Cytokine and autoantibody profiling related to histopathological features in primary Sjogren's syndrome.
OBJECTIVE
To investigate a potential correlation between circulating cytokine and autoantibody levels and histopathological features in subgroups of patients with primary SS (pSS).


METHODS
Minor salivary gland biopsies from a cohort of 141 patients fulfilling the American-European consensus classification criteria for pSS were re-examined and grouped according to focus score (FS) and germinal centre (GC) status; serum samples were analysed for autoantibodies, chemokines and cytokines.


RESULTS
Of the 115 available biopsies, 18 (16%) lacked characteristic focal mononuclear cell infiltrates [FS < 1 (FS-)] but patients were positive for Ro/SSA and/or La/SSB. IL-17, IL-1RA, IL-15, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, eotaxin, IFN-alpha and IL-4 levels were significantly increased in the 27 (23%) patients with ectopic GC formation (GC+) in the salivary glands compared with the GC- patients (n = 70). In addition, minor differences in cytokine levels were found when comparing age groups.


CONCLUSIONS
Degenerative changes observed in the minor salivary glands of patients with pSS may represent 'burned out' inflammation. The elevated levels of IL-4 found in these patients may influence the reduced salivary flow observed in GC+ patients. Increased titres of Th17-associated cytokines, IL-17, IL-1beta and the IL-23 subunit IL-12p40, may indicate a higher activity of these cells in GC+ patients. Differences in cytokine levels may be utilized when sub-grouping the SS patients into disease phases and may consequently have implications for treatment.
Reksten
Tove R
TR
Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway. tove.reksten@gades.uib.no
Jonsson
Malin V
MV
Szyszko
Ewa A
EA
Brun
Johan G
JG
Jonsson
Roland
R
Brokstad
Karl A
KA
D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D001706:Biopsy; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D020733:RNA, Small Cytoplasmic / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology; D012470:Salivary Glands, Minor / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000473:pathology; D000097585:SS-B Antigen; D000099207:SS-A Antigen
D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen; C116006:RO60 protein, human