Elevated plasmablast levels potential new diagnostic biomarker
By Phoebe Starr
San Diego, CA—The spectrum of immunoglobulin (Ig)G4-related disorders responds to treatment with rituximab, according to results of a new study, suggesting that elevated plasmablasts are a sensitive marker for these disorders. Lead investigator John H. Stone, MD, MPH, Director, Clinical Rheumatology, Massachusetts General Hospital, Boston, presented at the 2013 American College of Rheumatology meeting.
Despite its small size, this is the first study to demonstrate that a treatment is effective for this relatively recently described collection of diseases, said Dr Stone, who is one of the first researchers to describe IgG4-related disorders and their diagnoses.
“New therapeutic strategies are needed for IgG4-related disease,” Dr Stone said. “Glucocorticoids can be effective in many cases, but do not cure IgG4-related disease or lead to long-standing remissions in most cases.”
“Physicians might have used rituximab to treat IgG4-related disorders,” commented Arthur F. Kavanaugh, MD, Director, Center for Innovative Therapy, University of California, San Diego. “This is the first evidence we have that it works.”
Diagnosing IgG4-Related Disorders
The diagnosis of IgG4-related disorders encompasses a collection of approximately 12 different multiorgan rheumatic diseases that baffled doctors, who overall treated these conditions empirically with anti-inflammatory drugs. IgG4-related disorders can mimic Sjogren’s syndrome, granulomatosis with polyangiitis, systemic lupus erythematosus, and sarcoidosis, as well as infections and malignancies.
The prospective open-label trial enrolled 28 patients, mostly men (median age, 63 years) with confirmed IgG4-related disorders that affected various organ systems, including the eyes, salivary glands, hypopharynx, lungs, lymph nodes, pericardium, pancreas, biliary tract, retroperitoneum, kidneys, and prostate. All patients received rituximab 1000 mg on day 1 and day 15, along with methylprednisolone 100 mg.
Follow-up assessments were planned for 1, 3, 5, 6, 8, 10, and 12 months after the first rituximab dose. The primary end point was disease response, as measured by at least a 2-point decrease in the IgG4-Related Disease Responder Index, and by the ability to remain off of prednisone. Overall, 24 of 26 patients (92%) achieved the primary end point; they had no disease flares and no steroid requirement for 6 months. The mean Physician Global Assessment was 0 in 73% of the patients followed for ≥6 months.
Two participants required an increase in methylprednisolone after month 1. Two patients were hospitalized: 1 for Legionnaires’ disease, which was present at baseline, and 1 for autoimmune hemolytic anemia. No serious unexpected side effects were attributed to rituximab.
Dr Stone and colleagues found that elevated plasmablasts are a potential biomarker for IgG4-related disorders, which would help to identify these conditions, which are difficult to diagnose. If confirmed as a biomarker, using elevated plasmablast levels as a diagnostic tool may allow patients with IgG4-related disorders to forego prolonged steroid treatment.