Long-term effects of pediatric adenotonsillectomy on serum immunoglobulin levels: results of a randomized controlled trial Emma H. van den Akker, MD, PhD*; Elisabeth A. M. Sanders, MD, PhD†; Birgit K. van Staaij, MD, PhD‡; Ger T. Rijkers, PhD†; Maroeska M. Rovers, PhD*†‡; Arno W. Hoes, MD, PhD‡; and Anne G. M. Schilder, MD, PhD* Background: It remains controversial whether pediatric adenotonsillectomy ultimately results in decreased serum immuno- globulin levels and if so whether such a decrease is associated with increased susceptibility to upper respiratory tract infections (URIs). Objective: To evaluate changes in serum immunoglobulin levels in relation to occurrence of URIs in children participating in a randomized controlled trial on the effectiveness of adenotonsillectomy. Methods: A total of 300 children aged 2 to 8 years, with symptoms of recurrent throat infections or tonsillar hypertrophy, were randomly assigned to either adenotonsillectomy or watchful waiting (WW). Serum samples were collected at baseline and at 1-year follow-up. Occurrence of throat infections and other URIs during first-year follow-up was recorded in a diary by the child’s parents. Results: Paired serum samples were available for 123 children (63 in the adenotonsillectomy group and 60 in the WW group). IgG1 and IgG2 levels decreased but remained within the reference range for age in both study arms. IgM and IgA levels decreased as well but remained elevated. The IgA level in the adenotonsillectomy group decreased in significantly greater degree compared with the WW group, but this difference disappeared in cases where children experienced frequent URIs. In general, no relation between immunoglobulin levels and the number of throat infections or URIs at 1-year follow-up was found. Conclusions: Immunoglobulin levels of children undergoing adenotonsillectomy decreased from elevated to slightly elevated or reference values for age during 1-year follow-up irrespective of treatment (adenotonsillectomy or WW). IgA showed a greater decrease in the adenotonsillectomy group but rose to levels comparable with the WW group in cases of frequent URIs. This finding indicates that the remaining mucosa-associated lymphoid tissue can compensate for the loss of tonsil and adenoid tissue. Ann Allergy Asthma Immunol. 2006;97:251–256. INTRODUCTION The tonsils and adenoid are part of the Waldeyer ring and are important elements in the defense against airborne and ali- mentary organisms. They play an important immune-induc- tive role as components of mucosa-associated lymphoid tis- sue (MALT). 1 Tonsils contain B cells that, in response to antigens, differentiate to plasma cells and generate polymeric IgA, resulting in systemic immunity and mucosal immunity. 2 Adenotonsillectomy is one of the most frequently per- formed surgical procedures in children. Nevertheless, the ultimate effects of the procedure are still uncertain. 3–5 It has been hypothesized that the removal of the tonsils and adenoid in young children may cause a delay in development and a limited and less differentiated immune response. 1,6 This, in turn, might increase children’s susceptibility to respiratory infections rather than lead to the intended decrease of infec- tions by surgical removal of the infection focus. With respect to humoral immunity, several studies have reported a de- crease in serum immunoglobulin levels after adenotonsillec- tomy. 7–15 The relevance of these findings is however ques- tionable, since most of these studies did not include a randomly allocated nonsurgical control group and no associ- ated occurrence of respiratory infections could be found. 7,9,11,12 The present study aims to answer the following questions: (1) Do immunoglobulin levels change after adenotonsillec- tomy in children, and, if so, are these changes different from those in children managed nonsurgically for the same tonsil- lar complaints? (2) Are changes in serum immunoglobulin levels related to the occurrence of throat infections and other upper respiratory tract infections (URIs)? To answer these questions, we evaluated changes in immunoglobulin levels and the occurrence of URIs in a large population of children participating in a multicenter randomized controlled trial (RCT) on the effectiveness of adenotonsillectomy. * Department of Otorhinolaryngology, Wilhelmina Children’s Hospital/Uni- versity Medical Center Utrecht, The Netherlands. † Department of Pediatric Immunology, Wilhelmina Children’s Hospital/ University Medical Center Utrecht, The Netherlands. ‡ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands. This study was financially supported by the Dutch Health Care Insurance Board (OG-99-060). Received for publication August 9, 2005. Accepted for publication in revised form October 26, 2005. VOLUME 97, AUGUST, 2006 251