Synovial and serum B cell signature of autoantibody-negative rheumatoid arthritis vs autoantibody-positive rheumatoid arthritis and psoriatic arthritis

Author:

De Stefano Ludovico12ORCID,Bugatti Serena12,Mazzucchelli Iolanda1ORCID,Rossi Silvia2,Xoxi Blerina2,Bozzalla Cassione Emanuele12ORCID,Luvaro Terenzj1,Montecucco Carlomaurizio12,Manzo Antonio12

Affiliation:

1. Rheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Università di Pavia , Pavia, Italy

2. Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo , Pavia, Italy

Abstract

Abstract Objectives Autoantibody-negative RA differs from autoantibody-positive RA in several clinical aspects, possibly underpinned by pathogenetic differences. At present, the role of adaptive immune responses in autoantibody-negative RA remains unclear. Here, we investigated the synovial and serum immunophenotype indicative of B lymphocyte involvement across the spectrum of autoantibody-positive and -negative chronic arthritides. Methods Ultrasound-guided synovial biopsies were retrieved from 131 patients: 43 autoantibody-positive RA, 35 autoantibody-negative RA, 25 polyarticular PsA and 28 oligoarticular PsA. Samples were analysed for the degree of histological inflammation, B lymphocyte infiltration and the distribution of different pathotypes (lympho-myeloid, myeloid, pauci-immune). Serum levels of the B cell chemoattractant CXCL13 were compared among groups. Results Synovitis scores and CD68+ sublining macrophage infiltration were comparable irrespective of clinical diagnosis and disease subtype. In contrast, the degree of B lymphocyte infiltration and the frequency of lympho-myeloid synovitis in autoantibody-negative RA were lower than those of autoantibody-positive RA (mean [s.d.] 1.8 [1] vs 2.4 [0.6], P = 0.03, and 38.2% vs 62.9%, P = 0.07, respectively), and similar to polyarticular PsA. Oligoarticular PsA had the lowest B cell scores. Serum CXCL13 was associated with lympho-myeloid synovitis and followed a similar gradient, with the highest levels in autoantibody-positive RA, intermediate and comparable levels in autoantibody-negative RA and polyarticular PsA, and low levels in oligoarticular PsA. Conclusions The synovial and serum immunophenotype indicative of B lymphocyte involvement in autoantibody-negative RA differs from that of autoantibody-positive RA and more closely resembles that observed in polyarticular PsA. The pathobiological stratification of chronic inflammatory arthritides beyond clinical diagnosis may fuel personalized treatment strategies.

Funder

IRCCS Policlinico San Matteo Foundation

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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