Anti-RO/SSA and anti-La/SSB antibodies: Association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus

Novak, Glaucia V.; Marques, Mariana Correia; Balbi, Verena; Gormezano, Natali W.S.; Kozu, Kátia; Sakamoto, Ana Paula; Pereira, Rosa Maria Rodrigues; Terreri, Maria Teresa; Magalhães, Cláudia Saad; Guariento, Andressa; Sallum, Adriana Maluf Elias; Marini, Roberto; Ferriani, Virgínia Paes Leme; Barbosa, Cássia Maria Passarelli Lupoli; Castro, Tânia Caroline Monteiro de; Ramos, Valéria C.; Bonfá, Eloísa; Silva, Clóvis A.

doi:10.1016/j.autrev.2016.12.004

Cited by 50 publications

(44 citation statements)

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“…Rates of anti-Ro antibodies present in cSLE patients range from 23-56% and anti-La antibodies range from 7-37% [21][22][23]. However, there are very few reports of secondary SS in cSLE, mostly con ned to case series [5][6][7]. Our imaging ndings may represent subclinical disease that could manifest itself with more overt clinical symptoms as time goes on.…”

Section: Discussionmentioning

confidence: 97%

Findings and Feasibility of Major Salivary Gland Ultrasound in Childhood-Onset Systemic Lupus Erythematosus: A Pilot Study

McDonald

Vega‐Fernandez

Ting

2020

Preprint

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Background: Childhood-onset systemic lupus erythematosus (cSLE) is a complex autoimmune disorder with multi-organ manifestations and can be associated with other rheumatic diseases including Sjögren’s syndrome (SS). Salivary gland ultrasound (SGUS) represents a noninvasive tool to screen for salivary gland disease in rheumatic disease patients. The aims of this cross-sectional study were to determine feasibility of major SGUS in a clinic setting and to identify characteristics in a cohort of cSLE patients (without confirmed SS) that may be associated with salivary gland abnormalities consistent with secondary SS.Methods: Patients with SLE onset prior to age 18 were recruited. Patients completed questionnaires rating symptoms and underwent major SGUS examination. Disease and demographic differences were compared between cSLE patients with abnormal SGUS vs. cSLE patients with normal SGUS using t-tests and Fisher’s exact tests.Results: 31 cSLE patients were recruited, 84% were female, 55% were Caucasian. The average disease duration among all patients was 5 years. Average time to complete the SGUS examination and scoring protocol was 7 minutes. 35% of SGUS scores were abnormal and significantly associated with IgG level at diagnosis, and anti-Ro and anti-La antibodies.Conclusions: This is the first study to assess major SGUS in a cohort of patients with cSLE without prior diagnoses of SS. The SGUS protocol was feasible to perform by rheumatologists in a clinic setting. Although the sample size was small, SGUS abnormalities were identified in one-third of patients. IgG level at diagnosis and anti-Ro and anti-La antibodies may be associated with SGUS abnormalities.

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Section: Discussionmentioning

confidence: 97%

Findings and Feasibility of Major Salivary Gland Ultrasound in Childhood-Onset Systemic Lupus Erythematosus: A Pilot Study

McDonald

Vega‐Fernandez

Ting

2020

Preprint

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“…To date, the relationship between anti-SSA(Ro)-antibodies and neurological manifestations in pSS is not sufficiently understood, in particular since both antibody-negative courses and isolated antibody-positive associated myelitis have been described [7,8,10,19,24,25]. Only a few study groups have investigated the impact of CSF-anti-SSA(Ro)-antibodies in patients with neurological involvement of primary rheumatological disorders such as pSS or systemic lupus erythematosus, reporting an intrathecal synthesis occurring partly prior to systemic manifestation [9,26].…”

Section: Discussionmentioning

confidence: 99%

Clinical, Radiological, and Laboratory Features of Spinal Cord Involvement in Primary Sjögren’s Syndrome

Butryn

Neumann

Rolfes

et al. 2020

JCM

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Objective: To identify radiological and laboratory hallmarks in patients with primary Sjögren’s syndrome (pSS) presenting with spinal cord involvement. Methods: Clinical and laboratory routine parameters were analyzed in a retrospective multicenter case series of four patients who developed myelitis associated with pSS. Serological and cerebrospinal fluid (CSF) measurements of pSS associated anti-SSA(Ro)-antibodies were initiated, and CSF neurofilament light chain (NFL) levels were assessed. NFL values were compared with results from 15 sex- and age-matched healthy controls. Radiological assessment was performed using multi-sequence spinal cord magnetic resonance imaging. Results: Three of the four patients initially developed neurological signs suggestive of myelitis and were subsequently diagnosed with pSS. All patients presented a longitudinal spinal T2-hyperintense lesion in the cervical spinal cord, whereas only two patients showed pleocytosis and oligoclonal bands in the CSF. Median (range) CSF-NFL levels were significantly elevated in patients compared to controls (6672 pg/mL (621–50,000) vs. 585 pg/mL (357–729), p = 0.009). One patient showed sustained, highly increased NFL levels (50,000 pg/mL) in the initial assessment when radiological signs of axonal injury were still absent. Anti-SSA(Ro)-antibodies were found in the serum of three patients, while two patients additionally presented intrathecal anti-SSA(Ro)-antibody production. Elevated CSF-NFL levels and intrathecal synthesis of anti-SSA(Ro)-antibodies were associated with a relapsing and treatment-resistant disease course. Conclusion: Inflammatory spinal cord lesions associated with pSS are a rare but serious disease leading to severe disability. NFL and anti-SSA(Ro)-antibodies in CSF might serve as prognostic biomarkers and should be routinely assessed in patients with pSS.

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“…In addition, SSB is one of the down-regulated hub genes in PPI module. Autoantibodies to the encoded protein are found associated with some other autoimmune disease including Sjogren syndrome27 and systemic lupus erythematosus 28. Therefore, the processes including cilium assembly and eNOS activation, and some genes including RABEP1 and SSB would participant in progressive fibrosis and autoimmune response of lcSSc.The pathways of NCAM1 interactions and CREB phosphorylation through the activation of CaMKII were enriched by up-regulated genes.…”

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confidence: 99%

Abnormalities in endothelial form of nitric oxide synthase is pathogenic in limited cutaneous systemic sclerosis

Jia

Lei

2019

J of Cosmetic Dermatology

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Summary Background Limited cutaneous systemic sclerosis is one subtype of systemic sclerosis which is characterized by a prototypic multisystem fibrotic disorder. Objective This study aimed to further investigate the pathological mechanism of limited cutaneous systemic sclerosis (lcSSc). Methods The dataset GSE76807 generated from 10 lcSSc patients and five healthy controls was used. After the preprocessing of the original data, differentially expressed genes (DEGs) were identified and then performed functional analysis, protein–protein interaction (PPI) network and module analysis. Additionally, the transcription factors (TFs) and miRNAs which potentially regulating DEGs were identified and the co‐regulatory network was constructed. Finally, DEGs targeted by current drugs were identified. Real‐time quantitative PCR analyses of some DEGs in mice with lcSSc were performed. Results Total 203 up‐regulated and 189 down‐regulated DEGs were obtained. The up‐regulated genes were enriched in protein interactions at the synapses neuronal system, NCAM1 interactions, and CREB phosphorylation through the activation of CaMKII, while, cilium assembly, and endothelial form of nitric oxide synthase (eNOS) activation were enriched by down‐regulated genes. SCRT2 and RABEP1 regulated by miR‐218 were hub nodes in the network. DRD4 and GRIN2D were the main drug targets. RABEP1 and SSB were found lowly expressed in mice model with lcSSc. Conclusion Endothelial form of NOS activation would be suppressed, and the process of neuronal migration and outgrowth would be activated to participant in the pathological mechanism of lcSSc.

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Anti-RO/SSA and anti-La/SSB antibodies: Association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus

Cited by 50 publications

References 21 publications

Findings and Feasibility of Major Salivary Gland Ultrasound in Childhood-Onset Systemic Lupus Erythematosus: A Pilot Study

Findings and Feasibility of Major Salivary Gland Ultrasound in Childhood-Onset Systemic Lupus Erythematosus: A Pilot Study

Clinical, Radiological, and Laboratory Features of Spinal Cord Involvement in Primary Sjögren’s Syndrome

Abnormalities in endothelial form of nitric oxide synthase is pathogenic in limited cutaneous systemic sclerosis

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