Thank you for your inquiry.
I can well understand your puzzlement. The literature is indeed somewhat moot on this issue. But in actuality, an isolated elevation of IgA is not terribly uncommon according to my own personal experience. We have received a very similar question in the past, and for your interest, I am copying the inquiry and my response below. As you can see from my response, I did not have a definitive answer to the inquiry, and I am afraid I've learned nothing new since that response.
However, from a theoretical standpoint, I believe the isolated IgA is, since it is not monoclonal, related to the infections themselves. If so, over time, if she does not continue to experience such infections (and my guess is that she will not), the level of IgA should decline. What I would recommend therefore at this time is “watchful waiting” and repeating the IgA in 6 to12 months.
I think you have done due diligence in your evaluation and cannot think of any further study nor further treatment to add to your approach.
If you do repeat the IgA, we would love to have a follow-up regarding your results.
Finally, you did not mention how old her children were, but also, it is not unusual for us to see an increase in respiratory tract infections in young mothers who have children under the age of 12. So my best guess is that she may be catching the increased number of infections from her child, and that these are responsible for the isolated monoclonal IgA. Again, time will tell if this is the case.
Thank you again for your inquiry and we hope this response is helpful to you.
Phil Lieberman, M.D.
Causes of Elevated IgA
A referring PCP asked me today what could cause increase in IgA?
Her pt is 54 female with recurrent sinusitis and had Immune w/u with IgA 530 and normal IgG, IgM. the PCP then worked pt up further due to increase IgA and the following were all normal: SEP, Urine electrophoresis, metabolic panel, ANA, tissue transglut IgA, neutrophil cytoplasmic AB, and CBC. Pt is not an alcoholic.
I wonder if IgA could be elevated in chronic sinusitis or could this be just a normal varient for this pt or something more forebouding in the future?
Are further labs needed? A Dx? Yes the IgA was repeated 6 months later and still elevated thus the above w/u.
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.
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.
Background: Immunoglobulin levels are elevated in the older people. However, it is unknown whether these levels are related to mortality.
Objective: 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.