Elevated systemic antibodies towards commensal gut microbiota in autoinflammatory condition.
BACKGROUND
Familial Mediterranean fever (FMF) is an autoinflammatory condition, which is characterized by acute, self-limiting episodes of fever and serositis and chronic subclinical inflammation in remission. Here we investigated the consequence of this condition on the level of systemic antibodies directed towards common intestinal bacteria.


RESULTS
The level of systemic antibodies towards the antigens of Bacteroides, Parabacteroides, Escherichia, Enteroccocus and Lactobaccilus was measured by ELISA in FMF patients at various stages of the disease and in healthy controls. The difference between remission and attack was not significant. IgG antibodies against the antigens of Bacteroides, Parabacteroides, Escherichia and Enteroccocus were significantly increased in FMF compared to control while IgA levels were not significantly affected. Western blot analyses demonstrated the IgG reactivity against multiple antigens of commensal bacteria in FMF. Serological expression cloning was performed to identify these antigens. No single dominant antigen was identified; the response was generalized and directed against a variety of proteins from Bacteroides, Parabacteroides, Escherichia, and other gut commensals.


CONCLUSIONS
This autoinflammatory syndrome is characterized by the increased systemic reactivity against commensal gut microbiota. This is probably the consequence of hypersensitivity of the inflammasome in FMF that triggers the inflammation and contributes to the excessive translocation of bacteria and bacterial antigens through the gut barrier.
Manukyan
Gayane P
GP
Institute of Molecular Biology, National Academy of Sciences, Yerevan, Armenia.
Ghazaryan
Karine A
KA
Ktsoyan
Zhanna A
ZA
Khachatryan
Zaruhi A
ZA
Arakelova
Karine A
KA
Kelly
Denise
D
Grant
George
G
Aminov
Rustam I
RI
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000276:immunology*; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D010505:Familial Mediterranean Fever / Q000276:immunology* / Q000382:microbiology*; D005260:Female; D015723:Gene Library; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology*; D007422:Intestines / Q000382:microbiology*; D008297:Male; D008875:Middle Aged
D000906:Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G
Hosp Pract (1995). 1998 Apr 15;33(4):131-4, 139-40, 143-6 passim
9562837
Clin Biochem. 2008 Jul;41(10-11):920-2
18440310
Blood. 2000 May 15;95(10):3223-31
10807793
Nature. 2001 May 31;411(6837):603-6
11385577
Pathobiology. 2006;73(1):26-39
16785765
Nature. 2001 May 31;411(6837):599-603
11385576
J Biol Chem. 2003 Mar 14;278(11):8869-72
12527755
Gastroenterology. 2007 Apr;132(4):1359-74
17408640
Semin Immunol. 2007 Apr;19(2):70-83
17485224
Semin Immunol. 2007 Apr;19(2):127-35
17161619
Gut. 2004 Nov;53(11):1658-64
15479689
Nat Genet. 1997 Sep;17(1):25-31
9288094
Nature. 2006 Mar 9;440(7081):237-41
16407889
Semin Arthritis Rheum. 1998 Aug;28(1):48-59
9726336
Gastroenterology. 2004 Jul;127(1):224-38
15236188
Trends Immunol. 2001 Apr;22(4):205-11
11274926
Arthritis Rheum. 2002 Oct;46(10):2785-93
12384939
Methods Mol Med. 2004;94:91-106
14959824
Infect Immun. 2006 Jan;74(1):192-201
16368973
Nature. 2006 Mar 9;440(7081):233-6
16407888
J Bacteriol. 1991 Jan;173(2):697-703
1987160
Am J Gastroenterol. 2008 Feb;103(2):386-96
17924999
Nature. 2006 Mar 9;440(7081):228-32
16407890
Nat Rev Immunol. 2007 Jan;7(1):31-40
17186029
Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9982-7
16785446
Am J Physiol Gastrointest Liver Physiol. 2003 Sep;285(3):G621-9
12773301
Am J Physiol Gastrointest Liver Physiol. 2005 Feb;288(2):G403-6
15388489
Curr Biol. 2004 Nov 9;14(21):1929-34
15530394
Nat Rev Immunol. 2006 Mar;6(3):183-95
16498449
Mol Cell. 2003 Mar;11(3):591-604
12667444
Shock. 2002 Feb;17(2):139-45
11837790
J Clin Invest. 2004 May;113(9):1296-306
15124021
Gastroenterology. 2002 Sep;123(3):689-99
12198693
Gastroenterology. 2006 Jul;131(1):117-29
16831596
Cell. 2004 Jul 23;118(2):229-41
15260992
Proc Natl Acad Sci U S A. 1985 Oct;82(20):6955-9
2413450
J Biol Chem. 2006 Dec 1;281(48):36560-8
17008311
Arthritis Rheum. 1997 Oct;40(10):1879-85
9336425
Gastroenterology. 1994 Sep;107(3):643-9
8076751
Science. 2002 Nov 15;298(5597):1424-7
12434060
Am J Med. 2007 Mar;120(3):221-4
17349440
Arthritis Rheum. 2004 Nov;50(11):3679-89
15529356
Cell Death Differ. 2007 Aug;14(8):1457-66
17431422
Eur J Hum Genet. 2001 Jul;9(7):473-83
11464238
Curr Top Microbiol Immunol. 2006;305:127-60
16724804
Cell Death Differ. 2007 Sep;14(9):1583-9
17599094
J Biol Chem. 2003 Feb 21;278(8):5509-12
12514169
Science. 2005 Jun 10;308(5728):1635-8
15831718
Cell. 2005 Jul 15;122(1):107-18
16009137
Pediatr Surg Int. 2000;16(3):165-8
10786973
Cell. 1997 Aug 22;90(4):797-807
9288758