Cloning the Arterial IgA Antibody Response during Acute Kawasaki Disease

Rowley, Anne H.; Shulman, Stanford T.; Garcia, Francesca L.; Guzman-Cottrill, Judith A.; Miura, Masaru; Lee, Hannah L.; Baker, Susan C.

doi:10.4049/jimmunol.175.12.8386

Cited by 49 publications

(26 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The etiology of KD remains unknown despite 40 years of intensive studies, although the current paradigm is that KD is triggered by an infectious agent that elicits an inflammatory response directed at cardiovascular tissues in genetically susceptible hosts 2, 11 . 3, 4, 12 …”

Section: Introductionmentioning

confidence: 99%

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease–Associated Abdominal Aortic Aneurysm

Wakita

Kurashima

Crother

et al. 2016

ATVB

127

View full text Add to dashboard Cite

Objective Kawasaki disease (KD) is the most common cause of acquired cardiac disease in US children. In addition to coronary artery abnormalities and aneurysms, it can be associated with systemic arterial aneurysms. We evaluated the development of systemic arterial dilatation and aneurysms, including abdominal aortic aneurysm (AAA) in the Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis mouse model. Methods and Results We discovered that in addition to aortitis, coronary arteritis and myocarditis, the LCWE-induced KD mouse model is also associated with abdominal aorta dilatation and AAA, as well as renal and iliac artery aneurysms. AAA induced in KD mice was exclusively infrarenal, both fusiform and saccular, with intimal proliferation, myofibroblastic proliferation, break in the elastin layer, vascular smooth muscle cell loss, and inflammatory cell accumulation in the media and adventitia. Il1r−/−, Il1a−/−, and Il1a−/− mice were protected from KD associated AAA. Infiltrating CD11c+ macrophages produced active caspase-1 and caspase-1 or NLRP3 deficiency inhibited AAA formation. Treatment with IL-1R antagonist (Anakinra), anti-IL-1α, or anti-IL-1β mAb blocked LCWE-induced AAA formation. Conclusions Similar to clinical KD, the LCWE-induced KD vasculitis mouse model can also be accompanied by AAA formation. Both IL-1α and IL-1β play a key role, and that use of an IL-1R blocking agent that inhibits both pathways may be a promising therapeutic target not only for KD coronary arteritis, but also for the other systemic arterial aneurysms including AAA that maybe seen in severe cases of KD. The LCWE-induced vasculitis model may also represent an alternative model for AAA disease.

show abstract

Section: Introductionmentioning

confidence: 99%

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease–Associated Abdominal Aortic Aneurysm

Wakita

Kurashima

Crother

et al. 2016

ATVB

127

View full text Add to dashboard Cite

show abstract

“…7–9 The limited understanding of the etiologic agent(s) and cellular and molecular pathology of vasculitis, continues to thwart development of more efficacious treatments or cures. 10–12 …”

mentioning

confidence: 99%

Interleukin-1β Is Crucial for the Induction of Coronary Artery Inflammation in a Mouse Model of Kawasaki Disease

et al. 2012

View full text Add to dashboard Cite

Background Kawasaki disease (KD) is the most common cause of acute vasculitis and acquired cardiac disease in US children. Untreated, children may develop coronary artery aneurysms, myocardial infarction and sudden death as a result of the illness. Up to a third of KD patients fail to respond to intravenous gammaglobulin (IVIG), the standard therapy, and alternative treatments are being investigated. Genetic studies have indicated a possible role for IL-1β in KD. We therefore explored the role of IL-1β in a murine model of KD. Methods and Results Using an established mouse model of KD that involves injection of Lactobacillus casei cell wall extract (LCWE), we investigated the role of IL- 1β and caspase-1 (activated by the inflammasome and required for IL-1β maturation) in coronary arteritis, and evaluated the efficacy of IL-1 receptor antagonist (IL-1Ra) as a potential treatment. LCWE-induced IL-1β maturation and secretion was dependent on the NLRP3 inflammasome in macrophages. Both caspase1-deficient and IL-1R-deficient mice were protected from LCWE-induced coronary lesions. Injection of recombinant IL-1β to caspase-1-deficient mice restored the ability of LCWE to cause coronary lesions in response to LCWE. Furthermore, daily injections of the IL-1Ra prevented LCWE-mediated coronary lesions, up to three days after LCWE injection. Conclusions Our results strongly suggest that caspase-1 and IL-1β play critical roles in the development of coronary lesions in this KD mouse model, blocked by IL-1Ra. Therefore, anti-IL-1β treatment strategies may constitute an effective, more targeted treatment of KD to prevent coronary lesions.

show abstract

“…By examining tissue samples from fatal cases of KD, recent progress has been made in understanding KD aetiology and pathogenesis [17][18][19][20][21][22] . These studies revealed that oligoclonal IgA plasma cells infiltrate inflamed tissues, including coronary arteries 17,18 .…”

mentioning

confidence: 99%

Searching for the cause of Kawasaki disease — cytoplasmic inclusion bodies provide new insight

et al. 2008

Self Cite

View full text Add to dashboard Cite

Kawasaki disease (KD) has emerged as the most common cause of acquired heart disease in children in the developed world. The cause of KD remains unknown, although an as-yet unidentified infectious agent might be responsible. By determining the causative agent, we can improve diagnosis, therapy and prevention of KD. Recently, identification of an antigen-driven IgA response that was directed at cytoplasmic inclusion bodies in KD tissues has provided new insights that could unlock the mysteries of KD.

show abstract

Cloning the Arterial IgA Antibody Response during Acute Kawasaki Disease

Cited by 49 publications

References 18 publications

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease–Associated Abdominal Aortic Aneurysm

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease–Associated Abdominal Aortic Aneurysm

Interleukin-1β Is Crucial for the Induction of Coronary Artery Inflammation in a Mouse Model of Kawasaki Disease

Searching for the cause of Kawasaki disease — cytoplasmic inclusion bodies provide new insight

Contact Info

Product

Resources

About