Newer IgG4 testing proving effective in assessing patients

 

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.

 

Perhaps even better, studies in Europe have found that RT-qPCR testing for IgG4 RNA can be effective. This type of testing is easier than ELISPOT, and “they are finding the sensitivity to be much superior to nephelometry for immunoglobulin levels,” Dr. Khosroshahi said.

The higher the levels of IgG4, the more likely an IgG4-related disease diagnosis is warranted, and higher levels tend to lead to worse outcomes, she said.

She waved a caution flag, though: Other diseases can involve elevated IgG4, and even a normal IgG4 level does not necessarily rule out the disease. Other evaluations really form the cornerstone of the diagnosis of IgG4-related disease, she said.

“There should be characteristic histology and of course IgG4-staining, but more importantly, pattern of organ involvement. It’s very important,” Dr. Khosroshahi said. “If there is a mass in the pancreas and there is salivary gland and parotid gland swellings and other features of that going on, you are more concerned that that is a process going on.”

Dr. Khosroshahi had no relevant disclosures.

 

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.

 

Perhaps even better, studies in Europe have found that RT-qPCR testing for IgG4 RNA can be effective. This type of testing is easier than ELISPOT, and “they are finding the sensitivity to be much superior to nephelometry for immunoglobulin levels,” Dr. Khosroshahi said.

The higher the levels of IgG4, the more likely an IgG4-related disease diagnosis is warranted, and higher levels tend to lead to worse outcomes, she said.

She waved a caution flag, though: Other diseases can involve elevated IgG4, and even a normal IgG4 level does not necessarily rule out the disease. Other evaluations really form the cornerstone of the diagnosis of IgG4-related disease, she said.

“There should be characteristic histology and of course IgG4-staining, but more importantly, pattern of organ involvement. It’s very important,” Dr. Khosroshahi said. “If there is a mass in the pancreas and there is salivary gland and parotid gland swellings and other features of that going on, you are more concerned that that is a process going on.”

Dr. Khosroshahi had no relevant disclosures.

 

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.

 

Perhaps even better, studies in Europe have found that RT-qPCR testing for IgG4 RNA can be effective. This type of testing is easier than ELISPOT, and “they are finding the sensitivity to be much superior to nephelometry for immunoglobulin levels,” Dr. Khosroshahi said.

The higher the levels of IgG4, the more likely an IgG4-related disease diagnosis is warranted, and higher levels tend to lead to worse outcomes, she said.

She waved a caution flag, though: Other diseases can involve elevated IgG4, and even a normal IgG4 level does not necessarily rule out the disease. Other evaluations really form the cornerstone of the diagnosis of IgG4-related disease, she said.

“There should be characteristic histology and of course IgG4-staining, but more importantly, pattern of organ involvement. It’s very important,” Dr. Khosroshahi said. “If there is a mass in the pancreas and there is salivary gland and parotid gland swellings and other features of that going on, you are more concerned that that is a process going on.”

Dr. Khosroshahi had no relevant disclosures.