Autoantibody status in systemic sclerosis patients defines both cancer risk and survival with ANA negativity in cases with concomitant cancer having a worse survival

Watad, Abdulla; McGonagle, Dennis; Bragazzi, Nicola Luigi; Tiosano, Shmuel; Comaneshter, Doron; Shoenfeld, Yehuda; Cohen, Arnon D; Amital, Howard

doi:10.1080/2162402x.2019.1588084

Cited by 27 publications

(23 citation statements)

References 36 publications

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“…These autoantibodies might have a "protective effect" against cancer as suggested by a higher prevalence among RNA-PolIII positive patients without cancer (16 positive sera in 88 SSc patients without cancer versus 3 in 80 patients with cancer) [31]. So, anti-RPA194 antibodies may stem from the development of cancer in a subgroup of patients [31], which is in line with the putative role of autoimmunity in the control of cancer spreading [32].…”

Section: First Peak: the Close Temporal Relationship Between Ssc And mentioning

confidence: 71%

Biphasic Temporal Relationship between Cancers and Systemic Sclerosis: A Clinical Series from Montpellier University Hospital and Review of the Literature

Partouche

Goulabchand

Maria

et al. 2020

JCM

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Cancer among patients with systemic sclerosis (SSc) would appear to be more prevalent than in the general population. Pathophysiological hypotheses are multiple, involving intertwined factors such as immune system antitumoral response, oxygen species dysregulation, and immunosuppressive treatments. We aimed to identify SSc patients with cancer monitored at our center, describing their clinical and immunological characteristics, such as cancer-specific outcomes. We focused in particular on the temporal relationships between cancer onset and SSc diagnosis. A retrospective study was conducted on SSc patients from Montpellier University Hospital from 2003 to 2018. Clinical characteristics and outcomes of each SSc patient with cancer were recorded. Fifty-five patients with SSc and at least one cancer was included (median age 56 years (47–66)), with a median follow-up time of 11 years (4–15). Sixty-four metachronous malignancies were identified (12 patients had two cancers). Among them, early-onset cancer occurrences (±5 years from SSc diagnosis) included 23 cancers (39% breast cancers, 13% lung cancers, and 13% gastro-intestinal tract cancers). Twenty-two cancers occurred 10 years (±5 years) after SSc diagnosis (14% breast cancers, 23% gastrointestinal (GI) tract cancers, and 18% lung cancers). Patients without any of the two autoantibodies (anti-centromere (ACA) and anti-topoisomerase (ATA-scl70) antibodies) were more prevalent in the early-onset cancer subgroup (14 vs. 6, p = 0.02). This study brought to light two peaks of cancer occurrence in SSc patients. Early-onset cancers were associated with SSc with a specific immunological signature. Late-onset cancers might be the consequence of a subtle interplay between repeated target organ inflammation, immunosuppressant use, mesenchymal cell dysfunction and subsequent genetic alterations.

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Section: First Peak: the Close Temporal Relationship Between Ssc And mentioning

confidence: 71%

Biphasic Temporal Relationship between Cancers and Systemic Sclerosis: A Clinical Series from Montpellier University Hospital and Review of the Literature

Partouche

Goulabchand

Maria

et al. 2020

JCM

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“…It can either manifest as isolated thyroid disorder or in the context of systemic autoimmune diseases such as SLE or RA . Several studies have reported the association of autoimmune thyroid disorders with SSc . However, while most reports showed a robust link between hypothyroidism and SSc, an association with hyperthyroidism is yet to be established.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 Several studies have reported the association of autoimmune thyroid disorders with SSc. 16,22,23 However, while most reports showed a robust link between hypothyroidism and SSc, an association with hyperthyroidism is yet to be established. In a previous study, out of a total of 210 SSc patients, 14.3% were found to have autoimmune thyroid disorder, yet, only one patient had Graves' disease.…”

Section: Discussionmentioning

confidence: 99%

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Systemic sclerosis patients are at higher risk of hyperthyroidism and have a worse survival than those without hyperthyroidism: A nationwide population‐based cohort study

Akuka

Watad

Comaneshter

et al. 2019

Eur J Clin Investigation

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Background A high prevalence of thyroid disorders has been reported in patients with autoimmune diseases. The link between hyperthyroidism and systemic sclerosis (SSc) has been relatively overlooked, and only a few studies utilizing small samples or case reports have been reported so far. Objectives To investigate the association between SSc and hyperthyroidism. Methods We designed a case‐control study utilizing the medical database of the Clalit Health Services. Chi‐square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. Results The study included 2,431 SSc patients and 12,710 age‐ and sex‐matched controls. The mean age of the study population was 63.32 ± 18.06 years (median 66 years), and female‐to‐male ratio was 4.5:1. Age (P < .0001, OR 1.03 [95% CI 1.02‐1.04]), female sex (P = .0015, OR 1.86 [95% CI 1.27‐ 2.74]) and diagnosis of SSc (P = .0011, OR 1.81[95% CI 1.27‐2.58]) were all independently associated with hyperthyroidism. Patients with SSc and hyperthyroidism had 1.54‐fold increase of mortality rates during a mean follow‐up of 17 years than SSc patients without hyperthyroidism, even though at the Cox multivariate survival analysis, only age (HR 1.06 [95% CI 1.06‐1.07], P < .0001) and diagnosis of SSc (HR 2.35 [CI 2.06 to 2.69], P < .0001) resulted associated with a higher risk of mortality. Conclusions Hyperthyroidism is highly prevalent among SSc patients and can negatively impact on their survival rates. Therefore, a pre‐emptive screening may be warranted in all SSc patients. Further studies are needed to evaluate whether tight control and optimal treatment for hyperthyroidism may lead to a reduction of all‐cause mortality in patients with SSc.

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“…Despite the association of ANA with malignant disease, different studies have shown that patients with ANA had a more favorable cancer outcome when compared to patients negative for ANA, possibly explained by more vigorous activation of the immune system fighting against the malignant cells (16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Antinuclear Antibodies With a Homogeneous and Speckled Immunofluorescence Pattern Are Associated With Lack of Cancer While Those With a Nucleolar Pattern With the Presence of Cancer

2020

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Background: Different antinuclear antibody (ANA) patterns have been associated with the presence of cancer, while other are typically seen in autoimmune diseases. This study aims to investigate the association between ANA and cancer, focusing on patients with ANA with a nucleolar indirect immunofluorescence (IIF) pattern. Materials and Methods: ANA patterns and positivity of antibodies against nuclear antigens (NA), in particular those responsible for a nucleolar ANA pattern and/or associated with systemic sclerosis (CENP-A/B, fibrillarin, Ku, NOR-90, PM/Scl-100, PM/Scl-75, RNAP-III, Scl-70, Ro52/TRIM21, and Th/To) were analyzed and correlated to an internal database of patients with cancer. Results: The study included 15,728 patients who had an ANA analysis, 386 patients who had immunodot analysis for antibody/ies against/to specific NA and 15,701 patients diagnosed with cancer. The presence of ANA with a nucleolar pattern showed an increased relative risk (RR 1.5, 95%CI 1.03-2.3) for an associated cancer. Anti-Scl70 and anti-RNAP-III were associated with cancer in 15 and 14%, respectively. The presence of ANA with a homogeneous & speckled (HS) pattern was significantly associated with the absence of cancer (p < 0.01). Patients with a HS pattern were found to have a lower relative risk (RR 0.7, 95%CI 0.5-0.9) of having cancer compared to those with other patterns. Conclusions: Larger studies are needed to investigate which particular antibody/ies against/to specific NA is responsible for the association between nucleolar ANA and cancer, but anti-Scl70 and anti-RNAP-III, which is frequently associated with the presence of anti-RNAP-I, are good candidates to explain this association. Patients with a nucleolar pattern might be considered for cancer screening, in particular if they have anti-Scl70 and anti-RNAP-III antibodies.

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Autoantibody status in systemic sclerosis patients defines both cancer risk and survival with ANA negativity in cases with concomitant cancer having a worse survival

Cited by 27 publications

References 36 publications

Biphasic Temporal Relationship between Cancers and Systemic Sclerosis: A Clinical Series from Montpellier University Hospital and Review of the Literature

Biphasic Temporal Relationship between Cancers and Systemic Sclerosis: A Clinical Series from Montpellier University Hospital and Review of the Literature

Systemic sclerosis patients are at higher risk of hyperthyroidism and have a worse survival than those without hyperthyroidism: A nationwide population‐based cohort study

Antinuclear Antibodies With a Homogeneous and Speckled Immunofluorescence Pattern Are Associated With Lack of Cancer While Those With a Nucleolar Pattern With the Presence of Cancer

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