Evaluation of Inhibitory Antibodies against the Muscarinic Acetylcholine Receptor Type 3 in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Prevalence of Functional mAChR3 Auto-ab in PBC and PSC Patients
2.3. Baseline Characteristics
2.4. Evaluation of Treatment Response to Standard UDCA Therapy
2.5. Statistical Analysis
3. Results
3.1. Study Population
3.2. Prevalence of Functional mAChR3 Auto-ab in PBC and PSC
3.3. Relation between mAChR3 Auto-ab Status and Clinical and Laboratory Baseline Characteristics and Histological Stage of Patients
3.4. One-Year Treatment Response to UDCA in Correlation with Prevalence of Auto-ab in PBC and PSC
3.5. Relation between the Prevalence of Functional mAChR3inh+ Auto-ab and Long-Term Prognosis in PBC and PSC
3.6. Clinical Outcome in Correlation with Prevalence of Functional mAChR3 Auto-ab in PBC and PSC
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Parameter | mAChR3inh+ PBC | n | mAChR3− PBC | n | p |
---|---|---|---|---|---|
mAChR3inh+/− status in patients (%) | 11.8 | 46/389 | 88.2 | 343/389 | - |
Sex: female (%) | 91.3 | 42/46 | 92.1 | 316/343 | ns |
Age at time of diagnosis (years) | 58(18) | 31/ 46 | 55 (15) | 243/341 | ns |
Age > 40 (%) | 87.0 | 27/31 | 92.5 | 225/243 | ns |
Age < 40 (%) | 13.0 | 4/31 | 7.2 | 18/243 | ns |
AMA | 75.0 | 24/32 | 75.4 | 193/256 | ns |
Elastography (kPa) * | 8.5 (2.8) | 11/46 | 8.0 (4.7) | 157/343 | ns |
Clear signs of fibrosis based on ultrasound (%) ** | 65.0 | 13/20 | 49.6 | 120/242 | ns |
Advanced histological stage (%) *** | 63.6 | 7/11 | 38.7 | 41/106 | ns |
Sicca syndrome (%) | 17.9 | 5/28 | 15 | 39/260 | ns |
Autoimmune thyreoiditis (%) | 14.8 | 4/27 | 9.6 | 25/260 | ns |
Autoimmune hepatitis (%) | 14.3 | 4/28 | 17.3 | 45/260 | ns |
Rheumatic disorders (%) | 3.7 | 1/27 | 17.3 | 45/260 | ns |
Alanine aminotransferase (ULN) | 1.7 (1.9) | 45 | 1.3 (1.2) | 329 | 0.01 |
Aspartate aminotransferase (ULN) | 1.3 (1.5) | 46 | 0.9 (0.7) | 327 | 0.002 |
Alkaline phosphatase (ULN) | 4.0 (2.9) | 46 | 1.8 (1.9) | 332 | <0.001 |
Gamma-glutamyltransferase (ULN) | 5.4 (9.8) | 45 | 3.4 (5.2) | 332 | <0.001 |
Bilirubin (ULN) | 0.7 (0.8) | 46 | 0.4 (0.4) | 311 | <0.001 |
Albumin (g/dl) | 4.3 (0.5) | 23 | 4.4 (0.5) | 188 | ns |
INR | 1.1 (0.2) | 6 | 1.0 (0.1) | 67 | ns |
Platelet count (/nl) | 235 (97) | 37 | 260 (79) | 283 | ns |
Parameter | mAChR3inh+ PSC | n | mAChR3− PSC | n | p |
---|---|---|---|---|---|
mAChR3inh+/− status in patients (%) | 38.1 | 45/118 | 61.9 | 73/118 | - |
Sex: male (%) | 73.3 | 33/45 | 57.5 | 42/73 | ns |
Age at time of diagnosis (years) | 37 (15) | 42/45 | 33 (19) | 65/73 | ns |
Elastography (kPa) * | 7.9 (8.7) | 7/45 | 8.75 (6.25) | 8/73 | ns |
Clear signs of fibrosis based on ultrasound (%) ** | 50.0 | 19/38 | 50.9 | 28/55 | ns |
Advanced histological stage (%) *** | 20.6 | 7/34 | 28.4 | 19/67 | ns |
Ulcerative Colitis (%) | 51.1 | 23/45 | 57.5 | 42/73 | ns |
Crohn’s disease (%) | 15.6 | 7/45 | 9.6 | 7/73 | ns |
Autoimmune hepatitis (%) | 22.2 | 10/45 | 2.7 | 2/73 | 0.001 |
Alanine aminotransferase (ULN) | 1.93 (1.89) | 27 | 2.15 (2.53) | 46 | ns |
Aspartate aminotransferase (ULN) | 1.06 (0.75) | 28 | 1.06 (1.31) | 45 | ns |
Alkaline phosphatase (ULN) | 3.06 (4.36) | 26 | 2.78 (3.08) | 46 | ns |
Gamma-glutamyltransferase (ULN) | 4.93 (5.26) | 26 | 3.77 (6.24) | 46 | ns |
Bilirubin (ULN) | 0.7 (0.57) | 13 | 0.63 (0.51) | 26 | ns |
Albumin (g/dl) | 4.3 (1) | 15 | 4.4 (0.6) | 37 | ns |
Platelet count (/nl) | 278 (88.8) | 27 | 241 (114.9) | 45 | ns |
Parameter | mAChR3inh+ PBC | n | mAChR3− PBC | n | p |
Cirrhosis (%) | 64.4 | 29/45 | 42 | 140/333 | 0.019 |
Ascites, Varices (%) | 46.7 | 7/15 | 17.8 | 32/180 | 0.014 |
Carcinoma (HCC/CCC) (%) | 5.0 | 1/20 | 0.9 | 2/225 | ns |
Liver transplant (%) | 13.3 | 6/45 | 5.9 | 20/339 | ns |
Parameter | mAChR3inh+ PSC | n | mAChR3− PSC | n | p |
Cirrhosis (%) | 36.8 | 14/38 | 31.6 | 18/57 | ns |
Ascites (%) | 15.8 | 6/38 | 7.0 | 4/57 | ns |
Cholangiocarcinoma (HCC/CCC) (%) | 4.4 | 2/45 | 6.8 | 9/73 | ns |
Liver transplant (%) | 46.0 | 29/63 | 50.8 | 63/124 | ns |
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Wilde, A.-C.B.; Greverath, L.M.; Steinhagen, L.M.; de Chamorro, N.W.; Leicht, E.; Fischer, J.; Herta, T.; Berg, T.; Preuss, B.; Klein, R.; et al. Evaluation of Inhibitory Antibodies against the Muscarinic Acetylcholine Receptor Type 3 in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis. J. Clin. Med. 2022, 11, 681. https://doi.org/10.3390/jcm11030681
Wilde A-CB, Greverath LM, Steinhagen LM, de Chamorro NW, Leicht E, Fischer J, Herta T, Berg T, Preuss B, Klein R, et al. Evaluation of Inhibitory Antibodies against the Muscarinic Acetylcholine Receptor Type 3 in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis. Journal of Clinical Medicine. 2022; 11(3):681. https://doi.org/10.3390/jcm11030681
Chicago/Turabian StyleWilde, Anne-Christin Beatrice, Lena Maria Greverath, Lara Marleen Steinhagen, Nina Wald de Chamorro, Elise Leicht, Janett Fischer, Toni Herta, Thomas Berg, Beate Preuss, Reinhild Klein, and et al. 2022. "Evaluation of Inhibitory Antibodies against the Muscarinic Acetylcholine Receptor Type 3 in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis" Journal of Clinical Medicine 11, no. 3: 681. https://doi.org/10.3390/jcm11030681