Состояние аппендикулярной мышечной массы у женщин с ревматоидным артритом: фокус на иммунологические маркеры

Цель исследования – определить связь между аппендикулярной мышечной массой (АММ) и иммунологическими маркерами сыворотки крови у женщин с ревматоидным артритом (РА).
Материал и методы. У 200 женщин с РА (медиана возраста – 60,0 [52,5; 65,5] лет) проводилось определение АММ с помощью двухэнергетической рентгеновской абсорбциометрии для выявления наличия саркопенического фенотипа (СПФ); также выполнено определение уровня С-реактивного белка (СРБ), ревматоидного фактора, антител к циклическому цитруллинированному пептиду. У 87 пациенток исследовали уровни сывороточного миостатина, фоллистатина, интерлейкина 6 (ИЛ-6), рецепторов к ИЛ-6, инсулиноподобного фактора роста 1 (ИФР-1), адипонектина, лептина, фактора роста фибробластов 23 (ФРФ23), фактора некроза опухоли SF12 (superfamily member 12).
Результаты. Пациентки, имевшие и не имевшие СПФ, различались по уровню СРБ (медиана – 8,6 [1,3; 22,2] и 5,6 [1,2; 17,4] мг/л соответственно; р=0,041) и лептина (медиана – 3,8 [2,4; 5,7] и 5,4 [3,8; 6,9] нг/мл соответственно; р=0,030). АММ коррелировала с уровнем СРБ, фоллистатина и лептина. В линейном многофакторном регрессионном анализе выявлена взаимосвязь между мышечной массой и фоллистатином (β=–0,35; р=0,007), ИФР-1 (β=–0,38; р=0,002), лептином (β=0,36; р=0,004) и ФРФ23 (β=0,33; р=0,008).
Заключение. Проведенное исследование показало, что у больных РА состояние мышечной массы связано с уровнем фоллистатина, ИФР-1, лептина и ФРФ23.

1. Rosenberg I. Summary comments. Am J Clin Nutr. 1989;50:1231-1233. doi: 10.1093/ajcn/50.5.1231

2. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: Preferred definitions and conceptual frame-work. Clin Pharmacol Ther. 2001;69:89-95. doi: 10.1067/mcp.2001.113989

3. Ladang A, Beaudart C, Reginster JY, Al-Daghri N, Bruyère O, Burlet N, et al. Biochemical markers of musculoskeletal health and aging to be assessed in clinical trials of drugs aiming at the treatment of sarcopenia: Consensus paper from an Expert Group Meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d’Expérimentation en Santé (CARES SPRL), under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskeletal Conditions and Aging. Calcif Tissue Int. 2023;112:197-217. doi: 10.1007/s00223-022-01054-z

4. Ko DS, Kim YH, Goh TS, Lee JS. Altered physiology of mesenchymal stem cells in the pathogenesis of adolescent idiopathic scoliosis. World J Clin Cases. 2020;8(11):2102-2110. doi: 10.12998/wjcc.v8.i11.2102

5. Baker JF, England BR, George MD, Wysham K, Johnson T, Kunkel G, et al. Elevations in adipocytokines and mortality in rheumatoid arthritis. Rheumatology (Oxford). 2022;61(12):4924-4934. doi: 10.1093/rheumatology/keac191

6. Ngeuleu A, Allali F, Medrare L, Madhi A, Rkain H, Hajjaj-Hassouni N. Sarcopenia in rheumatoid arthritis: Prevalence, influence of disease activity and associated factors. Rheumatol Int. 2017;37(6):1015-1020. doi: 10.1007/s00296-017-3665-x

7. Müller R, Kull M, Põlluste K, Valner A, Lember M, Kallikorm R. Factors associated with low lean mass in early rheumatoid arthritis: A cross-sectional study. Medicina (Kaunas). 2019;55(11):730. doi: 10.3390/medicina55110730

8. Dietzel R, Wiegmann S, Borucki D, Detzer C, Zeiner KN, Schaumburg D, et al. Prevalence of sarcopenia in patients with rheumatoid arthritis using the revised EWGSOP2 and the FNIH definition. RMD Open. 2022;8(2):e002600. doi: 10.1136/rmdopen-2022-002600

9. Navarro-Ibarra MJ, Saucedo-Tamayo MDS, Alemán-Mateo H, Parra-Sánchez H, Othón-Ontiveros P, Hernández J, et al. Association between interleukin 6 and C-reactive protein serum levels and body composition compartments and components in breast cancer survivors. Biol Res Nurs. 2024;26(2):231-239. doi: 10.1177/10998004231207022

10. Wu X, Li X, Xu M, Zhang Z, He L, Li Y. Sarcopenia prevalence and associated factors among older Chinese population: Findings from the China Health and Retirement Longitudinal Study. PLoS One. 2021;16(3):e0247617. doi: 10.1371/journal.pone.0247617

11. Morawin B, Tylutka A, Bielewicz F, Zembron-Lacny A. Diagnostics of inflammaging in relation to sarcopenia. Front Public Health. 2023;11:1162385. doi: 10.3389/fpubh.2023.1162385

12. Сафонова ЮА. Серологические маркеры саркопении у людей в возрасте 65 лет и старше. Клиницист. 2023;17(4): 19-26.

13. Lee SJ, Lee YS, Zimmers TA, Soleimani A, Matzuk MM, Tsuchida K, et al. Regulation of muscle mass by follistatin and activins. Mol Endocrinol. 2010;24(10):1998-2008. doi: 10.1210/me.2010-0127

14. Bergen HR 3rd, Farr JN, Vanderboom PM, Atkinson EJ, White TA, Singh RJ, et al. Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass: Insights using a new mass spectrometry-based assay. Skelet Muscle. 2015;5:21. doi: 10.1186/s13395-015-0047-5

15. Maïmoun L, Mura T, Attalin V, Dupuy AM, Cristol JP, Avignon A, et al. Modification of muscle-related hormones in women with obesity: Potential impact on bone metabolism. J Clin Med. 2020;9(4):1150. doi: 10.3390/jcm9041150

16. White TA, LeBrasseur NK. Myostatin and sarcopenia: Opportunities and challenges – A mini-review. Gerontology. 2014;60(4):289-293. doi: 10.1159/000356740

17. Nakashima M, Toyono T, Akamine A, Joyner A. Expression of growth/differentiation factor 11, a new member of the BMP/TGFbeta superfamily during mouse embryogenesis. Mech Dev. 1999;80(2):185-189. doi: 10.1016/s0925-4773(98)00205-6

18. Baker JF, Von Feldt JM, Mostoufi-Moab S, Kim W, Taratuta E, Leonard MB. Insulin-like growth factor 1 and adiponectin and associations with muscle deficits, disease characteristics, and treatments in rheumatoid arthritis. J Rheumatol. 2015;42(11):2038-2045. doi: 10.3899/jrheum.150280

19. Jiang JJ, Chen SM, Chen J, Wu L, Ye JT, Zhang Q. Serum IGF-1 levels are associated with sarcopenia in elderly men but not in elderly women. Aging Clin Exp Res. 2022;34(10):2465-2471. doi: 10.1007/s40520-022-02180-2

20. Chen HT, Chung YC, Chen YJ, Ho SY, Wu HJ. Effects of different types of exercise on body composition, muscle strength, and IGF-1 in the elderly with sarcopenic obesity. J Am Geriatr Soc. 2017;65(4):827-832. doi: 10.1111/jgs.14722

21. Tabara Y, Okada Y, Ochi M, Ohyagi Y, Igase M. Associations between adiponectin and leptin levels and skeletal muscle mass and myosteatosis in older adults: The Shimanami Health Promoting Program Study. Geriatr Gerontol Int. 2023;(23):444-449. doi: 10.1111/ggi.14582

22. Memelink RG, Njemini R, de Bos Kuil MJJ, Wopereis S, de Vogel-van den Bosch J, Schoufour JD, et al. The effect of a combined lifestyle intervention with and without protein drink on inflammation in older adults with obesity and type 2 diabetes. Exp Gerontol. 2024;(190):112410. doi: 10.1016/j.exger.2024.112410

23. Teixeira LAC, Dos Santos JM, Parentoni AN, Lima LP, Duarte TC, Brant FP, et al. Adiponectin is a contributing factor of low appendicular lean mass in older community-dwelling women: A cross-sectional study. J Clin Med. 2022;11(23):7175. doi: 10.3390/jcm11237175

24. Baker JF, Katz P, Weber DR, Gould P, George MD, Long J, et al. Adipocytokines and associations with abnormal body composition in rheumatoid arthritis. Arthritis Care Res (Hoboken). 2023;75(3):616-624. doi: 10.1002/acr.24790

25. Si Y, Kazamel M, Benatar M, Wuu J, Kwon Y, Kwan T, et al. FGF23, a novel muscle biomarker detected in the early stages of ALS. Sci Rep. 2021;11(1):12062. doi: 10.1038/s41598-021-91496-6

26. Fukasawa H, Ishigaki S, Kinoshita-Katahashi N, Niwa H, Yasuda H, Kumagai H, et al. Plasma levels of fibroblast growth factor-23 are associated with muscle mass in haemodialysis patients. Nephrology (Carlton). 2014;19(12):784-790. doi: 10.1111/nep.12333

27. Avin KG, Vallejo JA, Chen NX, Wang K, Touchberry CD, Brotto M, et al. Fibroblast growth factor 23 does not directly influence skeletal muscle cell proliferation and differentiation or ex vivo muscle contractility. Am J Physiol Endocrinol Metab. 2018;315(4): E594-E604. doi: 10.1152/ajpendo.00343.2017