Reumatologia. 2020;58(6):357-366. doi: 10.5114/reum.2020.102000. Epub 2020 Dec 23.
The complement system in primary Sjögren's syndrome: the expression of certain cascade and regulatory proteins in labial salivary glands - observational study.
Reumatologia
Marta Legatowicz-Koprowska, Stanisław Nitek, Jolanta Czerwińska
Affiliations
Affiliations
- Department of Pathology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
- Department of Otolaryngology, Medical University of Warsaw, Poland.
PMID: 33456078
PMCID: PMC7792541 DOI: 10.5114/reum.2020.102000
Abstract
INTRODUCTION: The complement cascade and regulatory proteins are involved in the pathogenesis of the Sjögren's syndrome and other autoimmune diseases. The complement activation via the alternative pathway was recognized as a major pathogenic mechanism in autoimmune conditions. The aim of this study was to assess expression of complement cascade components and regulatory proteins in minor salivary glands in patients with primary Sjögren's syndrome (pSS).
MATERIALS AND METHODS: The expression of C1q and C5b-9 - membrane attack complex and regulatory proteins such as: membrane cofactor protein (MCP), decay-accelerating factor (DAF) and protectin were examined using immunochemistry method in specimens from biopsy of minor salivary glands in pSS patients. The biopsy material was obtained from 20 pSS patients, 5 patients with non-specific sialadenitis and from 5 patients with suspicion of dryness syndrome without sialadenitis confirmation.
RESULTS: None of the examined samples showed the expression of C1q or the effector C5b-9. Membrane cofactor protein expression was lower in pSS group than in both non-specific sialadenitis and noninflamed salivary glands. The inflammatory cells in pSS samples partially expressed MCP. There were differences in the sites and intensity of membrane protectin expression exclusively on the luminal surfaces in pSS; on the luminal and, partially, antiluminal surface in non-specific inflammation, and on the entire cell surface in unaffected salivary glands. There were no DAF expression in salivary gland tissue in biopsy specimens in all studied subjects.
CONCLUSIONS: The study demonstrated the absence of complement-cascade proteins (C1q, MAC) in the salivary glands of pSS patients, which may indicated a lack of local complement activation via the classical pathway and the observed gland tissue damage being due to a mechanism other than MAC-induced cytolysis. The differences in the expression of complement regulatory proteins between pSS, non-specific sialadenitis, and normal salivary glands may indicate that alternative functions of these regulatory proteins may be of greater significance in pSS. Low MCP expression in pSS in comparison with non-specific sialadenitis and normal salivary glands, may suggest altered modulation of cell-mediated immunity in pSS. The differences in the location and intensity of protectin (CD59) expression indicates a possibility of reducing the proinflammatory effect of protectin in pSS.
Copyright: © 2020 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.
Keywords: complement system proteins; membrane cofactor protein CD46; primary Sjogren’s syndrome; protectin CD59
Conflict of interest statement
The authors declare no conflict of interest.
References
- Best Pract Res Clin Rheumatol. 2012 Feb;26(1):105-17 - PubMed
- J Clin Exp Dent. 2017 Apr 1;9(4):e584-e589 - PubMed
- Eur J Immunol. 2003 Dec;33(12):3367-76 - PubMed
- Autoimmun Rev. 2012 Feb;11(4):281-7 - PubMed
- Immunology. 1993 Jul;79(3):341-7 - PubMed
- Mol Immunol. 2007 Jan;44(1-3):73-81 - PubMed
- Scand J Immunol. 1995 Apr;41(4):350-6 - PubMed
- N Engl J Med. 2001 Apr 5;344(14):1058-66 - PubMed
- Immune Netw. 2018 Feb 20;18(1):e11 - PubMed
- Nature. 2003 Jan 23;421(6921):388-92 - PubMed
- Blood. 1990 Jan 1;75(1):284-9 - PubMed
- Arthritis Res Ther. 2006;8(4):R130 - PubMed
- J Autoimmun. 2010 May;34(3):J276-86 - PubMed
- J Immunol. 2006 Mar 1;176(5):2915-23 - PubMed
- Lab Invest. 1992 Nov;67(5):608-16 - PubMed
- Mol Immunol. 2015 Feb;63(2):176-83 - PubMed
- Clin Immunol. 2006 Feb-Mar;118(2-3):127-36 - PubMed
- Arch Immunol Ther Exp (Warsz). 2009 Nov-Dec;57(6):393-407 - PubMed
- Lupus. 2015 Mar;24(3):315-20 - PubMed
- Rheumatology (Oxford). 2005 Jan;44(1):89-94 - PubMed
- Ann Rheum Dis. 1996 Dec;55(12):888-94 - PubMed
- Arthritis Rheum. 2010 Apr;62(4):1036-42 - PubMed
- Nat Rev Rheumatol. 2010 Sep;6(9):529-37 - PubMed
- J Exp Med. 1987 Mar 1;165(3):848-64 - PubMed
- Clin Exp Rheumatol. 1997 Nov-Dec;15(6):615-23 - PubMed
- Arthritis Rheum. 2004 Sep;50(9):3035-44 - PubMed
- Autoimmun Rev. 2018 Mar;17(3):215-225 - PubMed
- Nat Immunol. 2004 Oct;5(10):981-6 - PubMed
- Arthritis Rheumatol. 2017 Jan;69(1):35-45 - PubMed
- Immunology. 2001 Oct;104(2):207-14 - PubMed
- Mol Immunol. 2004 Jun;41(2-3):147-52 - PubMed
- J Clin Lab Anal. 2018 Nov;32(9):e22585 - PubMed
- Lab Invest. 1991 Nov;65(5):532-7 - PubMed
- J Immunol. 2006 Jul 15;177(2):1070-7 - PubMed
- J Immunol. 1991 Jun 15;146(12):4092-8 - PubMed
Publication Types