Subtype of B-cells Linked to Kidney Disease in AAV, Study Discovers

A subtype of antibody-producing B-cells was significantly higher in the bloodstream of ANCA-associated vasculitis (AAV) patients with active kidney involvement compared with those who were in remission and healthy individuals.

These findings may help monitor disease progression, as well as provide insights into AAV development, the researchers noted.

The study, “Increased frequency of IgD-CD27^hiCD38^hi B cells and its association with the renal involvement in ANCA-associated vasculitis,” was published in the journal Arthritis Research & Therapy.

In AAV, self-reactive antibodies bind to and overly activate immune cells called neutrophils, leading to inflammation and damage to small blood vessels, most commonly in the lungs and kidneys.

Normally, antibodies are generated by immune B-cells in response to infections, which can be subdivided into several subtypes, ranging from immature naive cells that never had contact with an infectious agent to fully mature, antibody-producing plasma cells. These subtypes are categorized based on the proteins found on their surface.

In several autoimmune diseases, including AAV, the distribution of these B-cell subtypes is altered. Among the various subtypes, autoreactive B-cells cause disease by producing and releasing self-reactive antibodies.

A study demonstrated that one B-cell subtype, referred to as IgD-CD27^hiCD38^hi, was 40 times higher in the bloodstream of people with systemic lupus erythematosus (SLE), an autoimmune inflammatory condition, than in healthy individuals.

These findings prompted researchers at the Peking University Institute of Nephrology in China to evaluate the frequency of these cells in AAV patients and whether they are associated with disease activity and kidney involvement.

The team collected blood samples from 26 adults with active AAV and from 18 patients who were in remission after receiving immunosuppressive therapy. Blood samples from five age- and gender-matched healthy individuals were also collected as controls.

B-cell subtypes were sorted by a technique known as flow cytometry. The frequency of IgD-CD27^hiCD38^hi cells within two B-cell populations that carry different protein markers on their surface (CD19 and CD45) was compared across the different groups.

According to the analysis, the frequency of IgD-CD27^hiCD38^hi B-cells among CD19-positive B-cells was significantly higher in AAV patients with active disease than in those who were in remission (median 7.29% vs. 4.08%) and controls (median 7.29% vs. 4.49%).

Likewise, the frequency of these cells within the population of CD45-positive cells was also significantly higher in active-disease participants compared with patients in remission (median 1.33% vs. 0.74%) and controls (median 1.33% vs. 0.53%).

No significant difference was seen in the frequency of IgD-CD27^hiCD38^hi cells between AAV patients in remission and controls in either population of B-cells.

Among eight patients who had blood samples collected during both active disease and remission, six showed a decrease in IgD-CD27^hiCD38^hi cells during remission, while two had a slight increase.

Statistical analysis also found a significant correlation between high levels of these cells and high creatinine and a low estimated glomerular filtration rate (eGFR), which are both indicators of kidney damage.

No significant associations were identified with other clinical parameters, including the levels of ANCA self-reactive antibodies, two inflammation markers (C-reactive protein and erythrocyte sedimentation rate), and the Birmingham Vasculitis Activity Score (BVAS), an assessment of AAV disease severity.

Lastly, researchers found that with active AAV, the percentage of total crescents in kidney biopsies — a sign of inflammatory kidney damage — was significantly higher in patients with elevated levels of IgD-CD27^hiCD38^hi B-cells than in patients with low levels (73.5% vs. 48.5%).

“Our study reports an increase of circulating IgD-CD27^hiCD38^hi B cells and its association with the severity of renal involvement in patients with active AAV, as it is possible that IgD-CD27^hiCD38^hi B cells are involved in the pathogenesis [development] of AAV, especially the renal involvement of AAV,” the researchers wrote.

“Our data might provide a new access to disease monitoring and pathogenesis investigation of AAV.”