- Email: [email protected]
Are free light chain immunoglobulins related to nasal local allergic rhinitis?
CORRESPONDENCE 677
J ALLERGY CLIN IMMUNOL VOLUME 126, NUMBER 3
6. Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 2000;343:1064-9. 7. Rachelefsky G. Inhaled corticosteroids and asthma control in children: assessing impairment and risk. Pediatrics 2009;123:353-6.
further studies are needed to investigate the possible function of FLCs in local hypersensitivity to aeroallergens. Carmen Rondo´n, MD, PhDa Gabriela Canto, MD, PhDb Javier Ferna´ndez, MD, PhDc Miguel Blanca, MD, PhDa
Available online June 25, 2010. doi:10.1016/j.jaci.2010.04.035
Are free light chain immunoglobulins related to nasal local allergic rhinitis? To the Editor: The study by Powe et al1 is the first to demonstrate the localization of free light chains (FLCs) in patients with allergic and nonallergic rhinitis in both tissue and nasal secretions by using immunohistochemical and ELISA techniques and opens up new avenues for the study of the nasal local hypersensitivity response. Three large groups of subjects are compared: patients with persistent allergic rhinitis (n 5 90) who had a positive skin prick test response to house dust mite and serum specific IgE, patients with nonallergic rhinitis with eosinophilia syndrome (NARES; n 5 90), and nonatopic healthy control subjects (n 5 90). A separate group of patients with idiopathic rhinitis of unknown cause (n 5 10) who were retrospectively identified from tissue archives was also included. The authors provide evidence of ‘‘significantly increased FLC-expressing cells in the mucosa of patients with persistent allergic and idiopathic rhinitis, localized in mast cells and plasma cells,’’ and increased FLC serum levels in subjects with NARES. They propose that ‘‘FLC may provide an additional non-IgE immune pathway to augment or replace IgE-mediated hypersensitivity in chronic mucosal inflammatory disease.’’ Accepting that the mechanisms involved require further study, we nevertheless believe that a few comments are warranted, given the relevance in this context of both idiopathic rhinitis and NARES. We wonder whether some of the patients with allergic and nonallergic rhinitis included in this study could have had local allergic rhinitis (LAR)? A number of studies have shown the existence of a new form of LAR,2 or entopy,3 with local production of specific IgE and a positive nasal allergen provocation test response in patients previously given diagnoses of idiopathic rhinitis and NARES.2,4 These patients might present with normal or low levels of total IgE in nasal secretions,4 but we do not believe this is sufficient to discriminate the existence of nasal IgEmediated hypersensitivity. In the report by Powe et al,1 no study was made of the response on nasal allergen provocation tests or the determination of specific IgE to aeroallergens in nasal secretions of the allergic and nonallergic patients studied. Might there have been a local production of specific IgE, as we have seen in our studies? Another question concerns whether FLC levels are associated with nasal mucosal inflammation or a local hypersensitivity response to aeroallergens. It would be interesting to conduct further comparative studies between patients with LAR or entopy and patients with idiopathic rhinitis or NARES without a local hypersensitivity response. The authors suggest that ‘‘mast cell activation and degranulation could be induced by a FLC-mediated mechanism.’’ We recently detected that patients with LARs who were sensitized to grass pollen have an important and persistent mast cell activation specifically induced by nasal exposure to the aeroallergen.5 Thus
From athe Allergy Service, Carlos Haya Hospital, Malaga, Spain; bthe Allergy Service, Infanta Leonor Hospital, Madrid, Spain; and cthe Allergy Service, Hospital Universitario de Elche, Alicante, Spain. E-mail: [email protected]. Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. REFERENCES 1. Powe DG, Groot Kormelink T, Sisson M, Blokhuis BJ, Kramer MF, Jones NS, et al. Evidence for the involvement of free light chain immunoglobulins in allergic and nonallergic rhinitis. J Allergy Clin Immunol 2010;125:139-45, e1-3. 2. Rondon C, Don˜a I, Torres MJ, Campo P, Blanca M. Evolution of patients with nonallergic rhinitis supports conversion to allergic rhinitis. J Allergy Clin Immunol 2009;123:1098-102. 3. Powe DG, Jagger C, KleinJan A, Carney AS, Jenkins D, Jones NS. ‘‘Entopy’’: localized mucosal allergic disease in the absence of systemic responses for atopy. Clin Exp Allergy 2003;33:1374-9. 4. Rondon C, Romero JJ, Lopez S, Antunez C, Martin-Casanez E, Torres MJ, et al. Local IgE production and positive nasal provocation test in patients with persistent nonallergic rhinitis. J Allergy Clin Immunol 2007;119:899-905. 5. Rondon C, Fernandez J, Lopez S, Campo P, Dona I, Torres MJ, et al. Nasal inflammatory mediators and specific-IgE production after nasal challenge with grass in local allergic rhinitis. J Allergy Clin Immunol 2009;124:1005-11. Available online August 9, 2010. doi:10.1016/j.jaci.2010.06.044
Reply To the Editor: We acknowledge the suggestion made by Rondo´n et al1 that some of the patients with nonallergic rhinitis investigated in our study might have ‘‘entopy’’2 (local mucosal allergy), and for clarity, this will be defined. Entopy is the presence of local mucosal allergy in the absence of systemic markers of atopy, and although it is commonly interpreted that this is IgE mediated, our original report does not implicitly specify this. Accordingly, although patients with allergic rhinitis undoubtedly have a local nasal mucosal IgE production component that might or might not contribute to the expression of atopy, they do not satisfy the definition of entopy because they are atopic. The emphasis of our present study is to provide a possible mechanism to explain nasal hypersensitivity in nonatopic subjects showing signs of local mast cell activation, as demonstrated by increased tryptase concentrations in nasal lavage specimens. We have shown that in these patients increased local concentrations of free light chains (FLCs) are present, and based on our previous work, we suggest that these FLCs might be involved in antigen-specific mast cell activation.3 Indeed, Rondo´n et al4 have shown that nonatopic patients might present with normal or low levels of total IgE but, importantly, have increased specific IgE levels in nasal secretions, and as the authors state, measurement of total IgE might not be sufficient to discriminate the existence of nasal IgE-mediated hypersensitivity. In our study we have analyzed nasal secretions from patients with nonatopic rhinitis with eosinophilic syndrome for the presence of specific IgE but no specific IgE to seasonal or perennial allergens was found (as stated in Table I of the article by Powe et al5). However, when we analyze concentrations of nasal total IgE on an individual basis (Fig 1), it is evident that a small percentage of the patients with nonatopic rhinitis with eosinophilic syndrome have
J ALLERGY CLIN IMMUNOL VOLUME 126, NUMBER 3
6. Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 2000;343:1064-9. 7. Rachelefsky G. Inhaled corticosteroids and asthma control in children: assessing impairment and risk. Pediatrics 2009;123:353-6.
further studies are needed to investigate the possible function of FLCs in local hypersensitivity to aeroallergens. Carmen Rondo´n, MD, PhDa Gabriela Canto, MD, PhDb Javier Ferna´ndez, MD, PhDc Miguel Blanca, MD, PhDa
Available online June 25, 2010. doi:10.1016/j.jaci.2010.04.035
Are free light chain immunoglobulins related to nasal local allergic rhinitis? To the Editor: The study by Powe et al1 is the first to demonstrate the localization of free light chains (FLCs) in patients with allergic and nonallergic rhinitis in both tissue and nasal secretions by using immunohistochemical and ELISA techniques and opens up new avenues for the study of the nasal local hypersensitivity response. Three large groups of subjects are compared: patients with persistent allergic rhinitis (n 5 90) who had a positive skin prick test response to house dust mite and serum specific IgE, patients with nonallergic rhinitis with eosinophilia syndrome (NARES; n 5 90), and nonatopic healthy control subjects (n 5 90). A separate group of patients with idiopathic rhinitis of unknown cause (n 5 10) who were retrospectively identified from tissue archives was also included. The authors provide evidence of ‘‘significantly increased FLC-expressing cells in the mucosa of patients with persistent allergic and idiopathic rhinitis, localized in mast cells and plasma cells,’’ and increased FLC serum levels in subjects with NARES. They propose that ‘‘FLC may provide an additional non-IgE immune pathway to augment or replace IgE-mediated hypersensitivity in chronic mucosal inflammatory disease.’’ Accepting that the mechanisms involved require further study, we nevertheless believe that a few comments are warranted, given the relevance in this context of both idiopathic rhinitis and NARES. We wonder whether some of the patients with allergic and nonallergic rhinitis included in this study could have had local allergic rhinitis (LAR)? A number of studies have shown the existence of a new form of LAR,2 or entopy,3 with local production of specific IgE and a positive nasal allergen provocation test response in patients previously given diagnoses of idiopathic rhinitis and NARES.2,4 These patients might present with normal or low levels of total IgE in nasal secretions,4 but we do not believe this is sufficient to discriminate the existence of nasal IgEmediated hypersensitivity. In the report by Powe et al,1 no study was made of the response on nasal allergen provocation tests or the determination of specific IgE to aeroallergens in nasal secretions of the allergic and nonallergic patients studied. Might there have been a local production of specific IgE, as we have seen in our studies? Another question concerns whether FLC levels are associated with nasal mucosal inflammation or a local hypersensitivity response to aeroallergens. It would be interesting to conduct further comparative studies between patients with LAR or entopy and patients with idiopathic rhinitis or NARES without a local hypersensitivity response. The authors suggest that ‘‘mast cell activation and degranulation could be induced by a FLC-mediated mechanism.’’ We recently detected that patients with LARs who were sensitized to grass pollen have an important and persistent mast cell activation specifically induced by nasal exposure to the aeroallergen.5 Thus
From athe Allergy Service, Carlos Haya Hospital, Malaga, Spain; bthe Allergy Service, Infanta Leonor Hospital, Madrid, Spain; and cthe Allergy Service, Hospital Universitario de Elche, Alicante, Spain. E-mail: [email protected]. Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. REFERENCES 1. Powe DG, Groot Kormelink T, Sisson M, Blokhuis BJ, Kramer MF, Jones NS, et al. Evidence for the involvement of free light chain immunoglobulins in allergic and nonallergic rhinitis. J Allergy Clin Immunol 2010;125:139-45, e1-3. 2. Rondon C, Don˜a I, Torres MJ, Campo P, Blanca M. Evolution of patients with nonallergic rhinitis supports conversion to allergic rhinitis. J Allergy Clin Immunol 2009;123:1098-102. 3. Powe DG, Jagger C, KleinJan A, Carney AS, Jenkins D, Jones NS. ‘‘Entopy’’: localized mucosal allergic disease in the absence of systemic responses for atopy. Clin Exp Allergy 2003;33:1374-9. 4. Rondon C, Romero JJ, Lopez S, Antunez C, Martin-Casanez E, Torres MJ, et al. Local IgE production and positive nasal provocation test in patients with persistent nonallergic rhinitis. J Allergy Clin Immunol 2007;119:899-905. 5. Rondon C, Fernandez J, Lopez S, Campo P, Dona I, Torres MJ, et al. Nasal inflammatory mediators and specific-IgE production after nasal challenge with grass in local allergic rhinitis. J Allergy Clin Immunol 2009;124:1005-11. Available online August 9, 2010. doi:10.1016/j.jaci.2010.06.044
Reply To the Editor: We acknowledge the suggestion made by Rondo´n et al1 that some of the patients with nonallergic rhinitis investigated in our study might have ‘‘entopy’’2 (local mucosal allergy), and for clarity, this will be defined. Entopy is the presence of local mucosal allergy in the absence of systemic markers of atopy, and although it is commonly interpreted that this is IgE mediated, our original report does not implicitly specify this. Accordingly, although patients with allergic rhinitis undoubtedly have a local nasal mucosal IgE production component that might or might not contribute to the expression of atopy, they do not satisfy the definition of entopy because they are atopic. The emphasis of our present study is to provide a possible mechanism to explain nasal hypersensitivity in nonatopic subjects showing signs of local mast cell activation, as demonstrated by increased tryptase concentrations in nasal lavage specimens. We have shown that in these patients increased local concentrations of free light chains (FLCs) are present, and based on our previous work, we suggest that these FLCs might be involved in antigen-specific mast cell activation.3 Indeed, Rondo´n et al4 have shown that nonatopic patients might present with normal or low levels of total IgE but, importantly, have increased specific IgE levels in nasal secretions, and as the authors state, measurement of total IgE might not be sufficient to discriminate the existence of nasal IgE-mediated hypersensitivity. In our study we have analyzed nasal secretions from patients with nonatopic rhinitis with eosinophilic syndrome for the presence of specific IgE but no specific IgE to seasonal or perennial allergens was found (as stated in Table I of the article by Powe et al5). However, when we analyze concentrations of nasal total IgE on an individual basis (Fig 1), it is evident that a small percentage of the patients with nonatopic rhinitis with eosinophilic syndrome have