BackgroundUndifferentiated Arthritis (UA) is defined as an inflammatory oligo/poly arthritis that does not fulfil criteria for a definitive diagnosis.Delay in diagnosis and treatment leads to poor prognosis. Previous studies have found differences in the cellular infiltrate between the synovitis of Rheumatoid Arthritis (RA) and Spondyloarthritis, including psoriatic arthritis (PsA)ObjectivesTo identify synovial biomarkers that may be useful to diagnose patients with early UAMethodsRetrospective longitudinal study.Patients with UA followed in our Arthritis Unit,who underwent arthroscopy between 2000 and 2014.Synovial biopsy were stained by immunohistochemistry with the following antibodies:CD3 for T cells,CD20 for B cells,CD79 for B cells,CD138 for plasma cells,CD31 for vessels,CD68 for macrophages,CD15 for neutrophils,CD117 for mast cells and hsp47 for fibroblasts, and quantified by Digital Image Analysis (Olympus).The same antibodies were evaluated in RA and PsA control groupsResults55 UA and 78 controls were included.Table 1 shows the clinical, serological and demographic characteristics.Among patients with UA, 23 (42%) patients met criteria for RA and 32 (58%) for PsA during follow-up.Synovitis of patients with UA had higher macrophage (CD68+) density in total tissue (p=0.008) and sublining (SL) (p=0.012) than the control group.The UA that evolved to RA had a higher density of CD3 T lymphocytes than the control RA group (p=0.014). No differences were observed in cells of adaptive immunity (CD20 B lymphocytes, CD138 plasma cells), innate immunity (CD117 mast cells, CD15 neutrophils), vessels (CD31) between the 4 groups.The area (%) stained by anti-hsp47 (synovial fibroblasts) in SL was higher in the RA control group than in the PsA (p=0.003)Table 1.Data are expressed as mean±SDUAUA-RAUA-PsApRAPsAp n=55n=23n=32n=40n=38 Age (years)47±1351±1344±120.05860±1254±130.065Sex (male)n (%)22 (40)6 (26)16 (50)0.07417 (43)23 (61)0.111Disease duration (years)3±43±23±40.1143±62±20.851Time of follow-up (years)7±48±46±40.0387±35±30.008CRP (mg/dL)2.7±3.92.4±1.93.0±4.90.1893.8±3.23.0±3.80.102DAS28 (ESR)4.17±1.054,83±1,063,63±0,940.0005,15±1,514,02±1,040.002ACPA n (%)4 (22)4 (22)0 (0)0.00030 (77)0 (0)0.000RF n (%)10 (7)9 (41)1 (3)0.00028 (70)1 (3)0.000csDMARD n (%)21 (41)7 (35)14 (45)0.47229 (73)19 (50)0.041bDMARD n (%)2 (4)0 (0)2 (6)0.2438 (20)6 (16)0.628PDN n (%)7 (13)3 (14)4 (13)0.85111 (28)5 (13)0.117ConclusionsThis is the first immunohistological study of synovitis in a significant group of patients with UA who developed AR or PsA during follow-up. Although there are some differences between the UA and control groups in the density of CD68+ macrophages and lymphocytes T CD3+, these do not appear to be useful for an early diagnosis of UA. On the other hand, unlike the results of some previous studies, we not found differences between the cellular infiltrate (adaptive immunity, innate immunity or vessels) in patients with RA and PsA. The fact that some patients with UA were undergoing treatment prior to synovial biopsy and its...

BackgroundUndifferentiated arthritis (UA) is defined as an inflammatory oligo-or polyarthritis that does not fulfil criteria for a definitive diagnosis. Earlier diagnosis would permits a better functional prognosis. Synovial tissue (ST) macrophages have been associated with disease activity, radiographic erosion and response to therapy in RA. Furthermore, it has been reported that M1 polarised macrophages predominate in RA synovitis, whereas M2 predominate in SpA synovitis.1 ObjectivesTo analyse polarised macrophages (M1 proinflammatory and M2 anti-inflammatory) in ST of patients with UA which evolved to RA or PsA, after a long follow-up, to explore their diagnostic value.MethodsTo determine the polarisation state of macrophages in ST obtained by arthroscopy from patients with UA that evolved to RA (UA-RA=8) or PsA (UA-PsA=9), the expression of proteins associated to GM-CSF-driven polarisation M1(INHBA, TNFα and MMP12) and M-CSF-driven polarisation M2(CD209) was assessed in ST CD163+macrophages. Patients with established RA(n=12) or PsA(n=10) were included as control. 4 µm cryosections of ST in OCT were blocked for 10 min with 1% human immunoglobulins and incubated with primary (1–5 µg/ml) and secondary antibodies. Imaging was performed with an inverted confocal microscope (SPE, Leica Microsystems) and glycerol immersion objective (ACS-APO 20x/NA 0.60). Single cell mean fluorescence intensity(MFI) was assessed using ImageJ software (National Institutes of Health, Bethesda, MD, USA). At least three random fields were evaluated for each type of ST, quantifying the expression of INHBA, TNF-α, MMP12 and CD209 in all segmented CD163+macrophages. Macrophages density was normalised based on selected tissue area(mm2). After background subtraction, data were plotted using GraphPad software (GraphPad Software, La Jolla, CA, USA).ResultsCD163+ sublining (SL) macrophages from UA-RA expressed abundantly the INHBA-encoded activin A, whereas TNFα and MMP12 were variably detected. Regarding the M-CSF-associated marker CD209, 2 populations of CD163+ macrophages were found in the SL of UA-RA, CD163+CD209+ and the other CD163+CD209-, with higher than 100 arbitrary units (au) for CD163+CD209+ and lower than 100 au for CD163+CD209-. Similarly, INHBA, MMP12 and TNFα expression and 2 populations of CD209 were detected in CD163+ macrophages from UA-PsA. Macrophage density was also found comparable between UA, with 650/mm2 in UA-RA and 649/mm2 in UA-PsA. Quantification of the above indicated markers in CD163 +ST macrophages from established RA and PsA revealed similar levels of INHBA, TNFα, MMP12 and CD209 than those from UA-RA and UA-PsA.ConclusionsThis study shows for the first time that the polarisation state of ST CD163+ macrophages in UA progressing to RA and PsA is similar to that of established RA and PsA in terms of INHBA, MMP12, TNFα and CD209 expression. Therefore, the inflammatory polarisation state of macrophages is similar in RA and PsA and it is already detected at the earlier steps.Reference[1] Vandooren B, et al. Arthritis...

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