Levels of Memory B-cells Help Diagnose, Measure Disease Activity of Primary Sjögren’s Patients

Decreased levels of memory B-cells, a kind of white blood cell, may help diagnose patients with primary Sjögren’s syndrome and determine the severity of their disease, a new study shows.

Tests based on memory B-cell levels potentially could be used as disease markers for predicting outcomes and tracking the effect of treatments in clinical trials.

The study, “Association between memory B-cells and clinical and immunological features of primary Sjögren’s syndrome and Sicca patients,” was published in the journal Rheumatology International.

Diagnosing primary Sjögren’s syndrome, especially in the early stages of the disease, remains difficult. At that point, many patients lack the autoantibodies associated with Sjögren’s and do no meet the criteria for diagnosis.

B-cell abnormalities are the hallmark of primary Sjögren’s syndrome and play a key role in disease processes and evolution. This led researchers at the Chronic Diseases Research Center, in Lisbon, Portugal, to investigate B-cell populations as a potential diagnostic tool for primary Sjögren’s syndrome.

The study included 57 Sjögren’s patients, 24 healthy people as controls, and 68 sicca patients. Sicca syndrome is a condition involving dryness, particularly of the eyes and mouth, when there is no evidence of autoimmune disease present. While sicca symptoms occur in the vast majority of Sjögren’s patients, not everyone with these symptoms has Sjögren’s.

Researchers measured the levels of different kinds of B-cells, which are white blood cell that produce  antibodies. In particular, memory B-cells —cells primed to mount a vigorous response to substances that have previously triggered immune reactions — were found to be decreased in the majority of the cases of Sjögren’s syndrome that were studied.

Researchers set out to establish the optimal cut-off point of memory B-cell levels that coincided with a diagnosis of Sjögren’s or sicca syndrome, to evaluate the test for use in diagnosis.

They also looked at the association between low memory B-cell levels and disease activity, as measured by the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI). An association between decreased memory B-cells and duration of disease also was examined. Both duration of disease and disease activity were found to be associated with decreased levels of memory B-cells.

Establishing the cut-off for total memory B-cells/µl at 58 or lower resulted in a specificity (true positive rate) of 0.88 and a sensitivity (true negative rate) of 0.60 for primary Sjögren’s syndrome. (“µl” is a symbol representing a microliter, which is one-millionth of a liter.)

Patients whose memory B-cell counts were at the cut-off value or less included 59.6% of Sjögren’s patients, 38.8% of sicca patients, and 12.5% of controls. When examining Switched-memory B-cells/µl, a subset of memory B-cells, a cut-off point of 23.5 yielded a specificity of 0.88 and a sensitivity of 0.54. A slightly lower percentage of Sjögren’s patients (54.4%) met this cut-off value, and 37.3% of sicca patients, and 12.5% of controls.

Investigators point out that while lower memory B-cell counts were indicative of longer disease duration and higher disease activity, further investigation in a larger sample of patients is needed before using this test as part of diagnostic tests for Sjögren’s.

“We have demonstrated that in pSS [primary Sjögren’s syndrome], the presence of lower memory B-cells counts was associated with a longer disease duration and a more active disease, which could represent a possible role as prognostic markers. Therefore, we aim to continue the present study in the future to include more patients, allowing us to clearly prove that these measurements may be used as clinical biomarkers for the follow-up of these patients,” they wrote.

“It remains to be clarified if decreased memory B-cells could complement the immunological items currently used for pSS diagnosis. If so, future classification criteria integrating such items could identify patients presently unclassifiable as pSS and allow their access to novel therapies and clinical trials,” they concluded.