SANDESTIN, FLA. – New forms of IgG4 testing could be more helpful in making diagnoses of immunoglobulin G4-related disease, an expert said at the annual Congress of Clinical Rheumatology, while cautioning that the diagnosis is more about histology and pattern of involvement than antibody testing.
Arezou Khosroshahi, MD, of Emory University, Atlanta, said that the IgG4 levels found in serum using nephelometry can often be low in patients who otherwise show signs of the disease, which can affect a wide array of organs and typically involves elevated IgG4. Newer forms of testing – enzyme-linked ImmunoSpot (ELISPOT) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) – could be more telling, she said.
She said she once had a 54-year-old woman as a patient who had enlarged bilateral lacrimal and salivary glands, with lymphadenopathy. She suspected IgG4 levels would be elevated, but, surprisingly, they weren’t.But she found that, on flow cytometry, 88% of the woman’s circulating B cells were positive for IgG4, so the woman was treated with rituximab to deplete these cells.
“When the B cells were gone, we had release of the IgG4 in the serum and now we could pick it up with nephelometry,” she said.
This missed IgG4 with nephelometry prompted researchers to turn to ELISPOT, a sensitive method to count antibody-secreting cells. The test works well by capturing the antibodies’ presence right after they’re secreted, before they can become lost to receptor binding or in other ways.
“This was a better assay to measure the IgG4 antibodies rather than nephelometry,” she said.