Autoantibodies in primary Sjögren's syndrome patients induce internalization of muscarinic type 3 receptors

Jin, Meihong; Hwang, Sung Min; Davies, AN; Shin, Yonghwan; Bae, Jun Seok; Lee, Jong Ho; Lee, Eun Bong; Park, Kyungpyo

doi:10.1016/j.bbadis.2011.11.012

Cited by 35 publications

(27 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggest that IgG from SS patients induce internalization of M 3 mAChR partly through a clathrinmediated pathway. They also provide support to the notion that antimAChR M 3 antibodies cause salivary dysfunction in patients with SS via both a reduction of calcium influx and the down-regulation of M 3 mAChR molecules on epithelial cells of salivary glands [76].…”

Section: Action Of Anti-muscarinic Acetylcholine Receptors Antibodiesmentioning

confidence: 57%

Autoantibodies against Muscarinic Acetylcholine Receptor on Exocrine Glands in Sjögren Syndrome

Reina

Borda²

2014

Dentistry

View full text Add to dashboard Cite

These investigations demonstrate that serum antibodies against muscarinic acetylcholine receptors (mAChR) in primary Sjögren syndrome (pSS) and associated Sjögren syndrome (aSS) bind and activate both cholinergic receptors of M 3 in salivary gland and M 1 in neonatal myocardium and in the cerebral frontal cortex area subtypes; triggering the production of the second messengers and proinflammatory mediators related to mAChR activation. In this way the cholinergic autoantibodies damages these receptors, which thus starts acting as an antigen. On this basis M 3 and M 1 mAChR IgG can be considered new markers of pSS/aSS allowing the differentiation between dry eye and mouth of autoimmune and non-autoimmune nature. Given that cholinergic autoantibodies also deregulate the parasympathetic system of the target organs, they can also be seen as a new factor contributing to the etiopathology of the syndrome.

show abstract

Section: Action Of Anti-muscarinic Acetylcholine Receptors Antibodiesmentioning

confidence: 57%

Autoantibodies against Muscarinic Acetylcholine Receptor on Exocrine Glands in Sjögren Syndrome

Reina

Borda²

2014

Dentistry

View full text Add to dashboard Cite

show abstract

“…[16] demonstrated that carbacholinduced calcium mobilization was inhibited by long-term incubation of the cells for 12 h with anti-M3R autoantibodies. The mechanism underlying the chronic inhibitory effect of anti-M3R autoantibodies shown in HSG cells was further investigated in primary cultured hSMG epithelial cells [13]. In hSMG cells, M3R was internalized via clathrin-mediated endocytosis by incubation with pSS IgG for longer than 30 min (Figure 1).…”

Section: Inhibition Of Muscarinic Receptor Function In Various Tissuementioning

confidence: 99%

“…These findings strongly suggest that anti-M3R autoantibodies have multifaceted effects, possibly not only through direct binding of anti-M3R autoantibodies to M3R but also by affecting other molecules involved in salivary secretion. [13]. Prior to pSS IgG incubation, M3R was located predominantly at the cell membrane, while clathrin was in the cytosol.…”

Section: Inhibition Of Muscarinic Receptor Function In Various Tissuementioning

confidence: 99%

“…Taken together, it seems likely that SGECs may be capable of functioning as professional antigen presenting cells (APCs) such as macrophages, dendritic cells and B cells to present antigens or autoantigens to T cells. Recently, we investigated the possibility that M3R can be internalized by pSS IgG incubation via both clathrin-dependent [13] and clathrin-independent endocytosis, in which marked down-regulation of MHC class I was observed (unpublished data). MHC class I expressed in all nucleated cells plays pivotal roles in both the innate and adaptive immune system by serving as a ligand of inhibitory killer cell immunoglobulinlike receptors (KIRs) on natural killer (NK) cells and by presenting intracellular antigens to cytotoxic T lymphocytes [51].…”

Section: Active Role Of Salivary Gland Epithelial Cells (Sgecs) In Ssmentioning

confidence: 99%

“…Anti-nuclear autoantibodies (ANA) and rheumatoid factor (RF) are also present with high prevalence in primary SS [6]. In addition, other autoantibodies found in SS patients are cryoglobulins, anti-smooth muscle antibodies (ASMA), anti-mitochondrial antibodies (AMA) [7,8], anti-centromere antibodies (ACA) [9], antibodies against cyclic citrullinated peptides (anti-CCP) [10], anti-carbonic anhydrase antibodies [11], anti-α fodrin antibodies [12] and anti-muscarinic autoantibodies [13][14][15][16][17]. These autoantibodies can be diagnostic or prognostic markers and are associated with some specific extra-glandular manifestations.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Potential Role of Autoantibodies against Muscarinic Type 3 Receptor in Pathogenesis of Sjogren’s Syndrome

Song¹

2014

J Clin Cell Immunol

View full text Add to dashboard Cite

Sjögren's Syndrome (SS) is a systemic autoimmune disease characterized by focal mononuclear cell infiltration into target organs such as salivary and lacrimal glands, leading to sicca symptoms. SS is characterized by the production of numerous circulating autoantibodies. The anti-muscarinic autoantibodies against the type 3 receptor (anti-M3R autoantibodies) in primary SS patients' sera has recently been studied as its possible involvement in the pathogenesis of SS and a capable diagnostic marker, since M3R plays critical roles in exocrine secretion and smooth muscle contraction. Anti-M3R autoantibodies in the sera of SS patients were detectable with high sensitivity and specificity and had broad inhibitory effects on the exocrine secretion and the smooth muscle contraction mediated by parasympathetic neurons. In Salivary Gland Epithelial Cells (SGECs), the inhibitory effect of SS autoantibodies on M3R function were verified at the cellular and molecular levels; anti-M3R autoantibodies inhibited carbachol-induced [Ca 2+ ]i increase and the activities of ion channels and membrane transporters, that are dependent on [Ca 2+ ]i. Anti-M3R autoantibodies appear to inhibit M3R function in two ways: acute desensitization of M3R by direct occupation of agonist binding sites of the receptor and the resulting receptor internalization. Abundant anti-M3R autoantibodies may bind to the remaining unoccupied M3Rs, thereby causing progressive and long-term loss of M3R function. Anti-M3R positivity in SS patients was also associated with some clinical manifestations such as leucopenia, anemia, and thrombocytopenia. In this review, we will discuss the prevalence of anti-M3R autoantibodies in the sera of SS patients, the inhibitory effect of anti-M3R autoantibodies in various tissues, and the potential role of anti-M3R autoantibodies with SGECs in the pathogenesis of SS.

show abstract

Mechanisms of Secretory Dysfunction in Autoimmune Sjögren’s Syndrome

Saleh

Singh

Katz

et al. 2021

Sjögren's Syndrome and Oral Health

View full text Add to dashboard Cite

Autoantibodies in primary Sjögren's syndrome patients induce internalization of muscarinic type 3 receptors

Abstract: pSS IgG induces 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.

Cited by 35 publications

References 39 publications

Autoantibodies against Muscarinic Acetylcholine Receptor on Exocrine Glands in Sjögren Syndrome

Autoantibodies against Muscarinic Acetylcholine Receptor on Exocrine Glands in Sjögren Syndrome

A Potential Role of Autoantibodies against Muscarinic Type 3 Receptor in Pathogenesis of Sjogren’s Syndrome

Mechanisms of Secretory Dysfunction in Autoimmune Sjögren’s Syndrome

Contact Info

Product

Resources

About