Anti-vinculin antibody assay could be answer for diagnosis of IBS

SAN DIEGO – A blood test for antibodies to vinculin, a protein involved in nerve cell migration, may allow objective diagnosis of irritable bowel syndrome, a condition historically diagnosed clinically, after a thorough workup excludes other possibilities.

Investigators led by Dr. Mark Pimentel, director of the GI Motility Program at the Cedars-Sinai Medical Center in Los Angeles, performed a multicenter validation study of the test among patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD), and healthy individuals.

Study results, reported at the annual meeting of the American College of Gastroenterology, showed that the anti-vinculin antibody test had a positive predictive value of at least 90% for distinguishing IBS from IBD.

And when analyses also took into account antibodies to cytolethal distending toxin B (CdtB) – a toxin produced by bacteria commonly associated with food poisoning – the positive predictive value was at least 94%.

"Elevated anti-vinculin antibodies are specific for IBS compared to IBD, and an increase in anti-vinculin antibodies with respect to anti-CdtB increases that specificity," Dr. Pimentel said, summing up the findings. "This may be the first serum diagnostic biomarker that can discriminate IBS from IBD, and it would help avoid unnecessary tests."

Additionally, the findings lend support to a pathogenic mechanism for postinfectious IBS suggested by a rodent model, whereby bacterial gastroenteritis gives rise to autoimmunity against vinculin in the digestive tract.

The assay may be useful in IBD research too, he noted. "One of the problems with IBD studies is those patients who don’t respond to therapies, and maybe they have IBS and they don’t have IBD. Maybe this test could be used to screen those patients out before the study begins."

A session attendee expressed reservations about the study, noting that some analyses compared IBS patients with healthy individuals, and that positive predictive values may not be the best statistic given the composition of the study population.

"We don’t need a test to tell us someone that has no symptoms versus someone that does. So this is the start of your validation, not the end of it," he said. "If you apply this to the population right now, I’ve done some calculations, your positive predictive value would be about 20%. So it’s not that great in clinical practice. ... I’m sure you will develop this more and it will get better, but right now, I don’t think this is ready for prime time."

"First, you can use a likelihood ratio, which accounts for the volumes of patients. ... Our likelihood ratio is between 3 and 4, which I hope gives you more confidence in it," Dr. Pimentel replied. "The second thing is that the patients who arrive in a doctor’s office are not healthy: They are going to have IBD or IBS or something else if they have diarrhea in the clinic."

In a related press briefing, Dr. Brian E. Lacy, of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., commented, "This is an incredibly important topic, when we are talking about prevalence rates of IBS – a conservative rate is 12% to 15% – and when you are talking about spending $20 billion to $30 billion a year diagnosing and treating IBS."

"For many patients, IBS is a diagnosis of exclusion; they undergo a battery of unnecessary tests which are usually fruitless because this is a functional bowel disorder," he added. "To possibly have a diagnostic test – a blood test – that could confidently make the diagnosis of IBS to me would be incredibly important. And I think for the community primary care providers, family practice doctors, who are not confident at diagnosing IBS, to have somebody say, ‘This is a great test, and we can not only make the diagnosis, but exclude or maybe improve our ability to exclude the patients with IBD,’ that would be incredibly important."

The test may also have implications for treatment, according to Dr. Pimentel. "Another question is, could this antibody test predict who will respond to antibiotics, or does it predict bacterial overgrowth or other treatable aspects of IBS?" he explained.

Finally, such a test would help validate IBS as a legitimate medical condition. "IBS is a very, very difficult illness because nobody understands it, and it kind of gets the short end of the stick because it is viewed as a lifestyle disorder instead of a legitimate disease," he commented. "So what I’d like to do in my career is to make IBS a real disease, not just a syndrome as it’s been for at least the last 2 decades."

Press briefing moderator Dr. Michael E. Cox of the Mercy Medical Center in Baltimore, said, "The $64,000 question is, when would this possibly be ready for prime time?"

"We are validating this antibody every day," Dr. Pimentel replied, although as yet, no companies are collaborating in developing the assay. "When it will be ready for prime time, I’m not sure."

In the study, the investigators assayed serum samples from 162 prospectively identified patients who met Rome III criteria for IBS, 30 patients with active IBD who were not receiving biologic agents, and 26 consecutive healthy individuals.

Across groups, about 70% of patients were female, with no significant differences in the sex and age distributions.

Results showed that the anti-vinculin antibody optical density (OD) reading was higher in patients with IBS than in patients with IBD (P less than .01) and healthy individuals (P less than .01), reported Dr. Pimentel.

Meanwhile, the anti-CdtB antibody OD reading was higher in the patients with IBD than in the patients with IBS (P = .02).

For distinguishing IBS from IBD, an anti-vinculin antibody OD reading exceeding 0.8 had a sensitivity of 43%, a specificity of 73%, and a positive predictive value of 90%.

There is a good rationale for simultaneously looking at anti-CdtB and anti-vinculin, according to Dr. Pimentel: In the model of postinfectious IBS, anti-vinculin antibodies persist over time, whereas anti-CdtB antibodies decline.

And indeed, in the study, the difference between the two OD readings (anti-vinculin minus anti-CdtB) was higher in the patients with IBS than in both the patients with IBD (P less than .0001) and the healthy individuals (P less than .001).

For distinguishing IBS from IBD, a difference exceeding 0.2 had a sensitivity of 41%, a specificity of 88%, and a positive predictive value of 94%.

A confounding issue is that about 10% of patients with IBD also have IBS, Dr. Pimentel noted. But a model taking this into account showed high positive predictive values for an anti-vinculin antibody OD reading exceeding 0.8 (92%) and for a difference between the OD readings of anti-vinculin and anti-CdtB exceeding 0.2 (97%).

Dr. Pimentel disclosed no relevant conflicts of interest.

SAN DIEGO – A blood test for antibodies to vinculin, a protein involved in nerve cell migration, may allow objective diagnosis of irritable bowel syndrome, a condition historically diagnosed clinically, after a thorough workup excludes other possibilities.

Investigators led by Dr. Mark Pimentel, director of the GI Motility Program at the Cedars-Sinai Medical Center in Los Angeles, performed a multicenter validation study of the test among patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD), and healthy individuals.

Study results, reported at the annual meeting of the American College of Gastroenterology, showed that the anti-vinculin antibody test had a positive predictive value of at least 90% for distinguishing IBS from IBD.

And when analyses also took into account antibodies to cytolethal distending toxin B (CdtB) – a toxin produced by bacteria commonly associated with food poisoning – the positive predictive value was at least 94%.

"Elevated anti-vinculin antibodies are specific for IBS compared to IBD, and an increase in anti-vinculin antibodies with respect to anti-CdtB increases that specificity," Dr. Pimentel said, summing up the findings. "This may be the first serum diagnostic biomarker that can discriminate IBS from IBD, and it would help avoid unnecessary tests."

Additionally, the findings lend support to a pathogenic mechanism for postinfectious IBS suggested by a rodent model, whereby bacterial gastroenteritis gives rise to autoimmunity against vinculin in the digestive tract.

The assay may be useful in IBD research too, he noted. "One of the problems with IBD studies is those patients who don’t respond to therapies, and maybe they have IBS and they don’t have IBD. Maybe this test could be used to screen those patients out before the study begins."

A session attendee expressed reservations about the study, noting that some analyses compared IBS patients with healthy individuals, and that positive predictive values may not be the best statistic given the composition of the study population.

"We don’t need a test to tell us someone that has no symptoms versus someone that does. So this is the start of your validation, not the end of it," he said. "If you apply this to the population right now, I’ve done some calculations, your positive predictive value would be about 20%. So it’s not that great in clinical practice. ... I’m sure you will develop this more and it will get better, but right now, I don’t think this is ready for prime time."

"First, you can use a likelihood ratio, which accounts for the volumes of patients. ... Our likelihood ratio is between 3 and 4, which I hope gives you more confidence in it," Dr. Pimentel replied. "The second thing is that the patients who arrive in a doctor’s office are not healthy: They are going to have IBD or IBS or something else if they have diarrhea in the clinic."

In a related press briefing, Dr. Brian E. Lacy, of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., commented, "This is an incredibly important topic, when we are talking about prevalence rates of IBS – a conservative rate is 12% to 15% – and when you are talking about spending $20 billion to $30 billion a year diagnosing and treating IBS."

"For many patients, IBS is a diagnosis of exclusion; they undergo a battery of unnecessary tests which are usually fruitless because this is a functional bowel disorder," he added. "To possibly have a diagnostic test – a blood test – that could confidently make the diagnosis of IBS to me would be incredibly important. And I think for the community primary care providers, family practice doctors, who are not confident at diagnosing IBS, to have somebody say, ‘This is a great test, and we can not only make the diagnosis, but exclude or maybe improve our ability to exclude the patients with IBD,’ that would be incredibly important."

The test may also have implications for treatment, according to Dr. Pimentel. "Another question is, could this antibody test predict who will respond to antibiotics, or does it predict bacterial overgrowth or other treatable aspects of IBS?" he explained.

Finally, such a test would help validate IBS as a legitimate medical condition. "IBS is a very, very difficult illness because nobody understands it, and it kind of gets the short end of the stick because it is viewed as a lifestyle disorder instead of a legitimate disease," he commented. "So what I’d like to do in my career is to make IBS a real disease, not just a syndrome as it’s been for at least the last 2 decades."

Press briefing moderator Dr. Michael E. Cox of the Mercy Medical Center in Baltimore, said, "The $64,000 question is, when would this possibly be ready for prime time?"

"We are validating this antibody every day," Dr. Pimentel replied, although as yet, no companies are collaborating in developing the assay. "When it will be ready for prime time, I’m not sure."

In the study, the investigators assayed serum samples from 162 prospectively identified patients who met Rome III criteria for IBS, 30 patients with active IBD who were not receiving biologic agents, and 26 consecutive healthy individuals.

Across groups, about 70% of patients were female, with no significant differences in the sex and age distributions.

Results showed that the anti-vinculin antibody optical density (OD) reading was higher in patients with IBS than in patients with IBD (P less than .01) and healthy individuals (P less than .01), reported Dr. Pimentel.

Meanwhile, the anti-CdtB antibody OD reading was higher in the patients with IBD than in the patients with IBS (P = .02).

For distinguishing IBS from IBD, an anti-vinculin antibody OD reading exceeding 0.8 had a sensitivity of 43%, a specificity of 73%, and a positive predictive value of 90%.

There is a good rationale for simultaneously looking at anti-CdtB and anti-vinculin, according to Dr. Pimentel: In the model of postinfectious IBS, anti-vinculin antibodies persist over time, whereas anti-CdtB antibodies decline.

And indeed, in the study, the difference between the two OD readings (anti-vinculin minus anti-CdtB) was higher in the patients with IBS than in both the patients with IBD (P less than .0001) and the healthy individuals (P less than .001).

For distinguishing IBS from IBD, a difference exceeding 0.2 had a sensitivity of 41%, a specificity of 88%, and a positive predictive value of 94%.

A confounding issue is that about 10% of patients with IBD also have IBS, Dr. Pimentel noted. But a model taking this into account showed high positive predictive values for an anti-vinculin antibody OD reading exceeding 0.8 (92%) and for a difference between the OD readings of anti-vinculin and anti-CdtB exceeding 0.2 (97%).

Dr. Pimentel disclosed no relevant conflicts of interest.

SAN DIEGO – A blood test for antibodies to vinculin, a protein involved in nerve cell migration, may allow objective diagnosis of irritable bowel syndrome, a condition historically diagnosed clinically, after a thorough workup excludes other possibilities.

Investigators led by Dr. Mark Pimentel, director of the GI Motility Program at the Cedars-Sinai Medical Center in Los Angeles, performed a multicenter validation study of the test among patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD), and healthy individuals.

Study results, reported at the annual meeting of the American College of Gastroenterology, showed that the anti-vinculin antibody test had a positive predictive value of at least 90% for distinguishing IBS from IBD.

And when analyses also took into account antibodies to cytolethal distending toxin B (CdtB) – a toxin produced by bacteria commonly associated with food poisoning – the positive predictive value was at least 94%.

"Elevated anti-vinculin antibodies are specific for IBS compared to IBD, and an increase in anti-vinculin antibodies with respect to anti-CdtB increases that specificity," Dr. Pimentel said, summing up the findings. "This may be the first serum diagnostic biomarker that can discriminate IBS from IBD, and it would help avoid unnecessary tests."

Additionally, the findings lend support to a pathogenic mechanism for postinfectious IBS suggested by a rodent model, whereby bacterial gastroenteritis gives rise to autoimmunity against vinculin in the digestive tract.

The assay may be useful in IBD research too, he noted. "One of the problems with IBD studies is those patients who don’t respond to therapies, and maybe they have IBS and they don’t have IBD. Maybe this test could be used to screen those patients out before the study begins."

A session attendee expressed reservations about the study, noting that some analyses compared IBS patients with healthy individuals, and that positive predictive values may not be the best statistic given the composition of the study population.

"We don’t need a test to tell us someone that has no symptoms versus someone that does. So this is the start of your validation, not the end of it," he said. "If you apply this to the population right now, I’ve done some calculations, your positive predictive value would be about 20%. So it’s not that great in clinical practice. ... I’m sure you will develop this more and it will get better, but right now, I don’t think this is ready for prime time."

"First, you can use a likelihood ratio, which accounts for the volumes of patients. ... Our likelihood ratio is between 3 and 4, which I hope gives you more confidence in it," Dr. Pimentel replied. "The second thing is that the patients who arrive in a doctor’s office are not healthy: They are going to have IBD or IBS or something else if they have diarrhea in the clinic."

In a related press briefing, Dr. Brian E. Lacy, of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., commented, "This is an incredibly important topic, when we are talking about prevalence rates of IBS – a conservative rate is 12% to 15% – and when you are talking about spending $20 billion to $30 billion a year diagnosing and treating IBS."

"For many patients, IBS is a diagnosis of exclusion; they undergo a battery of unnecessary tests which are usually fruitless because this is a functional bowel disorder," he added. "To possibly have a diagnostic test – a blood test – that could confidently make the diagnosis of IBS to me would be incredibly important. And I think for the community primary care providers, family practice doctors, who are not confident at diagnosing IBS, to have somebody say, ‘This is a great test, and we can not only make the diagnosis, but exclude or maybe improve our ability to exclude the patients with IBD,’ that would be incredibly important."

The test may also have implications for treatment, according to Dr. Pimentel. "Another question is, could this antibody test predict who will respond to antibiotics, or does it predict bacterial overgrowth or other treatable aspects of IBS?" he explained.

Finally, such a test would help validate IBS as a legitimate medical condition. "IBS is a very, very difficult illness because nobody understands it, and it kind of gets the short end of the stick because it is viewed as a lifestyle disorder instead of a legitimate disease," he commented. "So what I’d like to do in my career is to make IBS a real disease, not just a syndrome as it’s been for at least the last 2 decades."

Press briefing moderator Dr. Michael E. Cox of the Mercy Medical Center in Baltimore, said, "The $64,000 question is, when would this possibly be ready for prime time?"

"We are validating this antibody every day," Dr. Pimentel replied, although as yet, no companies are collaborating in developing the assay. "When it will be ready for prime time, I’m not sure."

In the study, the investigators assayed serum samples from 162 prospectively identified patients who met Rome III criteria for IBS, 30 patients with active IBD who were not receiving biologic agents, and 26 consecutive healthy individuals.

Across groups, about 70% of patients were female, with no significant differences in the sex and age distributions.

Results showed that the anti-vinculin antibody optical density (OD) reading was higher in patients with IBS than in patients with IBD (P less than .01) and healthy individuals (P less than .01), reported Dr. Pimentel.

Meanwhile, the anti-CdtB antibody OD reading was higher in the patients with IBD than in the patients with IBS (P = .02).

For distinguishing IBS from IBD, an anti-vinculin antibody OD reading exceeding 0.8 had a sensitivity of 43%, a specificity of 73%, and a positive predictive value of 90%.

There is a good rationale for simultaneously looking at anti-CdtB and anti-vinculin, according to Dr. Pimentel: In the model of postinfectious IBS, anti-vinculin antibodies persist over time, whereas anti-CdtB antibodies decline.

And indeed, in the study, the difference between the two OD readings (anti-vinculin minus anti-CdtB) was higher in the patients with IBS than in both the patients with IBD (P less than .0001) and the healthy individuals (P less than .001).

For distinguishing IBS from IBD, a difference exceeding 0.2 had a sensitivity of 41%, a specificity of 88%, and a positive predictive value of 94%.

A confounding issue is that about 10% of patients with IBD also have IBS, Dr. Pimentel noted. But a model taking this into account showed high positive predictive values for an anti-vinculin antibody OD reading exceeding 0.8 (92%) and for a difference between the OD readings of anti-vinculin and anti-CdtB exceeding 0.2 (97%).

Dr. Pimentel disclosed no relevant conflicts of interest.