Diagnostic classification of spondylarthropathy and rheumatoid arthritis by synovial histopathology: A prospective study in 154 consecutive patients

Abstract

Objective. To explore prospectively the value of synovial histopathology in comparison with the value of classic parameters for diagnostic classification of spondylarthropathy (SpA) and rheumatoid arthritis (RA) in patients with an atypical disease presentation.Methods. Synovial biopsy samples were obtained from 154 consecutive patients presenting for diagnostic evaluation; 67 patients fulfilled the classification criteria for RA, SpA, or other well-defined disease at the time of arthroscopy (cohort 1), and an additional 53 patients were classified after a full diagnostic reevaluation at 6 months (cohort 2). Synovial parameters with diagnostic value were identified in cohort 1 and were compared prospectively with classic diagnostic parameters in cohort 2.Results. Staining with anticitrulline, staining with monoclonal antibody 12A (recognizing HLA-DR shared epitope-human cartilage glycoprotein 39 263-275 complexes), and crystal deposition had positive predictive values (PPVs) for diagnosis of >90% in patients with an atypical disease presentation (cohort 2). Using these 3 parameters, a diagnosis was predicted by synovial histopathology in 39.6% of cohort 2 patients and turned out to be correct in 90.5% of these patients at 6 months of followup. Using a multiparameter model rather than single histopathologic parameters, even better results were obtained, with a diagnostic prediction in 79.2% of samples and a PPV of 81.0%. In comparison, a similar multiparameter model using classic diagnostic criteria rather than synovial histopathology performed poorly in cohort 2; the sensitivity was 56.6% and the PPV was 73.3%, with an inferior capacity to predict SpA. Especially for the presence of crystals and anticitrulline staining, the analysis of synovial tissue had a clear added value to the analysis of synovial fluid or serum in patients with an atypical presentation.Conclusion. This proof-of-concept study indicates that synovial histopathology can contribute to the multiparametric diagnostic classification of inflammatory arthritis in patients with an atypical presentation.

Absence of a classically activated macrophage cytokine signature in peripheral spondylarthritis, including psoriatic arthritis

“…However, a number of observations support the notion that the observed differences in SF mediators are related to impaired M1 polarization rather than to alterations of other cellular subsets. First, these data are consistent with the previously reported selective increase in the CD163ϩ subset in patients with SpA synovitis (6)(7)(8), as well as with our in vitro polarization experiments. Second, there was a selective decrease in M1 products rather than a global impairment of macrophage function, since we did not observe differences in M2 products between SpA and RA patients.…”

“…We previously reported a selective increase in macrophages expressing the alternative activation marker CD163 in the inflamed joints of patients with SpA as compared with patients with RA (6)(7)(8). Since this preferential polarization in SpA may be due to local factors rather than intrinsic alterations of macrophage differentiation, we first analyzed the effect of SF from SpA patients compared with SF from RA patients on the polarization of healthy donor peripheral blood monocytes in vitro.…”

“…Paraffin-embedded tissue sections were stained with hematoxylin and eosin. Global cellular infiltration, vascularity, and synovial lining hyperplasia were assessed by semiquantitative scoring (scale of 0-3 for each feature) by 2 independent observers (BV and DB) who were blinded to the diagnosis and clinical data, as extensively described and validated previously (6)(7)(8)(9)(10)(11). The scores assigned by the 2 observers never differed by Ͼ1 point.…”

“…Of interest, the total number of macrophages is similar in RA and SpA synovitis, but the subset expressing the M2 surface marker, CD163 (4,5), is clearly increased in the latter (6)(7)(8). Moreover, this specific macrophage subset, but not the total number of macrophages, is correlated with disease activity and reflects response to treatment in SpA (9)(10)(11).…”

Alterations of the synovial T cell repertoire in anti–citrullinated protein antibody–positive rheumatoid arthritis

“…Stainings were then performed using a 3-step immunoperoxidase method. Stained sections from group 1 tissues were scored on a semiquantitative 4-point scale by 2 independent observers (TC and DB) who were blinded with regard to clinical data, ACPA status, and RF status of the patients (38), whereas stained sections from group 2 tissues were analyzed by computer-assisted image analysis to determine the total number of positive cells per square millimeter using the QWin analysis system (Leica, Cambridge, UK) (39).…”