Synovial lymphoid neogenesis does not define a specific clinical rheumatoid arthritis phenotype.
OBJECTIVE
To investigate the relationship between lymphoid neogenesis in the synovium of patients with rheumatoid arthritis (RA) and characteristics of inflammation and disease severity.


METHODS
Arthroscopic synovial biopsy was performed in 103 patients with active RA (Disease Activity Score 28-joint assessment >or=3.2) who had not received treatment with biologic agents. Sections were stained and assessed by digital image analysis. Lymphocyte aggregates were counted and graded for size (1-3). Synovial lymphoid neogenesis was defined as the presence of grade 2 or 3 aggregates and subclassified based on the presence of follicular dendritic cells (FDCs).


RESULTS
Lymphoid neogenesis was present in 31% of the RA synovial tissues, whereas an additional 25% contained only grade 1 aggregates. FDCs were present in 28% of the samples with lymphoid neogenesis, corresponding to 8% of the total RA cohort. Histologically, synovia with lymphoid neogenesis showed increased infiltration by T and B lymphocytes, plasma cells, and macrophages, and increased expression of tumor necrosis factor alpha and lymphotoxin beta compared with samples without lymphoid neogenesis. Patients with lymphoid neogenesis also had higher C-reactive protein levels, erythrocyte sedimentation rates, and leukocyte and thrombocyte counts, but exhibited no increase in the severity of clinical signs and symptoms. Of importance, there was no relationship between the presence of lymphoid neogenesis and IgM rheumatoid factor or anti-citrullinated protein antibodies. The presence of lymphocyte aggregates with FDCs did not define a specific clinical phenotype compared with lymphocyte aggregates without FDCs.


CONCLUSIONS
These findings indicate that synovial lymphoid neogenesis is associated with more severe synovial and systemic inflammation, but this is not confined to a specific clinical subset of RA.
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Rogier M
RM
Thurlings
Carla A
CA
Wijbrandts
Reina E
RE
Mebius
Tineke
T
Cantaert
Huibert J
HJ
Dinant
Tineke C T M
TC
van der Pouw-Kraan
Cornelis L
CL
Verweij
Dominique
D
Baeten
Paul P
PP
Tak
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001706:Biopsy; D002097:C-Reactive Protein / Q000378:metabolism; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001323:Autoantibodies; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein