Involvement of neurotrophins and their receptors in spondyloarthritis synovitis: relation to inflammation and response to treatment.
OBJECTIVE
To investigate whether expression of the four members of the neurotrophin (NT) family and their four corresponding receptors is related to synovial inflammation in patients with spondyloarthritis (SpA).


METHODS
Synovial fluid (SF) and serum NTs and their receptors were measured by ELISA. Immunohistochemistry was used for synovial tissue biopsy specimens from patients with SpA, rheumatoid arthritis, and osteoarthritis (OA). In SpA synovium, immunoreactivity of the receptors trkA and NGFRp75 was also assessed before and after 12 weeks of treatment with the monoclonal anti-tumour necrosis factor alpha antibody, infliximab.


RESULTS
mRNA transcripts of all NTs and receptors were expressed in the inflamed synovium. At the protein level, brain derived neurotrophic factor and NT-3 were significantly higher in the SF of patients with SpA than in those with OA. In contrast, ELISA of serum samples showed that the highest member in SpA was NT-4. Immunohistochemistry demonstrated that the NT receptors trkA and NGFRp75 were highly expressed in the inflamed synovium of patients with SpA, correlating with vascularity and lymphoid aggregates, respectively. Additionally, immunoreactivity of both receptors was significantly decreased after infliximab treatment.


CONCLUSIONS
NTs and their receptors are expressed in inflamed peripheral joints of patients with SpA. Their expression is not constitutive but related to inflammation and they may be involved in the local disease processes.
Rihl
M
M
Hannover Medical School (MHH), Department of Rheumatology (OE 6850), Carl-Neuberg-Str 1, 30625 Hannover, Germany. Rihl.Markus@MH-Hannover.de
Kruithof
E
E
Barthel
C
C
De Keyser
F
F
Veys
E M
EM
Zeidler
H
H
Yu
D T Y
DT
Kuipers
J G
JG
Baeten
D
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015870:Gene Expression; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D020933:Neurotrophin 3 / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000503:physiopathology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000502:physiology*; D025241:Spondylarthritis / Q000188:drug therapy / Q000503:physiopathology*; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism; D013585:Synovitis / Q000378:metabolism / Q000503:physiopathology*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D000069285:Infliximab; D020917:Receptor, trkA