The nature of the clinical association that exists between Chlamydia airway infection and subsequent development of asthma in young children remains controversial. In an effort to find discriminative serological or biological markers to differentiate between patients with infection-mediated airway responsiveness and those with other aeroallergen-specific disease, we utilized Western blot techniques to determine and compare the Chlamydia-specific IgE response in the sera of 197 pediatric patients with chronic, severe respiratory disease.
The development of pathogen-specific IgE antibodies is not unique to Chlamydia infection. Numerous reports have demonstrated production of specific IgE antibodies in response to infection by pathogens, including a variety of viruses
[31–33] and Mycoplasma
. Emre et al, previously reported the presence of C. pneumoniae-specific IgE in a cohort of children with chronic respiratory disease, and suggested that production of specific IgE may be an underlying mechanism leading to reactive airway disease in some patients with C. pneumoniae infection
. With our larger cohort, our data is in line with this previous report and is strongly predictive of severe reactive airway disease and poor asthma outcome. To this end, while the role of pathogen-specific IgE antibodies has still not been fully determined, when studied, in most cases, the responses were associated with a poorer prognosis
Approximately 68% of the patients analyzed in the current study harbored chlamydial DNA and 54% produced detectable levels of specific IgE antibodies in response to chlamydial infection. Age matched, healthy controls had no detectable Chlamydia-specific IgE in their serum. There was also a significant association between the presence of Chlamydia-specific IgE antibodies in the serum and cultivable Chlamydia from BAL fluid, suggesting that the presence of viable, actively replicating organisms are more likely to induce pathogen-specific IgE production and could therefore lead to greater allergic type pathology. A limitation of the current study however, is that we were not able to assess individual BAL samples for the presence of Chlamydia-specific IgE because of limited sample volume and therefore have only qualitative data on BAL IgE from pools of 4–6 samples. However, we assessed individual serum samples that showed similar banding patterns as the pooled BAL samples. A second limitation is that our control cohort consisted of only 35 patients and we did not obtain BAL samples from these patients since this is a highly invasive procedure. These patients were not assessed clinically for any respiratory disease since they appeared healthy upon physical examination as part of a wellness checkup by a primary care physician. However, compared to the respiratory disease population, these healthy controls did not have Chlamydia-specific IgE antibodies in their sera, suggesting that this phenomenon is specific to a chronic, severe, respiratory disease.
Chlamydial antigens recognized by specific IgE antibodies were significantly different in the BAL and serum for C. trachomatis versus C. pneumoniae. It is not clear at the present time why these dramatic differences in antigen recognition exist. However, only 6 chlamydial antigens were recognized by either BAL or serum specific IgE in this patient cohort. The only obvious unique quality about these antigens is that they are surface exposed or secreted by the organism. We have assessed these proteins by utilizing reducing and non-reducing SDS-PAGE conditions with the same results. We confirmed the identity of the MOMP protein and the cLPS antigen using recombinant proteins but used the Chlamydia protein data base to match the most likely molecular weight for the other antigens. Further assessment of the patient cohort for the presence and level of total IgE confirmed that only 31% of patients who had Chlamydia-specific IgE had an overall elevated IgE level. This strongly suggests that patients who are assessed as non-atopic may nonetheless produce Chlamydia-specific IgE, which we hypothesize, could lead to airway pathology.
The primary biological function of IgE is to provide immunity against multicellular parasitic pathogens
. However, in developed countries with good sanitation where parasitic diseases are rare, IgE responses are most often directed against innocuous allergens resulting in type I allergic disease. Mouse-model studies have consistently demonstrated that inhalation of innocuous aerosolized protein antigens typically does not induce antigen-specific Th2 responses leading to IgE production
. However, it has been demonstrated that ongoing Th2 responses produced either by antigen challenge or infection during antigen inhalation can prevent the establishment of aerosol-induced IgE tolerance and lead instead to Th2 priming
. It is possible as suggested by Hollams et al, that upon bacterial infection Th2 cytokines may just be suppressing other pro-inflammatory cytokines, such as tumor necrosis factor-α and IL-1, as well as mediators such as prostaglandin, hence, counter-regulating the increased Th1 immune responses. However, since C. pneumoniae surface antigens have to be processed and presented by antigen presenting cells (APC) to activate T-cells and, thus, may not directly induce a Th2 response, this theory might not hold true in this case.