Rates of infiltration by macrophages and dendritic cells and expression of interleukin-18 and interleukin-12 in the chronic inflammatory lesions of Sjögren's syndrome: correlation with certain features of immune hyperactivity and factors associated with high risk of lymphoma development.
OBJECTIVE
To evaluate the expression profile of infiltrating macrophages and dendritic cells (DCs) as well as of interleukin-18 (IL-18) and IL-12 in the minor salivary gland (MSG) lesions of patients with Sjögren's syndrome (SS), and to assess the relationship of these factors with disease parameters.


METHODS
Macrophages, DCs, T cells, B cells, proIL-18, mature IL-18, and IL-12 were detected by single- and double-labeling immunohistochemistry in MSG specimens from 21 patients with primary SS (13 of 21 tested for IL-12), 7 patients with secondary SS, and 9 disease control patients. Expression profiles were assessed for correlations with various disease parameters, including adverse predictors of lymphoma development.


RESULTS
MSGs from patients with SS (but not from disease controls) manifested increased infiltration by macrophages and DCs, strong expression of IL-18 by macrophages (particularly in B cell-rich areas and in germinal center-like structures in primary SS), and expression of IL-12 by mononuclear cell infiltrates. In primary SS, high infiltration by macrophages correlated with SG enlargement (P = 0.01). The DC infiltration rate correlated positively with the macrophage infiltration rate (P = 0.04), occurrence of SG enlargement (P = 0.03), and presence of C4 hypocomplementemia (P = 0.05), and inversely with serum C4 complement levels (P = 0.001). The rate of infiltration by IL-18-expressing cells correlated positively with biopsy focus scores (P < 0.001), larger infiltrates of macrophages (P = 0.01), DCs (P = 0.01), and B cells (P = 0.02), and SG enlargement (P = 0.02), and negatively with serum C4 complement levels (P = 0.02). The rate of infiltration by IL-12-expressing cells correlated inversely with that by IL-18-expressing cells (P = 0.001), biopsy focus scores (P = 0.003), and SG enlargement (P = 0.01), and positively with serum C4 complement levels (P = 0.05).


CONCLUSIONS
In patients with primary SS, infiltration of the SG by macrophages and DCs and expression of IL-18 and IL-12 appear to play active roles in the expansion and organization of infiltrative injuries and have a correlation with certain predictors of lymphoma development.
Department of Pathophysiology, University of Athens School of Medicine, 75 Mikras Asias Street, Athens, Greece. menman@med.uoa.gr
M N
MN
Manoussakis
S
S
Boiu
P
P
Korkolopoulou
E K
EK
Kapsogeorgou
N
N
Kavantzas
P
P
Ziakas
E
E
Patsouris
H M
HM
Moutsopoulos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001706:Biopsy; D002465:Cell Movement; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism*; D008223:Lymphoma / Q000209:etiology* / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D009418:S100 Proteins / Q000378:metabolism; D012470:Salivary Glands, Minor / Q000378:metabolism / Q000473:pathology; D012859:Sjogren's Syndrome / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018664:Interleukin-12; D020382:Interleukin-18; D009418:S100 Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule