Single-specificity anti-Ku antibodies in an international cohort of 2140 systemic sclerosis subjects

S, Hoa; Hudson, Marie; Troyanov, Yves; Proudman, Susanna; Walker, Jenny; Stevens, Wendy; Nikpour, Mandana; Assassi, Shervin; Mayes,; M, Wang; M, Baron; Mj, Fritzler; Study, Genetics

doi:10.1097/md.0000000000004713

Cited by 60 publications

(30 citation statements)

References 59 publications

(74 reference statements)

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“…Conversely, other antibodies associated with a wide spectrum of autoimmune diseases and ILD such as anti-neutrophil cytoplasmic antibodies (ANCA) [37] and anti-Ku antibody should be considered [38,39]. Furthermore, some reports described patients with ANCA-positive interstitial pneumonia.…”

Section: Discussionmentioning

confidence: 99%

State of the art in interstitial pneumonia with autoimmune features: a systematic review on retrospective studies and suggestions for further advances

Sambataro

Sambataro²,

Torrisi

et al. 2018

Eur Respir Rev

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@ERSpublications IPAF retrospective cohorts show numerous differences between them. We propose some ideas to improve IPAF criteria http://ow.ly/eubC30jlGJO ABSTRACT The term interstitial pneumonia with autoimmune features (IPAF) has been proposed to define patients with interstitial lung disease (ILD) associated with autoimmune signs not classifiable for connective tissue diseases (CTDs). This new definition overcomes previous nomenclatures and provides a uniform structure for prospective studies through specific classification criteria.This work evaluates the characteristics of IPAF patients reported in the literature, to highlight potential limits through a comparative analysis and to suggest better performing classification criteria.Four retrospective studies on the IPAF population have been considered. The study subjects differed in age, sex, smoking habit, ILD pattern and outcomes. Another important difference lies in the diverse items considered in the classification criteria. The retrospective design of the studies and the absence from some of them of a rheumatologist clearly involved in the diagnosis may have influenced the data, but current IPAF criteria seem to include a rather heterogeneous population. To overcome these discrepancies, this review suggests a limitation in the use of single items and the exclusion of extremely specific CTD criteria. This should avoid the definition of IPAF for those diseases at different stages or at early onset. The investigation of a functional or morphological cut-off of pulmonary involvement would be useful.

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Section: Discussionmentioning

confidence: 99%

State of the art in interstitial pneumonia with autoimmune features: a systematic review on retrospective studies and suggestions for further advances

Sambataro

Sambataro²,

Torrisi

et al. 2018

Eur Respir Rev

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“…Antibodies to various components of this macromolecular DNA-PK complex have been reported in SLE and related SARD [84]. Although initially thought to be specific for polymyositis/SSc overlap syndrome [85], subsequent studies demonstrated that anti-Ku antibodies are also found in SLE, MCTD and SSc [86][87][88]. Additional studies revealed that anti-Ku antibodies were also detected in a variety of other SARD and were associated with polymyositis/SSc overlap syndrome in Japanese cohorts but with SLE and overlap syndromes in African-American cohorts [87].…”

Section: Dna-dependent Protein Kinase (Dna-pk/ku)mentioning

confidence: 99%

Challenges and Advances in SLE Autoantibody Detection and Interpretation

Choi

Fritzler

2019

Curr Treat Options in Rheum

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Purpose of review This review is an overview of key autoantibodies used in the diagnosis and management of SLE. Questions addressed are the advantages to but limitations of ANA testing and what are the key considerations in ordering ANA tests and then interpreting the ANA results. Recent findings There is a progressive move towards • Solid-phase multi-analyte arrays with algorithmic analysis (SPMAAA) • Closing the seronegative gap in SLE • Harmonization of ANA testing Summary As an approach to limiting morbidity and rising health care costs associated with SLE, the future of ANA testing should focus on making an accurate and actionable diagnosis of very early SLE. To achieve this goal, harmonization of autoantibody testing will be important. Autoantibodies in SLE Choi and Fritzler

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“…Myositis and arthritis combined with interstitial lung disease are the most prominent features of patients with this type of antibodies [46]. Moreover, it was found that individuals with anti-Ku are more likely to have a history of malignancy at the time of SSc diagnosis compared with anti-Ku-negative patients (27% vs. 8%) [47]. The overall increased risk was calculated as 4.6-fold higher in anti-Ku-positive patients.…”

Section: Anti-ku Antibodiesmentioning

confidence: 99%

“…The overall increased risk was calculated as 4.6-fold higher in anti-Ku-positive patients. The most commonly reported malignancies were melanoma, breast cancer and squamous cell skin cancer [47]. The link between anti-Ku antibodies and cancers might be explained by triggering autoimmunity via genetic alterations of the Ku antigen and molecular mimicry.…”

Section: Anti-ku Antibodiesmentioning

confidence: 99%

Antinuclear antibodies in systemic sclerosis associated with increased risk of malignancy

Stochmal¹,

Sar‐Pomian²,

Czuwara³

et al. 2018

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Patients with systemic sclerosis are at 1.5-5-fold increased risk of developing malignant diseases. It has been shown that some types of antinuclear antibodies associated with systemic sclerosis may have predictive value for development of malignant diseases in patients with systemic sclerosis. Patients with circulating anti-RNA polymerase III antibodies (RNAP) are at significantly increased risk of developing a malignant disease (breast cancer, followed by leukemias and gastrointestinal or gynecologic cancers) within 36 months from the onset of the disease (OR = 7.38). Thus, regular cancer screening is recommended in anti-RNAP III-positive patients. An increased prevalence of lung cancer was reported in patients with circulating anti-topoisomerase I antibodies (11.4%) compared to the median of 2.4% in all patients with systemic sclerosis. Among patients with circulating anti-centromere antibodies, individuals who are anti-CENP-F-positive are at increased risk of developing breast cancer or lung cancer. Anti-PM-Scl antibodies and anti-Ku antibodies are rare in systemic sclerosis, but may have some association with increased risk of malignancy in these patients as well. Thus, recent data indicate that in patients with systemic sclerosis, diverse disease-specific antinuclear antibodies may be associated with increased risk of developing malignant tumors and require especially careful preventive cancer screening. streszczenie U pacjentów z twardziną układową stwierdza się 1,5-5-krotnie podwyższone ryzyko zachorowania na choroby nowotworowe. Wykazano, że niektóre typy przeciwciał przeciwjądrowych związanych z twardziną układową mogą mieć wartość predykcyjną dla rozwoju chorób nowotworowych. U pacjentów z krążącymi przeciwciałami przeciw polimerazie III RNA (RNAP III) występuje znacznie zwiększone ryzyko rozwoju choroby nowotworowej (raka sutka, a także białaczek, nowotworów przewodu pokarmowego lub ginekologicznych) w czasie 36 miesięcy od rozpoznania twardziny układowej (OR = 7,38). W związku z tym u wszystkich pacjentów z krążącymi przeciwciałami anty-RNAP III zaleca się regularne badania przesiewowe w kierunku nowotworów. U pacjentów z krążącymi przeciwciałami przeciw topoizomerazie I stwierdzono zwiększoną częstość występowania raka płuca-11,4% w porównaniu corresponding Author/ Adres do korespondencji: prof. dr hab. n. med.

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Single-specificity anti-Ku antibodies in an international cohort of 2140 systemic sclerosis subjects

Abstract: Supplemental Digital Content is available in the text

Cited by 60 publications

References 59 publications

State of the art in interstitial pneumonia with autoimmune features: a systematic review on retrospective studies and suggestions for further advances

State of the art in interstitial pneumonia with autoimmune features: a systematic review on retrospective studies and suggestions for further advances

Challenges and Advances in SLE Autoantibody Detection and Interpretation

Antinuclear antibodies in systemic sclerosis associated with increased risk of malignancy

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