Mass spectrometry-based analysis of cerebrospinal fluid from arthritis patients-immune-related candidate proteins affected by TNF blocking treatment.
BACKGROUND
Signs of inflammation in cerebrospinal fluid (CSF) of rheumatoid arthritis patients correlate positively with fatigue, a central nervous system (CNS)-related symptom that can be partially suppressed by TNF blockade. This suggests a possible role for CNS inflammation in arthritis that may be affected by TNF blockade. We therefore investigated the effects of TNF blockade on the arthritis CSF proteome and how candidate proteins related to clinical measures of disease activity and inflammation.


METHODS
Mass spectrometry-based quantitative proteomic analysis was performed on CSF from seven polyarthritis patients before and during infliximab treatment. Treatment-associated proteins were identified using univariate (Wilcoxon signed rank test) and multivariate (partial least squares discriminant analysis (PLS-DA)) strategies. Relations between selected candidate proteins and clinical measures were investigated using the Spearman correlations. Additionally, selected proteins were cross-referenced to other studies investigating human CSF in a thorough literature search to ensure feasibility of our results.


RESULTS
Univariate analysis of arthritis CSF proteome revealed a decrease of 35 proteins, predominantly involved in inflammatory processes, following TNF blockade. Seven candidate proteins, Contactin-1 (CNTN1), fibrinogen gamma chain (FGG), hemopexin (HPX), cell adhesion molecule-3 (CADM3), alpha-1B-glycoprotein (A1BG), complement factor B (CFB), and beta-2-microglobulin (B2M), were selected for further studies based on identification by both univariate and multivariate analyses and reported detection in human CSF and known associations to arthritis. Decreased levels of FGG and CFB in CSF after treatment showed strong correlations with both erythrocyte sedimentation rate and disability scores, while CNTN1 and CADM3 were associated with pain.


CONCLUSION
Several immune-related proteins in the CSF of arthritis patients decreased during TNF blockade, including FGG and CFB that both correlated strongly with systemic inflammation. Our findings stress that also intrathecal inflammatory pathways are related to arthritis symptoms and may be affected by TNF blockade.
['Estelius|Johanna|J|', 'Lengqvist|Johan|J|', 'Ossipova|Elena|E|', 'Idborg|Helena|H|', 'Le Maître|Erwan|E|', 'Andersson|Magnus L A|MLA|', 'Brundin|Lou|L|', 'Khademi|Mohsen|M|', 'Svenungsson|Elisabet|E|', 'Jakobsson|Per-Johan|PJ|', 'Lampa|Jon|J|']
D000328:Adult D000368:Aged D018501:Antirheumatic Agents D001172:Arthritis, Rheumatoid D015815:Cell Adhesion Molecules D011415:Complement Factor B D005260:Female D005340:Fibrinogen D006801:Humans D007136:Immunoglobulins D000069285:Infliximab D013058:Mass Spectrometry D008875:Middle Aged D020543:Proteome D040901:Proteomics D000079424:Tumor Necrosis Factor Inhibitors
CSF Rheumatoid arthritis Proteomics Ankylosing spondylitis Anti-TNF Chronic inflammation Intrathecal inflammation Juvenile chronic arthritis Psoriatic arthritis