a prospective design, we included 197 T2DM, and 196 ND subjects, all with 
      clinical diagnosis of acute community-acquired bacterial infections. Functional 
      activities of the ficolin-3-mediated lectin (F3-LP), mannose binding 
      lectin-mediated lectin- (MBL-LP), classical (CP), and alternative pathways (AP), 
      as well as concentrations of complement activation products C4d and sC5b-9 were 
      determined. Functional in vitro activities of F3-LP and AP were significantly 
      higher in T2DM than in ND subjects, (median 64% vs. 45%, p = 0.0354 and 75 vs. 
      28%, p = 0.0013, respectively), indicating a decreased in vivo activation and 
      lack of consumption of F3-LP and AP in T2DM patients, whereas no difference in 
      functional capacities of CP and MBL-LP were observed between T2DM and ND 
      subjects. Diminished F3-LP and AP activation was most pronounced in diabetic 
      patients with urinary tract infections with positive microbiological culture 
      results for Escherichia coli bacteria. In the T2DM group 3-months mortality 
      significantly associated with diminished F3-LP and AP, but not with CP 
      activation. Concentrations of C4d and sC5b-9 were significantly lower in the T2DM 
      than in ND patients. In conclusion, we found impaired F3-LP activation and lack 
      of AP amplification during bacterial infections in patients with type 2 diabetes, 
      compared to non-diabetic subjects, suggesting a diminished complement mediated 
      protection to bacterial infections in T2DM.
FAU - Barkai, Laszlo Jozsef
AU  - Barkai LJ
AD  - 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
FAU - Sipter, Emese
AU  - Sipter E
AD  - 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
FAU - Csuka, Dorottya
AU  - Csuka D
AD  - 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
FAU - Prohaszka, Zoltan
AU  - Prohaszka Z
AD  - 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
FAU - Pilely, Katrine
AU  - Pilely K
AD  - Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 
      7631, Rigshospitalet, Faculty of Health and Medical Sciences, University of 
      Copenhagen, Copenhagen, Denmark.
FAU - Garred, Peter
AU  - Garred P
AD  - Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 
      7631, Rigshospitalet, Faculty of Health and Medical Sciences, University of 
      Copenhagen, Copenhagen, Denmark.
FAU - Hosszufalusi, Nora
AU  - Hosszufalusi N
AD  - 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20190320
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (FCN3 protein, human)
RN  - 0 (Lectins)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Complement Pathway, Alternative/*immunology
MH  - Complement Pathway, Mannose-Binding Lectin/*immunology
MH  - Diabetes Mellitus, Type 2/*immunology/microbiology
MH  - Escherichia coli/*immunology
MH  - Escherichia coli Infections/*immunology
MH  - Female
MH  - Humans
MH  - Lectins/*immunology
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Urinary Tract Infections/*immunology/microbiology
PMC - PMC6436462
OTO - NOTNLM
OT  - Escherichia coli
OT  - alternative pathway
OT  - bacterial infection
OT  - classical pathway
OT  - complement
OT  - ficolin-3
OT  - lectin pathway
OT  - type 2 diabetes
EDAT- 2019/04/06 06:00
MHDA- 2020/09/04 06:00
PMCR- 2019/01/01
CRDT- 2019/04/06 06:00
PHST- 2018/07/30 00:00 [received]
PHST- 2019/02/25 00:00 [accepted]
PHST- 2019/04/06 06:00 [entrez]
PHST- 2019/04/06 06:00 [pubmed]
PHST- 2020/09/04 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.00509 [doi]
PST - epublish
SO  - Front Immunol. 2019 Mar 20;10:509. doi: 10.3389/fimmu.2019.00509. eCollection 
      2019.