Q:

1/2/2014
I need to clarify a scenario with you. Patient got referred to me for low IgA. She is a 41 year-old lady with Pulmonary MAC and aspergillosis. She has a cavitary lesion in the lungs. There is a history of severe asthma in childhood.

She has selective IgA deficiency <7. IgG is 1270. IgM is 144. I wanted to vaccinate her to see the post vaccine response. But she reports cellulitis involving the entire arm after pneumococcal vaccine and less severe incidence with influenza vaccine.

Where do I go from here? Any further tests needed? I have ordered a baseline vaccine titre at the first visit. She is under treatment for MAC for a total duration of 1 year.

A:

Thank you for your inquiry.

First of all, I think it is important to consider the type of immune defect to which Mycobacterium avium infection is attributed. Mycobacteria cause intracellular infections and therefore the defense against them is not via antibody production but through intracellular immunity (lymphocytes and macrophages). Therefore, at least to my knowledge, an isolated IgA deficiency would not normally be thought to be responsible for Mycobacterium avium infection; nor would it be thought to be a cause of the aspergillus growth. Both aspergillus and Mycobacterium avium tend to infect individuals with pulmonary abnormalities such as bronchiectasis or cavitary lesions. Thus, I think it is more likely that the presence of these two organisms in this patient are related to the cavitary lesion and not a result of her isolated IgA deficiency.

In addition, there is no treatment for isolated IgA deficiency. Unless there is an associated IgG deficiency or markedly diminished response to immunization coupled with evidence of chronic bacterial infections such as chronic sinusitis, bronchiectasis, or recurrent pneumonia, one would not normally consider an immune evaluation in a patient who presents with an isolated IgA deficiency. With an IgG level of 1,270, in the absence of any evidence of recurrent and chronic bacterial respiratory tract infection as mentioned above, a poor response to a pneumococcal immunization would be unexpected. In addition, even if that response was diminished, the administration of immunoglobulin in this situation, without the clinical picture as mentioned above, would be debatable.

On the other hand, as you can see from the abstract copied below, isolated IgA deficiency can be associated with autoimmune disease, allergic disease, gastrointestinal problems, et cetera, all of which should be monitored. And it can progress to common variable immunodeficiency, so repeated levels of immunoglobulin are oftentimes done annually, and the patient is followed not only for recurrent bacterial infections but the other conditions associated with isolated IgA deficiency.

However, on the other hand, if you still wish to evaluate her response to immunization, I believe it could be done. I would consider giving the pneumococcal vaccine in graded doses. My suggestion would be to give the vaccine in 0.1 cc increments. It would be unlikely that she would have significantly large locals to this dose. You could administer the vaccine every two days in this fashion. The immune response should not be affected by this graded dosage protocol. The same could be done with influenza if you wished to look at influenza titers as well.

In summary, I would not feel compelled to evaluate this patient's antibody immune responsiveness unless there was evidence of increased bacterial respiratory tract infections (pneumonia, chronic sinusitis, bronchiectasis, et cetera). I do not think that the aspergillus and Mycobacterium avium are related to the IgA deficiency.

In addition, a significant deficiency in antibody response is unlikely with her IgG of 1,270. However, if you still wish to proceed, and there would certainly be no contraindication to doing that, and there are probably some who would argue that you should, I believe that you could successfully immunize her with a graded administration protocol.

Thank you again for your inquiry and we hope this response is helpful to you.

Semergen. 2013 Dec 18. pii: S1138-3593(13)00024-5. doi: 10.1016/j.semerg.2013.01.013. [Epub ahead of print]
[Importance of selective immunoglobulin A deficiency.]
[Article in Spanish]
Rojas-Torres DS1, Bastidas-Yaguana DK2, Sierra-Santos L3, Aguilar-Shea AL3.
Abstract
Selective IgA deficiency is the most common primary immunodeficiency. Little is known about the pathogenetic mechanisms leading to this disease. It is estimated that the incidence of this disease in Spain is 1:163. We report 3 cases diagnosed in Primary Care. Most people with selective IgA deficiency are usually asymptomatic and are diagnosed by chance, but patients with recurrent respiratory infections; gastrointestinal, allergic and autoimmune diseases can be associated with this disease. Although there is no treatment at present, its importance lies in the association with different diseases, such as coeliac disease or idiopathic thrombocytopenic purpura. Another important feature is the risk of anaphylaxis after transfusion, and the possible progression to Common Variable Immunodeficiency. It is important to know the vaccines that we can use due to the risk of disease.

J Clin Immunol. 2013 May;33(4):742-7. doi: 10.1007/s10875-012-9858-x. Epub 2013 Feb 7.
Clinical symptoms in adults with selective IgA deficiency: a case-control study.
Jorgensen GH, Gardulf A, Sigurdsson MI, Sigurdardottir ST, Thorsteinsdottir I, Gudmundsson S, Hammarström L, Ludviksson BR.
Author information
Department of Medicine, University of Iceland, Reykjavík, Iceland.
Abstract
Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency in Caucasians with a prevalence of 1/600 and is generally considered a mild disorder. In this study, the clinical status of 32 adults with SIgAD was investigated and compared to 63 age- and gender matched controls, randomly selected from a population database. The SIgAD individuals reported significantly more often contracting various upper and lower respiratory infections, with 8 (25.0 %) having been diagnosed with ≥1 pneumonia in the preceding two years, compared to one (1.6 %) control (p < 0.001). Furthermore, the SIgAD individuals were found to have increased proneness to infections and increased prevalence of allergic diseases and autoimmunity, with a total of 84.4 % being affected by any of these diseases, compared to 47.6 % of the controls (p < 0.01). This study challenges the common statement of SIgAD being a mild form of immunodeficiency. It also highlights the importance of using matched controls in PID clinical research to better detect clinically important manifestations.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology