The Potent Inhibitory Effect of β-D-Mannuronic Acid (M2000) as a Novel NSAID with Immunosuppressive Property on Anti-Cyclic Citrullinated Peptide Antibodies, Rheumatoid Factor and Anti-dsDNA Antibodies in Patients with Rheumatoid Arthritis.
OBJECTIVE
To investigate the inhibitory effect of β-D-mannuronic acid (M2000) on anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), antidouble strand DNA (anti-dsDNA) and acute phase reactants in rheumatoid arthritis (RA) patients.


METHODS
The study included 40 patients with RA who had an inadequate response to conventional therapy (identifier: IRCT2014011213739N2). The patients were permitted to continue the conventional therapy excluding NSAIDs. 21 of them were treated orally by M2000 at a dose of 500 mg twice daily for 12 weeks and the others did not. Serum samples were collected at baseline, 4 weeks and 12 weeks after treatment and were tested for the serum level of anti-CCP and anti-dsDNA antibodies using enzyme linked immunosorbent assay. The serum level of RF and C-reactive proteins (CRP) was determined by the immunoturbidimetric assay, respectively.


RESULTS
At baseline, all patients in the M2000 treated group and the control group were positive for anti-CCP, RF. moreover, 4 of 21 (19%) in the M2000 treated group and 2 of the 19 (10.5%) patients in the control group were positive for anti-dsDNA antibodies, respectively. The serum levels of anti-CCP, RF and anti-dsDNA were decreased significantly after M2000 therapy (p<0.001, p<0.001 and p<0.001, respectively). The reduction in the level of anti-CCP was positively correlated with disease activity, swollen joint count and CRP. Furthermore, the level of inflammatory markers ESR and CRP decreased significantly after M2000 therapy (p<0.001 and p<0.004, respectively).


CONCLUSIONS
M2000 shows inhibitory effect on anti-CCP, RF, anti-dsDNA antibodies and acute phase reactants in RA patients.
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran. Iran.
Hossein
H
Ahmadi
Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Science, Tehran. Iran.
Ahmad R
AR
Jamshidi
Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Science, Tehran. Iran.
Mahdi
M
Mahmoudi
Department of Biological and Environmental Sciences, University of Messina, Messina. Italy.
Salvatore
S
Cuzzocrea
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran. Iran.
Mohammad Javad
MJ
Fattahi
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran. Iran.
Anis
A
Barati
Institute of Fundamental Sciences, Massey University, Private Bag 11222, Palmerston North 4442. New Zealand.
Bernd H A
BHA
Rehm
Department of Neurology, National Hospital Organization Nagasaki Kawatana Medical Center, and Department of Neuroimmunology, Nagasaki University Graduate School of Biomedical Sciences. Japan.
Hidenori
H
Matsuo
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran. Iran.
Abbas
A
Mirshafiey
D000328:Adult; D000368:Aged; D000075422:Anti-Citrullinated Protein Antibodies / Q000097:blood; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D000974:Antibodies, Antinuclear / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D006603:Hexuronic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000097:blood
D000075422:Anti-Citrullinated Protein Antibodies; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000974:Antibodies, Antinuclear; D006603:Hexuronic Acids; D007166:Immunosuppressive Agents; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; C008324:mannuronic acid
Anti-CCP; Anti-dsDNA; M2000; RF; Rheumatoid arthritis