Neuroimmune Interactions in Sjögren’s Syndrome: Relationship of Exocrine Gland Dysfunction with Autoantibodies to Muscarinic Acetylcholine Receptor-3 and Mental Health Status Parameters

Abstract

Objectives: Antimuscarinic acetylcholine receptor-3 (m3AChR) autoantibodies have been described in primary Sjögren’s syndrome (pSS). The aim of this study was to compare various methods for their detection and to assess the contributions of anti-m3AChR and other immunological and psychosocial factors to the pathomechanism of secondary SS (sSS). Methods: Sixty-five rheumatoid arthritis (RA) patients, 103 systemic lupus erythematosus (SLE) patients, 76 pSS patients and 50 controls were compared. Three immunodominant epitopes of m3AChR were synthesized and used in ELISA. Two extracellular epitopes were also prepared in fusion with glutathione-S-transferase and one in conjugation with bovine serum albumin. Mental health status was assessed with the 36-item Short-Form Health Survey and Functional Assessment of Chronic Illness Therapy fatigue scale. Correlations were evaluated between glandular function and anti-m3AChR positivities and specificities, features of SLE and RA, and mental health parameters. Results: Fourteen RA and 27 SLE patients had sSS. The autoantibody levels to all epitopes of m3AChR were significantly higher in pSS and SLE patients than in the controls. The fusion protein forms discriminated RA from pSS and SLE; furthermore, the YNIP fusion protein also distinguished pSS from SLE. The prevalence and the mean levels of all autoantibodies did not differ statistically between sicca and non-sicca SLE or RA patients. Glandular dysfunction correlated with higher age in SLE and RA and an impaired health-related quality of life in SLE. Conclusions: The second and third extracellular loops of m3AChR are antigenic in pSS. Immunoassays with antigens as fusion peptides demonstrate the best performance. Sicca SLE patients have worse mental health status. Anti-m3AChR antibodies represent a peculiar example of neuroimmune interactions.

Psychosomatische Aspekte beim trockenen Auge

“…Sie sind mitverantwortlich für Verhaltensauffälligkeiten und Probleme mit der Zufriedenheit der Therapie [6]. Daraus abgeleitete Aussagen zum Umgang mit diesen Patienten könnten zur Verbesserung der Situation und damit der psychosomatischen Erkrankung führen.…”

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

“…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.…”

“…We further confirmed that both cyclized peptides, which correspond to parts of the second (M3R 205-221 ) and third (M3R 520-527 ) extracellular loop of M3R, showed high reactivity with pSS IgG using ELISA (unpublished data). Notably, Deak et al [20] reported that a GST-YNIP (M3R 506-521 ) fusion peptide showed higher sensitivity (86.5%) and specificity (100%) than those of GST-AGSE (M3R 184-227) (75.6% and 58.1%, respectively) in pSS patients. Tsuboi et al [27] found that variable autoantibodies were detectable against the N-terminal (M3R …”

“…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).…”

Meta-Analysis of Anti-Muscarinic Receptor Type 3 Antibodies for the Diagnosis of Sjögren Syndrome

“…Over the past decade, numerous studies have explored the value of anti-M3R antibodies in the process of diagnosing SS. However, inconsistent conclusions relating to the diagnostic performance of anti-M3R antibodies have been drawn [ 5 – 15 ]. The aim of this study was to systematically review the literature to determine the diagnostic performance of anti-M3R antibodies in patients with SS.…”