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Serum IgG subclasses vary by autoimmune disorder
Subclasses of serum immunoglobulin G were distinct but varied across autoimmune disorders, according to recently published research.
Researchers studied blood serum immunoglobulin G (IgG) levels from 102 patients (96 women) with primary Sjögren’s syndrome (pSS), 102 patients (93 women) with systemic sclerosis (SSc), 100 patients (92 women) with systemic lupus erythematosus (SLE) and 59 patients (57 women) with primary biliary cirrhosis (PBC) from the Department of Rheumatology, Peking Union Medical College Hospital (PUMCH), China. Forty healthy individuals were recruited from the Center of Health Examination, PUMCH, as a control group and provided serum samples, as well.
Analysis of serum samples showed that IgG1 and/or IgG3 were significantly increased in patients with pSS, SSc, SLE and PBC compared with healthy control participants, with the highest levels observed in patients with pSS.
Serum IgG2 levels were much lower in patients with pSS, SSc and SLE, but not in patients with PBC, in whom the levels were significantly higher than in patients with other autoimmune diseases; however, the levels were not significantly higher than in healthy participants, according to the researchers.
IgG4 was significantly lower and found in similar levels in patients with pSS, SSc and PBC, but no differences were seen in patients with SLE and healthy participants.
Of all patients with autoimmune disorders, only 23 (6.34%) had elevated levels of IgG4, and all had normal levels of IgG, suggesting that the IgG subclasses were preferentially produced through the pathogenesis of that particular disease.
The findings conflicted with prior investigations by Liu, et al., and Lin, et al., according to the researchers, who wrote that further inquiry is necessary and suggested that patient selection criteria may explain the discrepancies. – by Shirley Pulawski
Disclosures: The authors report no relevant financial disclosures.
Perspective
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IgG4 disease is clinically important and fascinating. For clinicians who are tempted to order IgG4 subclasses when thinking of this disorder, it is important to be able to define its test operating characteristics in term of specificity. Yes it is true that elevated IgG4 levels are not necessary for the diagnosis and may be transient during the long course of the illness, but none the less it is tempting to order a simple blood test when we have this syndrome on our mind and we need data to interpret the results in a Bayesian fashion.
Understanding test sensitivity and specificity is vital to correctly interpret results when placed in context of pretest probability. While we know a lot about immunoglobulin levels in health, we know far less in disease, particularly those that may represent clinical mimics of IgG4 disease. The excellent Department of Rheumatology at the Peking University Medical College Hospital (PUMCH) in Beijing has given us some valuable data to help address the question of specificity of IgG4 levels in mimicking conditions as well has provided insight into quantitative distribution of IgG subclasses in various rheumatic diseases. Not unexpectedly, IgG subclasses were perturbed in their quantity both absolutely and relatively when compared to healthy controls. Importantly, however, only a small number (about 6%) had elevated IgG4 levels in the range generally thought meaningful in IgG4 disease.
Thank you PUMCH investigators for a nice job of providing valuable data.
Reference:
Stone JH, et al. N Engl J Med. 2012;doi:10.1056/NEJMra1104650.