scholarly journals TANK prevents IFN-dependent fatal diffuse alveolar hemorrhage by suppressing DNA-cGAS aggregation

2021 ◽  
Vol 5 (2) ◽  
pp. e202101067
Author(s):  
Atsuko Wakabayashi ◽  
Masanori Yoshinaga ◽  
Osamu Takeuchi
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Critical Role ◽  
Vascular Endothelial Cell ◽  
Diffuse Alveolar Hemorrhage ◽  
Negative Regulator ◽  
Alveolar Hemorrhage ◽  
Type I ◽  
Systemic Lupus ◽  
Cytoplasmic Dna

Diffuse alveolar hemorrhage (DAH) is one of the serious complications associated with systemic lupus erythematosus, an autoimmune disease whose pathogenesis involves type I IFNs and cytokines. Here, we show that TANK, a negative regulator of the NF-κB signaling via suppression of TRAF6 ubiquitination, is critical for the amelioration of fatal DAH caused by lung vascular endothelial cell death in a mouse model of systemic lupus erythematosus. The development of fatal DAH in the absence of TANK is mediated by type I IFN signaling, but not IL-6. We further uncover that STING, an adaptor essential for the signaling of cytoplasmic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS), plays a critical role in DAH under Tank deficiency. TANK controls cGAS-mediated cGAMP production and suppresses DNA-mediated induction of IFN-stimulated genes in macrophages by inhibiting the formation of DNA-cGAS aggregates containing ubiquitin. Collectively, TANK inhibits the cGAS-dependent recognition of cytoplasmic DNA to prevent fatal DAH in the murine lupus model.

scholarly journals RECURRING AND REFRACTORY DIFFUSE ALVEOLAR HEMORRHAGE AS THE FIRST MANIFESTATION OF SYSTEMIC LUPUS ERYTHEMATOSUS – CASE REPORT

2021 ◽  
Author(s):  
Laura Maria Silva de Siqueira ◽  
Douglas Squizatto Leite ◽  
João Flávio Gomes Faria ◽  
Daniela Esteves Temporim ◽  
Matheus Zanata Brufatto ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Case Report ◽  
Lupus Erythematosus ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Systemic Lupus ◽  
Systemic Lupus Erythematosus Case

Henrique Pereira Sampaio , Luiz Eduardo Valente , Sula Glaucia Lage Drumond Pacheco , Sean Hideo Shirata Lanças

scholarly journals Systemic lupus erythematosus and diffuse alveolar hemorrhage, etiology and novel treatment strategies

Lupus ◽  
2020 ◽  
Vol 29 (4) ◽  
pp. 355-363 ◽  
Author(s):  
N K Al-Adhoubi ◽  
J Bystrom
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Factor Vii ◽  
Systemic Lupus ◽  
Mesenchymal Stem Cell Therapy

Diffuse alveolar hemorrhage is a severe respiratory complication of systemic lupus erythematosus. The illness develops over hours to a few days and is the systemic lupus erythematosus-associated syndrome with highest mortality. Although no specific symptoms have been identified, a number of features are associated with diffuse alveolar hemorrhage, with a drop in blood hemoglobin the most prominent. Dyspnea, blood-stained sputum, diffuse infiltrates identified by chest imaging, elevated single breath-diffusing capacity for monoxide, thrombocytopenia and C3 hypocomplementemia are other commonly reported signs of diffuse alveolar hemorrhage. The etiology is not completely understood but many patients develop diffuse alveolar hemorrhage concomitant with lupus nephritis, suggesting immune complex-driven pathology. Biopsy studies have identified both cases with capillaritis and a bland non-inflammatory phenotype. An animal model of diffuse alveolar hemorrhage has indicated requirement of B lymphocytes and complement receptor-mediated apoptotic body phagocytosis by monocytes as part of the pathogenesis. This review will discuss considerations when diagnosing the condition and available therapies. Infections and other causes of hemorrhage have to be excluded as these require different treatment strategies. Methylprednisolone and cyclophosphamide remain the most commonly used therapies. Plasmapheresis and rituximab are other beneficial treatment options. A few studies have also considered intrapulmonary Factor VII therapy, extracorporeal membrane oxygenation and mesenchymal stem cell therapy. There is an unmet need of better definition of diffuse alveolar hemorrhages etiology and pathology for development of improved treatment strategies.

scholarly journals An uncommon cause of diffuse alveolar hemorrhage in a young male

2019 ◽  
Vol 89 (2) ◽  
Author(s):  
Anshul Mittal ◽  
Jagdish Chander Suri ◽  
Shibdas Chakrabarti ◽  
Pranav Ish
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Young Male ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Systemic Lupus ◽  
Threatening Condition ◽  
Life Threatening

It is uncommon for Systemic lupus erythematosus (SLE) to present with diffuse alveolar hemorrhage (DAH) as the initial presentation. To diagnose this in a young male with no renal involvement is further uncommon. We report a case of a 16-year-old boy, who presented with hemoptysis and was eventually diagnosed as DAH with underlying SLE. Treatment with steroids and immunosuppressant helped in rapid recovery from this potentially life-threatening condition. This case highlights the need of defining diagnostic criteria for SLE in patients presenting as DAH and formulating guidelines for treatment of the same, especially in absence of co-existing lupus nephritis.

Diffuse alveolar hemorrhage in systemic lupus erythematosus: a retrospective study in China

Lupus ◽  
2010 ◽  
Vol 19 (11) ◽  
pp. 1326-1330 ◽  
Author(s):  
M. Shen ◽  
X. Zeng ◽  
X. Tian ◽  
F. Zhang ◽  
X. Zeng ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Retrospective Study ◽  
Lupus Erythematosus ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Systemic Lupus
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