Monogenic interferonopathies: Phenotypic and genotypic findings of CANDLE syndrome and its overlap with C1q deficient SLE.

Al‐Mayouf, Sulaiman M.; Alsaleem, Alhanouf; Almutairi, Nora; Alsonbul, Abdullah; Al-Zaid, Tariq; Alazami, Anas M.; Al‐Mousa, Hamoud

doi:10.1111/1756-185x.13228

Cited by 25 publications

(12 citation statements)

References 26 publications

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“…The patient we report had evidence of adaptive immune dysregulation, which included hypergammaglobulinemia in the context of positive autoantibody titers, including elevated titers for antinuclear antibodies and lymphocytic infiltration in the liver causing autoimmune hepatitis. Some authors have noted overlapping features in patients with SLE caused by C1q deficiency and CANDLE syndrome [4]. The patient we report also presented with SLE-like features, with painless oral ulcers, proteinuria, positive antinuclear antibody titer, positive anti-ß2-GP1 titer, hypocomplementemia, autoimmune hemolytic anemia, and thrombocytopenia, which, based on laboratory and clinical findings meant that he fulfilled the classification criteria of the American College of Rheumatology.…”

supporting

confidence: 56%

Systemic Autoimmunity in a Patient With CANDLE Syndrome

Yamazaki‐Nakashimada¹,

Santos-Chávez²,

Jesús³

et al. 2019

J Investig Allergol Clin Immunol

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supporting

confidence: 56%

Systemic Autoimmunity in a Patient With CANDLE Syndrome

Yamazaki‐Nakashimada¹,

Santos-Chávez²,

Jesús³

et al. 2019

J Investig Allergol Clin Immunol

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“…C1q AR SLE, AGS [18][19][20][21][22][23][24] C1r/C1s AD [7,25,26] C2 AR [27] C4 AR [28][29][30][31][32] Type…”

Section: Complement Pathwaymentioning

confidence: 99%

“…Deficiencies of proteins in the early steps of the complement pathway are generally associated with both autoimmune diseases and infections. Conversely, deficiencies in late complement proteins are merely associated with an increase in infection rates [18,106].…”

Section: Complement Pathwaymentioning

confidence: 99%

“…The frequency of SLE or SLE-like phenotype is approximately 90% in patients with C1q deficiency, 65% in C1r/C1s deficiency, 75% in C4 deficiency and 10% in C2 deficiency [7,[22][23][24]26,27,[110][111][112][113][114]. Compared to the polygenic form of SLE, more severe disease course, frequent cutaneous manifestations and a high mortality rate are noted [7,12,18,[22][23][24][25][26]114,115]. The association of C1q and C1r deficiency with an upregulation in type I IFN signaling may explain the increased prevalence of SLE in early complement deficient patients [18,112].…”

Section: Complement Pathwaymentioning

confidence: 99%

“…Compared to the polygenic form of SLE, more severe disease course, frequent cutaneous manifestations and a high mortality rate are noted [7,12,18,[22][23][24][25][26]114,115]. The association of C1q and C1r deficiency with an upregulation in type I IFN signaling may explain the increased prevalence of SLE in early complement deficient patients [18,112]. The phenotype of patients with early complement deficiencies can also be more severe due to recurrent infections.…”

Section: Complement Pathwaymentioning

confidence: 99%

See 2 more Smart Citations

New Horizons in the Genetic Etiology of Systemic Lupus Erythematosus and Lupus-Like Disease: Monogenic Lupus and Beyond

Demirkaya

Şahin

Romano

et al. 2020

JCM

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Systemic lupus erythematosus (SLE) is a clinically and genetically heterogeneous autoimmune disease. The etiology of lupus and the contribution of genetic, environmental, infectious and hormonal factors to this phenotype have yet to be elucidated. The most straightforward approach to unravel the molecular pathogenesis of lupus may rely on studies of patients who present with early-onset severe phenotypes. Typically, they have at least one of the following clinical features: childhood onset of severe disease (<5 years), parental consanguinity, and presence of family history for autoimmune diseases in a first-degree relative. These patients account for a small proportion of patients with lupus but they inform considerable knowledge about cellular pathways contributing to this inflammatory phenotype. In recent years with the aid of new sequencing technologies, novel or rare pathogenic variants have been reported in over 30 genes predisposing to SLE and SLE-like diseases. Future studies will likely discover many more genes with private variants associated to lupus-like phenotypes. In addition, genome-wide association studies (GWAS) have identified a number of common alleles (SNPs), which increase the risk of developing lupus in adult age. Discovery of a possible shared immune pathway in SLE patients, either with rare or common variants, can provide important clues to better understand this complex disorder, it’s prognosis and can help guide new therapeutic approaches. The aim of this review is to summarize the current knowledge of the clinical presentation, genetic diagnosis and mechanisms of disease in patents with lupus and lupus-related phenotypes.

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The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology Points to Consider for Diagnosis and Management of Autoinflammatory Type I Interferonopathies: CANDLE/PRAAS, SAVI, and AGS

Gedik

Lamot

Romano

et al. 2022

Arthritis & Rheumatology

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Objective Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome‐associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)–associated vasculopathy with onset in infancy (SAVI), and Aicardi‐Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of “points to consider” to improve diagnosis, treatment, and long‐term monitoring of patients with these rare diseases. Methods Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates, and an allied health care professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires, and consensus methodology, “points to consider” to guide patient management were developed. Results The Task Force devised consensus and evidence‐based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment, and long‐term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI, and AGS. Conclusion These points to consider represent state‐of‐the‐art knowledge to guide diagnostic evaluation, treatment, and management of patients with CANDLE/PRAAS, SAVI, and AGS and aim to standardize and improve care, quality of life, and disease outcomes.

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Monogenic interferonopathies: Phenotypic and genotypic findings of CANDLE syndrome and its overlap with C1q deficient SLE.

Cited by 25 publications

References 26 publications

Systemic Autoimmunity in a Patient With CANDLE Syndrome

Systemic Autoimmunity in a Patient With CANDLE Syndrome

New Horizons in the Genetic Etiology of Systemic Lupus Erythematosus and Lupus-Like Disease: Monogenic Lupus and Beyond

The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology Points to Consider for Diagnosis and Management of Autoinflammatory Type I Interferonopathies: CANDLE/PRAAS, SAVI, and AGS

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