Synovial Immunohistological Biomarkers of the Classification of Undifferentiated Arthritis Evolving to Rheumatoid or Psoriatic Arthritis

Abstract

Background: Undifferentiated arthritis (UA) is defined as an inflammatory arthritis that does not fulfill criteria for a definite diagnosis. Delay in reaching a specific diagnostic and therapy may lead to impaired functional outcomes. Our aim was to identify synovial biomarkers associated with definitive diagnostic classification in patients with UA.Methods: DMARD-naïve UA patients with available initial synovial tissue (ST) and a final diagnosis of rheumatoid arthritis (RA) or psoriatic arthritis (PsA) during follow-up were included and compared with patients with well-defined disease (RA or PsA). Clinical, arthroscopic, and pathological data were compared between groups. Pathology included quantitative immunohistochemical (IHC) analysis of cell types and human interferon-regulated MxA. Principal component analysis (PCA) was performed to extract disease patterns.Results: One hundred and five patients were included: 31 patients with DMARD-naïve UA (19 evolving to RA and 12 to PsA during a median follow up of 7 years), 39 with established RA, and 35 with established PsA. ST from the UA group showed higher macrophage density compared with the established RA and PsA groups. Patients with UA evolving to RA (UA-RA) showed higher MxA expression and CD3+ T-cell density compared with established RA. UA patients evolving to PsA (UA-PsA) showed increased vascularity and lining synovial fibroblast density compared with established PsA. Synovitis of UA-PsA patients showed more mast cells and lining fibroblasts compared with UA-RA. No between-group differences in local or systemic inflammation markers were found.Conclusions: Our results show differences in the cellular composition of UA synovium compared with RA and PsA, with higher density of the cellular infiltrate in the UA groups. Initial expression of the interferon inducible gene MxA could be a biomarker of progression to RA, while higher mast cell and fibroblastic density may be associated with PsA progression.

Histopathology of Psoriatic Arthritis Synovium—A Narrative Review

“…The analysis performed by immunohistochemistry demonstrates the presence of T (CD3+), B (CD20+), macrophage (CD68+), plasma (CD138+), mast (CD117+), and follicular dendritic (CD21+) cells in the inflammatory infiltrates. Overall, T lymphocyte and plasma cell amounts are lower than those observed in rheumatoid synovium (9,10,(12)(13)(14)16). The proportion of CD4+/CD8+ T lymphocytes, and CD4+ and mast cell infiltration, however, appears to be higher than in RA (12,17).…”

“…Following studies described indeed mild hyperplasia of the psoriatic synovium, as opposed to the significant hyperplasia found in the rheumatoid synovium (6)(7)(8). Interestingly, higher numbers of lining fibroblasts have been found in the synovium of patients with undifferentiated arthritis who progressed to PsA, compared to that of patients who ended up diagnosed with RA (9). Synovial lining layer thickness varies in psoriatic synovium, ranging from 2 to 5 cells, with an average thickness of 3 cells (7,8,10).…”

The Crucial Questions on Synovial Biopsy: When, Why, Who, What, Where, and How?

“…In rheumatology clinical practice, thanks to the great feasibility and safety of ultrasound-guided needle biopsy and needle arthroscopy, pathobiology may become a key component in the management and treatment decision-making process (10). For clinical and research purposes, histopathology and modern applications of molecular biology on synovial tissue are focused on the following major areas:…”

“…-Classification of early undifferentiated arthritis. Since an early diagnosis and treatment of chronic inflammatory arthritis are linked to better long-term outcomes in terms of prevention of irreversible structural damage, nowadays the number of undifferentiated arthritis defined as inflammatory arthritis not satisfying classification criteria for RA (10,11) is increasing. For this reason, an unmet need is the identification of biomarkers able to detect the patient who will develop RA or peripheral SpAs and differentiate them from those who will develop self-limiting or degenerative diseases.…”

Will rheumatologists ever pick up the arthroscope again?

“…Macroscopic, 61‐66 microscopic, 67‐73 and molecular 74‐82 features of synovium were characterized, with a particular interest in early disease states, 83‐96 including pre‐clinical 97‐100 and even normal synovium 101 . Differences between various disease states were discerned 102‐116 . The arthroscope was used extensively to assess effects of various treatments, both intra‐articular 117 and systemic 56,118‐159 .…”