B Cells Key in Takayasu Arteritis

In Takayasu arteritis, as in systemic lupus erythematosus, greater numbers of circulating plasmablasts coincided with increased disease activity.

The finding is the first to extensively describe B-cell disturbances in this poorly understood disease, "which was previously thought to have a mainly T-cell–mediated pathogenesis," according to the researchers.

Moreover, the finding offers hope that B-cell depletion therapy may be an option for these patients, added Dr. Bimba F. Hoyer in the January 2012 issue of Annals of the Rheumatic Diseases.

Dr. Hoyer of the Charité Universitätsmedizin Berlin and colleagues looked at blood samples from 17 women with Takayasu arteritis according to American College of Rheumatology disease criteria.

Patients’ median age at disease onset was 25 years, their median disease duration was 90 months, and the median age at analysis was 39 years.

A second cohort of nine women without Takayasu arteritis but with systemic lupus erythematosus (SLE) was also studied (mean age, 32 years), as was a control group of eight healthy women and one man (mean age, 35.5 years).

Cells were analyzed for expression of CD20, CD19, CD27, and HLA-DR.

"B-cell depletion therapy seems to be a useful option for refractory Takayasu arteritis."

"Unlike active SLE, which is characterized by lymphocytopenia, total lymphocyte and B-cell counts in patients with [Takayasu arteritis] were not significantly lower than those in healthy donors," wrote the authors (Ann. Rheum. Dis. 2012;71:75-9).

However, they did find that B-cell subsets were "considerably altered" in active Takayasu arteritis. For example, they found an increased number and frequency of CD19⁺/CD20^–/CD27^high antibody-secreting cells in patients with Takayasu arteritis compared with healthy donors (2,800 vs. 1,200, respectively; P = .027), as well as a lower total number of naive B cells (28,000 vs. 110,000; P = .012) and a higher number of memory B cells (78,000 vs. 48,000; P = .049).

They also found an increased number of plasmablasts among active Takayasu arteritis patients (11 of the 17 total patients), both in relation to healthy donors (7,800 vs. 975; P = .027) and in relation to the inactive Takayasu arteritis cohort (n = 6), where the mean was 535 (P = .0056).

"This strongly resembles the findings in SLE, where plasmablast expansion serves as a marker of disease activity," wrote the authors. Indeed, the number of plasmablasts in the active SLE patients was identical to that in the active Takayasu arteritis patients, at 7,800.

Based on these findings, three patients who were refractory to other treatments were subsequently treated with rituximab, "so far successfully," wrote the authors. The case studies of these patients were published in a supplement to the current study.

"The observed correlation between the plasmablast numbers and active Takayasu arteritis, as well as the beneficial effects of B-cell depletion therapy, suggests a potential of plasmablasts as biomarkers of disease activity and for interventions targeting B cells," they wrote.

Moreover, "B-cell depletion therapy seems to be a useful option for refractory Takayasu arteritis, and its potential should be evaluated in controlled trials," they added.

"Other factors influencing B-cell differentiation and plasma cells may also emerge as novel therapeutic targets."

The study was supported by the Deutsche Forschungsgemeinschaft (the German Research Foundation) and Roche Pharma AG, the maker of rituximab. The authors stated that they had no individual competing interests to disclose.

In Takayasu arteritis, as in systemic lupus erythematosus, greater numbers of circulating plasmablasts coincided with increased disease activity.

The finding is the first to extensively describe B-cell disturbances in this poorly understood disease, "which was previously thought to have a mainly T-cell–mediated pathogenesis," according to the researchers.

Moreover, the finding offers hope that B-cell depletion therapy may be an option for these patients, added Dr. Bimba F. Hoyer in the January 2012 issue of Annals of the Rheumatic Diseases.

Dr. Hoyer of the Charité Universitätsmedizin Berlin and colleagues looked at blood samples from 17 women with Takayasu arteritis according to American College of Rheumatology disease criteria.

Patients’ median age at disease onset was 25 years, their median disease duration was 90 months, and the median age at analysis was 39 years.

A second cohort of nine women without Takayasu arteritis but with systemic lupus erythematosus (SLE) was also studied (mean age, 32 years), as was a control group of eight healthy women and one man (mean age, 35.5 years).

Cells were analyzed for expression of CD20, CD19, CD27, and HLA-DR.

"B-cell depletion therapy seems to be a useful option for refractory Takayasu arteritis."

"Unlike active SLE, which is characterized by lymphocytopenia, total lymphocyte and B-cell counts in patients with [Takayasu arteritis] were not significantly lower than those in healthy donors," wrote the authors (Ann. Rheum. Dis. 2012;71:75-9).

However, they did find that B-cell subsets were "considerably altered" in active Takayasu arteritis. For example, they found an increased number and frequency of CD19⁺/CD20^–/CD27^high antibody-secreting cells in patients with Takayasu arteritis compared with healthy donors (2,800 vs. 1,200, respectively; P = .027), as well as a lower total number of naive B cells (28,000 vs. 110,000; P = .012) and a higher number of memory B cells (78,000 vs. 48,000; P = .049).

They also found an increased number of plasmablasts among active Takayasu arteritis patients (11 of the 17 total patients), both in relation to healthy donors (7,800 vs. 975; P = .027) and in relation to the inactive Takayasu arteritis cohort (n = 6), where the mean was 535 (P = .0056).

"This strongly resembles the findings in SLE, where plasmablast expansion serves as a marker of disease activity," wrote the authors. Indeed, the number of plasmablasts in the active SLE patients was identical to that in the active Takayasu arteritis patients, at 7,800.

Based on these findings, three patients who were refractory to other treatments were subsequently treated with rituximab, "so far successfully," wrote the authors. The case studies of these patients were published in a supplement to the current study.

"The observed correlation between the plasmablast numbers and active Takayasu arteritis, as well as the beneficial effects of B-cell depletion therapy, suggests a potential of plasmablasts as biomarkers of disease activity and for interventions targeting B cells," they wrote.

Moreover, "B-cell depletion therapy seems to be a useful option for refractory Takayasu arteritis, and its potential should be evaluated in controlled trials," they added.

"Other factors influencing B-cell differentiation and plasma cells may also emerge as novel therapeutic targets."

The study was supported by the Deutsche Forschungsgemeinschaft (the German Research Foundation) and Roche Pharma AG, the maker of rituximab. The authors stated that they had no individual competing interests to disclose.

In Takayasu arteritis, as in systemic lupus erythematosus, greater numbers of circulating plasmablasts coincided with increased disease activity.

The finding is the first to extensively describe B-cell disturbances in this poorly understood disease, "which was previously thought to have a mainly T-cell–mediated pathogenesis," according to the researchers.

Moreover, the finding offers hope that B-cell depletion therapy may be an option for these patients, added Dr. Bimba F. Hoyer in the January 2012 issue of Annals of the Rheumatic Diseases.

Dr. Hoyer of the Charité Universitätsmedizin Berlin and colleagues looked at blood samples from 17 women with Takayasu arteritis according to American College of Rheumatology disease criteria.

Patients’ median age at disease onset was 25 years, their median disease duration was 90 months, and the median age at analysis was 39 years.

A second cohort of nine women without Takayasu arteritis but with systemic lupus erythematosus (SLE) was also studied (mean age, 32 years), as was a control group of eight healthy women and one man (mean age, 35.5 years).

Cells were analyzed for expression of CD20, CD19, CD27, and HLA-DR.

"B-cell depletion therapy seems to be a useful option for refractory Takayasu arteritis."

"Unlike active SLE, which is characterized by lymphocytopenia, total lymphocyte and B-cell counts in patients with [Takayasu arteritis] were not significantly lower than those in healthy donors," wrote the authors (Ann. Rheum. Dis. 2012;71:75-9).

However, they did find that B-cell subsets were "considerably altered" in active Takayasu arteritis. For example, they found an increased number and frequency of CD19⁺/CD20^–/CD27^high antibody-secreting cells in patients with Takayasu arteritis compared with healthy donors (2,800 vs. 1,200, respectively; P = .027), as well as a lower total number of naive B cells (28,000 vs. 110,000; P = .012) and a higher number of memory B cells (78,000 vs. 48,000; P = .049).

They also found an increased number of plasmablasts among active Takayasu arteritis patients (11 of the 17 total patients), both in relation to healthy donors (7,800 vs. 975; P = .027) and in relation to the inactive Takayasu arteritis cohort (n = 6), where the mean was 535 (P = .0056).

"This strongly resembles the findings in SLE, where plasmablast expansion serves as a marker of disease activity," wrote the authors. Indeed, the number of plasmablasts in the active SLE patients was identical to that in the active Takayasu arteritis patients, at 7,800.

Based on these findings, three patients who were refractory to other treatments were subsequently treated with rituximab, "so far successfully," wrote the authors. The case studies of these patients were published in a supplement to the current study.

"The observed correlation between the plasmablast numbers and active Takayasu arteritis, as well as the beneficial effects of B-cell depletion therapy, suggests a potential of plasmablasts as biomarkers of disease activity and for interventions targeting B cells," they wrote.

Moreover, "B-cell depletion therapy seems to be a useful option for refractory Takayasu arteritis, and its potential should be evaluated in controlled trials," they added.

"Other factors influencing B-cell differentiation and plasma cells may also emerge as novel therapeutic targets."

The study was supported by the Deutsche Forschungsgemeinschaft (the German Research Foundation) and Roche Pharma AG, the maker of rituximab. The authors stated that they had no individual competing interests to disclose.