当前位置： SCI文献检索 > IMMUNOBIOLOGY期刊下所有文献 > Patients with inhibitory and neutralizing auto-antibodies to interferon-γ resemble the sporadic adult-onset phenotype of Mendelian Susceptibility to Mycobacterial Disease (MSMD) lacking Bacille Calmette-Guerin (BCG)-induced diseases.

Patients with inhibitory and neutralizing auto-antibodies to interferon-γ resemble the sporadic adult-onset phenotype of Mendelian Susceptibility to Mycobacterial Disease (MSMD) lacking Bacille Calmette-Guerin (BCG)-induced diseases.

Abstract：

:To recognize patients with inhibitory and neutralizing auto-antibodies to interferon-γ (AutoAbs-IFN-γ) presenting with the sporadic phenotype of Mendelian Susceptibility to Mycobacterial Disease (MSMD) mainly characterized by recurrent intracellular mycobacterium or/and salmonella infections, we comprehensively investigated IL12/23-IFN-γ signaling, candidate genetic sequencings or/and protein expressions of IL12RB1, IFNRG1, IL12p40, IFNRG2, STAT1, IKKA, NEMO, CYBB and IRF8 in four patients. Their serum was further titrated to detect AutoAbs-IFN-γ, for which the biological activity was assessed in Jurkat T cells. The patients mainly presented with recurrent non-tuberculous mycobacterium osteomyelitis and lymphadenopathy (Mycobacterium abscessus, chelonae and avium intracellular complex), and salmonella sepsis (S. enterica serogroup B, C2 and D). Additionally, Penicillium marneffei, varicella-zoster virus, and herpes simplex virus infections occurred. Inhibitory and neutralizing IFN-γ downstream signaling was elucidated in Jurkat cell lines as decreased MHC class I and phosphorylated STAT1 expression. Together with 24 patients from the PubMed search, the majority of the AutoAbs-IFN-γ patients were Asian (25/28). The most common involvement was lymph nodes (in 22/28), lungs (19/28) and bones (12/28). Mycobacterium avium complex (in 14) and chelonae (7) were the most common pathogens from 40 isolations. In contrast to those with the mild form of MSMD phenotype, AutoAbs-IFN-γ patients, in the absence of BCG-induced diseases, had a more persistent course and poor response to IFN-γ treatment. In conclusion, AutoAbs-IFN-γ patients may have a sporadic adult-onset MSMD phenotype in Asian regions endemic for mycobacterial infections.

journal_name

Immunobiology

journal_title

Immunobiology

authors

Lee WI,Huang JL,Wu TS,Lee MH,Chen IJ,Yu KH,Liu CY,Yang CH,Hsieh MY,Lin YL,Shih YF,Jaing TH,Huang SC,Kuo TT,Ku CL

doi

10.1016/j.imbio.2012.08.281

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

762-71

issue

5

eissn

0171-2985

issn

1878-3279

pii

S0171-2985(12)00497-4

journal_volume

218

pub_type

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