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Cholinoreceptor Autoantibodies in Sjögren Syndrome

S. Reina1, B. Orman1, J.M. Anaya2, L. Sterin-Borda1,3, and E. Borda1,3,*

1 Pharmacology Unit, School of Dentistry, University of Buenos Aires, M.T. de Alvear 2142-4° "B", 1122 AAH Buenos Aires, Argentina;
2 Rheumatology Department, School of Medicine, Universidad Pontificia de Medellín, Colombia; and
3 Argentine National Research Council (CONICET), Buenos Aires, Argentina


Figure 1
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Figure 1. Actions of serum and IgG from pSS patients on PGE2 generation. (Upper panel) Effects of increasing concentrations of serum (A) and pSS IgG (B) on PGE2 production on an isolated rat submandibular gland. Values represent the mean ± SEM of 10 different individual serum or IgG samples from each group, performed in triplicate. *p < 0.001 vs. groups II and III. (Lower panel) Concentration-response curves of pSS IgG on PGE2 production on an isolated rat submandibular gland in the absence or in the presence of muscarinic acetylcholine receptor antagonists (C), and in the presence of M1, M3, and M4 synthetic peptides (D). The blocker agents were used at 1 x 10–6 M, and the peptides at 1 x 10–5 M. Values represent the mean ± SEM of 7 different individual serum or corresponding IgG samples from group I, performed in duplicate. *p < 0.01 vs. pirenzepine, 4-DAMP, and tropicamide. **p < 0.001 vs. M1 peptide, M3 peptide, and M4 peptide. [Group designations as in the Table: Group I, 15 women with primary Sjögren syndrome and with dry mouth; Group II, 16 post-menopausal women with dry mouth and without Sjögren syndrome; and Group III, 18 healthy, pre-menopausal women without any systemic disease (control group).]

 

Figure 2
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Figure 2. Influence of different inhibitors on pSS IgG and RT-PCR analysis. (A) Concentration-response curves of pSS IgG in the absence or in the presence of 5 x 10–6 M OBAA or 1 x 10–4 M aspirin or 4 x 10–8 M rofecoxib. Results are expressed as mean ± SEM of 6 individual pSS IgG samples performed in duplicate. *p < 0.001 vs. pSS IgG alone; **p < 0.005 vs. pSS IgG alone. (B) Effect of pSS IgG on PGE2 production by a rat submandibular gland. Glands were treated with pSS IgG alone or in the presence of calcium-blocking agents (verapamil, 5 x 10–5 M; thansigargin, 1 x 10–6 M) or with a calcium ionophore agent (A 23187, 1 x 10–6 M) alone. Values are mean ± SEM of 6 individual pSS IgG samples performed in duplicate. *p < 0.005 vs. pSS IgG. (C) RT-PCR products of COX-1 and COX-2 obtained from rat submandibular gland alone (basal) or in the presence of 1 x 10–7 M pSS IgG. (D) The densitometry analysis of 7 individual IgG sample tests performed in duplicate. Values are mean ± SEM. Note that the COX-2 band in the presence of pSS IgG increased significantly (p < 0.001) compared with the basal COX-2 band.

 

Figure 3
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Figure 3. PGE2 production on serum and saliva from different groups: 15 women with pSS (group I), 16 post-menopausal women with dry mouth and without SS (group II), and 18 healthy pre-menopausal women (group III). Solid lines: mean values ± SEM. p < 0.001 between group I and groups II and III.

 





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