Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Autoantibodies in Primary Sjgren Syndrome Patients Induce Internalization of Muscarinic Type 3 Receptors.
Jin1, Meihong, Hwang1, Sung-Min, Davies1, Alexander J., Shin1, Yonghwan, Bae1, Jun-Seok, Lee1, Chongho, Choi2, Byoong-Yong
Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocyte infiltration into the salivary and lachrymal glands, leading to dry mouth and eyes. The presence of functional autoantibodies against muscarinic type 3 receptor (M3R) in SS has been reported. However, the pathological role of these autoantibodies in the development of SS still remains to be elucidated.
Purified IgGs were obtained from normal (control) and primary SS patients' sera (pSS IgG). Internalization of M3R and clathrin was analyzed by biochemical assay and immunofluorescence confocal microscopy in human submandibular gland (hSMG) acinar cells. Cytoplasmic free Ca2+ concentration ([Ca2+]i) was measured by microspectrofluorimetry.
Incubation of hSMG cells with pSS IgG (1mg/ml) significantly decreased M3R expression levels at the membrane. Carbachol-induced [Ca2+]i transients (CICTs) in these cells were also inhibited by pSS IgG. In contrast to pSS IgG, control IgG had no effect on both the M3R expression level and CICTs. We found that binding of pSS IgG to M3R induces phosphorylation of M3R, and that pSS IgG-induced M3R internalization is prevented by lysosomal inhibitor, chloroquine. In addition, pSS IgG decreased membrane clathrin expression, which was inhibited by atropine. Our immunofluorescence study further confirmed that pSS IgG induces a co-localization of M3R with clathrin and subsequent internalization of M3R.
pSS IgG induces an internalization of M3R partly through a clathrin-mediated pathway. The results suggest M3R internalization as a potential mechanism to explain the exocrinopathy seen in pSS patients.
To cite this abstract, please use the following information:
Jin, Meihong, Hwang, Sung-Min, Davies, Alexander J., Shin, Yonghwan, Bae, Jun-Seok, Lee, Chongho, et al; Autoantibodies in Primary Sjgren Syndrome Patients Induce Internalization of Muscarinic Type 3 Receptors. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :491