Hasibe ARTAÇ, Hülya ÖZDEMİR, Hatice TÜRK DAĞI, Ayça EMSEN, Rumeysa Olcay BAYRAM

Reference ranges for serum immunoglobulin (IgG, IgA, and IgM) and IgG subclass levels in healthy children

Background/aim: The serum immunoglobulin levels are used routinely in clinical practice because they provide key information onthe humoral immune status. This study aimed to determine the age-related reference values of serum immunoglobulin levels in healthychildren.Materials and methods: A total of 330 healthy children, aged between 0 and 18 years, were included in this study. The serumimmunoglobulin levels were measured using a nephelometric method in a total of 11 groups, each group consisting of 30 individuals,and IgG subclasses in 6 groups of children aged more than 2 years.Results: The serum IgG levels were high during the newborn period, decreased until the sixth month, and again increased to a maximumlevel at the age of 18 years. The level of IgA was found to be extremely low in the newborn period and then increased with age. While thelowest value was in the newborn period for serum IgM level, the highest value was in the 16- to 18-year-old period. The IgG subclassesvaried depending on the age groups.Conclusion: The updated reference intervals of immunoglobulin levels in children may be used for the accurate diagnosis of immunedeficiencies.

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1. Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, Keller M, Kobrynski LJ, Komarow HD, Mazer B et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol 2015; 136: 1186- 1205.
2. Zhang H, Li P, Wu D, Xu D, Hou Y, Wang Q, Li M, Li Y, Zeng X, Zhang F et al. Serum IgG subclasses in autoimmune diseases. Medicine (Baltimore) 2015; 94: e387.
3. Fallatah HI, Akbar HO. Elevated serum immunoglobulin G levels in patients with chronic liver disease in comparison to patients with autoimmune hepatitis. Libyan J Med 2010; 5: 4857.
4. Bousfiha A, Jeddane L, Picard C, Ailal F, Bobby Gaspar H, AlHerz W, Chatila T, Crow YJ, Cunningham-Rundles C, Etzioni A et al. The 2017 IUIS Phenotypic classification for primary immunodeficiencies. J Clin Immunol 2018; 38: 129-143.
5. Grimbacher B. ESID Registry Working Party. The European Society for Immunodeficiencies (ESID) registry 2014. Clin Exp Immunol 2014; 178: 18-20.
6. Kilic SS, Ozel M, Hafizoglu D, Karaca NE, Aksu G, Kutukculer N. The prevalences [correction] and patient characteristics of primary immunodeficiency diseases in Turkey--two centers study. J Clin Immunol 2013; 33: 74-83.
7. Yorulmaz A, Artaç H, Kara R, Reisli İ. Retrospective evaluation of 1054 patients with primary immunodeficiency. Asthma Allergy Immunology 2008; 6: 127-134.
8. Tezcan İ, Berkel Aİ, Ersoy F, Sanal Ö. Sağlıklı Türk çocukları ve erişkinlerde türbimetrik yöntemle bakılan serum immünglobülin düzeyleri. Çocuk Sağlığı ve Hastalıkları Dergisi 1996; 39: 649-656 (article in Turkish).
9. Aksu G, Genel F, Koturoğlu G, Kurugöl Z, Kütükçüler N. Serum immunoglobulin (IgG, IgM, IgA) and IgG subclass concentrations in healthy children: a study using nephelometric technique. Turk J Pediatr 2006; 48: 19-24.
10. Baskın Y, Yiğitbaşı T, Afacan G. Reference intervals for serum immunoglobulin (IGA, IGG, IGM) and IGG subclasses in healthy subjects. Turk J Biochem 2010; 35: 325-332.
11. Vries E, European Society for Immunodeficiencies (ESID) members. Patient-centred screening for primary immunodeficiency, a multi-stage diagnostic protocol designed for non-immunologists: 2011 update. Clin Exp Immunol 2012; 167: 108-119.
12. Belldegrin A, Shoenfeld Y, Pick Al, Vana D. Age related distribution of serum immunoglobulin concentration in 1003 healthy children and adults. Biomedicine 1980; 33: 8-12.
13. Stiehm ER, Fudenberg HH. Serum levels of immune globulins in health and disease: a survey. Pediatrics 1966; 37: 715-727.
14. Pressac M, Allouche F, Circaud R, Aymard P. Evaluation of human IgG subclass assays on Beckman array. Ann Clin Biochem 1995; 32: 281-288.
15. Solberg HE. The IFCC recommendation on estimation of reference intervals. The RefVal program. Clin Chem Lab Med 2004; 42: 710-714.
16. Soldin SJ, Bailey J, Beatey J, Bjorn S, Hicks JM. Pediatric reference ranges for immunoglobulins G, A and M on the Behring nephelometer. Clin Chem 1996; 42: S308.
17. Parker AR, Skold M, Ramsden DB, Ocejo-Vinyals JG, López-Hoyos M, Harding S. The clinical utility of measuring IgG subclass immunoglobulins during immunological investigation for suspected primary antibody deficiencies. Lab Med 2017; 48: 314-325.
18. Schauer U, Stemberg F, Rieger CH, Borte M, Schubert S, Riedel F, Herz U, Renz H, Wick M, Carr-Smith HD et al. IgG. IgG subclass concentrations in certified reference material 470 and reference values for children and adults determined with the binding site reagents. Clin Chem 2003; 49: 1924-1929.
19. Sitcharungsi R, Ananworanich J, Vilaiyuk S, Apornpong T, Bunupuradah T, Pornvoranunt A, Nouanthong P, Phasomsap C, Khupulsup K, Pancharoen C et al. HIV-NAT 108 Study Group. Nephelometry determined serum immunoglobulin isotypes in healthy Thai children aged 2-15 years. Microbiol Immunol 2012; 56: 117-122.