Thank you for your recent inquiry.
Unfortunately I am not sure that I can be of any practical help to you in this regard. If one looks up a list of causes of elevated IgA, you see a total of 48 different diagnoses. They are divided into infections, neoplastic disorders, autoimmune disorders, neoplasms, congenital disorders, immune deficiencies (e.g., Wiskott-Aldrich, et cetera), poisonings (acute alcoholic hepatitis), and gastrointestinal diseases such as gluten enteropathy. However, none of these seem to fit your patient, and I doubt that any further evaluation would be fruitful in determining the underlying cause.
The most important thing that one can do is rule out monoclonality. The family physician seeing your patient has effectively done this with a serum protein electrophoresis, but if you wanted to add a more definitive touch, you could order an immunoelectrophoresis or an immunofixation. This would of course conclusively rule out any monoclonal elevation of IgA such as would occur in a malignancy. However, this of course is highly unlikely in the presence of a normal serum protein electrophoresis.
I can only add some anecdotal comments in that it is not terribly unusual to see elevations of IgA of this magnitude without known cause. In the course of working up individuals, we have seen several instances of nonspecific polyclonal elevation of IgA, and since these workups have been done to rule out immunodeficiency because of recurrent sinusitis, I have always attributed the elevated IgA levels to a response to recurrent bacterial sinusitis. You have alluded to this in your inquiry, and I certainly think this is a likely possibility. However, I could find no confirmation of this etiology in the literature. I have not been able to find any reference that has looked at this issue and documented repeated sinusitis as a cause for an elevated polyclonal serum IgA. Thus although the possibility seems rational, a role for recurrent bacterial sinusitis in producing an elevated IgA has not been conclusively documented in the literature.
Once again, returning to anecdotal experience, none of the patients that we have seen with polyclonal elevations of IgA, to my knowledge, have developed any complications, and have not experienced a clinical course any different from those patients with recurrent bacterial sinusitis and normal IgA levels. It may be reassuring for you to note that an elevated IgA in a woman is not a bad prognostic sign as evidenced by the abstract copied below. In a man, however, it evidently has been associated with an increase in mortality.
In summary, I think the most likely explanation for the elevated IgA, since it appears to be polyclonal, is a response to bacterial sinusitis. If you wanted to work it up further, the only thing that you might do would be to further document the polyclonal nature of the elevation by doing an immunoelectrophoresis or immunofixation. Finally, I doubt that this finding indicates a bad prognosis.
Thank you again for your inquiry and we hope this response is helpful to you.
Gerontology. 2009;55(2):179-85. Epub 2008 Oct 7.
IgA level is associated with risk for mortality in an eighty-year-old population.
Torisu T, Takata Y, Ansai T, Soh I, Awano S, Sonoki K, Kagiyama S, Nakamichi I, Yoshida A, Hamasaki T, Matsumoto T, Iida M, Takehara T.
Division of General Internal Medicine, Department of Health Promotion, Kyushu Dental College, Kokurakita-ku, Kitakyushu, Japan. email@example.com
BACKGROUND: Immunoglobulin levels are elevated in the older people. However, it is unknown whether these levels are related to mortality.
OBJECT: To evaluate the association between immunoglobulin levels and mortality.
METHODS: The study population included 697 individuals (277 males and 420 females) of 1,282 eighty-year-old individuals residing in the Fukuoka prefecture, Japan. The participants were followed for 4 years after the baseline examination.
RESULTS: The hyper-IgA group, defined as a serum IgA level >400 mg/dl, had high mortality using Kaplan-Meier analysis (log rank, p=0.037). Multivariate Cox regression analyses revealed a high risk of mortality (hazard rate=1.233, 95% confidence interval 1.109-1.491, p=0.031) after adjusting for covariates. The high risk of mortality in the hyper-IgA group was significant in males, but not in females. Moreover, Kaplan-Meier analysis revealed that IgA was related to cancer mortality in males (log rank, p=0.031), but not to pneumonia or cardiovascular disease. IgM and IgG levels were not related to high risk of mortality.
CONCLUSION: Serum IgA levels appear to be a predictor of mortality, especially cancer mortality in males.
Phil Lieberman, M.D.