Orthotopic implantation of inflamed synovial tissue from RA patients induces a characteristic arthritis in immunodeficient (SCID) mice.
The objective of this work was to study in more detail the human/murine SCID arthritis model with special emphasis on characteristic features initiated by rheumatoid arthritis (RA) synovial membrane (SM) as compared to appropriate control tissues. Small tissue samples from RA-SM, healthy lymph node, healthy SM, and granulomatous tissue of human origin were implanted into the left knee joint of mice with severe combined immunodeficiency (SCID), and the joints were analysed histologically after 7 days. In addition, a time course study, including non-invasive monitoring by serological parameters (human IgM, IgG, and IL-6) and Tc-99m-scintigraphy, was performed for up to 4 weeks on RA-SM recipients. All tissue implants induced transient exudative joint inflammation while RA-SM initiated a characteristic arthritis with pannus tissue of high cellular density, erosion, multinuclear giant cells, lining cell hyperplasia, fibroblast-like cell layers, chondroideal metaplasia, and fibrin deposits. Significantly elevated levels of human immunoglobulin and characteristic signs of chronic inflammation persisted for more than 4 weeks. We conclude that the hu/mu SCID arthritis with RA-SM implants comprises features of non-specific inflammation which is also transiently seen with control tissues but develops characteristic features of chronic RA-like synovitis thereafter.
Sack
U
U
Institute of Clinical Immunology and Transfusion Medicine, University of Leipzig, Germany.
Kuhn
H
H
Kämpfer
I
I
Genest
M
M
Arnold
S
S
Pfeiffer
G
G
Emmrich
F
F
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000209:etiology* / Q000276:immunology; D004195:Disease Models, Animal; D006099:Granuloma / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology; D015850:Interleukin-6 / Q000032:analysis; D007719:Knee Joint / Q000033:anatomy & histology / Q000276:immunology; D008198:Lymph Nodes / Q000637:transplantation; D051379:Mice; D016513:Mice, SCID; D011877:Radionuclide Imaging; D013583:Synovial Membrane / Q000033:anatomy & histology / Q000276:immunology / Q000637:transplantation*; D013669:Technetium Tc 99m Medronate / Q000378:metabolism; D013997:Time Factors; D018183:Transplantation Chimera
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015850:Interleukin-6; D013669:Technetium Tc 99m Medronate