PMID- 23720341
OWN - NLM
STAT- MEDLINE
DCOM- 20140122
LR  - 20161018
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Linking)
VI  - 169
IP  - 2
DP  - 2013 Aug
TI  - Possible involvement of matrix metalloproteinase-3 in the pathogenesis of 
      macroprolactinaemia in some patients with rheumatoid arthritis.
PG  - 203-9
LID - 10.1530/EJE-13-0170 [doi]
AB  - OBJECTIVE: Macroprolactin primarily comprises a complex of prolactin (PRL) and 
      IgG molecules, particularly anti-PRL autoantibodies. However, it is unknown why 
      autoantibodies against PRL develop in certain subjects. This study aimed to 
      elucidate post-translational modifications in the PRL molecule that may be 
      involved in the pathogenesis of macroprolactinaemia. METHODS: Macroprolactinaemia 
      was screened with a polyethylene glycol method in 238 patients with rheumatoid 
      arthritis (RA) and 302 control subjects and confirmed by gel chromatography. We 
      examined the relationship between macroprolactinaemia and several RA-related 
      laboratory tests including matrix metalloproteinase-3 (MMP-3) and anti-cyclic 
      citrullinated peptide (CCP) antibody titres. The effect of MMP-3 on the PRL 
      molecule was examined by western blotting. RESULTS: Patients with RA exhibited a 
      significantly higher prevalence of macroprolactinaemia (15/238; 6.3%) than the 
      young control subjects (5/219 subjects; 2.3%), but the prevalence was not 
      different from that observed in the elderly control subjects (5/83 subjects; 
      6.0%). The prevalence of macroprolactinaemia in patients with elevated MMP-3 
      levels (9.68%) was significantly higher than that in those with normal MMP-3 
      levels (2.63%). Digestion of PRL with MMP-3 produced vasoinhibins with several 
      molecular species. Serum total and free PRL levels in RA patients were higher 
      than those in the age- and gender-matched control subjects. The levels of 
      macroprolactin were not significantly correlated with those of RA-specific 
      anti-CCP antibody. CONCLUSIONS: We speculate that elevated MMP-3 levels may lead 
      to the formation of new epitopes on the PRL molecule that might trigger an immune 
      response to produce anti-PRL autoantibodies in some patients with RA. Such 
      post-translational modifications may possibly contribute to the increased 
      prevalence of macroprolactinaemia in elderly subjects.
FAU - Adachi, Takashi
AU  - Adachi T
AD  - Department of Orthopedics, Kansai Medical University, Osaka, Japan.
FAU - Hattori, Naoki
AU  - Hattori N
FAU - Ishihara, Takashi
AU  - Ishihara T
FAU - Iida, Hirokazu
AU  - Iida H
FAU - Saito, Takanori
AU  - Saito T
FAU - Miyashima, Shigeo
AU  - Miyashima S
FAU - Shimatsu, Akira
AU  - Shimatsu A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130706
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (Autoantibodies)
RN  - 0 (prolactin, polymeric)
RN  - 9002-62-4 (Prolactin)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Arthritis, Rheumatoid/*blood/*enzymology
MH  - Autoantibodies/blood/immunology
MH  - Blotting, Western
MH  - Case-Control Studies
MH  - Female
MH  - Humans
MH  - Linear Models
MH  - Male
MH  - Matrix Metalloproteinase 3/*blood
MH  - Middle Aged
MH  - Prolactin/*blood
EDAT- 2013/05/31 06:00
MHDA- 2014/01/23 06:00
CRDT- 2013/05/31 06:00
PHST- 2013/05/31 06:00 [entrez]
PHST- 2013/05/31 06:00 [pubmed]
PHST- 2014/01/23 06:00 [medline]
AID - EJE-13-0170 [pii]
AID - 10.1530/EJE-13-0170 [doi]
PST - epublish
SO  - Eur J Endocrinol. 2013 Jul 6;169(2):203-9. doi: 10.1530/EJE-13-0170. Print 2013 
      Aug.