Table 3 Summary of studies investigating markers of endothelial injury listed in descending chronological order
From: Tight junction structure, function, and assessment in the critically ill: a systematic review
Study | Study design | Disease process | Method of TJ assessment | # of Pts (controls) | TJ proteins studied | Major findings |
|---|---|---|---|---|---|---|
Aslan et al. 2017 [59] | Cross-sectional study | Severe sepsis | Post-mortem kidney biopsy; RT-PCR | 19 (12) | Claudin-5; occludin | Increased claudin-5 mRNA expression associated with sepsis and no significant difference in occludin mRNA expression |
Du et al. 2017 [56] | Cross-sectional study | Fatal heat stroke | Post-mortem brain biopsy; IHC; RT-PCR | 23 (23) | Claudin-5; occludin; ZO-1 | No significant difference in staining of claudin-5, occludin or ZO-1 between heat stroke and control group |
Halbgebauer et al. 2017 [57] | Prospective observational study | Polytrauma | Serum ELISA | 30 (0) | Claudin-5 | Increased serum claudin-5 (20 to 400Â ng/mL) levels associated with hemorrhagic shock, serum lactate and need for transfusion |
Ji et al. 2017 [50] | Randomized prospective study | Ischemic stroke | Serum ELISA | 16 (14) | Claudin-5; ZO-1 | No difference in claudin-5 or ZO-1 (NR) between treatment groups in the acute phase, but decreased serum claudin-5 (338 versus 408Â ng/mL) in the treatment group after 10Â days |
Suwarto et al. 2017 [60] | Prospective observational study | Dengue fever | Serum ELISA | 103 (0) | Claudin-5 | Significantly increased serum claudin-5 (17.4 to 81.1Â ng/mL) levels associated with dengue with severe plasma leakage as compared to dengue fever and dengue hemorrhagic fever |
Zhao et al. 2016 [61] | Cross-sectional study | Sepsis | Serum ELISA | 51 (0) | Claudin-5; occludin; ZO-1 | Increased serum occludin (285versus 607Â pg/mL) and ZO-1 (54 versus 735Â pg/mL) in severe sepsis and septic shock and negatively associated with survival. Increased serum ZO-1, but not occludin, associated with multiple organ dysfunction syndrome. No significant differences found in claudin-5 levels (281 versus 263Â pg/mL) between survivors and non-survivors and MODS and non-MODS groups |
Denk et al. 2015 [58] | Prospective observational study | Polytrauma | Serum ELISA | 8 (10) | JAM-A | Increased serum JAM-A (4 to 10Â ng/mL) correlated with APACHE-II and SOFA scores |
Jiao et al. 2015 [53] | Prospective observational study | Intracranial hemorrhage (ICH) | CSF and serum ELISA | 22 (17) | Claudin-5; occludin; ZO-1 | Increased claudin-5, occludin, and ZO-1 in the CSF (1302, 10, 934 versus 157, 0.5, 181Â pg/mL respectively) but not in the serum (89, 13, 2008 versus 126, 11, 2173Â pg/mL respectively) of ICH patients compared to controls. CSF TJ proteins have higher sensitivity and specificity in diagnosis of ICH than serum proteins |
Wichapoon et al. 2014 [62] | Cross-sectional study | Plasmodium falciparum malaria | Post-mortem kidney biopsy; IHC | 20 (10) | ZO-1 | Decreased ZO-1 expression associated with acute kidney injury in malaria patients |
Klaus et al. 2013 [63] | Prospective observational study | Sepsis | Serum ELISA | 25 (38) | Zonulin | Increased serum zonulin (3.4 versus 6.6Â ng/mL) levels in septic patients compared to control patients |
Brito et al. 2012 [55] | Case report | Kernicterus | Post-mortem brain biopsy; IHC | 1 (1) | Claudin-5 | Increased claudin-5 tissue staining in the kernicteric patient |
Kazmierski et al. 2012 [51] | Prospective observational study | Ischemic stroke | Serum ELISA | 458 (0) | Claudin-5; occludin; ZO-1 | Increased serum occludin (0 to 0.08Â pg/mL) and claudin-5/ZO-1 ratio (0 to 1.47 and 0.57 to 1.48 RU/mL respectively) is associated with hemorrhagic conversion and correlates with markers of neuron injury (S100B) |
Haarmann et al. 2010 [52] | Prospective observational study | Ischemic stroke and multiple sclerosis | Serum ELISA | 13 (45) | JAM-A | No significant change in serum JAM-A (7 to 15Â ng/mL) level over time in ischemic stroke |
Brown et al. 1999 [64] | Prospective observational study | Cerebral malaria | Post-mortem brain biopsy; IHC | 14 (10) | Occludin; vinculin; ZO-1 | Decreased tissue staining of ZO-1, occludin, and vinculin |
Castejon OJ 1980 [54] | Cross-sectional study | Cerebral edema in trauma, tumor or malformation | Brain biopsy; EM | 17 (0) | Zonulin | Endothelial junctional morphology is altered in moderate and severe cerebral edema |