HLA-DRB1 and HLA-DQB1 Are Associated with Adult-Onset Immunodeficiency with Acquired Anti-Interferon-Gamma Autoantibodies

<div><p>Recently a newly identified clinical syndrome of disseminated non-tuberculous mycobacterial diseases (with or without other opportunistic infections in adult patients who were previously healthy, has been recognized in association with an acquired autoantibody to interferon-gamma. This syndrome is emerging as an important cause of morbidity and mortality, especially among people of Asian descent. Trigger for the production of this autoantibody remains unknown, but genetic factors are strongly suspected to be involved. We compared HLA genotyping between 32 patients with this clinical syndrome, and 38 controls. We found that this clinical syndrome was associated with very limited allele polymorphism, with HLA-DRB1 and DQB1 alleles, especially HLA-DRB1*15:01, DRB1*16:02, DQB1*05:01 and DQB1*05:02. Odds ratio of DRB1*15:01, DRB1*16:02, DQB1*05:01 and DQB1*05:02 were 7.03 (95% CI, 2.18–22.69, P<0.0001, 9.06 (95% CI, 2.79–29.46, P<0.0001), 6.68 (95% CI, 2.29–19.52, P = 0.0004), and 6.64 (95% CI, 2.30–19.20, P = 0.0004), respectively. Further investigation is warranted to provide better understanding on pathogenesis of this association.</p></div

Demographic characteristics, pathogen, affected site and outcome of patients with disseminated non-tuberculous mycobacterial infections or other opportunistic infections who had positive anti-IFN- γ autoantibody.

<p>*F = Female</p><p>**M = Male</p><p>***<i>M</i>. = <i>Mycobacterium</i></p><p>****LN = Lymph node</p><p>*****BAL = Bronchoalveolar lavage.</p><p>Demographic characteristics, pathogen, affected site and outcome of patients with disseminated non-tuberculous mycobacterial infections or other opportunistic infections who had positive anti-IFN- γ autoantibody.</p

HLA class II genotypes of 32 affected individuals with disseminated opportunistic infection and positive anti- IFN- γ autoantibody (case group).

<p>HLA class II genotypes of 32 affected individuals with disseminated opportunistic infection and positive anti- IFN- γ autoantibody (case group).</p

HLA class II genotypes of healthy volunteers (No. 1–30) and pulmonary tuberculosis (No. 31–36) without anti- IFN- γ autoantibody (control group).

<p>HLA class II genotypes of healthy volunteers (No. 1–30) and pulmonary tuberculosis (No. 31–36) without anti- IFN- γ autoantibody (control group).</p

Amino acid sequence alignment of various HLA-DQB1 subtypes.

<p>Amino acid sequence alignment of various HLA-DQB1 subtypes.</p

Amino acid sequence alignment of various HLA-DRB1 subtypes.

<p>Amino acid sequence alignment of various HLA-DRB1 subtypes.</p