The role of BAFF and APRIL in rheumatoid arthritis

Shabgah, Arezoo Gowhari; Sarabi, Zhaleh Shariati; Tavakkol‐Afshari, Jalil; Mohammadi, Mojgan

doi:10.1002/jcp.28445

Cited by 66 publications

(53 citation statements)

References 145 publications

(189 reference statements)

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“…Our results were concordant with earlier reports demonstrating high serum APRIL levels in serum and synovial tissue of RA patients [23,24]. Our results could be explained on the basis that in the early phase of RA disease, the APRIL is produced signi cantly by dendritic cells, which leads to an increase in the proliferation of B cells; and ultimately, B cells are differentiated by APRIL producing autoantibodies [25]. Macrophages, on the other hand, are considered to be the source of APRIL in the con rmed phase of the disease [26], causes the accumulation of plasma cells in the joint, further increasing the production of in ammatory cytokines such as TNF, IL-1, and IL-6 [18].…”

Section: Discussionsupporting

confidence: 93%

Serum A Proliferation-Inducing Ligand and MicroRNA-223 are Associated with Rheumatoid Arthritis: Diagnostic and Prognostic Implications

Taha

Shaker

Taha³

et al. 2020

Preprint

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Background: Current blood-based tests for rheumatoid arthritis (RA) have inherent limitations, necessitating the need for additional new biomarkers for its diagnosis and monitoring disease activity and responsiveness to therapy. microRNAs (miRNAs) and a proliferation-inducing ligand (APRIL) are deregulated in RA and were linked to its pathogenesis. This study investigated serum levels of APRIL, miR-223 and miR-155 in RA patients, their potential as diagnostic and prognostic biomarkers, and their correlation with disease activity and clinicopathological data.Methods: 120 Egyptian patients with RA and 130 healthy controls were included. Serum miRNAs and APRIL were assayed by RT-qPCR and ELISA, respectively. Results: Serum APRIL and miR-223 were significantly upregulated, while miR-155 was unchanged in RA patients compared to controls. Serum miR-223 discriminated RA patients from controls with AUC=0.85, whereas serum APRIL superiorly distinguished the two groups with AUC=1 (sensitivity and specificity= 100% at cutoff>4.19 ng/ml) by receiver-operating-characteristic analysis. Serum miR-223 was a significant predictor for RA diagnosis in multivariate logistic regression analysis. In RA group, serum APRIL was positively correlated with disease activity score (DAS28-CRP). Serum miR-223 expression was positively correlated with serum miR-155, APRIL levels and with the presence of subcutaneous nodules. Serum miR-155 levels were correlated with antinuclear antibody titer in reverse direction.Conclusion: our results suggest serum APRIL and miR-223 could serve as potential biomarkers of RA, with miR-223 as a predictor of RA risk and APRIL as an excellent biomarker of disease activity. Our data could be implicated for accurate and blood-based non-invasive diagnosis and prognosis of RA.

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Section: Discussionsupporting

confidence: 93%

Serum A Proliferation-Inducing Ligand and MicroRNA-223 are Associated with Rheumatoid Arthritis: Diagnostic and Prognostic Implications

Taha

Shaker

Taha³

et al. 2020

Preprint

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“…A recent trial called ROSE aiming to explore the effectiveness of abatacept in RA-SS justifies the crosstalk of T cells between the two diseases [40]. Additionally, B cells are considered as central actors of SS pathogeny, and excess B cell activating factor (BAFF) level is likely to mediate autoreactive B cell accumulation [41], while in the pathogenesis of RA, B cells are involved mainly by producing autoantibodies targeted citrullinated proteins [42]. Previous studies have shown that elevated BAFF levels were positively correlated with RF/ACPA and radiographic progression in RA patients [43][44][45].…”

Section: Adaptive Immune Systemmentioning

confidence: 99%

Overlapping Sjogren’s syndrome reduces the probability of reaching target in rheumatoid arthritis patients: a propensity score matched real-world cohort from 2009 to 2019

Zhang

Gao

et al. 2020

Arthritis Res Ther

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Background: Overlapping Sjogren's syndrome (SS) is not uncommon in rheumatoid arthritis (RA) and considered as a probable detrimental factor of RA. But data on the impact of overlapping SS on RA therapeutic response is limited. Our current study aimed to identify the effect in a real-world cohort from 2009 to 2019. Methods: The medical records of RA patients who visited the rheumatology clinic of our medical center from 2009 to 2019 were reviewed. Their composite disease activity scores at each follow-up point were collected. The therapeutic response between RA patients with SS (RA-SS) and without (RA-noSS) was compared. To correct confounders which may affect the therapeutic response, both propensity score matched and unmatched cohorts were analyzed by using the Cox proportional hazards model. Results: Among the 1099 RA patients, 129 (11.7%) overlapped with SS were validated by positive anti-SSA or a minor salivary gland biopsy with histological changes suggestive of SS. After propensity score matching based on their baseline characteristics, 126 of 129 RA-SS and 126 of 970 RA-noSS patients were statistically extracted. Overlapping SS was associated with a 29%, 26%, 18%, and 22% lower probability of reaching remission defined by DAS28-ESR, DAS28-CRP, SDAI, and CDAI in RA patients, respectively. Similar decreased probability of reaching low disease activity was also observed. Although ESR was most significantly affected (HR 0.69, 95% CI 0.61-0.79), other component of composite RA disease activity score was also affected by overlapping SS. Stratification by age, RF/ ACPA status, or baseline DAS28-CRP was not associated with change of results. Conclusions: Overlapping SS is associated with lower probability of reaching remission or low disease activity in RA patients and should be regarded as one of the poor prognostic factors.

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“…Our results were concordant with earlier reports demonstrating high serum APRIL levels in serum and synovial tissue of RA patients (Tayel et al 2013 ; Boghdadi et al 2015 ). Our results could be explained on the basis that in the early phase of RA disease, the APRIL is produced significantly by dendritic cells, which leads to an increase in the proliferation of B cells; and ultimately, B cells are differentiated by APRIL producing autoantibodies (Shabgah et al 2019 ). Macrophages, on the other hand, are considered to be the source of APRIL in the confirmed phase of the disease (Ancuta et al 2017 ), causes the accumulation of plasma cells in the joint, further increasing the production of inflammatory cytokines such as TNF, IL-1, and IL-6 (Zhao et al 2014 ).…”

Section: Discussionmentioning

confidence: 87%

Serum a proliferation-inducing ligand and MicroRNA-223 are associated with rheumatoid arthritis: diagnostic and prognostic implications

Taha

Shaker

Abdelsalam³

et al. 2020

Mol Med

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Background Current blood-based tests for rheumatoid arthritis (RA) have inherent limitations, necessitating the need for additional new biomarkers for its diagnosis and monitoring disease activity and responsiveness to therapy. MicroRNAs (miRNAs) and a proliferation-inducing ligand (APRIL) are deregulated in RA and were linked to its pathogenesis. This study investigated serum levels of APRIL, miR-223 and miR-155 in RA patients, their potential as diagnostic and prognostic biomarkers, and their correlation with disease activity and clinicopathological data. Methods One hundred and twenty Egyptian patients with RA and 130 healthy controls were included. Serum miRNAs and APRIL were assayed by RT-qPCR and ELISA, respectively. Results Serum APRIL and miR-223 were significantly upregulated, while miR-155 was unchanged in RA patients compared to controls. Serum miR-223 discriminated RA patients from controls with AUC = 0.85, whereas serum APRIL superiorly distinguished the two groups with AUC = 1 (sensitivity and specificity = 100% at cutoff> 4.19 ng/ml) by receiver-operating-characteristic analysis. Serum miR-223 was a significant predictor for RA diagnosis in multivariate logistic regression analysis. In RA group, serum APRIL was positively correlated with disease activity score (DAS28-CRP). Serum miR-223 expression was positively correlated with serum miR-155, APRIL levels and with the presence of subcutaneous nodules. Serum miR-155 levels were correlated with antinuclear antibody titer in reverse direction. Conclusion Our results suggest serum APRIL and miR-223 could serve as potential biomarkers of RA, with miR-223 as a predictor of RA risk and APRIL as an excellent biomarker of disease activity. Our data could be implicated for accurate and blood-based non-invasive diagnosis and prognosis of RA.

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The role of BAFF and APRIL in rheumatoid arthritis

Cited by 66 publications

References 145 publications

Serum A Proliferation-Inducing Ligand and MicroRNA-223 are Associated with Rheumatoid Arthritis: Diagnostic and Prognostic Implications

Serum A Proliferation-Inducing Ligand and MicroRNA-223 are Associated with Rheumatoid Arthritis: Diagnostic and Prognostic Implications

Overlapping Sjogren’s syndrome reduces the probability of reaching target in rheumatoid arthritis patients: a propensity score matched real-world cohort from 2009 to 2019

Serum a proliferation-inducing ligand and MicroRNA-223 are associated with rheumatoid arthritis: diagnostic and prognostic implications

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