Anti-CD20 (rituximab) therapy for anti–IFN-γ autoantibody–associated nontuberculous mycobacterial infection

Browne, Sarah K.; Zaman, Rifat; Sampaio, Elizabeth P.; Jutivorakool, Kamonwan; Rosen, Lindsey B.; Ding, Li; Pancholi, Minjal J.; Yang, Liyu; Priel, Debra Long; Uzel, Gülbû; Freeman, Alexandra F.; Hayes, Carlton E.; Baxter, Roger; Cohen, Stuart H.; Holland, Steven M.

doi:10.1182/blood-2011-12-395707

Cited by 163 publications

(134 citation statements)

References 27 publications

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“…Although antibody levels may decrease with disease quiescence, they can persist for years. 30 Therefore, it remains unknown whether the autoantibody-negative patients with disseminated opportunistic infections that had resolved had another underlying disorder or whether anti–interferon-γ autoantibodies can resolve completely.…”

Section: Discussionmentioning

confidence: 99%

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Adult-Onset Immunodeficiency in Thailand and Taiwan

Browne¹,

et al. 2012

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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.

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Section: Discussionmentioning

confidence: 99%

“…Since many patients with anti–interferon-γ autoantibodies remain actively infected despite antimicrobial therapy, this observation suggests that therapeutic targeting of anti–interferon-γ autoantibodies may warrant investigation. 5,30 …”

Section: Discussionmentioning

confidence: 99%

Adult-Onset Immunodeficiency in Thailand and Taiwan

Browne¹,

et al. 2012

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“…Although the mechanism of antibody production and the acquisition of neutralizing capacity remain unknown, some reports have speculated on the association between the antibody and NTM infection. Two groups from the USA reported the utility of rituximab against disseminated NTM in patients with anti-IFN-g autoantibodies [4,5]. The subjects went into remission along with reduction in the concentration or neutralizing capacity of anti-IFNg autoantibodies as a consequence of rituximab administration.…”

Section: Discussionmentioning

confidence: 99%

“…In most cases, the causative agents of disseminated NTM include Mycobacterium avium complex (MAC) and rapid-growing mycobacteria [1e3]. The concentration or neutralizing capacity of anti-IFN-g autoantibodies was reduced after the initiation of anti-mycobacterial agents and rituximab in a few cases [4,5]. A case of disseminated Mycobacterium gordonae and Mycobacterium mantenii in a patient with anti-IFN-g autoantibodies is described.…”

Section: Introductionmentioning

confidence: 99%

Disseminated Mycobacterium gordonae and Mycobacterium mantenii infection with elevated anti-IFN-γ neutralizing autoantibodies

Hase

Morimoto

Sakagami

et al. 2015

Journal of Infection and Chemotherapy

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“…; STAT1 phosphorylation index: 47, control 407) was identified in the serum using an enzymelinked immunosorbent assay (ELISA), although the trigger for the production of anti-IFN-γ autoantibodies remains unidentified. While the antibody titers may decrease in association with the amelioration of disease, it has also been reported that elevated titers can persist for years (6).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary <i>Mycobacterium fortuitum</i> Infection with Cervical Lymphadenitis in a Patient Carrying Autoantibodies to Interferon-γ

et al. 2014

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A 74-year-old woman was referred to our hospital for an evaluation of unidentified pneumonia. She gradually developed a high-grade fever with a growing infiltrative shadow on chest CT and an enlarging bilateral cervical mass. She was diagnosed with a pulmonary Mycobacterium fortuitum (M. fortuitum) infection with cervical lymphadenitis based on the results of an open biopsy of the cervical lymph node. While the patient's clinical condition resolved almost completely after treatment with multiple antibiotics, neutralizing autoantibodies to interferon-gamma (IFN-γ) were identified in her serum. The progression of disseminated M. fortuitum infection in immunocompetent patients may be affected by the presence of autoantibodies to IFN-γ.

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Anti-CD20 (rituximab) therapy for anti–IFN-γ autoantibody–associated nontuberculous mycobacterial infection

Cited by 163 publications

References 27 publications

Adult-Onset Immunodeficiency in Thailand and Taiwan

Adult-Onset Immunodeficiency in Thailand and Taiwan

Disseminated Mycobacterium gordonae and Mycobacterium mantenii infection with elevated anti-IFN-γ neutralizing autoantibodies

Pulmonary <i>Mycobacterium fortuitum</i> Infection with Cervical Lymphadenitis in a Patient Carrying Autoantibodies to Interferon-γ

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