Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy.
Considering the relation between synovial inflammation and global disease activity in rheumatoid arthritis (RA) and the distinct but heterogeneous histology of spondyloarthropathy (SpA) synovitis, the present study analyzed whether histopathological features of synovium reflect specific phenotypes and/or global disease activity in SpA. Synovial biopsies obtained from 99 SpA and 86 RA patients with active knee synovitis were analyzed for 15 histological and immunohistochemical markers. Correlations with swollen joint count, serum C-reactive protein concentrations, and erythrocyte sedimentation rate were analyzed using classical and multiparameter statistics. SpA synovitis was characterized by higher vascularity and infiltration with CD163+ macrophages and polymorphonuclear leukocytes (PMNs) and by lower values for lining-layer hyperplasia, lymphoid aggregates, CD1a+ cells, intracellular citrullinated proteins, and MHC-HC gp39 complexes than RA synovitis. Unsupervised clustering of the SpA samples based on synovial features identified two separate clusters that both contained different SpA subtypes but were significantly differentiated by concentration of C-reactive protein and erythrocyte sedimentation rate. Global disease activity in SpA correlated significantly with lining-layer hyperplasia as well as with inflammatory infiltration with macrophages, especially the CD163+ subset, and with PMNs. Accordingly, supervised clustering using these synovial parameters identified a cluster of 20 SpA patients with significantly higher disease activity, and this finding was confirmed in an independent SpA cohort. However, multiparameter models based on synovial histopathology were relatively poor predictors of disease activity in individual patients. In conclusion, these data indicate that inflammatory infiltration of the synovium with CD163+ macrophages and PMNs as well as lining-layer hyperplasia reflect global disease activity in SpA, independently of the SpA subtype. These data support a prominent role for innate immune cells in SpA synovitis and warrant further evaluation of synovial histopathology as a surrogate marker in early-phase therapeutic trials in SpA.
Baeten
Dominique
D
Department of Rheumatology, Ghent University Hospital, Ghent, Belgium. dominique.baeten@ugent.be
Kruithof
Elli
E
De Rycke
Leen
L
Boots
Anemieke M
AM
Mielants
Herman
H
Veys
Eric M
EM
De Keyser
Filip
F
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015535:Arthritis, Psoriatic / Q000097:blood / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000473:pathology; D001327:Autoimmune Diseases / Q000097:blood / Q000473:pathology; D001707:Biopsy, Needle; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D002956:Citrulline / Q000276:immunology; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006965:Hyperplasia; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000150:complications; D007719:Knee Joint / Q000473:pathology*; D008264:Macrophages / Q000145:classification / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology*; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000032:analysis; D012720:Severity of Illness Index; D025242:Spondylarthropathies / Q000097:blood / Q000150:complications / Q000473:pathology*; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000473:pathology; D013583:Synovial Membrane / Q000473:pathology*; D013585:Synovitis / Q000097:blood / Q000473:pathology*; D000098902:CD163 Antigen
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D002956:Citrulline; D002097:C-Reactive Protein
Ann Rheum Dis. 2003 Jul;62(7):635-8
12810425
Ann Rheum Dis. 2005 Apr;64(4):529-36
15388510
Arthritis Rheum. 2004 Feb;50(2):444-51
14872486
Arthritis Rheum. 2004 Apr 15;51(2):154-9
15077254
Arthritis Rheum. 1988 Mar;31(3):315-24
3358796
N Engl J Med. 2004 Apr 15;350(16):1595-7
15084689
Arthritis Rheum. 2004 May;50(5):1611-23
15146432
Arthritis Rheum. 2004 May;50(5):1636-41
15146434
Artif Intell Med. 2004 May;31(1):45-55
15182846
Ann Rheum Dis. 2004 Jul;63(7):769-73
15194570
Arthritis Rheum. 2004 Sep;50(9):2931-41
15457462
Rheumatology (Oxford). 1999 Nov;38(11):1074-80
10556258
Clin Rheumatol. 1999;18(6):434-41
10638766
Rheumatology (Oxford). 2000 Jan;39(1):43-9
10662872
Ann Rheum Dis. 2000 Dec;59(12):945-53
11087697
Arthritis Rheum. 2001 Jan;44(1):186-95
11212159
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
11309499
Ann Rheum Dis. 2001 Aug;60(8):750-5
11454638
Arthritis Rheum. 2001 Oct;44(10):2255-62
11665966
J Pathol. 2002 Mar;196(3):343-50
11857499
Proc Natl Acad Sci U S A. 2002 May 14;99(10):6567-72
12011421
Cell Mol Biol (Noisy-le-grand). 2002 May;48(3):285-93
12030433
Arthritis Rheum. 2002 Oct;46(10):2776-84
12384938
Arthritis Rheum. 1991 Oct;34(10):1218-27
1930310
Arthritis Rheum. 1996 Jan;39(1):115-24
8546720
Arthritis Rheum. 1997 Feb;40(2):217-25
9041933
Am J Pathol. 1997 Nov;151(5):1311-9
9358757
Rheumatol Int. 1997;17(4):159-68
9440147
Arthritis Rheum. 1998 Aug;41(8):1481-8
9704648
Springer Semin Immunopathol. 1998;20(1-2):5-22
9836366
J Rheumatol. 1999 Apr;26(4):971-4
10229430
Arthritis Rheum. 2004 Dec;50(12):3783-91
15593225
Arthritis Res Ther. 2003;5(6):271-8
14680502