STING-Associated Vasculopathy with Onset in Infancy in Three Children with New Clinical Aspect and Unsatisfactory Therapeutic Responses to Tofacitinib

Tang, Xiaolei; Xu, Hui; Zhou, Chunju; Peng, Yun; Liu, Hui; Liu, Jinrong; Li, Huimin; Yang, Hongxiao; Zhao, Shunying

doi:10.1007/s10875-019-00690-9

Cited by 48 publications

(58 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our systematic review of the literature showed that the median age of onset in our study was 3 months after birth, with 64.7% (33/51) of patients suffering from both skin and respiratory lesions. However, the spectrum of disease manifestations continues to grow as more genotypes related to SAVI are discovered, including arthritis, myositis, kidney damage, brain damage, photosensitivity, hair loss, and thyroid damage (2,3,8,9,11,18,20,22,25). In support of this, 3 cases without skin lesion (21,25) and 16 cases without pulmonary impairment (1,2,11,18) have been reported, suggesting the clinical phenotypes of SAVI are more diverse than was previously thought.…”

Section: Discussionmentioning

confidence: 82%

Stimulator of Interferon Genes-Associated Vasculopathy With Onset in Infancy: A Systematic Review of Case Reports

et al. 2020

View full text Add to dashboard Cite

Objective: To summarize and analyze the manifestations of stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI).Methods: A systematic literature review was performed including cases from January 1, 2014, to February 1, 2020, using PubMed, OVID, CNKI, and WanFang. This included all the literature containing comparatively complete clinical data. Statistical analysis was performed using SPSS 20.0 to analyze the difference in age of onset, severity of skin lesions, and respiratory symptoms between SAVI patients with p.N154S and p.V155M mutations.Results: A total of 25 papers were included reporting on 51 individuals, of whom 17 had familiar inheritance of their mutation. Patients included 27 males and 24 females, and 8 fatal cases were observed. A total of 10 mutation sites have been reported in the STING gene, with p.V155M being the most prevalent. We identified SAVI as an early-onset disease with a median age of onset of 3 months after birth. Skin lesions were the most common symptoms of SAVI, found in 94.1% (48/51) of patients, while 76% (19/25) who had undergone a skin biopsy showed vasculopathy. Involvement of the lungs was identified in 68.6% (35/51) of patients, while only 22.2% (4/18) who had undergone a lung biopsy showed vasculopathy. Of 20 patients, 19 had increased immunoglobulin, mainly IgG. Furthermore, 45.1% (23/51) of patients had a positive low titer or were transiently positive for antinuclear antibodies. Of the 18 patients treated with JAK inhibitors, 6 relapsed and 2 died of acute respiratory failure caused by viral infection. Patients with p.N154S mutation had an earlier disease onset (p = 0.002) and more severe skin lesions (p < 0.001) than those patients with p.V155M mutation.Conclusion: SAVI is an early-onset disease accompanied by skin and lung lesions whose clinical presentation varies among patients with different genotypes. Therapeutic effects of JAK inhibitors are unsatisfactory.

show abstract

Section: Discussionmentioning

confidence: 82%

Stimulator of Interferon Genes-Associated Vasculopathy With Onset in Infancy: A Systematic Review of Case Reports

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Five case series or case report articles (2 full text articles, 2 congress abstracts, and one 1 letter to the editor) were published in rheumatology ( n = 3) and allergy–immunology ( n = 2) journals [ 27 – 31 ]. On average, 10.4 (range 5–18) authors located in Germany, Russia, Italy, China, and South Korea contributed to each study.…”

Section: Resultsmentioning

confidence: 99%

“…2 Studies that have assessed the expression of interferon target genes as a tool to evaluate treatment response. See footnote to Table 1 for definitions of SAVI, CANDLE, FCh-L and GOF-STAT1 journals [27][28][29][30][31]. On average, 10.4 (range 5-18) authors located in Germany, Russia, Italy, China, and South Korea contributed to each study.…”

Section: Mapping Studiesmentioning

confidence: 99%

Efficacy and Safety of Janus Kinase Inhibitors in Type I Interferon-Mediated Monogenic Autoinflammatory Disorders: A Scoping Review

Gómez-Arias

Gómez-García

Hernández-Parada

et al. 2021

Dermatol Ther (Heidelb)

View full text Add to dashboard Cite

Importance: Type I interferon (IFN)-mediated monogenic autoinflammatory disorders (interferonopathies) are childhood-onset rare multisystemic diseases with limited treatment options. The Janus kinase (JAK) inhibitors are promising potential therapeutic candidates for immune-mediated chronic inflammatory skin diseases.Objective: To review the use of JAK inhibitors to improve decision-making when treating interferonopathies with cutaneous manifestations. Evidence Review: The MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science databases were searched for studies that used JAK protein inhibitors to treat IFN-related monogenic diseases with cutaneous manifestations in humans. The search results are reported using the scoping review approach.Findings: Seventeen open-label studies assessing the efficacy of ruxolitinib, baricitinib, or tofacitinib reported variable responses in patients with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) and related syndromes, stimulator of IFN genes [STING]-associated vasculopathy with onset in infancy (SAVI), familial chilblain lupus (FCh-L), gain-of-function mutations of STAT1 (GOF-STAT1), or Aicardi-Goutiéres syndrome. JAK inhibitors improved clinical and analytical parameters and decreased flare numbers, plasma inflammatory markers, and expression of IFN-stimulated genes. BK viremia and upper respiratory infections were the most frequent and severe adverse events. Significant heterogeneity in efficacy assessment methods and poor reporting of safety events were detected.Pedro Jesú s Gó mez Arias and Francisco Gó mez-García have contributed equally to this work.

show abstract

“…However, this classi cation system had some limitations. In recent, immune disorders caused by gene mutation, such as COPA syndrome and STING-associated vasculopathy with onset in infancy (SAVI) were found to develop DAH [22,23] . SpC dysfunction with the I73T mutation was also found to develop autoimmunity accompanying with DAH [24] .…”

Section: Discussionmentioning

confidence: 99%

The Role of Monocytes/Macrophages In The Pathogenesis of Immune Associated Diffuse Alveolar Hemorrhage

Wei¹,

Chen²,

Liu³

et al. 2021

Preprint

View full text Add to dashboard Cite

Backgroud The studies in the immnue associated diffuse alveolar hemorrahge (DAH) animal models showed that monocytes/macrophages played an critical role in the pathogenesis.Whether monocytes/macrophages contribute to the pathogenesis of immune associated DAH in human is still unknow. The aim of this study was to explore the role of monocytes/macrophages in the pathogenesis of immune associated DAH in human.Methods This study was conducted in two parts. In the first part, 37 children with immune associated DAH were included (DAH group), and 18 healthy children were recruited as the controls (HC group). Peripheral blood monocyte subtype was analyzed using flow cytometry. In the second part, 24 children with immune associated DAH were included (DAH group), and 13 children with acute airway foreingn body or mild benign airway stenosis were included as the controls (HC group). Bronochoalveolar lavage fluid (BALF) was collected using bronchoscope. Cytokines in the BALF supernatant were detected using cytometric bread array. BALF supertanant was used to stimulated the macrophages in vitro. The mRNA relative expressions of IL-1β, TNFα, IL-6, TGM2, CD163 and MRC1 were detected using quantitative real-time PCR, and the expressions of CD14, CD80, CD86, CD163 and CD206 were detected using flow cytometry. Results 1. The percentage of classical monocyte was significantly increased, whereas the percentages of intermediate and non-classical monocyte were significantly decreased in the DAH group, when compared to those in the HC group. 2. The levels of MCP-1, IL-6 and IL-8 were all significantly higher in the BALF supernatant from the DAH group, when compared to those form the HC group. 3. The mRNA relative expressions of IL-1β and IL-6 as well as the expression of CD86 were significantly higher, whereas the mRNA relative expression of MRC1 as well as the expressions of CD163 and CD206 were significantly lower under the stimulation of BALF supernatant from the DAH group, when compared to that from the HC group. Conclusions Monocytes/macrophages might participate in the pathogenesis of immune associated DAH in human by enhanced M1 polarization.

show abstract

STING-Associated Vasculopathy with Onset in Infancy in Three Children with New Clinical Aspect and Unsatisfactory Therapeutic Responses to Tofacitinib

Cited by 48 publications

References 23 publications

Stimulator of Interferon Genes-Associated Vasculopathy With Onset in Infancy: A Systematic Review of Case Reports

Stimulator of Interferon Genes-Associated Vasculopathy With Onset in Infancy: A Systematic Review of Case Reports

Efficacy and Safety of Janus Kinase Inhibitors in Type I Interferon-Mediated Monogenic Autoinflammatory Disorders: A Scoping Review

The Role of Monocytes/Macrophages In The Pathogenesis of Immune Associated Diffuse Alveolar Hemorrhage

Contact Info

Product

Resources

About