IMSYC immunologic synovitis score: A new score for synovial membrane characterization in inflammatory and non-inflammatory arthritis

Najm, Aurélie; Goff, Benoît Le; Venet, Guillaume; Garraud, Thomas; Amiaud, Jérôme; Biha, Noura; Charrier, Céline; Touchais, S.; Crenn, Vincent; Blanchard, Frédéric; Krenn, Veit

doi:10.1016/j.jbspin.2018.04.004

Cited by 21 publications

(20 citation statements)

References 18 publications

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“…Plasmocytes infiltration was observed in all RA and in 33-43% of non-RA biopsies, whereas PMN infiltration was present in 75% of RA biopsies and in 0-10% of non-RA biopsies. The histological score highlighted an inflammatory continuum through the 24 biopsies with an overlap between the 3 studied pathologies in agreement with other publications (1,2,15). It emphasizes the absence of a unique pattern for each studied disease and the heterogeneity of cell infiltration, either quantitatively and qualitatively.…”

Section: Discussionsupporting

confidence: 88%

“…Macrophage infiltration was also determined by using immunohistochemistry with an anti-CD68 antibody [anti-CD68 (KP-1) Primary Antibody, Ventana Medical System], and the CD68 expression was scored separately using a semi-quantitative 4 scale score (0-3) with 0 for no infiltration, 1, 2 and 3 for respectively mild, moderate and severe infiltration using a pre-defined atlas (15). The histological score was determined by the sum of the components, as for other methods (14,15), leading to a maximum of 18.…”

Section: Histological Scorementioning

confidence: 99%

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Proteins involved in the endoplasmic reticulum stress are key players in synovitis of osteoarthritis, chronic pyrophosphate arthropathy and rheumatoid arthritis, and correlate with the histological score

Seny

Bianchi

Baiwir

et al. 2020

Preprint

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Background: It is now well recognized that osteoarthritis (OA) synovial membrane presents inflammatory components. The aim of this work is to provide evidence that similar inflammatory mechanisms exist among the three pathologies presenting an inflammatory gradient: OA, chronic pyrophosphate arthropathy (CPPA) and rheumatoid arthritis (RA).Methods: Synovial biopsies of OA (n=9), CPPA (n=7) and RA (n=8) patients were first characterized by a histological score based on synovial hyperplasia and infiltration of lymphocytes, plasma cells, polymorphonuclear and macrophages. All biopsies were also analyzed by 2D-nano-UPLC-ESI-Q-Orbitrap for protein identification and quantification. Protein levels were correlated with the histological score.Results: Histological score was in the range of 3 to 8 for OA, 5 to 13 for CPPA and 12 to 17 for RA. Of the 4336 proteins identified by mass spectrometry, 51 proteins were selected for their strong correlation (p<0.001) with the histological score of which 11 proteins (DNAJB11, CALR, ERP29, GANAB, HSP90B1, HSPA1A, HSPA5, HYOU1, LMAN1, PDIA4, and TXNDC5) were involved in the endoplasmic reticulum (ER) stress. Protein levels of S100A8 and S100A9 were significantly higher in RA compared to OA (for both) or to CPPA (for S100A8 only) and also significantly correlated with the histological score. Eighteen complement component proteins were identified, but only one (complement C1q subcomponent, subunit B and C) was weakly correlated with the histological score.Conclusions: This study highlights the inflammatory gradient existing between OA, CPPA and RA synovitis either at the protein level or at the histological level. Inflamed synovitis was characterized by the overexpression of ER stress proteins.

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Section: Discussionsupporting

confidence: 88%

Section: Histological Scorementioning

confidence: 99%

Proteins involved in the endoplasmic reticulum stress are key players in synovitis of osteoarthritis, chronic pyrophosphate arthropathy and rheumatoid arthritis, and correlate with the histological score

Seny

Bianchi

Baiwir

et al. 2020

Preprint

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“…In our analysis of the subcomponents of the Krenn score (online supplementry table S5, online supplementary material), we show that US Doppler data are not correlated to any of the Krenn components in ERA visit 6-month data, which is not seen in any other group. The Krenn score does not include immunohistochemistry markers (eg, CD31), which could be used for a more precise assessment of synovial neovascularisation which could be of a central role in the ERA groups synovitis score 20. Further studies of this relationship in patients with ERA with longer observation periods are needed to evaluate why some patients with marked disease activity reduction on imaging still have ongoing histological synovitis progress.…”

Section: Discussionmentioning

confidence: 99%

“…Only samples with intact lining layer were used for grading of tissue inflammation. Synovial tissue inflammation was quantified by application of the previously validated synovitis (Krenn) score (0–9), semiquantative scores (0–4) for CD3, CD20, CD68 and CD138 and by determining the dominant pathotype of the biopsies as either lymphoid (L), myeloid (M) or fibroid (F) 6 18–20. The Krenn score was calculated as an average of three different biopsies in each patient, by scorer (SAJ) blinded for patient ID and patient group.…”

Section: Methodsmentioning

confidence: 99%

Six-month prospective trial in early and long-standing rheumatoid arthritis: evaluating disease activity in the wrist through sequential synovial histopathological analysis, RAMRIS magnetic resonance score and EULAR-OMERACT ultrasound score

et al. 2019

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IntroductionStandardised scoring systems for rheumatoid arthritis (RA) joint disease activity include Larsen score for radiographs, rheumatoid arthritis magnetic resonance imaging score (RAMRIS) for MRI and using the European League Against Rheumatisms-Outcome Measures in Rheumatology (EULAR-OMERACT) score for ultrasound (US) images. The aim of this prospective study was to investigate the relationship between histological synovitis and radiological synovitis, assessed by conventional X-ray, US and MRI of the wrist radiocarpal joint.Methods20 patients with treatment naive early RA (ERA) and 20 with long-standing RA (LRA) were enrolled in a 6-month prospective study. Patients with RA underwent US-guided synovial biopsy, X-ray and US of the wrist at enrolment and 6 months. MRI at baseline and also at 6 months for the ERA group, and scored with the RAMRIS system. X-ray was scored by Larsen score and US by the EULAR-OMERACT system. Synovial biopsy inflammation was determined by the Krenn score.ResultsIn the ERA group at baseline, Krenn score was correlated strongly with both US combined score (r = 0.77 p < 0.001) and MRI synovitis score (r = 0.85 p < 0.001), while uncorrelated at 6 months. In the LRA group at baseline, these scores correlated strongly (r = 0.83, p < 0.001) to moderately (r = 0.61, p = 0.002), and persisted at 6 months for US score (r = 0.81 p < 0.001). For all patients with RA, change in Krenn score between baseline and 6 months was correlated with both change in US combined score (r = 0.65, p < 0.001) and change in MRI synovitis score (r = 0.50, p = 0.03).ConclusionThe MRI RAMRIS synovitis score and EULAR-OMERACT US scoring system are sensitive measures of histological synovitis in LRA and ERA. After 6 months, this correlation persists in the established RA group, but not in the ERA group. Overall, decreases in MRI/US synovitis are associated with reductions in histological synovitis. The study validates the use of MRI RAMRIS and EULAR-OMERACT US scores as surrogate markers of histological synovitis in established RA and early untreated RA.

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“…Macrophage infiltration was also determined by using immunohistochemistry with an anti-CD68 antibody [anti-CD68 (KP-1) Primary Antibody, Ventana Medical System], and the CD68 expression was scored separately using a semi-quantitative 4 scale score (0-3) with 0 for no infiltration, 1, 2 and 3 for respectively mild, moderate and severe infiltration using a pre-defined atlas 15 . The histological inflammatory score was determined by the sum of the components, as for other methods 14,15 , leading to a maximum of 18.…”

mentioning

confidence: 99%

Proteins involved in the endoplasmic reticulum stress are modulated in synovitis of osteoarthritis, chronic pyrophosphate arthropathy and rheumatoid arthritis, and correlate with the histological inflammatory score

Seny

Bianchi

Baiwir

et al. 2020

Sci Rep

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2D-nano-UPLC-ESI-Q-Orbitrap 2 Dimensional-nano-ultra performance liquid chromatography-electrospay ionization-Q-Orbitrap CALR Calreticulin CPPA Chronic pyrophosphate arthropathy CRP C-reactive protein DAMPS Damage-associated molecular patterns ER Endoplasmic reticulum ERAD ER-associated degradation FLS Fibroblast-like synoviocytes GRP78 Glucose-regulated protein 78 kDa LC-MS/MS Liquid chromatography-tandem mass spectrometry LFQ Label free quantification MRI Magnetic resonance imaging OA Osteoarthritis PMN Polymorphonuclear cells PSM Peptide spectrum match RA Rheumatoid arthritis TLR Toll-like receptors TXNDC5 Thioredoxin domain-containing protein 5 UPR Unfolded protein response US Ultrasonography Osteoarthritis (OA) was for long considered as a degenerative cartilage disease for which synovitis was only visualized in the late stages and considered as secondary to mechanic aggression of bone and cartilage degradation. However, several observations demonstrated that synovitis could appear even in the early stages of OA. Synovium can also acquire an "inflammatory" phenotype in OA with similar characteristics than those observed in rheumatoid arthritis (RA) for which synovitis is the hallmark: [i.e. synovial lining and villous hyperplasia, infiltration by macrophages and lymphocytes, neo-angiogenesis and fibrosis] 1,2. Using magnetic resonance imaging (MRI), Roemer et al. noted a synovitis in 96.3% of knee joints with effusion and in 70% of knee joint without effusion 3. We previously published by using ultrasonography (US) examination that 53.7% (322/600) of patients with painful knee OA had no sign of inflammation whereas 2.7% (16/600) had synovitis alone, 14.2% (85/600) had both synovitis and effusion and 29.5% (177/600) had joint effusion alone 4. US knee synovitis and US joint effusion were significantly associated with a more severe radiological grade (Kellgren-Lawrence grade ≥ 3) and a moderate-important joint effusion at clinical examination 4. Further, several other studies have confirmed the correlation between synovitis area observed by MRI and specific histologic features of synovitis 5. Two major pathways at least can explain the development of synovitis: activation of toll-like receptors (TLR) and activation of the complement cascade 1. Endogenous "damage-associated molecular patterns" (DAMPS) can activate the innate immune response through TLRs recognition promoting pro-inflammatory mediators secretion 6,7. Activation of the complement cascade induces complement deposits sparsely found in the synovium of OA patients. Deposits of synovial complement components were only observed during acute OA flare but not during chronic OA 8. More recently, proteomic analyses of OA synovial fluids 9,10 and transcriptomic studies of OA synovial membranes 10 confirmed the expression and activation of complement in joints 11. Proteomic analysis of synovial tissue was rarely performed 12,13 and none was compared to the histological pattern of synovium. In this work, we compared protein profiles generated by a proteomic s...

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IMSYC immunologic synovitis score: A new score for synovial membrane characterization in inflammatory and non-inflammatory arthritis

Cited by 21 publications

References 18 publications

Proteins involved in the endoplasmic reticulum stress are key players in synovitis of osteoarthritis, chronic pyrophosphate arthropathy and rheumatoid arthritis, and correlate with the histological score

Proteins involved in the endoplasmic reticulum stress are key players in synovitis of osteoarthritis, chronic pyrophosphate arthropathy and rheumatoid arthritis, and correlate with the histological score

Six-month prospective trial in early and long-standing rheumatoid arthritis: evaluating disease activity in the wrist through sequential synovial histopathological analysis, RAMRIS magnetic resonance score and EULAR-OMERACT ultrasound score

Proteins involved in the endoplasmic reticulum stress are modulated in synovitis of osteoarthritis, chronic pyrophosphate arthropathy and rheumatoid arthritis, and correlate with the histological inflammatory score

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