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Management of children with primary and secondary hypogammaglobulinemia (literature review)

Modern pediatrics. Ukraine. 2019.5(101):123-132; doi 10.15574/SP.2019.101.123
T.A. Marunchyn, A.P. Volokha
Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine

For citation: Marunchyn TA, Volokha AP. (2019). Management of children with primary and secondary hypogammaglobulinemia (literature review). Modern Pediatrics.Ukraine. 5(101): 123-132. doi 10.15574/SP.2019.101.123
Article received: Apr 23, 2019. Accepted for publication: Sep 12, 2019.

Primary hypogammaglobulinemiae are the most frequent forms of primary immunodeficiency, count more than 50% of congenital pathology of the immune system. Secondary hypogammaglobulinemia occur as a reason of hematological malignancies, intake of immunosuppressive or anticonvulsant drugs, exudative enteropathy, nephrotic syndrome. The prevalence of secondary hypogammaglobulinemia is 30 times higher according to primary hypogammaglobulinemia. The overall therapeutic goals of immunoglobulin replacement therapy are to reduce morbidity and mortality and to provide a patient with the best quality of life. There is a need for clinical research to evaluate the efficacy of immunoglobulin replacement therapy in children with primary hypogammaglobulinemia and to provide clear recommendations for the prevention of complications of recurrent infections, in particular bronchiectasis. The clinical and immunological indicators of hypogammaglobulinemia that develop in patients with nephrotic syndrome and intestinal lymphangioectasia have not been sufficiently studied. Clear guidelines and protocols for the management of children with secondary hypogammaglobulinemia are lacking in Ukraine.
No conflict of interest was declared by the authors.
Key words: primary and secondary hypohammaglobulinemia, antibody deficiency, infectious syndrome, bronchiectasis, children.


1. Bondarenko AV. (2015). Diagnostics of primary immunodeficiencies. Family medicine. 4(60): 154–160

2. Bondarenko AV. (2015). Social aspects of primary immunodeficiencies. Sovremennaya pediatriya.8 (72): 120–123. https://doi.org/10.15574/SP.2015.71.120

3. Volokha AP. (2009). Features of the course of primary antibody deficiencies in children, determination of early criteria of diagnostics and rationale of differentiated approaches to treatment. Dissertation. Kyiv: Ministry of Health of Ukraine, National O. O. Bohomolets Medical University: 42.

4. Approved by the guidelines of treatment of children by the specialty «Pediatric Immunology» with the changes made in accordance with the Ministry's Order No.1082 from 21.12.2012: Order of the Ministry of Health of Ukraine dated 09.07.2004 No.355. Kyiv, 2012: 1–2.

5. Chernyshova LI, Volokha AP, Kostyuchenko LV. (2013). Pediatric immunology: a textbook. Kyiv: VSV Medicine: 720.

6. Chernyshova LI, Volokha AP. (2006). Primary antibody deficiencies. The art of treatment. 2: 16–21.

7. Alanko S, Pelliniemi TT, Salmi TT. (1992). Recovery of blood B-lymphocytes and serum immunoglobulins after chemotherapy for childhood acute lymphoblastic leukemia. Cancer. 69(6): 1481–1486. https://doi.org/10.1002/1097-0142(19920315)69:6<1481::AID-CNCR2820690628>3.0.CO;2-L

8. Azizi G, Ahmadi M, Abolhassani H, Yazdani R et al. (2016, Dec 24). Autoimmunity in Primary Antibody Deficiencies. Int Arch Allergy Immunol. 171(3–4): 180–193. https://doi.org/10.1159/000453263; PMid:28013299

9. Bansal AK, Vishnubhatla S, Bakhshi S. (2015). Correlation of serum immunoglobulins with infection-related parameters during induction chemotherapy of pediatric acute myeloid leukemia: a prospective study. Pediatr Hematol Oncol. 32(2): 129–37. https://doi.org/10.3109/08880018.2014.955620; PMid:25250972

10. Bonagura V, Kaplan B, Jongco A. (2016). Management of primary antibody deficiency syndromes. Ann Allergy Asthma Immunol. 117: 620–626. https://doi.org/10.1016/j.anai.2016.08.016; PMid:27979019

11. Compagno N, Malipiero G, Cinetto F, Agostini C. (2014, Dec 08). Immunoglobulin replacement therapy in secondary hypogammaglobulinemia. Frontiers in Immunology. 5(626): 1–6. https://doi.org/10.3389/fimmu.2014.00626; PMid:25538710 PMCid:PMC4259107

12. Cunningham-Rundles C. (2010). How I treat common variable immune deficiency. Blood. 116(1): 7–15. https://doi.org/10.1182/blood-2010-01-254417; PMid:20332369 PMCid:PMC2904582

13. Dorna MB, Santos CJ, Castro AP, Oliveira LA et al. (2016, Sept). Primary hypogammaglobulinemia: The impact of early diagnosis in lung complications. Scielo. 62(6): 530–536. https://doi.org/10.1590/1806-9282.62.06.530; PMid:27849230

14. Duraisingham S, Buckland M, Dempster J, Lorenzo L, Grigoriadou S, Longhurst H. (2014, June 27). Primary vs. Secondary Antibody Deficiency: Clinical Features and Infection Outcomes of Immunoglobulin Replacement. Plos one. 9(6): e100324. https://doi.org/10.1371/journal.pone.0100324; PMid:24971644 PMCid:PMC4074074

15. Fioredda F. (2012). Immunity against hepatitis B and measles vaccination after chemotherapy for acute lymphoblastic leukaemia in children: revaccination policy. Rev Bras Hematol Hemoter. 34(4): 254–264. https://doi.org/10.5581/1516-8484.20120065; PMid:23049435 PMCid:PMC3460396

16. Ibanez MI et al. (2003). Humoral immunity in pediatric patients with acute lymphoblastic leukaemia. Allergol Immunopathol (Madr). 31(6): 303–310. https://doi.org/10.1157/13055208; PMid:14670284

17. Inci M, Gokahmetoglu S, Kaynar L, Ercal BD, Durmaz S, Buyukoglan R. (2011, March). Investigation of Epstein—Barr virus serology and DNA in bone marrow transplant recipients. African Journal of Microbiology Research. 5(5): 496–500.

18. Jiang F, Torgerson TR, Ayars AG. (2015). Health-related quality of life in patients with primary immunodeficiency disease. J Allergy Asthma Clin Immunol. 11(2): 1–11. https://doi.org/10.1186/s13223-015-0092-y; PMid:26421019 PMCid:PMC4587876

19. Kidon MI, Handzel ZT, Schwartz R, Altboum I, Stein M, Israel Zan-Bar. (2004, Oct 21). Symptomatic hypogammaglobulinemia in infancy and childhood — clinical outcome and in vitro immune responses. BMC Family Practice. 5(23): 1–7. https://doi.org/10.1186/1471-2296-5-23; PMid:15498106 PMCid:PMC529469

20. Lingman-Framme J, Fasth A. (2013). Subcutaneous immunoglobulin for primary and secondary immunodeficiencies: an evidence-based review. Drugs.73(12): 1307–1319. https://doi.org/10.1007/s40265-013-0094-3; PMid:23861187

21. Makatsori M, Kiana-Alikhan S, Manson AL, Verma N et al. (2014, Oct). Hypogammaglobulinaemia after rituximab treatment-incidence and outcomes. Q J Med. 107(10): 821–828. https://doi.org/10.1093/qjmed/hcu094; PMid:24778295

22. Nilsson A, De Milito A, Engstrom P, Nordin M et al. (2002). Current chemotherapy protocols for childhood acute lymphoblastic leukemia induce loss of humoral immunity to viral vaccination antigens. Pediatrics. 109 (6): 1–6. https://doi.org/10.1542/peds.109.6.e91; PMid:12042585

23. Nobre FA, Gonzalez IG, Simao RM, de Moraes Pinto MI, Costa-Carvalho BT. (2014). Antibody levels to tetanus, diphtheria, measles and varicella in patients with primary immunodeficiency undergoing intravenous immunoglobulin therapy: a prospective study. BMC Immunology. 15(26): 1–7. https://doi.org/10.1186/1471-2172-15-26; PMid:24952415 PMCid:PMC4074853

24. Patel SY, Carbone J, Jolles S. (2019, February 08). The Expanding Field of Secondary Antibody Deficiency: Causes, Diagnosis, and Management. Frontiers in Immunology. 10(33): 1–15. https://doi.org/10.3389/fimmu.2019.00033; PMid:30800120 PMCid:PMC6376447

25. Perez E, Orange J, Bonilla F, Chinen J et al. (2017 March). Update on the use of immunoglobulin in human disease: A review of evidence. J Allergy Clin Immunol. 139(3): S1–S45. https://doi.org/10.1016/j.jaci.2016.09.023; PMid:28041678

26. Philip H Li, Chak-Sing Lau. (2017). Secondary antibody deficiency and immunoglobulin replacement. Hong Kong Bulletin on Rheumatic Diseases. 17(1): 1–5. https://doi.org/10.1515/hkbrd-2017-0001

27. Raanani P, Gafter-Gvili A, Paul M, Ben/Bassat I, Leibovici L, Raanani SO. (2008). Immunoglobulin prophylaxis in hematological malignancies and hematopoietic stemcell transplantation (Review). The Cochrane Collaboration. Published by John Wiley & Sons, Ltd: 4: 1–139. https://doi.org/10.1002/14651858.CD006501.pub2; PMid:18843719.

28. Riches PG, Hobbs JR. (1979). Mechanisms in secondary hypogammaglobulinaemia. J Clin Pathol Suppl (R Coll Pathol). 13: 15–22. https://doi.org/10.1136/jcp.s3-13.1.15; PMid:391824 PMCid:PMC1521589

29. Smith SS, Torgerson TR, Ochs HD. (2010). Subcutaneous immunoglobulin replacement therapy in the treatment of patients with primary immunodeficiency disease. Therapeutics and Clinical Risk Management. 6: 1–10. https://doi.org/10.2147/TCRM.S4353

30. Srivastava S, Wood P. (2016, Dec). Secondary antibody deficiency — causes and approach to diagnosis. Clinical Medicine. 16(6): 571–576. https://doi.org/10.7861/clinmedicine.16-6-571; PMid:27927823 PMCid:PMC6297325

31. Suez D, Kriv ‘an G, Jolles S, Stein M, Gupta S, Paris K. (2019). Safety and tolerability of subcutaneous immunoglobulin 20% in primary immunodeficiency diseases from two continents. Immunotherapy. 11(12): 1057 — 1065. https://doi.org/10.2217/imt-2019-0057; PMid:31268374

32. Titman P, Allwood Z, Gilmour C, Malcolmson C et al. (2014). Quality of Life in Children with Primary Antibody Deficiency. J Clin Immunol. 34(7): 844–852. https://doi.org/10.1007/s10875-014-0072-x; PMid:25005831 PMCid:PMC4165866

33. Ueda M, Berger M, Gale RP, Lazarus HM. (2018, Mar). Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation. Blood Rev. 32(2): 106–115. https://doi.org/10.1016/j.blre.2017.09.003; PMid:28958644

34. Van Tilburg CM et al. (2012). Impact of treatment reduction for childhood acute lymphoblastic leukemia on serum immunoglobulins and antibodies against vaccinepreventable diseases. Pediatr Blood Cancer. 58(5): 701–707. https://doi.org/10.1002/pbc.23258; PMid:21793184

35. Van Tilburg CM, Sanders EA, Rovers MM, Wolfs TF, Bierings MB. (2006). Loss of antibodies response to (re-)vaccination in children after treatment for acute lymphocytic leukemia: a systematic review. Leukemia. 20(10): 1717–1722. https://doi.org/10.1038/sj.leu.2404326; PMid:16888619

36. Windegger TM, Lambooy CA, Hollis L, Morwood K, Weston H, Fung YL. (2017). Subcutaneous Immunoglobulin Therapy for Hypogammaglobulinemia Secondary to Malignancy or Related. Drug Therapy Transfusion Medicine Reviews. 31(1): 45–50. https://doi.org/10.1016/j.tmrv.2016.06.006; PMid:27450021

37. Yong PL, Boyle J, Ballow M et al. (2009). Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies: a working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy Asthma and Immunology. Clin Immunol. 1–9. https://doi.org/10.1016/j.jaci.2016.09.023; PMid:28041678