High Interferon Response, Low B Cells Presage Rheumatoid Arthritis

BERLIN – The combination of an elevated level of interferon gene expression and a low level of circulating B cells identified patients with arthralgia who had a high rate of progression to rheumatoid arthritis in a validation study of 115 patients at one center.

After 2 years of follow-up, about 70% of patients with a high level of interferon gene expression and a low level of B cells in their peripheral blood had developed rheumatoid arthritis (RA), while in contrast about 20% of arthralgia patients with low interferon gene expression and a high B-cell level developed RA, Joyce Lubbers said at the annual European Congress of Rheumatology.

Some of Ms. Lubbers’ associates on the study had previously shown, in a different group of 109 patients with arthralgia, that high interferon gene expression was linked to an increased rate of progression to RA, and that high expression of genes involved in B-cell activation was linked to a reduced risk for progressing to RA (Arthritis Rheum. 2010;62:694-704). Hence, the new findings that Ms. Lubbers reported validated the results of the previous study.

"We’ve now shown this in two independent cohorts, and we’re looking at a third group," said Ms. Lubbers, a researcher working on inflammatory disease profiling at VU University Medical Center in Amsterdam.

In practice, these easily obtained lab markers – interferon gene expression and B cell count – can couple with a patient’s clinical profile to estimate the risk of developing RA.

The next step is to test whether an intervention in arthralgia patients at high risk for progression to RA can delay or prevent the progression, or make RA less severe once it develops. Researchers in Amsterdam are currently testing whether treatment of high-risk arthralgia patients with rituximab can have a positive effect on RA progression, she said in an interview.

The study included 115 patients with arthralgia who did not have RA, joint erosions, or a history of treatment with any disease-modifying antirheumatic drug at one center in Amsterdam. During a median 23 months of follow-up, 44 patients (38%) developed RA, after a median of 8 months.

At baseline, the researchers calculated an interferon gene score for each patient, based on their expression of seven different genes involved in responses to interferon. Patients who progressed to RA had an average interferon score at baseline that was about twice the average in the nonprogressors. At 2 years of follow-up, about 60% of the high gene expressors had progressed to RA, compared with about 30% of the low expressors, a statistically significant difference.

Adding data on the number of peripheral blood B cells, quantified by fluorescent-activated cell sorting, produced a statistically significant refinement of the progression rate.

It makes physiologic sense that interferon responses and blood levels of B cells would correlate with progression to early-stage RA, Ms. Lubbers said. A low level of B cells in blood suggests that a higher than normal number of B cells had migrated out of the blood and into tissue, such as into the synovium, Ms. Lubbers said.

Ms. Lubbers said that she had no disclosures. The VU Medical Center has a patent pending on using the markers studied for identifying preclinical RA.

BERLIN – The combination of an elevated level of interferon gene expression and a low level of circulating B cells identified patients with arthralgia who had a high rate of progression to rheumatoid arthritis in a validation study of 115 patients at one center.

After 2 years of follow-up, about 70% of patients with a high level of interferon gene expression and a low level of B cells in their peripheral blood had developed rheumatoid arthritis (RA), while in contrast about 20% of arthralgia patients with low interferon gene expression and a high B-cell level developed RA, Joyce Lubbers said at the annual European Congress of Rheumatology.

Some of Ms. Lubbers’ associates on the study had previously shown, in a different group of 109 patients with arthralgia, that high interferon gene expression was linked to an increased rate of progression to RA, and that high expression of genes involved in B-cell activation was linked to a reduced risk for progressing to RA (Arthritis Rheum. 2010;62:694-704). Hence, the new findings that Ms. Lubbers reported validated the results of the previous study.

"We’ve now shown this in two independent cohorts, and we’re looking at a third group," said Ms. Lubbers, a researcher working on inflammatory disease profiling at VU University Medical Center in Amsterdam.

In practice, these easily obtained lab markers – interferon gene expression and B cell count – can couple with a patient’s clinical profile to estimate the risk of developing RA.

The next step is to test whether an intervention in arthralgia patients at high risk for progression to RA can delay or prevent the progression, or make RA less severe once it develops. Researchers in Amsterdam are currently testing whether treatment of high-risk arthralgia patients with rituximab can have a positive effect on RA progression, she said in an interview.

The study included 115 patients with arthralgia who did not have RA, joint erosions, or a history of treatment with any disease-modifying antirheumatic drug at one center in Amsterdam. During a median 23 months of follow-up, 44 patients (38%) developed RA, after a median of 8 months.

At baseline, the researchers calculated an interferon gene score for each patient, based on their expression of seven different genes involved in responses to interferon. Patients who progressed to RA had an average interferon score at baseline that was about twice the average in the nonprogressors. At 2 years of follow-up, about 60% of the high gene expressors had progressed to RA, compared with about 30% of the low expressors, a statistically significant difference.

Adding data on the number of peripheral blood B cells, quantified by fluorescent-activated cell sorting, produced a statistically significant refinement of the progression rate.

It makes physiologic sense that interferon responses and blood levels of B cells would correlate with progression to early-stage RA, Ms. Lubbers said. A low level of B cells in blood suggests that a higher than normal number of B cells had migrated out of the blood and into tissue, such as into the synovium, Ms. Lubbers said.

Ms. Lubbers said that she had no disclosures. The VU Medical Center has a patent pending on using the markers studied for identifying preclinical RA.

BERLIN – The combination of an elevated level of interferon gene expression and a low level of circulating B cells identified patients with arthralgia who had a high rate of progression to rheumatoid arthritis in a validation study of 115 patients at one center.

After 2 years of follow-up, about 70% of patients with a high level of interferon gene expression and a low level of B cells in their peripheral blood had developed rheumatoid arthritis (RA), while in contrast about 20% of arthralgia patients with low interferon gene expression and a high B-cell level developed RA, Joyce Lubbers said at the annual European Congress of Rheumatology.

Some of Ms. Lubbers’ associates on the study had previously shown, in a different group of 109 patients with arthralgia, that high interferon gene expression was linked to an increased rate of progression to RA, and that high expression of genes involved in B-cell activation was linked to a reduced risk for progressing to RA (Arthritis Rheum. 2010;62:694-704). Hence, the new findings that Ms. Lubbers reported validated the results of the previous study.

"We’ve now shown this in two independent cohorts, and we’re looking at a third group," said Ms. Lubbers, a researcher working on inflammatory disease profiling at VU University Medical Center in Amsterdam.

In practice, these easily obtained lab markers – interferon gene expression and B cell count – can couple with a patient’s clinical profile to estimate the risk of developing RA.

The next step is to test whether an intervention in arthralgia patients at high risk for progression to RA can delay or prevent the progression, or make RA less severe once it develops. Researchers in Amsterdam are currently testing whether treatment of high-risk arthralgia patients with rituximab can have a positive effect on RA progression, she said in an interview.

The study included 115 patients with arthralgia who did not have RA, joint erosions, or a history of treatment with any disease-modifying antirheumatic drug at one center in Amsterdam. During a median 23 months of follow-up, 44 patients (38%) developed RA, after a median of 8 months.

At baseline, the researchers calculated an interferon gene score for each patient, based on their expression of seven different genes involved in responses to interferon. Patients who progressed to RA had an average interferon score at baseline that was about twice the average in the nonprogressors. At 2 years of follow-up, about 60% of the high gene expressors had progressed to RA, compared with about 30% of the low expressors, a statistically significant difference.

Adding data on the number of peripheral blood B cells, quantified by fluorescent-activated cell sorting, produced a statistically significant refinement of the progression rate.

It makes physiologic sense that interferon responses and blood levels of B cells would correlate with progression to early-stage RA, Ms. Lubbers said. A low level of B cells in blood suggests that a higher than normal number of B cells had migrated out of the blood and into tissue, such as into the synovium, Ms. Lubbers said.

Ms. Lubbers said that she had no disclosures. The VU Medical Center has a patent pending on using the markers studied for identifying preclinical RA.