Skip to main content

Advertisement

SpringerLink
Log in

Juvenile-Onset Immunodeficiency Secondary to Anti-Interferon-Gamma Autoantibodies

  • Original Article
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Immunodeficiency secondary to anti-interferon-gamma (anti-IFN-γ) autoantibodies was first described in 2004 as an acquired defect in the IFN-γ pathway leading to susceptibility to multiple opportunistic infections, including dimorphic fungi, parasites, and bacteria, especially tuberculosis and non-tuberculous mycobacterium (NTM) species. It has so far only been described in adult patients. We present 2 cases of disseminated NTM infections in otherwise immunocompetent children. A 16-year-old girl with Sweet’s syndrome–like neutrophilic dermatosis developed recurrent fever and cervical lymphadenitis secondary to Mycobacterium abscessus. A 10-year-old boy with a history of prolonged fever, aseptic meningitis, aortitis, and arteritis in multiple blood vessels developed thoracic vertebral osteomyelitis secondary to Mycobacterium avium complex. Both patients were found to have positive serum neutralizing anti-IFNγ autoantibodies. Testing for anti-IFNγ autoantibodies should be considered in otherwise healthy immunocompetent hosts with recurrent or disseminated NTM infection. This represents a phenocopy of primary immunodeficiency which has been recently described only in adults. We report the first two cases of this phenomenon to affect children.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Dorman SE, Holland SM. Interferon-gamma and interleukin-12 pathway defects and human disease. Cytokine Growth Factor Rev. 2000;11(4):321–33.

    Article  CAS  PubMed  Google Scholar 

  2. Döffinger R, Helbert MR, Barcenas-Morales G, Yang K, Dupuis S, Ceron-Gutierrez L, et al. Autoantibodies to interferon-gamma in a patient with selective susceptibility to mycobacterial infection and organ-specific autoimmunity. Clin Infect Dis. 2004;38(1):e10–4.

    Article  PubMed  Google Scholar 

  3. Höflich C, Sabat R, Rosseau S, Temmesfeld B, Slevogt H, Döcke WD, et al. Naturally occurring anti-IFN-gamma autoantibody and severe infections with Mycobacterium cheloneae and Burkholderia cocovenenans. Blood. 2004;103(2):673–5.

    Article  CAS  PubMed  Google Scholar 

  4. Browne SK, Burbelo PD, Chetchotisakd P, Suputtamongkol Y, Kiertiburanakul S, Shaw PA, et al. Adult-onset immunodeficiency in Thailand and Taiwan. N Engl J Med. 2012;367(8):725–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Patel SY, Ding L, Brown MR, Lantz L, Gay T, Cohen S, et al. Anti-IFN-gamma autoantibodies in disseminated nontuberculous mycobacterial infections. J Immunol. 2005;175(7):4769–76.

    Article  CAS  PubMed  Google Scholar 

  6. Baerlecken N, Jacobs R, Stoll M, Schmidt RE, Witte T. Recurrent, multifocal Mycobacterium avium-intercellulare infection in a patient with interferon-gamma autoantibody. Clin Infect Dis. 2009;49(7):e76–8.

    Article  CAS  PubMed  Google Scholar 

  7. Kampmann B, Hemingway C, Stephens A, Davidson R, Goodsall A, Anderson S, et al. Acquired predisposition to mycobacterial disease due to autoantibodies to IFN-gamma. J Clin Invest. 2005;115(9):2480–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Koya T, Tsubata C, Kagamu H, Koyama K, Hayashi M, Kuwabara K, et al. Anti-interferon-gamma autoantibody in a patient with disseminated Mycobacterium avium complex. J Infect Chemother. 2009;15(2):118–22.

    Article  PubMed  Google Scholar 

  9. Tanaka Y, Hori T, Ito K, Fujita T, Ishikawa T, Uchiyama T. Disseminated Mycobacterium avium complex infection in a patient with autoantibody to interferon-gamma. Intern Med. 2007;46(13):1005–9.

    Article  PubMed  Google Scholar 

  10. Wongkulab P, Wipasa J, Chaiwarith R, Supparatpinyo K. Autoantibody to interferon-gamma associated with adult-onset immunodeficiency in non-HIV individuals in Northern Thailand. PLoS One. 2013;8(9):e76371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liu TT, Weng SW, Wang MC, Huang WT. Nontuberculous mycobacterial infection with concurrent IgG4-related lymphadenopathy. APMIS. 2016;124(3):216–20.

    Article  CAS  PubMed  Google Scholar 

  12. O’Connell E, Rosen LB, LaRue RW, Fabre V, Melia MT, Auwaerter PG, et al. The first US domestic report of disseminated Mycobacterium avium complex and anti-interferon-γ autoantibodies. J Clin Immunol. 2014;34(8):928–32.

    Article  CAS  PubMed  Google Scholar 

  13. Hanitsch LG, Löbel M, Müller-Redetzky H, Schürmann M, Suttorp N, Unterwalder N, et al. Late-onset disseminated Mycobacterium avium intracellulare complex infection (MAC), cerebral toxoplasmosis and Salmonella sepsis in a German Caucasian patient with unusual anti-interferon-gamma IgG1 autoantibodies. J Clin Immunol. 2015;35(4):361–5.

    Article  CAS  PubMed  Google Scholar 

  14. Kampitak T, Suwanpimolkul G, Browne S, Suankratay C. Anti-interferon-γ autoantibody and opportunistic infections: case series and review of the literature. Infection. 2011;39(1):65–71.

    Article  CAS  PubMed  Google Scholar 

  15. Chi CY, Lin CH, Ho MW, Ding JY, Huang WC, Shih HP, et al. Clinical manifestations, course, and outcome of patients with neutralizing anti-interferon-γ autoantibodies and disseminated nontuberculous mycobacterial infections. Medicine (Baltimore). 2016;95(25):e3927.

    Article  CAS  Google Scholar 

  16. Filipe-Santos O, Bustamante J, Chapgier A, Vogt G, de Beaucoudrey L, Feinberg J, et al. Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features. Semin Immunol. 2006;18:347–61.

    Article  CAS  PubMed  Google Scholar 

  17. Revoltella RP. Natural and therapeutically-induced antibodies to cytokines. Biotherapy. 1998;10:321–31.

    Article  CAS  PubMed  Google Scholar 

  18. Ku CL, Lin CH, Chang SW, Chu CC, Chan JF, Kong XF, et al. Anti-IFN-γ autoantibodies are strongly associated with HLA-DR*15:02/16:02 and HLA-DQ*05:01/05:02 across Southeast Asia. J Allergy Clin Immunol. 2016;137(3):945–8.e8.

    Article  CAS  PubMed  Google Scholar 

  19. Chi CY, Chu CC, Liu JP, Lin CH, Ho MW, Lo WJ, et al. Anti-IFN-γ autoantibodies in adults with disseminated nontuberculous mycobacterial infections are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster virus infection. Blood. 2013;121(8):1357–66.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

L.Y.A.C. has been supported by Clinician Scientist Award (CSA), Individual Research Grant (IRG), Bedside & Bench (B&B) grants, and the Training Fellowship Award from the National Medical Research Council (NMRC), Singapore. He also acknowledges the Synthetic Biology Research & Development Programme (SBP) from the National Research Foundation, Seed Fund grant from National University Health System and the Microbiome BIGHEART grant of the National University of Singapore.

Author information

Authors and Affiliations

  1. Rheumatology and Immunology Service, Department of Paediatric Subspecialties, KK Women’s and Children’s Hospital, Singapore, Singapore

    Woei-Kang Liew, Bianca S. W. Chan, Lena Das & Thaschawee Arkachaisri

  2. Infectious Diseases Service, Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore, Singapore

    Koh-Cheng Thoon, Chia-Yin Chong, Natalie W. H. Tan & Duo-Tong Cheng

  3. Dermatology Service, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore, Singapore

    Michelle S. Y. Ng & Mark Jean Aan Koh

  4. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Chiung-Hui Huang

  5. Genome Institute of Singapore, A*STAR, Singapore, Singapore

    Jyn-Ling Kuan

  6. Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore, Singapore

    Louis Y. A. Chai

  7. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Louis Y. A. Chai

Authors
  1. Woei-Kang Liew
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Koh-Cheng Thoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chia-Yin Chong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Natalie W. H. Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Duo-Tong Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bianca S. W. Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michelle S. Y. Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lena Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Thaschawee Arkachaisri
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chiung-Hui Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jyn-Ling Kuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Louis Y. A. Chai
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Mark Jean Aan Koh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Jean Aan Koh.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liew, WK., Thoon, KC., Chong, CY. et al. Juvenile-Onset Immunodeficiency Secondary to Anti-Interferon-Gamma Autoantibodies. J Clin Immunol 39, 512–518 (2019). https://doi.org/10.1007/s10875-019-00652-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-019-00652-1

Keywords

Search

Navigation