Katherine Rodewald Millen

Serum and Urine Thioflavin-T–Enhanced Fluorescence in Severe PreeclampsiaNovelty and Significance

Common features of amyloid-like proteotoxic aggregates are the ability to bind Congo red (congophilia) and to induce fluorescence of thioflavin-T (ThT). Based on the prior discovery that women with preeclampsia exhibit urine congophilia, we proposed that amyloid-like protein aggregates present in urine also circulate in the bloodstream and this feature is linked to disease severity and clinical phenotype. ThT fluorescence was investigated in 217 paired serum and urine samples from women with severe features of preeclampsia (n=101; median [interquartile range] gestational age [GA], 32 [29–35] weeks), mild features of preeclampsia (n=22; GA, 36 [36–37] weeks), chronic hypertension (n=15; GA, 38 [37–39] weeks), healthy pregnant controls (n=57; GA, 39 [38–39] weeks), and nonpregnant controls (n=22). Serum and urine fluorescence attributable to advanced glycation end products was measured in the same samples with correction for autofluorescence. There were no GA-related changes in ThT fluorescence, although near-term serum ThT fluorescence increased compared with nonpregnant state. Compared with healthy pregnant controls, serum and urine ThT fluorescence was increased in severe features of preeclampsia (P<0.001 for both) but not in mild features of preeclampsia or chronic hypertension. Except for chronic hypertension, advanced glycation end products–related fluorescence of serum or urine did not differ from controls. Urine congophilia had a stronger relationship with preeclampsia severity compared with either urine or serum ThT fluorescence. However, serum ThT fluorescence was independently associated with clinical features of hemolysis, elevated liver enzyme levels, and low platelet levels syndrome (P=0.003). We demonstrate that ThT fluorescence, a marker of amyloid-like aggregates, is increased in serum of women with preeclampsia and likely because of their cytotoxicity associated with hemolysis, elevated liver enzyme levels, and low platelet levels syndrome.

Evidence for participation of neutrophil gelatinase-associated lipocalin/matrix metalloproteinase-9 (NGAL•MMP-9) complex in the inflammatory response to infection in pregnancies complicated by preterm birth.

Neutrophil gelatinase‐associated lipocalin (NGAL) is expressed in neutrophils and involved in innate immunity by sequestering iron. NGALs ability to complex with matrix metalloproteinase‐9 (MMP‐9) and extend its gelatinolytic activity led us to investigate its role in pregnancies complicated by preterm birth (PTB) and intra‐amniotic infection/inflammation (IAI).