PMID- 30089120
OWN - NLM
STAT- MEDLINE
DCOM- 20181221
LR  - 20181221
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 12
IP  - 8
DP  - 2018 Aug
TI  - Aberrant plasma MMP and TIMP dynamics in Schistosoma - Immune reconstitution 
      inflammatory syndrome (IRIS).
PG  - e0006710
LID - 10.1371/journal.pntd.0006710 [doi]
LID - e0006710
AB  - BACKGROUND: Among the different faces of immune reconstitution inflammatory 
      syndrome (IRIS) developing in HIV-patients, no clinical definition has been 
      reported for Schistosomiasis-IRIS (Schisto-IRIS). Although Schisto-IRIS remains 
      largely uninvestigated, matrix metalloproteinases (MMP) and tissue inhibitors of 
      metalloproteinases (TIMP) have previously been associated with S. mansoni 
      infection and tuberculosis-IRIS. Here, we aimed to investigate the relevance of 
      these markers in Schisto-IRIS. METHODOLOGY: Patients were diagnosed with IRIS 
      related to S. mansoni within a cohort of patients with Schistosomiasis-HIV 
      co-infection, using a clinical working definition of Schisto-IRIS. We compared 9 
      patients who developed Schisto-IRIS to 9 Schisto+HIV+ controls who did not, and 9 
      Schisto-HIV+ controls. Plasma levels of MMP-1, MMP-7, MMP-10, TIMP-1, TIMP-2, 
      sCD14, intestinal fatty-acid binding protein, C-reactive protein, and 8 
      anti-nuclear antibodies (ANA) were analyzed prior to and during 3 months of ART. 
      PRINCIPAL FINDINGS: Although no differences were observed for MMP-1 and -7, 
      MMP-10 levels decreased significantly in Schisto+HIV+ controls during 3 months of 
      ART (p = 0.005) while persisting in Schisto-IRIS patients at significantly higher 
      levels compared to Schisto-HIV+ controls (p</=0.030). In contrast TIMP-1 levels 
      only decreased significantly in Schisto-IRIS patients (p = 0.012), while TIMP-2 
      levels were lower compared to Schisto+HIV+ controls at 2 weeks (p = 0.007), 1 
      month (p = 0.005) and 3 months (p = 0.031) of ART. Five out of 8 ANAs studied 
      decreased significantly in Schisto-IRIS patients after 1 month of ART(p</=0.039), 
      whereas only 1 ANA decreased for Schisto+HIV+ controls (p = 0.027). 
      CONCLUSIONS/SIGNIFICANCE: In this study, we propose a working definition for the 
      diagnosis of Schisto-IRIS in resource limited settings. We report persistent 
      plasma levels of MMP-10, along with a more pronounced decrease in TIMP-1 and 
      ANA-levels, and low levels of TIMP-2 during 3 months of ART. Corresponding to the 
      clinical symptoms, these data suggest that Schisto-IRIS is marked by unbalanced 
      MMP/TIMP dynamics which favor inflammation.
FAU - Goovaerts, Odin
AU  - Goovaerts O
AUID- ORCID: 0000-0002-4959-4677
AD  - Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, 
      Belgium.
FAU - Mwinzi, Pauline N M
AU  - Mwinzi PNM
AD  - Neglected Tropical Diseases Unit, Centre for Global Health Research, Kenya Medial 
      Institute, Kisumu, Kenya.
FAU - Muok, Erick M O
AU  - Muok EMO
AD  - Neglected Tropical Diseases Unit, Centre for Global Health Research, Kenya Medial 
      Institute, Kisumu, Kenya.
FAU - Ceulemans, Ann
AU  - Ceulemans A
AD  - Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, 
      Belgium.
FAU - Colebunders, Robert
AU  - Colebunders R
AD  - Epidemiology for Global Health Institute, University of Antwerp, Antwerp, 
      Belgium.
FAU - Kestens, Luc
AU  - Kestens L
AD  - Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, 
      Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180808
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Biomarkers)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Biomarkers
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Coinfection
MH  - Female
MH  - HIV Infections
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/*diagnosis/*etiology
MH  - Kenya/epidemiology
MH  - Male
MH  - Matrix Metalloproteinases/blood/*metabolism
MH  - Schistosoma mansoni
MH  - Schistosomiasis mansoni/*complications/epidemiology/immunology
MH  - Tissue Inhibitor of Metalloproteinases/blood/*metabolism
PMC - PMC6101407
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/08/09 06:00
MHDA- 2018/12/24 06:00
PMCR- 2018/08/08
CRDT- 2018/08/09 06:00
PHST- 2018/02/15 00:00 [received]
PHST- 2018/07/22 00:00 [accepted]
PHST- 2018/08/20 00:00 [revised]
PHST- 2018/08/09 06:00 [pubmed]
PHST- 2018/12/24 06:00 [medline]
PHST- 2018/08/09 06:00 [entrez]
PHST- 2018/08/08 00:00 [pmc-release]
AID - PNTD-D-18-00244 [pii]
AID - 10.1371/journal.pntd.0006710 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2018 Aug 8;12(8):e0006710. doi: 10.1371/journal.pntd.0006710. 
      eCollection 2018 Aug.