Adult-onset immunodeficiency in Thailand and Taiwan

N Engl J Med. 2012 Aug 23;367(8):725-34. doi: 10.1056/NEJMoa1111160.

Abstract

Background: Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown.

Methods: We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained.

Results: Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-γ in normal cells. High-titer anti-interferon-γ autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte-macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering.

Conclusions: Neutralizing anti-interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.).

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Antibodies, Neutralizing / blood*
  • Autoantibodies / blood*
  • Autoimmune Diseases / immunology*
  • CD4 Lymphocyte Count
  • Female
  • Humans
  • Interferon-gamma / immunology*
  • Male
  • Middle Aged
  • Mycobacterium Infections / immunology*
  • Mycoses / immunology
  • Opportunistic Infections / immunology*
  • Taiwan
  • Thailand
  • Tuberculosis, Pulmonary / immunology
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Autoantibodies
  • IFNG protein, human
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT00814827