Humoral immune profiling of mycobacterial antigen recognition in sarcoidosis and Löfgren’s syndrome using high-content peptide microarrays

Ferrara, Giovanni; Valentini, Davide; Rao, Martin; Wahlström, Jan; Grünewald, Johan; Larsson, Lars-Olof; Brighenti, Susanna; Dodoo, Ernest; Zumla, Alimuddin; Maeurer, Markus

doi:10.1016/j.ijid.2017.01.021

Cited by 13 publications

(12 citation statements)

References 38 publications

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“…Since the mechanism of action of CFA-induced granulomatosis is unclear, the CFA injection method is not commonly adopted. Mycobacterium tuberculosis (MTB), which may cause sarcoidosis (18, 19), was used to develop animal models of MTB-induced sarcoidosis. Drake et al found Mycobacterium 16S rRNA and rpoB sequences in sarcoidosis tissue specimens (20).…”

Section: Discussionmentioning

confidence: 99%

IL-17A Can Promote Propionibacterium acnes-Induced Sarcoidosis-Like Granulomatosis in Mice

Song

Zhao

et al. 2019

Front. Immunol.

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The etiology of sarcoidosis is unknown. In this study, Propionibacterium acnes (PA) was used to induce sarcoidosis-like granulomatous inflammation in a mouse model. Wild-Type (WT) C57BL/6 mice were divided into three groups: (1) WT-PA group; (2) WT-PA + Incomplete Freund's Adjuvant (IFA) group; and (3) WT-PBS group. Loose granuloma formation was observed in the lungs on day 56 in the WT-PA and WT-PA + IFA groups. The proportions of peripheral Th17 cells in the WT-PA ( p = 0.0004) and WT-PA + IFA groups ( p = 0.0005) were significantly higher than that in the WT-PBS group. The proportions of peripheral Treg cells in the WT-PA ( p < 0.0001) and WT-PA + IFA groups ( p < 0.0001) were lower than that in the WT-PBS group. Then, to explore the mechanism of IL-17, Wild-Type (WT) C57BL/6 mice were divided into three groups: (1) WT-PBS group (2) WT-PA group; (3) WT-PA + mouse IL-17A neutralizing antibody (IL-17Ab) group. IL-17A gene knockout mice (KO) were divided into two groups: (1) KO -PA group; (2) KO-PBS group. The KO-PA and WT-PA + IL-17Ab groups showed reduced inflammation and no loose granuloma formation on day 56. As compared to the WT-PA group, the ratio of peripheral Th17 in the KO-PA ( p < 0.0001) and WT-PA + IL-17Ab groups ( p < 0.0001) decreased, while the ratio of peripheral Treg in the KO-PA ( p < 0.0001) and WT-PA + IL-17Ab ( p = 0.0069) groups increased on day 56. Hence, PA can be used to establish a mouse model of sarcoidosis-like granuloma. IL-17A plays an important role in experimental sarcoidosis-like granuloma formation.

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Section: Discussionmentioning

confidence: 99%

IL-17A Can Promote Propionibacterium acnes-Induced Sarcoidosis-Like Granulomatosis in Mice

Song

Zhao

et al. 2019

Front. Immunol.

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“…While patients with PAP harboring ATP-binding cassette deficiency are prone to opportunistic lung infections (Goldschmidt et al, 2003; Borie et al, 2011), TB or mycobacterial infections in general, it has also been implicated in the pathogenesis of sarcoidosis (van Enschot and van Balkom, 2013; Ferrara et al, 2017), suggesting an overall impaired host defense involving pulmonary surfactant disbalance. Interestingly, ABCA1 loss in murine alveolar macrophages enhanced pro-inflammatory immune responses in the lung and clearance of bacterial infection (Draper et al, 2010), which requires well-designed studies in humans.…”

Section: Pulmonary Surfactants In the Context Of Lung Immunometabolismmentioning

confidence: 99%

Immunometabolism and Pulmonary Infections: Implications for Protective Immune Responses and Host-Directed Therapies

et al. 2019

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BACKGROUND Central immune effector functions, e.g., the development of long-term immunological memory, homing to target tissues and effective immune-surveillance are, in part, determined by metabolic programming, which plays a role not only in cellular physiology yet also in immunopathology (Shehata et al., 2017; Gardiner, 2019). A better understanding of the dynamic role of metabolic programming may devise new ways of targeted therapeutic intervention(s). Preclinical and clinical studies in patients with non-communicable diseases link metabolic cellular impairment with immune dysfunction (Hotamisligil, 2017). A shift in metabolite requirement appears to govern the nature and dynamics of the immune response in the host-largely involving glucose or lipids and

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“…В основе метода лежит анализ релеевского уширения, рассеянного на определенный угол лазерного луча на «свободно» диффундирующих в растворе рассеивателях. Достоинством способа ДСР является то, что это точный диффузиометрический метод, позволяющий определить иммунные комплексы больших размеров -от единиц нанометров до десятков микрон, что позволяет без внесения внешних возмущающих воздействий получать информацию о распределении иммунных комплексов по размерам в биологических жидкостях [8,12,17]. Уникальность метода динамического светорассеяния заключается в возможности регистрации образования макромолекулярных комплексов в сложных биологических системах, не прибегая к фракционированию или каким-либо другим процедурам, нарушающим нативные условия, в которых происходит комлексообразование, что позволяет получать более детальную информацию [7].…”

Section: т 21 №unclassified

“…Недавние исследования показали ведущую роль иммунологических нарушений в развитии саркоидоза [12,14,15,16]. Роль сывороточных иммуноглобулинов в формировании гранулемы до конца не ясна, возможно, их участие заключается в формировании гранулем путем присоединения к иммунным комплексам.…”

Section: Introductionunclassified

Autoimmune Origin of Sarcoidosis: Determination of Specific Immune Complexes in Patients With Respiratory Sarcoidosis

et al. 2019

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The etiology of sarcoidosis is not completely understood. A hypothesis exists about the relationship between sarcoidosis and a complex of pathological autoimmune reactions that occur under the influence of triggering factors. In this study, specific immune complexes in the blood plasma of patients have been determined, which can indirectly reveal the causes of the disease.The study included 33 patients with lung sarcoidosis (I group), compared to 24 healthy donors who served as a control group (II group). The patients underwent standard examination. Their blood plasma was investigated by the dynamic light scattering method with addition of tuberculosis antigens (ESAT-6/SFP-10) and “lung healthy tissue extract”. Statistical analysis was performed using the Statistica 7.0 program. Test results were considered significant at p < 0.05.Аccording to the data obtained, addition of ESAT-6/SFP-10 to patient’s blood plasma almost did not lead to the formation of immune complexes in most samples. Meanwhile, development of such complexes after addition of “lung tissue extract” was revealed in all the patients. The immune complexes were not detected in any donor from control group after stimulation with both kinds of antigens (p < 0.01).The data on distinct formation of immune complexes with the addition of “lung healthy tissue extract” in patients with lung sarcoidosis may be considered an indirect evidence for occurrence of autoimmune reaction under the influence of some pathogenic factors. Absence of de novo immune complex formation after addition of tuberculosis antigens (ESAT-6/SFP-10) makes it unlikely any direct effects of tuberculosis bacteria upon development of sarcoidosis.

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Humoral immune profiling of mycobacterial antigen recognition in sarcoidosis and Löfgren’s syndrome using high-content peptide microarrays

Abstract: Specific IgG recognition patterns for M. tuberculosis antigens in sarcoidosis patients re-affirm mycobacterial involvement in sarcoidosis, providing biologically relevant targets for future studies pertaining to diagnostics and immunotherapy.

Cited by 13 publications

References 38 publications

IL-17A Can Promote Propionibacterium acnes-Induced Sarcoidosis-Like Granulomatosis in Mice

IL-17A Can Promote Propionibacterium acnes-Induced Sarcoidosis-Like Granulomatosis in Mice

Immunometabolism and Pulmonary Infections: Implications for Protective Immune Responses and Host-Directed Therapies

Autoimmune Origin of Sarcoidosis: Determination of Specific Immune Complexes in Patients With Respiratory Sarcoidosis

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