Journal of Clinical Immunology

, Volume 37, Issue 3, pp 311–318 | Cite as

Serial Serum Immunoglobulin G (IgG) Trough Levels in Patients with X-linked Agammaglobulinemia on Replacement Therapy with Intravenous Immunoglobulin: Its Correlation with Infections in Indian Children

  • Deepti SuriEmail author
  • Sagar Bhattad
  • Avinash Sharma
  • Anju Gupta
  • Amit Rawat
  • Shobha Sehgal
  • Surjit Singh
  • Sudhir Gupta
Original Article


Patients with primary antibody deficiency (PAD) are being increasingly diagnosed in the developing world. However, care of these children continues to remain suboptimal due to financial and social constraints. Immunoglobulin (Ig) trough level is an important predicting factor for infections in children on replacement immunoglobulin therapy. There are no data on this aspect from the developing world. Therefore, we studied serial immunoglobulin G (IgG) trough levels in 14 children with X-linked agammaglobulinemia (XLA) receiving replacement intravenous immunoglobulin (IVIG). Infections during the course of enrolment were documented prospectively. Mean age at the time of diagnosis was 5.1 years (range 2–11 years). Mean time from onset of symptoms and initiation of therapy was 3.3 years. Two children had established chronic lung disease prior to enrolment. Total numbers of major and minor infections were 7 and 40, respectively. At a mean dose of 414 mg/kg/month of IVIG, mean trough IgG level was 435 mg/dl. Median IgG trough levels during the episodes of major and minor infections were 244 and 335 mg/dl, respectively. An escalation in IVIG dose of 100 mg/kg produced an increase in serum IgG levels by 53.6 mg/dl. Median trough IgG level of 354 mg/dl was found to be protective with 64% sensitivity and 75% specificity. A median dose of 397 mg/kg was required to keep children free of infections. Despite financial constraints and several challenges in the context of a developing country, children with XLA have good outcome on replacement immunoglobulin therapy. Furthermore, mean biological trough IgG levels are much lower than reported in for Western patients; however, studies involving larger number of subjects are required in future to draw firm conclusions.


IgG trough Hypogammaglobulinemia IVIG replacement Primary immune deficiency 



We wish to thank all the patients who participated to this study as well as their families. We acknowledge support from the Foundation for Primary Immunodeficiency Diseases, California, for funds for immunoglobulin therapy to these children. God’s Child Foundation, Pediatric Medical Support Society, Kusum Arora Memorial Trust, Sukhmani Foundation, Veerawali Foundation Nanhi Jaan, Chandigarh, and other philanthropists also provided drugs to these children.

We also acknowledge the Indian Council of Medical Research, India, and the Department of Health Research, Ministry of Health and Family welfare, Government of India, for supporting the “Centre for Advanced Research in Primary Immune Deficiency Diseases” at the Advanced Pediatric Center, PGIMER, Chandigarh, India, vide Grant No. GIA/48/2014-DHR. The funding agencies had no role in study design, data collection and analysis, preparation of manuscript, or decision to publish.

Compliance with Ethical Standards

All patients/parents provided written informed consent.

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Gupta S, Madkaikar M, Singh S, Sehgal S. Primary immunodeficiencies in India: a perspective. Ann N Y Acad Sci. 2012;1250:73–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Al-Tamemi S, Elnour I, Dennison D. Primary immunodeficiency diseases in Oman: five years’ experience at sultan qaboos university hospital. World Allergy Organ J. 2012;5(5):52–6.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Verma S, Sharma PK, Sivanandan S, Rana N, Saini S, Lodha R, Kabra SK. Spectrum of primary immune deficiency at a tertiary care hospital. Indian J Pediatr. 2008;75(2):143–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Aghamohammadi A, Mohammadinejad P, Abolhassani H, Mirminachi B, Movahedi M, Gharagozlou M, et al. Primary immunodeficiency disorders in Iran: update and new insights from the third report of the national registry. J Clin Immunol. 2014;34(4):478–90.CrossRefPubMedGoogle Scholar
  5. 5.
    Durandy A, Kracker S, Fischer A. Primary antibody deficiencies. Nat Rev Immunol. 2013;13(7):519–33.CrossRefPubMedGoogle Scholar
  6. 6.
    Boyle JM, Buckley RH. Population prevalence of diagnosed primary immunodeficiency diseases in the United States. J Clin Immunol. 2007;27(5):497–502.CrossRefPubMedGoogle Scholar
  7. 7.
    Goel V, Kumar D, Kumar R, Mathur P, Singh S. Community acquired enterococcal urinary tract infections and antibiotic resistance profile in North India. J Lab Physicians. 2016;8:50–4.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kini AR, Shetty V, Kumar AM, Shetty SM, Shetty A. Community-associated, methicillin-susceptible, and methicillin-resistant Staphylococcus aureus bone and joint infections in children: experience from India. J Pediatr Orthop Part B. 2013;22:158–66.CrossRefGoogle Scholar
  9. 9.
    Diagnostic and clinical care guidelines for primary immunodeficiency diseases. Immune deficiency foundation. Buckley RH (Ed). 2nd ed. 2009.Google Scholar
  10. 10.
    Bruton OC. Agammaglobulinemia. Pediatrics. 1952;9(6):722–8.PubMedGoogle Scholar
  11. 11.
    Chapel H, Prevot J, Gaspar HB, Español T, Bonilla FA, Solis L, et al. Editorial Board for Working Party on Principles of Care at IPOPI. Primary immune deficiencies - principles of care Front Immunol. 2014;5:627.PubMedGoogle Scholar
  12. 12.
    Eijkhout HW, van Der Meer JW, Kallenberg CG, et al. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med. 2001;135:165–74.CrossRefPubMedGoogle Scholar
  13. 13.
    Roifman CM, Berger M, Notarangelo LD. Management of primary antibody deficiency with replacement therapy: summary of guidelines. Immunol Allergy Clin N Am. 2008;28:875–6.CrossRefGoogle Scholar
  14. 14.
    Lucas M, Lee M, Lortan J, Lopez-Granados E, Misbah S, Chapel H. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol. 2010;125:1354–60.CrossRefPubMedGoogle Scholar
  15. 15.
    Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: a meta-analysis of clinical studies. Clin Immunol. 2010;137:21–30.CrossRefPubMedGoogle Scholar
  16. 16.
    Bonagura VR, Marchlewski R, Cox A, Rosenthal DW. Biologic IgG level in primary immunodeficiency disease: the IgG level that protects against recurrent infection. J Allergy Clin Immunol. 2008;122(1):210–2.CrossRefPubMedGoogle Scholar
  17. 17.
    Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, et al. IPINet investigators. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 2011;31(3):315–22.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Deepti Suri
    • 1
    Email author
  • Sagar Bhattad
    • 1
  • Avinash Sharma
    • 1
  • Anju Gupta
    • 1
  • Amit Rawat
    • 1
  • Shobha Sehgal
    • 2
  • Surjit Singh
    • 1
  • Sudhir Gupta
    • 3
  1. 1.Pediatric Allergy and Immunology Unit, Advanced Pediatrics CentrePostgraduate Institute of Medical Education and ResearchChandigarhIndia
  2. 2.Department of ImmunopathologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
  3. 3.Division of Basic and Clinical ImmunologyUniversity of CaliforniaIrvineUSA

Personalised recommendations