Two New Tests Definitively Distinguish  Diarrhea-Predominant Irritable Bowel Syndrome

Enzyme-linked immunosorbent assays (ELISAs) assessing plasma levels of antibodies to cytolethal distending toxin B (CdtB) and vinculin could be the first tests to definitively detect diarrhea-predominant irritable bowel syndrome (D-IBS) and to distinguish D-IBS from inflammatory bowel disease (IBD) (Plos One 2015; doi:10.1371/journal.pone.0126438).

D-IBS—the most common gastrointestinal disorder in the U.S., affecting about 10% of the population—is considered a functional condition with no known organic biomarker. Symptoms include diarrhea, chronic bloating, constipation, gas, and abdominal pain, but clinical criteria for D-IBS do not exclude IBD. This leads to an extensive diagnostic work-up to distinguish D-IBS and IBD.

Emerging research suggests gut microbiota plays a role in D-IBS, and has shown that D-IBS patients have alterations in their small bowel microbial flora. About 10% of those who develop acute gastroenteritis have long-term D-IBS symptoms—also known as post-infectious IBS—which might be linked to changes in gut microbiota. Post-infectious IBS occurs primarily after infection with Campylobacter jejuni, Salmonella, Escherichia coli, and Shigella, all of which produce CdtB.

The authors hypothesized that past exposure to CdtB led to detectable immunity to CdtB and autoimmunity to vinculin. They used ELISAs with complete recombinant Campylobacter CdtB protein and full-length human vinculin protein as antigens.

The study involved 2,681 subjects between ages 18 and 65, including 2,375 D-IBS patients, 142 with IBD, 121 with celiac disease, as well as 43 healthy controls. The researchers found that anti-CdtB and anti-vinculin titers were significantly higher in D-IBS participants compared with those who had IBD, celiac disease, or who were healthy controls. The area-under-the-receiver operating curves were 0.81 and 0.62 for anti-CdtB and anti-vinculin­, respectively, in diagnosing D-IBS versus IBD. Neither anti-CdtB nor anti-vinculin were as robust in distinguishing D-IBS from celiac disease.

“Having an early diagnosis means patients can avoid years of invasive tests and visits to specialists that often leave them with more questions than answers,” said lead author, Mark Pimentel. “With these new blood tests, many patients will now be able to proceed right to therapy for their condition.”

The tests are being marketed under the name IBSchek, and are produced by Commonwealth Laboratories in Salem, Massachusetts.

Higher Levels of Quantitative Fetal Fibronectin Linked to Increased Risk of Premature Birth

Risk of spontaneous pre-term birth rises with increasing levels of fetal fibronectin, suggesting a role for quantitative as opposed to traditional qualitative fetal fibronectin results in assessing risk of premature birth (Obstet Gynecol 2015;125:1168–76).

Better identifying women at highest risk of preterm delivery would enable targeted surveillance and prophylactic interventions, according to the study authors. Cervicovaginal fluid fetal fibronectin measurements have been established as a negative predictor of spontaneous preterm birth after 22 weeks of pregnancy. Testing for fetal fibronectin traditionally has been qualitative, with positive or negative results based on a threshold of 50 ng/mL, but the positive predictive value (PPV) of this method is <20%, limiting its use. Retrospective studies have suggested that quantitated fetal fibronectin levels are proportional to risk of preterm birth.

This led the researchers to conduct a prospective, multi-center study, evaluating the predictive accuracy of a quantitative fetal fibronectin assay using a novel bedside analyzer.

The study involved 1,448 women between 22 and 27 weeks of gestation considered at high risk for spontaneous preterm delivery because of factors such as prior spontaneous preterm delivery, rupture of membranes, or previous spontaneous second trimester miscarriage. Clinicians had access to routine qualitative fetal fibronectin results, but the quantitative results remained blinded until after study participants delivered.

The risk of preterm births grew with increased levels of fetal fibronectin, rising from 2.7% to 47.6% with fetal fibronectin ranging from <10 ng/mL to ≥500 ng/mL. A threshold of 200 ng/mL had a PPV of 37.7, with specificity of 96%.

Clinical Utility of Urine Aquaporin-1, Perilipin-2 Demonstrated in Identifying Renal Cell Carcinoma

A prospective cohort study found that participants with pathologically-confirmed renal cell carcinoma (RCC) had significantly higher levels of urine aquaporin-1 (AQP1) and perilipin-2 (PLIN2) than did both healthy controls and a 720- person screening population, yielding 100% sensitivity and 100% and 91% specificity, respectively, in distinguishing RCC (JAMA Oncol 2015;1:204–12). The findings, which build upon the researchers’ prior research involving AQP1 and PLIN2, demonstrate the clinical utility of these biomarkers in diagnosing RCC, and meet phase 3 criteria of diagnostic cancer biomarker development; namely that they diagnose early preclinical disease.

The researchers have been investigating AQP1 and PLIN2 as they seek to find a biomarker to facilitate population screening for RCC. Early RCC diagnosis is associated with increased 5-year survival, and early detection also makes possible minimally invasive treatments, with associated lower costs and fewer complications than later-stage treatments.

The screening population included patients undergoing routine abdominal computed tomography. The researchers used an enzyme-linked immunosorbent assay (ELISA) to measure AQP1 and a western blot to measure PLIN2. Median AQP1 levels in the RCC patients was 225 ng/mg urine creatinine versus 1.1 ng/mg urine creatinine in healthy controls, 0 ng/mg urine creatinine in screening patients without history of cancer, and 1.0 ng/mg urine creatinine in screening patients with a history of cancer. Median concentrations of PLIN2 also were significantly higher in RCC patients than in the other cohorts.