[Mucosal administration of alpha-fodrin inhibits experimental Sjögren's syndrome autoimmunity].
OBJECTIVE
To explore the effect of mucosal administration of alpha-fodrin in inhibition of autoimmunity in Sjögren's syndrome (SS).


METHODS
Thirty-four 4-week-old NOD mice were randomly divided into 4 equal groups: to be immunized by nasal administration of alpha-fodrin 1 microg/dose and 10 microg/dose respectively every two days (experimental groups), and phosphate-buffered saline (PBS) or glutathion2 S-tansferase4 (GST) (control groups). The weekly volume of water drinking was calculated. The salivary flow was maintained. Serum samples were obtained to detect the anti-SSA, anti-SSB, RF, ANA, anti- -fodrin and anti-type 3 muscarinic acetylcholine receptor polypeptide (M3RP) by immunofluorescence or ELISA. The cytokines of IFN-gamma and IL-10 were measured with ELISA. The salivary glands were examined by HE staining and immunohistochemical analysis. Flow cytometry was used to detect the proportion of Foxp3+ CD4+ CD25+ T cells.


RESULTS
The titers of anti- -fodrin antibody and M3RP antibody of the mice immunized with-fodrin were lower than those of the 2 control groups (all P < 0.05), however, there was not significant differences between these two a-fodrin immunized groups. Five of the 8 mice in the GST group, 5 mice in the PBS group, 2 mice in the alpha-fodrin 1 microg/dose group, and 3 mice in the alpha-fodrin 10 microg/dose showed ANA positive. The serum IFN-gamma levels in the mice of alpha-fodrin 1 microg/dose and 10 microg/dose groups, PBS group, and GST group were (42 +/- 16), (37 +/- 15), (87 +/- 18), and (72 +/- 11) pg/ml respectively, those of the fodrin groups being significantly lower than those of the control groups (all P < 0.05). There were not significant differences in the level of serum IL-10 among these four groups. The numbers of Foxp3+ CD4 CD25+ regulatory T cells were higher in the fodrin groups than in the PBS and GST control groups (all P < 0.05). The lymphocytic infiltration and expression of alpha-fodrin were decreased in the alpha-fodrin administrated groups. The volume of water drinking of the alpha-fodrin 1 microg/dose group, alpha-fodrin 10 microg/dose group, PBS group, and GST group were (39.2 +/- 2.1), (40.4 +/- 2.5), (49.3 +/- 3.1), and (51.6 +/- 2.8) ml respectively.


CONCLUSIONS
Mucosal administration of alpha-fodrin effectively inhibits the progression of experimental Sjögren's syndrome autoimmunity.
He
Jing
J
Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing 100044, China.
Zhao
Jin-xia
JX
Wang
Hui
H
Li
Zhan-guo
ZG
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology; D002352:Carrier Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D016688:Mice, Inbred NOD; D008840:Microfilament Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology; D011897:Random Allocation; D012859:Sjogren's Syndrome / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013049:Spectrin
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D002352:Carrier Proteins; D008840:Microfilament Proteins; D013049:Spectrin