title: Autoantibodies to novel membrane and cytosolic antigens of the lachrymal gland in primary Sjögren's syndrome.
abstract: Sjögren's syndrome (SS) is a prototypical systemic autoimmune disease, where autoimmune processes lead to the dysfunction of the exocrine glands. The key feature of the disease is autoimmune exocrinopathy, causing reduced tear secretion and subsequent keratoconjunctivitis sicca (KCS). The aim of this study was to investigate the connection between the presence of autoantibodies to lachrymal gland antigens and the reduced tear production in patients with primary SS. Ninety-nine patients, 90 women and 9 men, were investigated in the study. Twenty healthy young women served as controls. Enzyme-linked immunosorbent assay (ELISA) and Western blotting were applied to detect autoantibodies to antigen fractions prepared from the human lachrymal gland membrane and cytosolic fractions. Autoantibodies of the IgG, IgA and IgM isotypes to the lachrymal membrane and cytosolic fractions were detected in about one third (27%) of the patients with primary SS. IgA antobodies to the membrane and cytosolic fractions occurred most frequently in SS patients. A significant difference was found in the presence of IgA antibodies to the membrane lachrymal fraction between patients and controls given in ELISA indices (1.23 +/- 0.3 vs 1 +/- 0.19, p < 0.001). IgG, IgA, and IgM isotypes of autoantibodies directed to the membrane lachrymal fraction of 200-180, 120-116, 80-70, 58, 50, 48.5, 40 and 28.8 kDa were also identified in patients. Membrane IgG antibody levels showed a positive correlation (R = 0.998; p = 0.045) with the clinical loss of secretory function (Schirmer's test values). Positive correlation was found between membrane IgM and anti-SS-A levels (R = 0.962; p = 0.038) and also between cytosolic IgM antibodies and anti-SS-A levels (R = 0.982; p = 0.018). IgG, IgA and IgM types of autoantibodies may play a role in the development of the impaired lachrymal secretion and therefore may be involved in the pathogenesis of KCS.
authors: Division of Clinical Immunology, 3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. peter.szodoray@gades.uib.no
authors: Peter
authors: P
authors: Szodoray
authors: Katalin
authors: K
authors: Koczok
authors: Antonia
authors: A
authors: Szanto
authors: Ildiko Fanny
authors: IF
authors: Horvath
authors: Britt
authors: B
authors: Nakken
authors: Ildiko
authors: I
authors: Molnar
authors: Margit
authors: M
authors: Zeher
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D003600:Cytosol / Q000276:immunology; D005260:Female; D006801:Humans; D007638:Keratoconjunctivitis Sicca / Q000276:immunology; D007765:Lacrimal Apparatus / Q000166:cytology / Q000276:immunology*; D008297:Male; D008566:Membranes / Q000276:immunology; D008875:Middle Aged; D012859:Sjogren's Syndrome / Q000276:immunology*
chemical_list: D001323:Autoantibodies
references: Arthritis Rheum. 1998 Dec;41(12):2238-48
references: 9870881
references: Gastroenterology. 1996 May;110(5):1579-86
references: 8613065
references: Invest Ophthalmol Vis Sci. 2000 Mar;41(3):826-31
references: 10711700
references: Ann Rheum Dis. 2002 Jun;61(6):554-8
references: 12006334
references: J Rheumatol. 2004 Mar;31(3):504-7
references: 14994395
references: Crit Rev Oral Biol Med. 2001;12(3):244-51
references: 11497375
references: J Immunol. 2001 Nov 1;167(9):5449-56
references: 11673564
references: Ann Rheum Dis. 2002 Jun;61(6):482-4
references: 12006316
references: Clin Immunol Immunopathol. 1987 Nov;45(2):235-43
references: 3117465
references: Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4
references: 388439
references: Arthritis Rheum. 1999 Aug;42(8):1673-81
references: 10446867
references: J Rheumatol. 1997 Aug;24(8):1552-7
references: 9263150
references: Scand J Immunol. 2002 Nov;56(5):456-69
references: 12410795
references: Invest Ophthalmol Vis Sci. 1998 Jan;39(1):151-6
references: 9430556
references: Scand J Rheumatol. 2000;29(6):341-8
references: 11132201
references: Clin Immunol Immunopathol. 1993 Jan;66(1):26-32
references: 8440071
references: Arthritis Rheum. 1999 Apr;42(4):697-702
references: 10211883
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: Science. 1997 Apr 25;276(5312):604-7
references: 9110981
references: J Rheumatol. 2005 Jan;32(1):197; author reply 197-8
references: 15630756
references: J Endocrinol Invest. 1995 Jun;18(6):408-14
references: 7594233
references: J Exp Med. 1994 Apr 1;179(4):1317-30
references: 7511686
references: Clin Exp Immunol. 1996 Jun;104(3):454-9
references: 9099930
references: Am J Ophthalmol. 1994 Jan 15;117(1):120-1
references: 7904795