title: Macrophage migration inhibitory factor (MIF) and thyroid hormone alterations in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
abstract: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine known to be released from lymphocytes, macrophages and endothelial cells and also in animal models shown to be inducible with glucocorticoids (GC). In contrast, thyroxine seems to antagonize MIF activity. To investigate whether MIF is increased in active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and possible correlations with GC dosing and thyroid hormone levels, 27 consecutive patients with active AAV were studied and followed prospectively. Disease activity was assessed using Birmingham Vasculitis Activity Score 2003 (BVAS) at baseline and at follow-up at 3 and 6 months, along with MIF, thyroid hormones free triiodothyronine (fT3) and free thyroxine (fT4), C-reactive protein (CRP) and creatinine. MIF was elevated significantly at baseline compared with follow-up at 3 and 6 months (8,618 pg/mL versus 5,696 and 6,212 respectively; P < 0.002) but did not correlate to CRP, GC dose, creatinine or organ involvement. fT3 was depressed significantly at baseline compared with follow-up (1.99 pg/mL versus 2.31 and 2.67 respectively; P = 0.01) and correlated inversely to the BVAS score at baseline. We found a significant correlation between the MIF/fT4 ratio at baseline versus MIF/fT4 ratio at 6 months (ρ = 0.52, P < 0.005) and a trend between the baseline MIF/fT3 ratio versus MIF/fT3 ratio at 6 months (ρ = 0.39, P = 0.05). These results suggest a possible role for MIF and thyroid status in AAV. Further studies could reveal whether the association between AAV and thyroid hormone levels in the context of elevated MIF may present a link as well as a target of treatment.
authors.affiliation: Department of Renal Medicine, Karolinska University Hospital, Department of Clinical Sciences, Intervention and Technology, Karolinska Institute, Stockholm, Sweden. Marten.wendt@karolinska.se
authors.forename: Mårten
authors.initials: M
authors.lastname: Wendt
authors.forename: Ola
authors.initials: O
authors.lastname: Börjesson
authors.forename: Aune
authors.initials: A
authors.lastname: Avik
authors.forename: Johan
authors.initials: J
authors.lastname: Bratt
authors.forename: Björn
authors.initials: B
authors.lastname: Anderstam
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Miller
authors.forename: Iva
authors.initials: I
authors.lastname: Gunnarsson
authors.forename: Annette
authors.initials: A
authors.lastname: Bruchfeld
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood*; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood*; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013963:Thyroid Hormones / Q000097:blood*
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D013963:Thyroid Hormones; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
references.citation: QJM. 1994 Nov;87(11):671-8
references.pmid: 7820541
references.citation: Nephrol Dial Transplant. 2007 Dec;22(12):3508-15
references.pmid: 17686815
references.citation: N Engl J Med. 2003 Jul 3;349(1):36-44
references.pmid: 12840090
references.citation: Nature. 1995 Sep 7;377(6544):68-71
references.pmid: 7659164
references.citation: Ann Intern Med. 2006 Aug 15;145(4):247-54
references.pmid: 16908915
references.citation: Mol Med. 2009 Mar-Apr;15(3-4):70-5
references.pmid: 19081768
references.citation: N Engl J Med. 2010 Jul 15;363(3):211-20
references.pmid: 20647198
references.citation: J Exp Med. 1999 Jan 18;189(2):341-6
references.pmid: 9892616
references.citation: Circulation. 2008 Mar 25;117(12):1594-602
references.pmid: 18362243
references.citation: N Engl J Med. 2010 Jul 15;363(3):221-32
references.pmid: 20647199
references.citation: J Am Soc Nephrol. 2010 May;21(5):745-52
references.pmid: 20395376
references.citation: Arthritis Rheum. 1999 Aug;42(8):1601-8
references.pmid: 10446857
references.citation: Clin Rheumatol. 2006 May;25(3):368-72
references.pmid: 16391884
references.citation: Lupus. 2011 Oct;20(10):1035-41
references.pmid: 21646314
references.citation: Drug News Perspect. 2010 May;23(4):257-64
references.pmid: 20520854
references.citation: Expert Opin Ther Targets. 2010 Mar;14(3):253-64
references.pmid: 20148714
references.citation: Ann Otol Rhinol Laryngol. 2001 Nov;110(11):1035-40
references.pmid: 11713914
references.citation: Intensive Care Med. 2001 Aug;27(8):1412-5
references.pmid: 11511957
references.citation: Arthritis Rheum. 1997 Feb;40(2):371-80
references.pmid: 9041949
references.citation: Arthritis Rheum. 2011 Apr;63(4):960-70
references.pmid: 21452319
references.citation: Mol Med. 2012 Mar 27;18:215-23
references.pmid: 22113497
references.citation: Arthritis Rheum. 1992 Nov;35(11):1322-9
references.pmid: 1445449
references.citation: Invest Ophthalmol Vis Sci. 1999 Jan;40(1):247-50
references.pmid: 9888451
references.citation: N Engl J Med. 1971 Apr 29;284(17):938-42
references.pmid: 5551803
references.citation: Arthritis Rheum. 2005 Feb 15;53(1):108-13
references.pmid: 15696557
references.citation: J Rheumatol. 2004 Feb;31(2):268-73
references.pmid: 14760795
references.citation: South Med J. 2002 May;95(5):506-13
references.pmid: 12005007
references.citation: Arthritis Rheum. 2013 Jan;65(1):1-11
references.pmid: 23045170
references.citation: Proc Natl Acad Sci U S A. 2011 May 17;108(20):8224-7
references.pmid: 21536912
references.citation: Best Pract Res Clin Endocrinol Metab. 2011 Oct;25(5):745-57
references.pmid: 21925075