Clinical associations of autoantibodies to human muscarinic acetylcholine receptor 3213–228 in primary Sjögren's syndrome

Abstract

The presence of m3AChR(213-228) antibodies is a common feature in pSS. Although it is significantly more common in pSS than in the comparison groups, anti-m3AChR(213-228) positivity is not exclusive to pSS.

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

“…Naito et al found that altered peptides derived from the second extracellular domain of M3R inhibited IFN-γ production by suppressing the number of IFN-γ-producing T cells in patients with SS [42]. A finding was also reported that leucopenia, a common extra-glandular manifestation seen in SS patients, was significantly more common in anti-M3R 213-228 positive pSS patients (53%) than in those without this antibody (14%) [21]. In an aforementioned report [26], anti-M3R 205-220 positivity was associated with hematological abnormalities, such as leucopenia, anemia, and thrombocytopenia in pSS.…”

“…However, the variation in the sensitivity was quite large, ranging from 0% to 97% (Table 1). Naito et al [25] observed only 11/122 (9%) anti-M3R positivity in pSS patients using the M3R 213-237 peptide, while Kovács et al [21] found that 66 out of 73 (90%) pSS patients were anti-M3R 213-228 -positive, using a peptide-GST fusion protein. He et al [26] demonstrated that the sensitivity (62.2%) and specificity (95.1%) of the cyclic M3R 205-220 peptide were higher than that of the linear peptide (56.1% and 84.7%, respectively).…”

“…These results indicate that the physiologic structure of M3R peptides such as in the case of GSTfusion protein or dimerized peptide or cyclic peptides is important to detect the exact epitopes with high sensitivities. The specificity of anti-M3R autoantibodies in SS was also variable but in a high range from 58.1% to 100%, compared to healthy controls [20,21,26]. The functional epitopes on M3R to the anti-M3R autoantibodies in patients with pSS are also variable depending on the method used.…”

“…The presence of autoantibodies against muscarinic type 3 receptors (anti-M3R autoantibodies) in the sera of patients with SS has been investigated by several researchers in the last two decades and is an emerging candidate to be part of the diagnostic criteria for primary SS due to its high specificity [20,21]. However, the sensitivity of anti-M3R autoantibodies is extremely variable ranging from 0% to 97% depending on the methods used to detect them (Table 1).…”

Modulation of c-Jun NH<sub>2</sub>-Terminal (JNK) by Cholinergic Autoantibodies from Patients with Sjögren’s Syndrome

“…In particular; antibodies to the antigens SS-A/Ro and SS-B/ La are commonly used in the diagnosis of pSS [2]. The presence of subtypes M 1 [3], M 3 [4,5] and M 4 [6] specific autoantibodies in 83% -90% persons with pSS [7] is an important advance towards understanding the pathogenesis of pSS not only in terms of impaired glandular function, but also because of peripheral parasympathetic dysfunction associated with the disease [8,9].…”