Ann Allergy Asthma Immunol 114 (2015) 433e434
Contents lists available at ScienceDirect
Correspondence
Role of IgA and IgM in severity of atopic dermatitis We read with great interest the article by Celiksoy et al1 recently published in the Annals of Allergy, Asthma & Immunology. The authors described a cross-sectional study performed in children with atopic dermatitis (AD). They did not find an association between the severity of disease and hypogammaglobulinemia or low levels of IgG, IgA, and IgM in patients with AD. Although a total of 160 patients with AD were included in the study, only 28 (17.5%) had hypogammaglobulinemia and most had IgG deficiency, and they did not report the number of patients with IgA or IgM deficiency. Although Celiksoy et al did not find an association between the severity of AD and median IgA and IgM levels, it seems better to evaluate the correlation between SCORAD (Scoring Atopic Dermatitis) and immunoglobulin levels. Secretory IgA, which is present in mucosal secretions, has a broad protective function, and in the case of selective IgA deficiency, the mucosa appears to be less protected and more vulnerable to enteric toxins and pathogenic microorganisms.2 It has been postulated that low production of IgA is believed to increase atopic sensitization because of a decrease in the protective effect of secretory IgA on the mucosal surface, which in turn facilitates the passage of allergens through the respiratory and gastrointestinal tracts.3 Besides, high levels of secretory IgA seemed to protect sensitized children from developing allergic symptoms during the first 2 years of life.4 Ludviksson et al5 reported not only the frequency but also the severity of allergic manifestations to be increased in children with low to normal serum IgA levels. In addition, adult patients with selective IgM deficiency can present with allergic rhinitis, asthma, and eczema.6 In our recent study7 of 250 children with AD, we also evaluated the association between severity of AD and hypogammaglobulinemia. Among 250 patients with AD, 125 patients had at least one low serum immunoglobulin level (group 1), and 125 had normal serum immunoglobulin levels (group 2). There was no difference between group 1 and 2 according to age, sex, SCORAD index, severity of AD (mild, moderate, or severe), total eosinophil count, percentage of eosinophil, and familial allergic disorders. However, there was a negative correlation between serum IgA levels and SCORAD index within the patients who had low serum IgA levels Disclosures: Authors have nothing to disclose.
(r ¼ 0.509, P ¼ .04). The correlation between IgA and SCORAD was stronger when the patients had both low serum IgA and IgM levels, and decreased levels of serum IgA and IgM were associated with increased severity of AD.7 In conclusion, especially IgA but also IgM deficiency may be related to severity of AD, but the present data, including our results, are not enough to confirm whether there is a cause-and-effect relationship between hypogammaglobulinemia and AD. Therefore, prospective studies are needed to better understand the association between hypogammaglobulinemia and AD. lu, MD* Mustafa Erkoçog Can Naci Kocabas¸, MDy *Department of Pediatric Allergy and Immunology Abant Izzet Baysal University Faculty of Medicine Bolu, Turkey y Department of Pediatric Allergy and Immunology la Sıtkı Koçman University Faculty of Medicine Mug la, Turkey Mug [email protected]
References [1] Celiksoy MH, Topal E, Sancak R, Catal F, Sogut A. Relationship between hypogammaglobulinemia and severity of atopic dermatitis. Ann Allergy Asthma Immunol. 2014;113:467e469. [2] Mantis NJ, Rol N, Corthesy B. Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol. 2011;4:603e611. [3] Woof JM, Kerr MA. The function of immunoglobulin A in immunity. J Pathol. 2006;208:270e282. [4] Bottcher MF, Haggstrom P, Bjorksten B, Jenmalm MC. Total and allergenspecific immunoglobulin A levels in saliva in relation to the development of allergy in infants up to 2 years of age. Clin Exp Allergy. 2002;32: 1293e1298. [5] Ludviksson BR, Eiriksson TH, Ardal B, Sigfusson A, Valdimarsson H. Correlation between serum immunoglobulin A concentrations and allergic manifestations in infants. J Pediatr. 1992;121:23e27. [6] Goldstein MF, Goldstein AL, Dunsky EH, Dvorin DJ, Belecanech GA, Shamir K. Selective IgM immunodeficiency: retrospective analysis of 36 adult patients with review of the literature. Ann Allergy Asthma Immunol. 2006;97: 717e730. lu M, et al. The relationship between low serum [7] Toyran M, Akan A, Erkoçog immunoglobulin levels and severity of atopic dermatitis in young children. Pediatr Allergy Immunol Pulmonol. 2013;26:152e156.
Author response Nearly half of patients with selective IgA deficiency also have atopic dermatitis.1 Atopic dermatitis is also common in patients with selective IgM deficiency.2 It has been suggested that atopic dermatitis is more severe in hypogammaglobulinemic patients. For example, Disclosures: Authors have nothing to disclose.
Wang et al3 reported on severe atopic dermatitis in 8 patients with transient hypogammaglobulinemia. However, 6 patients in that study later developed asthma. It is difficult to determine whether the underlying cause of severe atopic dermatitis in these patients was atopy or hypogammaglobulinemia. To conclude whether atopic dermatitis is severe, patients with hypogammaglobulinemia
http://dx.doi.org/10.1016/j.anai.2014.12.009 1081-1206/Ó 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
434
Correspondence / Ann Allergy Asthma Immunol 114 (2015) 433e434
should be compared with those with atopic dermatitis who have normal immunoglobulin levels using the SCORAD (Scoring Atopic Dermatitis) index.4 In a recent study, we performed this comparison and found that IgG levels were low in patients with atopic dermatitis but that IgM and IgA levels were similar to those of healthy children. In addition, no correlation was observed between serum levels of IgG, IgA, and IgM and the severity of atopic dermatitis.5 Recently, Toyran et al6 also reported no significant association between IgM and/or IgA deficiency and atopic eczema severity. They reported no correlation between SCORAD index and serum IgM and/or IgA level in patients with atopic eczema. However, they reported a weak negative correlation (r ¼ 0.05, P ¼ .04) between serum IgA levels and atopic eczema severity. Because IgA or IgM deficiencies are defined clinically as levels at least 2 SDs below the age-defined norms,7 the correlation analysis is not appropriate. For these reasons, we believe that an association between IgA and IgM deficiency and severity of atopic eczema was not demonstrated in this report. Mehmet Halil Celiksoy, MD* Erdem Topal, MDy Recep Sancak, MD* *Department of Pediatrics Division of Pediatric Allergy and Immunology
Ondokuz Mayıs University Samsun, Turkey y Department of Pediatrics Division of Pediatric Allergy and Immunology Inonu University Turgut Ozal Medical Center Malatya, Turkey [email protected] References [1] Aghamohammadi A, Cheraghi T, Gharagozlou M, et al. IgA deficiency: correlation between clinical and ımmunological phenotypes. J Clin Immunol. 2009; 29:130e136. [2] Al-Herz W, McGeady SJ, Gripp KW. 22q11.2 deletion syndrome and selective IgM deficiency: an association of a common chromosomal abnormality with a rare immunodeficiency. Am J Med Genet. 2004;127:99e100. [3] Wang AS, Liang MG, Schneider LC, et al. Severe atopic dermatitis and transient hypogammaglobulinemia in children. Pediatr Dermatol. 2012;29:73e78. [4] Severity scoring of atopic dermatitis: the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1993;186:23e31. [5] Celiksoy MH, Topal E, Sancak R, et al. Relationship between hypogammaglobulinemia and severity of atopic dermatitis. Ann Allergy Asthma Immunol. 2014;113:467e469. lu M, et al. The relationship between low serum [6] Toyran M, Akan A, Erkoçog ımmunoglobulin levels and severity of atopic dermatitis in young children. Pediatr Allergy Immunol Pulmonol. 2013;26:152e156. lu G, et al. Serum immunoglobulin (IgG, IgM, IgA) and [7] Aksu G, Genel F, Koturog IgG subclass concentrations in healthy children: a study using nephelometric technique. Turk J Pediatr. 2006;48:19e24.
Contents lists available at ScienceDirect
Correspondence
Role of IgA and IgM in severity of atopic dermatitis We read with great interest the article by Celiksoy et al1 recently published in the Annals of Allergy, Asthma & Immunology. The authors described a cross-sectional study performed in children with atopic dermatitis (AD). They did not find an association between the severity of disease and hypogammaglobulinemia or low levels of IgG, IgA, and IgM in patients with AD. Although a total of 160 patients with AD were included in the study, only 28 (17.5%) had hypogammaglobulinemia and most had IgG deficiency, and they did not report the number of patients with IgA or IgM deficiency. Although Celiksoy et al did not find an association between the severity of AD and median IgA and IgM levels, it seems better to evaluate the correlation between SCORAD (Scoring Atopic Dermatitis) and immunoglobulin levels. Secretory IgA, which is present in mucosal secretions, has a broad protective function, and in the case of selective IgA deficiency, the mucosa appears to be less protected and more vulnerable to enteric toxins and pathogenic microorganisms.2 It has been postulated that low production of IgA is believed to increase atopic sensitization because of a decrease in the protective effect of secretory IgA on the mucosal surface, which in turn facilitates the passage of allergens through the respiratory and gastrointestinal tracts.3 Besides, high levels of secretory IgA seemed to protect sensitized children from developing allergic symptoms during the first 2 years of life.4 Ludviksson et al5 reported not only the frequency but also the severity of allergic manifestations to be increased in children with low to normal serum IgA levels. In addition, adult patients with selective IgM deficiency can present with allergic rhinitis, asthma, and eczema.6 In our recent study7 of 250 children with AD, we also evaluated the association between severity of AD and hypogammaglobulinemia. Among 250 patients with AD, 125 patients had at least one low serum immunoglobulin level (group 1), and 125 had normal serum immunoglobulin levels (group 2). There was no difference between group 1 and 2 according to age, sex, SCORAD index, severity of AD (mild, moderate, or severe), total eosinophil count, percentage of eosinophil, and familial allergic disorders. However, there was a negative correlation between serum IgA levels and SCORAD index within the patients who had low serum IgA levels Disclosures: Authors have nothing to disclose.
(r ¼ 0.509, P ¼ .04). The correlation between IgA and SCORAD was stronger when the patients had both low serum IgA and IgM levels, and decreased levels of serum IgA and IgM were associated with increased severity of AD.7 In conclusion, especially IgA but also IgM deficiency may be related to severity of AD, but the present data, including our results, are not enough to confirm whether there is a cause-and-effect relationship between hypogammaglobulinemia and AD. Therefore, prospective studies are needed to better understand the association between hypogammaglobulinemia and AD. lu, MD* Mustafa Erkoçog Can Naci Kocabas¸, MDy *Department of Pediatric Allergy and Immunology Abant Izzet Baysal University Faculty of Medicine Bolu, Turkey y Department of Pediatric Allergy and Immunology la Sıtkı Koçman University Faculty of Medicine Mug la, Turkey Mug [email protected]
References [1] Celiksoy MH, Topal E, Sancak R, Catal F, Sogut A. Relationship between hypogammaglobulinemia and severity of atopic dermatitis. Ann Allergy Asthma Immunol. 2014;113:467e469. [2] Mantis NJ, Rol N, Corthesy B. Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol. 2011;4:603e611. [3] Woof JM, Kerr MA. The function of immunoglobulin A in immunity. J Pathol. 2006;208:270e282. [4] Bottcher MF, Haggstrom P, Bjorksten B, Jenmalm MC. Total and allergenspecific immunoglobulin A levels in saliva in relation to the development of allergy in infants up to 2 years of age. Clin Exp Allergy. 2002;32: 1293e1298. [5] Ludviksson BR, Eiriksson TH, Ardal B, Sigfusson A, Valdimarsson H. Correlation between serum immunoglobulin A concentrations and allergic manifestations in infants. J Pediatr. 1992;121:23e27. [6] Goldstein MF, Goldstein AL, Dunsky EH, Dvorin DJ, Belecanech GA, Shamir K. Selective IgM immunodeficiency: retrospective analysis of 36 adult patients with review of the literature. Ann Allergy Asthma Immunol. 2006;97: 717e730. lu M, et al. The relationship between low serum [7] Toyran M, Akan A, Erkoçog immunoglobulin levels and severity of atopic dermatitis in young children. Pediatr Allergy Immunol Pulmonol. 2013;26:152e156.
Author response Nearly half of patients with selective IgA deficiency also have atopic dermatitis.1 Atopic dermatitis is also common in patients with selective IgM deficiency.2 It has been suggested that atopic dermatitis is more severe in hypogammaglobulinemic patients. For example, Disclosures: Authors have nothing to disclose.
Wang et al3 reported on severe atopic dermatitis in 8 patients with transient hypogammaglobulinemia. However, 6 patients in that study later developed asthma. It is difficult to determine whether the underlying cause of severe atopic dermatitis in these patients was atopy or hypogammaglobulinemia. To conclude whether atopic dermatitis is severe, patients with hypogammaglobulinemia
http://dx.doi.org/10.1016/j.anai.2014.12.009 1081-1206/Ó 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
434
Correspondence / Ann Allergy Asthma Immunol 114 (2015) 433e434
should be compared with those with atopic dermatitis who have normal immunoglobulin levels using the SCORAD (Scoring Atopic Dermatitis) index.4 In a recent study, we performed this comparison and found that IgG levels were low in patients with atopic dermatitis but that IgM and IgA levels were similar to those of healthy children. In addition, no correlation was observed between serum levels of IgG, IgA, and IgM and the severity of atopic dermatitis.5 Recently, Toyran et al6 also reported no significant association between IgM and/or IgA deficiency and atopic eczema severity. They reported no correlation between SCORAD index and serum IgM and/or IgA level in patients with atopic eczema. However, they reported a weak negative correlation (r ¼ 0.05, P ¼ .04) between serum IgA levels and atopic eczema severity. Because IgA or IgM deficiencies are defined clinically as levels at least 2 SDs below the age-defined norms,7 the correlation analysis is not appropriate. For these reasons, we believe that an association between IgA and IgM deficiency and severity of atopic eczema was not demonstrated in this report. Mehmet Halil Celiksoy, MD* Erdem Topal, MDy Recep Sancak, MD* *Department of Pediatrics Division of Pediatric Allergy and Immunology
Ondokuz Mayıs University Samsun, Turkey y Department of Pediatrics Division of Pediatric Allergy and Immunology Inonu University Turgut Ozal Medical Center Malatya, Turkey [email protected] References [1] Aghamohammadi A, Cheraghi T, Gharagozlou M, et al. IgA deficiency: correlation between clinical and ımmunological phenotypes. J Clin Immunol. 2009; 29:130e136. [2] Al-Herz W, McGeady SJ, Gripp KW. 22q11.2 deletion syndrome and selective IgM deficiency: an association of a common chromosomal abnormality with a rare immunodeficiency. Am J Med Genet. 2004;127:99e100. [3] Wang AS, Liang MG, Schneider LC, et al. Severe atopic dermatitis and transient hypogammaglobulinemia in children. Pediatr Dermatol. 2012;29:73e78. [4] Severity scoring of atopic dermatitis: the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1993;186:23e31. [5] Celiksoy MH, Topal E, Sancak R, et al. Relationship between hypogammaglobulinemia and severity of atopic dermatitis. Ann Allergy Asthma Immunol. 2014;113:467e469. lu M, et al. The relationship between low serum [6] Toyran M, Akan A, Erkoçog ımmunoglobulin levels and severity of atopic dermatitis in young children. Pediatr Allergy Immunol Pulmonol. 2013;26:152e156. lu G, et al. Serum immunoglobulin (IgG, IgM, IgA) and [7] Aksu G, Genel F, Koturog IgG subclass concentrations in healthy children: a study using nephelometric technique. Turk J Pediatr. 2006;48:19e24.
