LowC4,C4AandC4Bgene copy numbers are stronger risk factors for juvenile-onset than for adult-onset systemic lupus erythematosus

Pereira, Kaline Medeiros Costa; Faria, Atila Granado A.; Liphaus, Bernadete L.; Jesús, Adriana Almeida de; Silva, Clóvis A.; Carneiro‐Sampaio, Magda; Andrade, Luís Eduardo Coelho

doi:10.1093/rheumatology/kev436

Cited by 38 publications

(24 citation statements)

References 19 publications

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“…The present study confirmed, also in the peculiar blended Brazilian ethnicity, the association between low total C4 and C4A GCN and adult SLE previously reported in other ethnicities [7][8][9], and expanded this concept to low C4B GCN. This result corroborates a previous study with 90 patients with juvenile SLE and 170 patients with adult-onset SLE in Brazilian population, which showed a strong association with low number of copies of C4, C4A and C4B with SLE, remarkably in juvenile-onset lupus [26]. In addition, the present study originally demonstrated the impact of a lower C4A GCN on the progression of the disease.…”

Section: Discussionsupporting

confidence: 93%

“…While the association between low C4 GCN and SLE has been consistently demonstrated, the impact of C4 CNV on the disease phenotypes remains controversial. In our previous study in juvenile-onset SLE, the low GCN for total C4 and C4A was associated with pericarditis [26]. A study in Chinese Han patients reported an association between low C4A deficiency and arthritis [7], while a more recent study reported serositis as the only clinical manifestation associated with low C4A GCN [17].…”

Section: Discussionmentioning

confidence: 89%

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Impact of C4, C4A and C4B gene copy number variation in the susceptibility, phenotype and progression of systemic lupus erythematosus

et al. 2019

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Background: Complement component 4 (C4) gene copy number (GCN) affects the susceptibility to systemic lupus erythematosus (SLE) in different populations, however the possible phenotype significance remains to be determined. This study aimed to associate C4A, C4B and total C4 GCN and SLE, focusing on the clinical phenotype and disease progression. Methods: C4, C4A and C4B GCN were determined by real-time PCR in 427 SLE patients and 301 healthy controls, which underwent a detailed clinical evaluation according to a pre-established protocol. Results: The risk of developing SLE was 2.62 times higher in subjects with low total C4 GCN (< 4 copies, OR = 2.62, CI = 1.77 to 3.87, p < 0.001) and 3.59 times higher in subjects with low C4A GCN (< 2 copies; OR = 3.59, CI = 2.15 to 5.99, p < 0.001) compared to those subjects with normal or high GCN of total C4 (≥4) and C4A (≥2), respectively. An increased risk was also observed regarding low C4B GCN, albeit to a lesser degree (OR = 1.46, CI = 1.03 to 2.08, p = 0.03). Furthermore, subjects with low C4A GCN had higher permanent disease damage as assessed by the Systemic Lupus International Collaborating Clinics-Damage Index (SLICC-DI; median = 1.5, 95% CI = 1.2-1.9) than patients with normal or high copy number of C4A (median = 1.0, 95% CI = 0.8-1.1; p = 0.004). There was a negative association between low C4A GCN and serositis (p = 0.02) as well as between low C4B GCN and arthritis (p = 0.02). Conclusions: This study confirms the association between low C4 GCN and SLE susceptibility, and originally demonstrates an association between low C4A GCN and disease severity.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 89%

Impact of C4, C4A and C4B gene copy number variation in the susceptibility, phenotype and progression of systemic lupus erythematosus

et al. 2019

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“…A recent research showed that low total C4, C4A, and C4B gene copy number (GCN) were associated with a stronger risk for developing cSLE than adult SLE. Additionally, low total C4 and C4A GCN were risk factors for pericarditis in cSLE patients [13].…”

mentioning

confidence: 91%

Childhood-onset systemic lupus erythematosus: early disease manifestations that the paediatrician must know

Silva¹

2016

Expert Review of Clinical Immunology

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“…[32] In addition, deficiencies in components of the complement system are prone to develop SLE. [33] …”

Section: Discussionmentioning

confidence: 99%

Increased risk of systemic lupus erythematosus in pregnancy-induced hypertension

et al. 2016

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Dysregulation of the immune system plays a role in the pathogenesis of both, pregnancy-induced hypertension (PIH) and systemic lupus erythematosus (SLE). It is well known that SLE predisposes to be complicated with PIH. However, few studies have attempted to investigate whether PIH increased subsequent SLE risk.The objectives of this study were to assess the association between PIH and subsequent SLE risk and identify predictive risk factors.Patients with newly diagnosed PIH were selected from the Taiwan National Health Insurance Research Database (NHIRD) and compared with a matched cohort without PIH based on age and the year of delivery. The incidence of new-onset SLE was evaluated in both cohorts. The overall observational period was from January 1, 2000 to December 31, 2013.Among the 23.3 million individuals registered in the NHIRD, 29,091 patients with PIH and 116,364 matched controls were identified. The incidence of SLE was higher among patients with PIH than in the matched controls (incidence rate ratio [IRR] = 4.02, 95% confidence interval [CI] 3.98–4.05, P < 0.0001). The IRR for subsequent SLE development remained significantly higher in all stratifications during the follow-up years. The multivariate Cox regression model was performed and the results showed that PIH may be an independent risk factors for the development of subsequent SLE (hazard ratio [HR] = 2.87, 95% CI 2.07–3.98, P < 0.0001). Moreover, multivariate Cox regression model was used again among the PIH cohort only in order to identify the possible risk factors for subsequent SLE in the population with PIH.Patients with PIH may have higher risk of developing newly diagnosed SLE than those without PIH. In addition, among individuals who have experienced PIH, those younger than 30 years, having experienced preeclampsia/eclampsia, single parity, preterm birth, or chronic kidney disease, may display an increased subsequent risk of SLE.

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LowC4,C4AandC4Bgene copy numbers are stronger risk factors for juvenile-onset than for adult-onset systemic lupus erythematosus

Abstract: Low total C4, C4A and C4B GCN were associated with a stronger risk for developing JSLE than aSLE. Additionally, low total C4 and C4A GCN are risk factors for pericarditis in JSLE.

Cited by 38 publications

References 19 publications

Impact of C4, C4A and C4B gene copy number variation in the susceptibility, phenotype and progression of systemic lupus erythematosus

Impact of C4, C4A and C4B gene copy number variation in the susceptibility, phenotype and progression of systemic lupus erythematosus

Childhood-onset systemic lupus erythematosus: early disease manifestations that the paediatrician must know

Increased risk of systemic lupus erythematosus in pregnancy-induced hypertension

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