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 anti-cytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte–macrophage colony-stimulating factor. No other anti-cytokine 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.

A series of four meta-phenylene-bridged bis-benzimidazolium chlorides were synthesized as precursors to rigid, monoanionic, CCC-pincer N-heterocyclic carbene ligands. For ligands with mesityl, 3,5-xylyl, or 3,5-di-tert-butylphenyl side groups, reaction with [Ir(1,5-cyclooctadiene)Cl] 2 in acetonitrile with either excess triethylamine or stoichiometric cesium fluoride as base gave neutral, iridium(III) pincer complexes of the formula Ir(CCC)HCl(MeCN), which were purified by chromatography on silica gel. Metalation failed under these conditions for a 2,6-diisopropylphenyl-substituted derivative. In combination with NaO t Bu, these complexes form active catalysts for the acceptorless dehydrogenation of cyclooctane and for arene C-H borylation in neat arene solvent.

Three new iridium complexes of meta-phenylene-bridged bis-N-heterocyclic carbene CCC-pincer ligands were synthesized and characterized. For a pincer ligand with 2,6-diisopropylphenyl N-substituents, a six-coordinate iridium(III) complex of the formula Ir(CCC)HCl(MeCN) was formed. In contrast, ligands with t-butyl or adamantyl N-substituents gave five-coordinate iridium(III) complexes of the formula Ir(CCC)HCl. These iridium complexes, along with two previously described iridium complexes, were tested for activity in the catalytic transfer-dehydrogenation of n-octane at 150 °C. The new complexes were inactive for this reaction, while two previously reported catalysts were modestly active: a mesityl-substituted derivative gave 12 turnovers, and a 3,5-di-t-butylphenyl-substituted variant gave 10 turnovers. In contrast, these complexes were shown to be highly active catalysts for the isomerization of terminal alkenes, under conditions much milder than those required for transfer-dehydrogenation.

This particle-based multiplex assay can reproducibly characterize anticytokine autoantibodies. This efficient and inexpensive approach to diagnosing and monitoring anticytokine autoantibodies has clinical applications.