Simple blood test can accurately spot and track multi-organ IgG4-RD
IgG4 levels correlate with extent of disease, can help differentiate disorders
Measuring a specific type of antibody in the blood called immunoglobulin G4 (IgG4) is proving to be a highly effective tool for doctors to diagnose, assess, and monitor the rare and complex condition known as IgG4-related disease (IgG4-RD).
A study found that elevated IgG4 levels correlate strongly with multi-organ involvement, helping doctors understand the disease’s extent and track how well treatment is working. Crucially, the test also helps distinguish IgG4-RD from other conditions that might cause high antibody levels.
The study, “Clinical and laboratory characteristics of IgG4-related disease involving multiple organs,” was published in Clinical Rheumatology.
The single-center study in China looked at data from 88 adults with IgG4-RD, 50 healthy people, and 468 people with high IgG4 levels but who did not have IgG4-RD.
“Elevated [blood] IgG4 levels are associated with multi-organ involvement, underscoring their utility in assessing disease extent,” researchers wrote, adding that IgG4 “is indispensable for monitoring therapeutic response.”
Distinguishing IgG4-RD from other conditions
Contrary to what happens in IgG4-RD, IgG4 levels do not necessarily drop after treatment in people with other conditions associated with high antibody levels. This may be a potential diagnostic criterion to differentiate IgG4-RD from other diseases.
IgG4-RD occurs when immune cells, particularly those producing the IgG4 antibody, infiltrate tissues and drive persistent inflammation, which can lead to scarring and the development of tumor-like masses that disrupt organ function. The disease can affect any body part, and typically affects more than one tissue or organ.
“The murky waters of diagnosis are further muddied by the fact that high [blood] IgG4 can occur in a variety of non-IgG4-RD conditions, including allergic reactions, infections, and even malignancies,” the researchers wrote.
In the study, most patients were men (80%), with a median age of 60 years, slightly older in men versus in women (61.5 vs. 54.5). The median time to diagnosis was one month.
More than half (52.3%) showed involvement of two or more organs, while the remaining 47.7% had a single organ affected. The most commonly involved organs were the pancreas (39.7%), lymph nodes (32.9%), bile ducts (23.8%), eyes (20.4%), and lungs (19.3%).
Median levels of IgG4 in the blood were significantly higher in IgG4-RD patients than in the 50 healthy individuals (6.8 vs. 0.79 g/L). A cut-off value of 1.935 g/L accurately distinguished patients from healthy individuals.
Median levels of IgG4 were significantly higher among patients with multiple organs affected relative to those with single organ involvement (8.5 vs. 5.76 g/L). The researchers set a cut-off value of 9.05 g/L, above which patients with multi-organ involvement could be distinguished from those with a single organ affected.
Among 16 patients with data after six months of standard treatment, median IgG4 levels dropped significantly from 6.33 to 2.37 g/L.
These findings indicate “IgG4 levels are instrumental in diagnosing, assessing disease progression, and monitoring treatment response, though their interpretation should be integrated with other clinical indicators,” the researchers wrote.
Combining IgG4 measurements with other laboratory tests, such as C-reactive protein (a marker of inflammation) and liver enzymes, may improve diagnostic accuracy, they noted.
Limitations and future direction
By analyzing data from 468 people with high IgG4 levels but without IgG4-RD, the team found a number of other conditions associated with elevated IgG4, with the most common being ANCA-associated vasculitis (AAV), an autoimmune disease causing inflammation in small blood vessels.
While people with AAV had high blood IgG4 levels, these “remained unchanged post-treatment,” the researchers wrote.
While this study suggests IgG4 as a diagnostic marker for IgG4-RD, the researchers noted its limitation to Han Chinese patients. They wrote, “Future investigations would benefit from focusing on prospective, multicenter studies, boasting larger sample sizes to affirm these findings.”
In a letter to the editor, researchers in Pakistan noted that the current study did not consider the effects of treatments on IgG4 levels, with standard glucocorticoids known to rapidly reduce IgG4 levels, while other immunosuppressants maintaining levels for long periods of time.
They added that more studies should confirm an IgG4-RD diagnosis based also on tissue analysis. To make the study more precise and reliable, “a longer follow-up period should be provided to counter relapse of disease, make the same treatment plans for every patient, and consider other diseases that may elevate the IgG4 levels.”
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