Immunogenicity of hylan g-f 20 in Guinea pigs and mice.
OBJECTIVE
To determine the product-specific immunogenicity of a chemically-modified sodium hyaluronate derivative, hylan G-F 20, that is used in the treatment of osteoarthritis of the knee.


METHODS
Guinea pigs were subcutaneously immunized with hylan G-F 20 (Synvisc) once a week for 3 weeks. After resting, these animals received an intradermal challenge with hylan to elicit allergic skin reactions. Animal sera were tested for the presence of hylan-specific antibodies by homologous passive cutaneous anaphylaxis (PCA) assay and of anti-hylan IgG by ELISA. Further, mice were similarly immunized with hylan, and their sera were analyzed by heterologous PCA assay in rats and by ELISA for anti-hylan Ig(G+M) and anti-hylan IgE.


RESULTS
In the guinea pig studies, acute and delayed erythematous skin reactions were elicited in immunized animals after the intradermal challenge with hylan. The sera of hylan-immunized guinea pigs showed positive reaction in the homologous PCA assay and significantly high amount of anti-hylan IgG, whereas the sera did not show any cross-reactivity against sodium hyaluronate. Hylan also exhibited immunogenicity in mice of 3 inbred strains, and C3H/HeN mice showed higher production of anti-hylan antibodies than Balb/c and C57BL/6 mice.


CONCLUSIONS
Hylan G-F 20 exhibited immunogenicity in guinea pigs and mice. Recent reported severe acute inflammatory reactions in human patients after repeated intraarticular injections of hylan G-F 20 might involve product-specific, immune-mediated mechanisms.
Sasaki
Masanori
M
Central Research Laboratories, Seikagaku Corporation, Tokyo, Japan. sasaki2@seikagaku.co.jp
Miyazaki
Tatsuya
T
Nakamura
Takehiko
T
Takahashi
Toyomi
T
Miyauchi
Satoshi
S
Iwata
Hisashi
H
D000818:Animals; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006168:Guinea Pigs; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology; D007106:Immune Sera / Q000008:administration & dosage; D007154:Immune System Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D013045:Species Specificity
D007106:Immune Sera; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C049816:hylan; D006820:Hyaluronic Acid