Analysis of the interleukin-12/interferon-γ pathway in children with non-tuberculous mycobacterial cervical lymphadenitis

Serour, Francis; Mizrahi, Avraham; Somekh, Eli; Feinberg, Jacqueline; Pïcard, Capucine; Casanova, Jean‐Laurent; Dalal, Ilan

doi:10.1007/s00431-006-0338-2

Cited by 17 publications

(10 citation statements)

References 42 publications

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“…Instead, no significant differences were found in stimulated IL-12p40 and IFN-γ concentrations in cell cultures between 11 patients with non-TB mycobacterial cervical lymphadenitis and healthy controls from Israel. 21 Despite the negative result, the authors considered MSMD possible. In the present study, only 64% of the former BCG osteitis patients had measurable IL-12 concentration after BCG stimulation in cell cultures, but after BCG+IFN-γ stimulation, IL-12 was measurable in all cases.…”

Section: Discussionmentioning

confidence: 99%

Interferon-gamma-dependent Immunity in Bacillus Calmette-Guérin Vaccine Osteitis Survivors

Pöyhönen¹,

Kröger

Mäkinen

et al. 2016

The Pediatric Infectious Disease Journal

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Background Inborn errors of interferon-gamma (IFN-γ) –mediated immunity underlie disseminated disease caused by Mycobacterium bovis Bacillus Calmette-Guérin (BCG) live vaccines. We hypothesized that some patients with osteitis after BCG vaccination may have an impaired IFN-γ immunity. Our aim was to investigate IL-12 and IFN-γ ex-vivo production stimulated with BCG and BCG+IFN-γ or BCG+IL-12, respectively, in BCG osteitis survivors. Methods Fresh blood samples were collected from 132 former BCG osteitis Finnish patients now aged 21-49 years, and IL-12 and IFN-γ were measured in cell cultures with and without stimulation with BCG and with BCG+IFN-γ or BCG+IL-12, respectively. As a pilot study, known disease-causing genes controlling IFN-γ immunity (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, IRF8, NEMO and CYBB) were investigated in 20 selected patients by whole-exome -sequencing. Results By the limit of <5th percentile, ex-vivo IL-12 concentration and increase in concentration was low in five, and ex-vivo IFN-γ concentration and increase in concentration was low in six patients (including two samples with both IL-12 and IFN-γ findings). By the limit of <10th percentile, an additional six and four patients were respectively detected (including two samples with both findings). With two exceptions, low concentrations and low increases in concentrations picked-up the same cases. Mutations in known disease-causing IFN-γ-related genes were not found in any of these patients. Conclusion These findings call for searching of mutations in new genes governing IFN-γ-dependent immunity to live BCG vaccine.

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Section: Discussionmentioning

confidence: 99%

Interferon-gamma-dependent Immunity in Bacillus Calmette-Guérin Vaccine Osteitis Survivors

Pöyhönen¹,

Kröger

Mäkinen

et al. 2016

The Pediatric Infectious Disease Journal

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“…Another study showed [8,9] that IL-18 can inhibit a variety of tumors, the production of malignant ascites, and can prevent tumors from metastasizing to the lung or from infi ltrating into surrounding tissues, and, as a result, can extend the survival time. Furthermore, the anti-tumor activity of IL-18 is not dependent on internal factors of IL-12 and IFN-γ [10] . The IL-18 receptor is obtained from the purifi ed lymphoma cell strains (IL-1Rrp).…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of serum IL-18 and IL-18BP in patients with benign or malignant primary liver tumors

Guan

Liao

Lou

et al. 2009

Clin. Oncol. Cancer Res.

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OBJECTIVETo study the relationship between the serum levels of IL-18 and IL-18BP in the development and growth of primary liver cancer, benign liver tumors and liver cirrhosis and to determine the value of serum IL-18 and IL-18BP in the diagnosis of primary liver cancer. METHODS The serum levels of IL-18 and IL-18BP in 36 patients with primary hepatic carcinoma (PHC) were detected. Eighteen patients were diagnosed with various benign liver tumors and 21 patients with cirrhosis of liver (LC), determined by using an ELISA assay. The serum levels of AFP in 36 patients with primary liver cancer were examined. The relationship among levels of serum IL-18, IL-18BP and AFP in the primary liver cancer was explored. RESULTS The sIL-18 levels in PHC were signifi cantly lower than in control group, the benign liver tumor group and the LC group. The sIL-18BP in PHC was signifi cantly higher than that in control group, benign liver tumor group and LC group (P < 0.001). There was a close correlation between the levels of IL-18, IL-18BP and clinical stage in PHC: the later clinical stages had lower levels of IL-18 and higher levels of IL-18BP while the earlier clinical stages had higher levels of IL-18 and lower levels of IL-18BP. There was a negative correlation between serum levels of IL-18 and AFP in the PHC group (r = -0.7152, n = 36, P < 0.01), and there was a positive correlation between serum levels of IL-18 BP and AFP in the patients with PHC (r = 0.6315, n = 36, P < 0.01). The IL-18 and IL-18BP in the patients with various benign liver tumors or LC were significantly higher than those in control group. The differences were statistically signifi cant (P < 0.01). CONCLUSION Serum levels of IL-18 and IL-18BP can reflect the immune function of patients with primary liver cancer, with various benign liver tumors or with LC and can also be indicative of the clinic stage of primary liver cancer. It can be used to assist in making a diagnosis and in determining the clinical stage of PHC. Detecting AFP concurrently can help make the diagnosis of primary liver cancer more precise. KEY WORDS: benign-malignant primary liver tumor, primary hepatic carcinoma (PHC), liver cirrhosis (LC), serum interleukin 18 (sIL-18), serum interleukin 18 link albumen (sIL-18BP)

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“…These children typically present in the first 5 years of life and presumably become infected after the organisms invade small oral abrasions after ingestion. [1][2][3][4] Surgical resection is curative, and infection typically does not recur. NTM infection outside of cervical lymph nodes is much less common in children, but may occur as localized disease in immunocompetent children after direct inoculation, such as skin infection with Mycobacterium marinum after an aquatic exposure.…”

Section: Introductionmentioning

confidence: 99%

Intrathoracic nontuberculous mycobacterial infections in otherwise healthy children

Freeman

Olivier

Rubio

et al. 2009

Pediatric Pulmonology

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Background Nontuberculous mycobacterial (NTM) infection is typically associated with lymphadenitis in immune competent children, and disseminated disease in children with immune deficiencies. Isolated pulmonary NTM disease is seen in cystic fibrosis, and is increasingly recognized in immunocompetent elderly women, where it is associated with an increased incidence of cystic fibrosis transmembrane regulator (CFTR) mutations. Thoracic NTM infection has been reported rarely in otherwise healthy children. We aimed to determine whether otherwise healthy children with pulmonary NTM disease had immunologic abnormalities or CFTR mutations. Study Design Clinical presentations of five otherwise healthy children with pulmonary NTM were reviewed. Immunologic studies were performed including a complete blood cell count (CBC), flow cytometric lymphocyte phenotyping and IFN-gamma receptor expression, in vitro cytokine stimulation, and serum immunoglobulin levels. Mutational analysis was performed for CFTR. Results The children ranged in age from 12 months to 2.5 years at diagnosis. Four presented with new onset wheezing or stridor failing bronchodilator therapy. One child was asymptomatic. Endobronchial lesions and/or hilar lymph nodes causing bronchial obstruction were identified in all patients. Mycobacterium avium complex was cultured from four patients, and M. abscessus from one patient. All patients were successfully treated with anti-mycobacterial therapy with or without surgery. No definitive immunologic abnormalities were identified. No clinically significant mutations were found in CFTR. Conclusions Pulmonary NTM infection should be considered in otherwise healthy young children presenting with refractory stridor or wheezing with endobronchial lesions or hilar lymphadenopathy. It does not appear to be associated with recognized underlying immune deficiency or CFTR mutations.

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Analysis of the interleukin-12/interferon-γ pathway in children with non-tuberculous mycobacterial cervical lymphadenitis

Cited by 17 publications

References 42 publications

Interferon-gamma-dependent Immunity in Bacillus Calmette-Guérin Vaccine Osteitis Survivors

Interferon-gamma-dependent Immunity in Bacillus Calmette-Guérin Vaccine Osteitis Survivors

Clinical significance of serum IL-18 and IL-18BP in patients with benign or malignant primary liver tumors

Intrathoracic nontuberculous mycobacterial infections in otherwise healthy children

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